Ped Core

The A.S.P.E.N.
Pediatric Nutrition Support

Core Curriculum
EDITOR-IN-CHIEF
Mark R. Corkins, MD, CNSP, SPR, FAAP
Associate Professor
Indiana University School of Medicine, Riley Hospital for Children
Indianapolis, IN
SECTION EDITORS
Jane Balint, MD
Director, Intestinal Support Service
Pediatric Gastroenterology, Hepatology and Nutrition
Nationwide Childrens Hospital
Columbus, OH
Elizabeth Bobo, MS, RD, LDN, CNSD
Clinical Dietitian, Gastroenterology and Nutrition
Nemours Childrens Clinic
Jacksonville, FL
Steve Plogsted, PharmD, BCNSP
Clinical Pharmacy Specialist
Nutrition Support Pharmacist
Columbus, OH
Jane Anne Yaworski, MSN, RN
Clinical Nurse Specialist/Nutrition Support Service/Intestinal Care Center
Childrens Hospital of Pittsburgh
Pittsburgh, PA
MANAGING EDITOR
Nina D. Seebeck
AMERICAN SOCIETY FOR PARENTERAL AND ENTERAL NUTRITION
The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) is a scientific society whose members are health care professionalsphysicians, dietitians, nurses, pharmacists, other allied health professionals, and researchersdedicated to assuring that every patient receives optimal
nutrition care.
A.S.P.E.N.s mission is to serve as a preeminent, interdisciplinary, nutrition society dedicated to patient-centered clinical practice worldwide through
advocacy, education, and research in specialized nutrition support.
NOTE: This publication is designed to provide accurate authoritative information in regard to the subject matter covered. It is sold with the understanding that the publisher is not engaged in rendering medical or other professional advice. Trademarked commercial product names are used only
for education purposes and do not constitute endorsement by A.S.P.E.N.
This publication does not constitute medical or professional advice, and should not be taken as such. To the extent the information published herein
may be used to assist in the care of patients, this is the result of the sole professional judgment of the attending health professional whose judgment is
the primary component of quality medical care. The information presented herein is not a substitute for the exercise of such judgment by the health
professional.
All rights reserved. No part of this may be used or reproduced in any manner whatsoever without written permission from A.S.P.E.N. For information write: American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), 8630 Fenton Street, Suite 412, Silver Spring, MD 20910-3805; (301)
587-6315, www.nutritioncare.org, email: [email protected].
Copyright 2010. American Society for Parenteral and Enteral Nutrition.

ISBN: 978-1-889622-14-9
Printed in the United States of America.
Contents
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Reviewers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii
Acknowledgments & Dedication. . . . . . . . . . . . . . . . . . . . . . . xix
PART I
INTRODUCTORY AND BASIC PHYSIOLOGY
1. Mechanics of Nutrient Intake. . . . . . . . . . . . . . . . . . . . . . . 3
Carol G. McKown, DDS, MS
Anna M. Dusick, MD
7. Water-Soluble Essential Micronutrients. . . . . . . . . . . . . . 56

Winston Koo, MBBS, FACN, CNS
Judith Christie, RN, MSN
May Saba, PharmD, BCNSP
Mirjana Lulic-Botica, BSc, BCPS
Letitia Warren, RD, CSP
8. Fat-Soluble Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
9. Fluids and Electrolytes. . . . . . . . . . . . . . . . . . . . . . . . . . . 87

Gerald L. Schmidt, PharmD, BCNSP
2.Gross Digestion Principles: Gastric Grinding

and Gastrointestinal Motility. . . . . . . . . . . . . . . . . . . . . . 11
PART II
AGE-SPECIFIC NUTRITION FOR GROWTH
ANDDEVELOPMENT
3. Carbohydrates: Changes with Development. . . . . . . . . . . 17
10. Nutrition and Early Development. . . . . . . . . . . . . . . . . 105
Jane P. Balint, MD
Seema Mehta, MD
Robert J. Shulman, MD
4. Fats. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Peggy R. Borum, PhD
5.Protein Digestion, Absorption, and Metabolism. . . . . . . . 31

Richard A. Helms, PharmD
Emma M. Tillman, PharmD
Anup J. Patel, MD
John A. Kerner, MD
6. Minerals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Russell J. Merritt, MD, PhD, FAAP

Barbara Marriage, PhD, RD
Ricardo Rueda, MD, PhD
11. Human Milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

Jacqueline J. Wessel, RD, CNSD
12. Infant Formulas and Complementary Feeding. . . . . . . 129

Kelly Green-Corkins, MS, RD, CNSD
Timothy Sentongo, MD
13. Growth Assessment and Monitoring . . . . . . . . . . . . . . 143

14. Obesity and Metabolic Disorders. . . . . . . . . . . . . . . . . 149

Michelle Battista, BS, PhD Candidate
Robert Murray, MD
15. Lipid Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162

Shirley Huang, MD
Melanie Katrinak, RD, CSP, LDN
iii
iv
CONTENTS
16. Use of Fad and Popular Diets. . . . . . . . . . . . . . . . . . . . 169

Catherine Christie, PhD, RD
Julia A. Watkins, PhD, MPH
Judith C. Rodriguez, PhD, RD
17. Sports Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

Jackie Buell, PhD, RD, LD, ATC, LAT
Diane L. Habash, PhD, RD, LD
PART III
DISEASE STATES AND NUTRITION
18. Developmental Delay . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Kathleen J. Motil, MD, PhD
19. Eating Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204

Christina Fitzgerald, MS, RD, LDN
Betsy Hjelmgren, MS, RD, LDN, CSP
20. Food Allergies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213

Mary Beth Feuling, MS, RD, CD, CNSD
Michael B. Levy, MD
Praveen S. Goday, MBBS, CNSP
21. Diabetes Mellitus and Other Endocrine Disorders. . . . 226

Diane Olson, RD, CNSD, CSP, LD
W. Frederick Schwenk II, MD
22. Inborn Errors of Metabolism . . . . . . . . . . . . . . . . . . . . 232

Bridget Reineking, MS, RD, CD
Sandra van Calcar, PhD, RD, CD
23. Cardiac Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247

Anupama Chawla, MD, CNSP, DCH (UK)
Janice Antino, RD, MS, CNSD, CSP
Mindy Freudenberg, RD, MS, CNSD
24. Renal Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256

Christina L. Nelms, MS, RD, CSP, CNSC, LD
Marisa Juarez, MPH, RD, LD
Bradley A. Warady, MD
25. Gastrointestinal Disease. . . . . . . . . . . . . . . . . . . . . . . 283

Donald George, MD
26. Hepatic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302

Samuel A. Kocoshis, MD
Renee A. Wieman, RD, CSP, LD, CNSD
27. Intestinal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
30.Oncology, Hematopoietic Transplant,

and Survivorship. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
Nancy Sacks, MS, RD, LDN
Elizabeth Wallace, RD, CNSC, LDN
Seema Desai, MS, RD, LDN, CNSD
Vinod K Prasad, MD, MRCP (London)
David Henry, MS, BCOP
Virginia Guzikowski, MSN, CRNP
Liesje Nieman Carney, RD, CNSD, LDN
Beth Bogucki Wright, MS, RD, CSP, LDN
Susan Rheingold, MD
31. Trauma and Burns . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378

Arlet G. Kurkchubasche, MD
32. Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387

PART IV
NUTRITION CARE OF THE PEDIATRIC PATIENT
33.Assessment of Nutrition Status by Age
and Determining Nutrient Needs. . . . . . . . . . . . . . . . . 409
Jennifer Blair, MA, RD, CSP, LDN
34.Parenteral and Enteral Nutrition Support:

Determining the Best Way to Feed. . . . . . . . . . . . . . . . 433
Andrea Nepa, MS, RD, CSP, LDN
Sherri Shubin Cohen, MD, MPH
Amy Dean, MPH, RD, LDN
Colleen Yanni, MS, RD, LDN
Goldie Markowitz, MSN, CRNP
35. Implementation of the Plan. . . . . . . . . . . . . . . . . . . . . 448

Beth Lyman, RN, MSN
Jennifer M. Colombo, MD
Jodi L. Gamis, OTR
36.Evaluation and Monitoring of Pediatric Patients

Receiving Specialized Nutrition Support . . . . . . . . . . . 460
Elaina Szeszycki, PharmD, BCNSP
Wendy Cruse, MMSc, RD, CNSD
Michelle Strup, PharmD
37. Ethical Issues in the Provision of Nutrition . . . . . . . . . 477

Patrick M. Jones, MD, MA
Brian Carter, MD
Robert H. Squires, Jr., MD
28. Pulmonary Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . 323

Allison Mallowe, RD, LDN
Suzanne Michel, MPH, RD, LDN
Maria Mascarenhas, MBBS
29. Organ Transplantation. . . . . . . . . . . . . . . . . . . . . . . . . 337

Anita Nucci, PhD, RD, LD
Sharon Strohm, MBA, RD, LDN
Neelam Katyal, MS, RD, LDN
Beth Lytle, RD, LDN
Test Your Knowledge Answers. . . . . . . . . . . . . . . . . . . . . . . . 487

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495
Contributors

Certified Specialist in Pediatric Nutrition, Registered Dietitian
Stony Brook University Hospital
Stony Brook, NY
Brian S. Carter, MD
Professor of Pediatrics
Vanderbilt University Medical Center
Nashville, TN
Jane P. Balint, MD
Columbus, OH
Anupama Chawla, MD, CNSP, DCH (UK)

Director of Pediatric Gastroenterology and Nutrition
Stony Brook, NY

The Ohio State University
OSUN Interdisciplinary PhD Program
Columbus, OH
Clinical Dietitian III
The Childrens Hospital of Philadelphia
Philadelphia, PA
Clinical Dietitian, Gastroenterology and Nutrition
Jacksonville, FL
Peggy R. Borum, PhD
Professor of Human Nutrition
University of Florida
Gainesville, FL
Director of Sports Nutrition, Department of Human Nutrition
College of Education and Human Ecology
Ohio State University
Columbus, OH

Chair, Department of Nutrition and Dietetics
University of North Florida
Jacksonville, FL
Childrens Hospital of Michigan
Detroit, MI
Medical Director, Pediatric Feeding and Swallowing Center
Philadelphia, PA
Pediatric Gastroenterology Fellow
Childrens Mercy Hospital
Kansas City, MO
Associate Professor
Indiana University School of Medicine,
Riley Hospital for Children
Indianapolis, IN
vi
CONTRIBUTORS

Pediatric Dietitian
Indianapolis, IN
Clinical Dietitian
Philadelphia, PA
Clinical Dietitian
Duke University Medical Center
Durham, NC
Anna M. Dusick, MD
Associate Professor of Clinical Pediatrics
Indianapolis University School of Medicine
Indianapolis, IN
Clinical Dietitian Specialist
Childrens Hospital of Wisconsin
Milwaukee, WI
Owner/President
Nourished, Nutrition and Wellness Services
Chicago, IL
Certified Nutrition Support Dietitian, Registered Dietitian
Stony Brook, NY
Jodi L. Gamis, OTR
Occupational Therapist
Kansas City, Missouri
Donald E. George, MD
Division Chief Gastroenterology
Jacksonville, FL
Associate Professor
Medical College of Wisconsin
Milwaukee, WI

Clarian Home Care
Indianapolis, IN
Nurse Practitioner
Division of Oncology
Philadelphia, PA
Bionutrition Clinical Research Manager
General Clinical Research Center
Ohio State University
Columbus, OH
Department of Clinical Pharmacy
The University of Tennessee Health Science Center
Memphis, TN
David W. Henry, MS, BCOP
Associate Professor, Pharmacy Practice
University of Kansas Medical Center
Kansas City, KS
Betsy Hjelmgren, MS, RD, LD, CSP
Founder, Feed to Succeed
Chicago, IL
Shirley Huang, MD
Medical Director, Healthy Weight Program
Attending Physician, Division of GI, Hepatology and Nutrition
Philadelphia, PA
Clinical Fellow (Neonatology)
Vanderbilt Childrens Hospital
Nashville, TN
Pediatric Renal Dietitian
Texas Childrens Hospital
Houston, TX
Clinical Nutritionist
Philadelphia, PA
CONTRIBUTORS

Clinical Dietitian
Pittsburgh, PA 15213

Clinical DietitianPediatric
Philadelphia, PA
John A. Kerner, MD
Stanford University
Palo Alto, CA

Pediatric Nurse Practitioner
Philadelphia, PA
University of Cincinnati College of Medicine
Director, Nutrition and Small Bowel Transplantation
Cincinnati Childrens Hospital Medical Center
Cincinnati, OH

Senior Research Scientist
Abbott Nutrition
Columbus, OH

Clinical Director, NICU
Hutzel Womens Hospital
Carman and Ann Adams Department of Pediatrics
Wayne State University
Detroit, MI
Associate Professor of Surgery and Pediatrics
Alpert Medical School
Brown University
Providence, RI
Michael B. Levy, MD
Associate Professor
Allergy-Immunology
Milwaukee, WI
Hutzel Womens Hospital
Detroit, MI
Beth Lyman, RN, MSN
Senior Program Coordinator for the Nutrition Support Team
Kansas City, MO
Beth Lytle, RD, LDN
Clinical Dietitian
Pittsburgh, PA
vii

Section Chief, Nutrition, Division of Gastroenterology
andNutrition
Associate Professor of Pediatrics
University of Pennsylvania School of Medicine
Philadelphia, PA
Owner/President
Carol G. McKown, M.S., D.D.S., P.C
Volunteer Faculty, Riley Hospital Pediatric Dentistry Dept.
Carmel, IN
Seema Mehta, MD
Department of Pediatric Gastroenterology,
Hepatology, and Nutrition
Baylor College of Medicine
Houston, TX
Director of Medical Affairs
Abbott Nutrition
Columbus, OH
Medical Director, Nutrition Support & Intestinal Rehabilitation
Childrens Hospital of Los Angeles
Keck School of Medicine
University of Southern California
Los Angeles, CA
Clinical Dietitian, Pediatric Cystic Fibrosis Center
Philadelphia, PA
viii
CONTRIBUTORS

USDA/ARS Childrens Nutrition Research Center
Houston, TX
Susan R. Rheingold, MD
Assistant Professor of Pediatrics
Philadelphia, PA
Robert Murray, MD
Center for Healthy Weight and Nutrition
Columbus, OH

Professor
Jacksonville, FL

Clinical Nutrition Specialist, Pediatric Renal Dietitian
Childrens Mercy Hospitals and Clinics
Kansas City, KS

Associate Director Discovery Technology
Abbott Nutrition
Granada, Spain

Philadelphia, PA

Department of Pharmacy Practice
Detroit, MI

Clinical Dietitian IV, Publication Specialist
Philadelphia, PA
Assistant Professor
Georgia State University
Division of Nutrition
Atlanta, GA
Diane L. Olson, RD, CNSD, CSP, LD
Mayo Clinic College of Medicine
Rochester, MN
Anup J. Patel, MD
Stanford University
Palo Alto, CA
Vinod K. Prasad, MD, MRCP (London)
Attending Physician
Pediatric Bone Marrow and Stem Cell Transplant Service
Duke University Medical Center
Durham, NC
Childrens Hospital of WisconsinMilwaukee
Milwaukee, WI

Clinical Dietitian/Research Coordinator
Philadelphia, PA
Nutrition Specialist
Shands Jacksonville
Jacksonville, FL
Clinical Associate Professor
University of Florida College of Pharmacy
Gainesville, FL
Mayo Clinic College of Medicine
Rochester, MN
Assistant Professor
University of Chicago
Chicago, IL
Texas Childrens Hospital Foundation Chair
in Pediatric Gastroenterology
Childrens Nutrition Research Center
Houston, TX
CONTRIBUTORS

Clinical Director, Pediatric Gastroenterology
Pittsburgh, PA

Detroit, MI

Dietitian Coordinator
Pittsburgh, PA

Associate Professor
Department of Nutrition and Dietetics
Jacksonville, FL

Home Infusion Pharmacist
Clarian Home Care
Indianapolis, IN

Neonatal Nutritionist
Cincinnati Childrens Hospital
Cincinnati, OH

Clinical Pharmacist Nutrition Support and Pediatric
Gastroenterology
Indianapolis, IN
Renee A. Wieman, RD, CSP, LD, CNSD

Registered Dietician II
Liver and Intestinal Transplantation Services and
Comprehensive Nutrition Center
Cincinnati, OH

Fellow, Department of Clinical Pharmacy
The University of Tennessee Health Science Center
Memphis, TN
Sandy van Calcar, PhD, RD, CD
Metabolic Dietitian
Biochemical Genetics Program
University of WisconsinMadison
Madison, WI
Clinical Dietitian
Philadelphia, PA
University of Missouri-Kansas City School of Medicine
Associate Chairman, Department of Pediatrics
Chief, Section of Pediatric Nephrology
Director, Dialysis and Transplantation
The Childrens Mercy Hospital
Kansas City, MO

Clinical Dietician IV, Technology Specialist
Clinical Nutrition Development
Philadelphia, PA
Clinical Dietitian & Education Coordinator (Outpatient)
Philadelphia, PA
ix
Reviewers
Judith M. Bailer, BS, RD, LDN

Clinical Dietitian II
Childrens Hospital of Philadelphia
Philadelphia, PA
Jane P. Balint, MD
Columbus, OH
Laura E. Beerman, RD, CNSD
Regional Home Nutrition Support Dietitian
Walgreens-Optioncare Home IV Infusion Company
Omaha, NE
Jatinder Bhatia, MD
Professor and Chief, Section of Neonatology
Medical College of Georgia
Augusta, GA
Susan Carlson, MMSc, RD, CSP, LD
Neonatal Dietitian
University of Iowa Childrens Hospital at
The University of Iowa Hospitals and Clinics
Iowa City, IA
Pamela Charney, PhD, RD
Lecturer, Nutrition Sciences and
Affiliate Associate Professor, Pharmacy
University of Washington
Seattle, WA
Katherine H. Chessman, PharmD, FCCP, BCPS, BCNSP

Professor, Clinical Pharmacy and Outcome Sciences;
Clinical Pharmacy Specialist, Pediatrics/Pediatric Surgery
South Carolina College of Pharmacy
Medical University of South Carolina Campus
Medical University of South Carolina Childrens Hospital
Charleston, SC
Michael L. Christensen, PharmD
Stevens Professor, Pharmacy Director
Department of Clinical Pharmacy
University of Tennessee Health Science Center and
Le Bonheur Childrens Medical Center
Memphis, TN
Conrad R. Cole, MD, MPH, MSc
Assistant Professor
Division of Gastroenterology, Hepatology and Nutrition
Department of Pediatrics
Emory University School of Medicine
Atlanta, GA
Associate Professor
Indiana University School of Medicine
Indianapolis, IN
Kimberly Cover, MS, RD, CSSD, LDN
Sports Nutrition Therapist/Clinical Specialist
The Sports Medicine and Performance Center
of the Childrens Hospital of Philadelphia
King of Prussia, PA
xi
xii
REVIEWERS

Pediatric Dietitian
Indianapolis, IN
Douglas Drenckpohl, MS, RD, CNSC, LDN
Advanced Practice Dietitian-Neonatal
Childrens Hospital of Illinois at
OSF Saint Francis Medical Center
Peoria, IL
Jeanne Ann Farrell, MS, RD, CNSC, LD/N
Clinical Dietitian
All Childrens Hospital
St. Petersburg, FL
Dianne Frazier, PhD, MPH, RD
University of North Carolina
Department of Pediatrics, Division of Genetics and Metabolism
Chapel Hill, NC
Associate Professor
Milwaukee, WI
David E. Goldstein, MD
Professor Emeritus
University of Missouri Health Sciences Center
Columbia, MO
Susan Goode, MS, RD, MD
Tufts University School of Medicine
Attending Physician
Pediatric Gastroenterology & Nutrition
Baystate Childrens Hospital
Springfield, MA
Barbara Goodin, MS, RD
Pediatric Nutrition Specialist in Cystic Fibrosis,
Inborn Errors of Metabolism and Diabetes
University of Virginia Health System
Department of Pediatrics/Div of Genetics
Metabolic Diseases Program
Charlottesville, VA
Lori Grant, MEd, RD, CSP, LD
Pediatric Dietitian
The University of Texas Health Science Center at San Antonio
San Antonio, TX

Clarian Home Care
Indianapolis, IN
Kathleen M. Gura, BS, PharmD, BCNSP
Clinical Pharmacy Specialist GI/Nutrition
Associate Professor Pharmacy Practice
Childrens Hospital Boston
Massachusetts College of Pharmacy and Health Sciences
Boston, MA
Geraldine Hennies, RN III
Nutrition Support Nurse, Case Manager
Cincinnati, OH
Simon Horslen, MB ChB FRCPCH
Professor of Pediatrics, Medical Director,
Liver & Intestine Transplantation
University of Washington and Seattle Childrens Hospital
Seattle, WA
Shirley Huang, MD
Medical Director, Healthy Weight Program
Attending Physician, Division of GI, Hepatology and Nutrition
Philadelphia, PA
Susanna Y. Huh, MD, MPH
Instructor in Pediatrics
Harvard Medical School, Childrens Hospital Boston
Boston, MA
Khursheed Jeejeebhoy, MBBS, PhD, FRCPC
Emeritus Professor of Medicine
University of Toronto and St. Michaels Hospital
Toronto Ontario Canada
Doron D. Kahana, MD, FAAP
Assistant Clinical Professor
Pediatric Gastroenterology & Nutrition
Harbor-UCLA Medical Center
Torrance, CA
Ajay Kaul, MBBS, MD
Director, Impedance/Motility Disorders Program
Cincinnati, OH
REVIEWERS
Craig Lawrence Kien, MD, PhD

The Mary Kay Davignon Green and Gold Professor,
Depts. of Pediatrics and Medicine
The University of Vermont College of Medicine
Burlington, VT
Angela Kirkwood, RN, BSN, IBCLC, RLC
Nurse Feeding Specialist and
Board Certified Lactation Consultant
Childrens Hospital of Pittsburgh of UPMC
Clinical Nutrition Department
Pittsburgh, PA
Ronald E. Kleinman, MD
Physician in Chief, Massachusetts General Hospital for Children
Chair, Department of Pediatrics
Chief, Pediatric Gastrointestinal and Nutrition Unit
Massachusetts General Hospital
Charles Wilder Professor of Pediatrics
Harvard Medical School
Boston, MA
Susan Konek, MA, RD, CSP, CNSD, LDN
Director of Clinical Nutrition
Philadelphia, PA
Carolyn Kusenda, MS, RD, CNSD, LD
Neonatal Nutrition Support Specialist/Clinical
Nutrition Manager
Childrens National Medical Center
Washington, DC
Joel Lim, MD
Assistant Professor of Clinical Pediatrics
Indiana University
Indianapolis, IN
Allison M. Mallowe, RD, LDN
Clinical Pediatric Dietitian
Philadelphia, PA
Maria R Mascarenhas, MBBS
Section Chief, Nutrition, Division of
Gastroenterology and Nutrition
Philadelphia, PA
xiii
Carrie McFarland, RD, CNSD

Pediatric and Neonatal Clinical Dietitian
UCSF Medical Center
San Francisco, CA
Clare McLaughlin, RD, CNSD, CSP
Pediatric Dietitian
Clarian Health Inc.
Indianapolis, IN
Catherine M. McDonald, PhD, RD, CNSD
Clinical Dietitian
Primary Childrens Medical Center
Salt Lake City, UT
Kate Micucci, MS, RD, LD
Dietitian Specialist
The University of Pittsburgh Medical Center
Boardman, OH
Shideh Mofidi, MS, RD, CSP
Metabolic Dietitian and Clinical Coordinator in the Inherited
Metabolic Disease Center
Maria Fareri Childrens Hospital
West Chester, NY
Linda V. Muir, MD
Dietitian, Pediatric Gastroenterologist
Swedish Medical Center
Seattle, WA
Assistant Professor
Georgia State University
Atlanta, GA
Patricia OBrien, RD
Senior Supervising Dietitian, Pediatric
University of California at Davis Health System
Sacramento, CA
Surekha Pendyal, MSc, MEd, RD
Metabolic Nutritionist
University of North Carolina
Chapel Hill, NC
Barbara Robinson, MPH, RD, CNSD
Pediatric Nutrition Specialist
Hasbro Childrens Hospital
Clinical Teaching Associate
Alpert Medical School of Brown University
Providence, RI
xiv
REVIEWERS
Jill Rockwell, RD, LD, CNSD

Childrens Medical Center Dallas
Dallas, TX
Carol J. Rollins, MS, RD, CNSD, PharmD, BCNSP
Coordinator, Nutrition Support Team
University Medical Center
Tucson, AZ
William O. San Pablo, Jr., MD
Director, Nutrition Support and
Inflammatory Bowel Disease Program
Childrens Mercy Hospital and Clinics,
UMKC School of Medicine
Kansas City, MO
Sue Schiller, RD
Pediatric Clinical Dietitian III
Inova Fairfax Hospital for Children
Falls Church, VA
Assistant Professor of Pediatrics,
Director Pediatric Nutrition Support Service
The University of Chicago Medical Center
Chicago, IL
Texas Childrens Hospital Foundation Chair
in Pediatric Gastroenterology
Childrens Nutrition Research Center
Houston, TX
Eric Sibley, MD, PhD

Stanford University School of Medicine
Palo Alto, CA
Edwin Simpser, MD
Chief Medical Officer
St. Marys Hospital for Children
Assistant Professor of Pediatrics, NYU School of Medicine
Bayside, NY
Jonathan M. Spergel, MD, PhD
Chief, Allergy Section
Director, Center for Pediatric Eosinophilic Disorders
Division of Allergy and Immunology
Philadelphia, PA
Nancy Spinozzi, RD, LDN
Renal Dietitian
Childrens Hospital
Boston, MA
Christina J. Valentine, MD, MS, RD
Medical Director, Neonatal Nutrition and Lactation
Section of Neonatology, The Ohio State University and
Columbus, OH
Wendy Wittenbrook, MA, RD, CSP, LD
Clinical Dietitian
Texas Scottish Rite Hospital for Children
Dallas, TX
Foreword
I am very pleased to be asked to write the foreward to The

A.S.P.E.N. Pediatric Nutrition Support Core Curriculum
an outgrowth of the pediatric section concept which Russ
Merritt, MD, PhD, Bill Byrne, MD, Walter Faubion, RN,
and I started in the early 1980s. We recognized early on the
importance of programmatic recognition within A.S.P.E.N.
of the special needs of infants and children, and the advantages of continuing the multidisciplinary approach to
pediatric nutrition which has been the hallmark of the
success of the A.S.P.E.N. model. The evolution of the art and
science of pediatric nutrition support is well demonstrated
in the postgraduate courses, seminars, workshops, round
tables, and paper/poster presentations that have punctuated our annual clinical congresses.
The Pediatric Nutrition Support Core Curriculum is a
well-earned and anticipated culmination of the multidisciplinary approach developed and refined over the years. It
has been shaped by A.S.P.E.N.s Standards of Practice, Clinical Guidelines, and Interdisciplinary Nutritional Support
Competencies. In addition, it is designed to serve as: (1) a
companion resource to the A.S.P.E.N. Nutrition Support
Practice Manual, and the A.S.P.E.N. Nutrition Support Core
Curriculum: A Case-Based Approachthe Adult Patient; (2)
an educational resource for those preparing for the specialization certification examination in nutrition support; (3) a
valuable clinical resource for the generalist: and (4) an interdisciplinary document that recognizes both the common
body of knowledge and the unique skills that each member
of the multidisciplinary team possesses. Currently, there are
general guidelines that allude to the importance of nutrition
for infants and children and the need for training in pediatric nutrition. However, there is no defined curriculum
that states explicitly what a pediatric caregiver is required
to know. Dr. Corkins, his co-authors, and all of us who have

lived and contributed to the evolution of pediatric nutrition
science believe that a well-organized and disciplined core
curriculum for pediatric caregivers is greatly needed.
A wide range of specialty fields require a working knowledge of pediatric nutrition and form our target audience:
dietetics, nursing, pharmacy, medicine, gastroenterology,
surgery, and pediatrics. In addition to the expected comprehensive treatment of the basics of developmental physiology
of the digestive process and the nutrition requirements
of various organ systems, chapters include Obesity and
Metabolic Disorders, Use of Fad and Popular Diets, Sports
Nutrition, Implementation of the Plan, and Ethical Issues in
the Provision of Nutrition. Each chapter contains evidencebased background information emphasizing core science,
intended for the professional who already possesses a basic
understanding of the principles of food biochemistry, and
nutrition in wellness and disease. The layout of each chapter
includes a table of contents, learning objectives, and a
concluding set of self-assessment questions to test the readers understanding of the subject matter.
It is my hope that this book will provide an effective
learning experience and referenced resource for all health
professionals caring for infants and children, leading to
improved patient care.
John R. Wesley, MD, FACS, FAAP
Adjunct Professor of Surgery
Pediatric Surgery
Childrens Memorial Medical Center
Feinberg School of Medicine
Northwestern University
xv
Preface
The A.S.P.E.N. Pediatric Nutrition Support Core Curriculum

is the result of a question. One of the pediatric residency
directors asked me several years ago if A.S.P.E.N. had a
curriculum for teaching the residents about nutrition. They
had been looking for a way to teach the residents nutrition
and found nothing. I sadly told her no. It turned out that in
the pediatric section I was not the only person who saw the
need for a pediatric core curriculum.
This curriculum is designed to start with the basic
nutrition physiology then progress through the principles
for nutrition in disease states. It ends with the nuts and
bolts for daily care. Each chapter begins with an outline of
the important contents of that chapter and then ends with
test your knowledge questions. These are designed to
help you find out if you learned the important concepts of
the chapter. What this curriculum doesnt have is in-depth
coverage of neonatal nutrition, although some of this is
covered in the context of the physiology of development.
It is also not exhaustive in its coverage of nutrition in the
various disease states. This is designed to be the pediatric
core curriculum; to be a disease-specific specialist will
require study beyond this starting point. The desire here
is to create a firm foundation of pediatric nutrition that
anyone can build on any way they wish.
Mark R. Corkins
Editor-in-Chief
xvii
Acknowledgments & Dedication
I have to thank Michelle Spangenburg and Nina Seebeck

for keeping everything on track to pull this book together.
Ialso must thank my Associate EditorsJane Balint, Elizabeth Bobo, Steve Plogsted, and Jane Anne Yaworskifor
their input and help with the legwork that goes into pulling
lots of authors and reviewers together and helping with
ideas to improve the curriculum. Finally, I wish to thank
Amy Cevario and Pattie Covert at Clayton Design Group.
I have to dedicate this book to the best pediatric
learning experience ever, my children and my personal
dietitian, best friend, and wife, Kelly.
Mark R. Corkins
Editor-in-Chief
xix
PART I
INTRODUCTORY AND
BASIC PHYSIOLOGY
1. Mechanics of Nutrient Intake. . . . . . . . . . . . . . . . . . . . 3

Anna M. Dusick, MD
2.Gross Digestion Principles: Gastric Grinding
and Gastrointestinal Motility. . . . . . . . . . . . . . . . . . . 11
Jane P. Balint, MD
3. Carbohydrates: Changes with Development. . . . . . . . 17
Seema Mehta, MD
4. Fats. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Peggy R. Borum, PhD
5. Protein Digestion, Absorption, and Metabolism. . . . . 31
Anup J. Patel, MD
John A. Kerner, MD
6. Minerals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
7. Water-Soluble Essential Micronutrients. . . . . . . . . . . 56
8. Fat-Soluble Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . 74
9. Fluids and Electrolytes. . . . . . . . . . . . . . . . . . . . . . . . 87
Mechanics of Nutrient Intake
Mark R. Corkins, MD, CNSP, SPR, FAAP, Carol G. McKown, DDS, MS, and Anna M. Dusick, MD
Learning Objectives
CONTENTS
Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Appetite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mastication/Dentition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Feeding Development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3
3
4
5
Swallowing
Feeding Skills in the First Year
Feeding Skills in the Second Year
Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Feeding Teams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1. Understand how societal and behavioral influences

guide food consumption.
2. Identify the psychological, mechanical, biochemical, and
hormonal inputs that determine appetite and intake.
3. Describe the developmental stages in deglutition
and corresponding changes in appropriate feedings
inchildren.
Background
This is a curriculum for nutrition in the pediatric age group.

Thus, by necessity, it focuses on the biological and physiological needs of pediatric patients. Unlike other areas of
medicine directed by genetic programming, a great deal of
emotions and memories are associated with nutrition right
from the start. The original source of nutrition is food, yet
food is so much more than nutrition. It is symbolic, from
the stalk of wheat in the A.S.P.E.N. logo to the traditional
birthday cake. Marion Winkler, in her 2007 A.S.P.E.N.
presidential address, related the story of the foods her
mother requested when dying from cancer. Winkler realized that it was about more than just food, stating It was
always about the nostalgic stories that surrounded the food,
the memories, the social aspects, and the companionship of
the sharing ofmeals.1
Appetite
When we begin to explore the desire to eat, we realize that

appetite has a cultural aspect.2 Part of this derives from the
environment; certain foods are more available in different
geographic regions, and one cultures delicacy may be unacceptable in another. Childrens memories and associations
will thus influence their intake. 3 Also, human beings will
3
THE A.S.P.E.N. PEDIATRIC NUTRITION SUPPORT CORE CURRICULUM
eat some foods just because they taste good. The reward of
taste stimulates feeding even in the absence of a true energy
deficit.4
There are critical periods of infant development that
hinge upon exposures to new tastes and textures. Genetic
input affects the sense of taste itself, including the strength
of response to sweet, salty, bitter, and sour. 5 Studies show
that breastfed infants have greater willingness to try
new tastes2,6; this is believed to be from their exposure
to various flavors in breast milk. Early exposure to tastes
determines taste and food preferences before the child
develops neophobia. 2 Neophobia is the developmental stage
between 18 months to 2 years of age when children resist
trying new foods. 2,5 The more a child is exposed to a taste,
the more likely it is to be accepted as a preferred taste. 5,6
Studies indicate that it may take 5 to 10 exposures before
a food becomes an accepted taste. 6 Also, there appears to
be a critical period for beginning solid foods, due to their
texture, which is before 10 months of age. Northstone et al
reported on long-term feeding problems related to acceptance of the taste and texture of foods.7 Feeding difficulties
in children identified by 9,360 parents were found to occur
more often in those children whose parents delayed initiating solid foods until after 10 months of age.7
Biological preferences are also altered by modeling
that children see when observing their parents and peers.2,5
Eating with others influences the feeding behaviors and the
food preferences that children ultimately develop.6
Appetite control is centered in the hypothalamus of the
brain and integrates information from multiple sources.4,8
The general level of appetite is influenced by the amount
of the hormone, leptin, produced by the bodys adipose
tissue.4,9 The liver also sends appetite-influencing signals
to the brain, primarily through the energy products fat and
glucose and the level of adenosine triphosphate (ATP) in
the liver cells.8 The insulin level produced by the pancreas
in response to serum glucose levels influences the general
appetite level as well.4,8 Leptin and insulin suppress inhibition, or drive the appetite, via the hypothalamus.10
The first stage in appetite is the cephalic phase, which
is a biological response to feeding cues. This concept was
first presented by Ivan Pavlov. Pavlov demonstrated that
he could condition dogs to salivate at the ringing of a bell
by developing an association with feedings.11 A variety of
studies have shown that visual, olfactory, gustatory, tactile,
and auditory inputs stimulate processes in the salivary
glands, gastrointestinal (GI) tract, pancreas, and cardiovascular and renal systems.12 These responses are quick
and prepare the body for the digestion and absorption of
2010 A.S.P.E.N. www.nutritioncare.org
the anticipated meal.12 The rest of the responses from the

stomach and small intestine tend to decrease appetite.9
Once beyond the cephalic phase, appetite level is
modified by inputs from the enteric nervous system (ie,
from chemical and stretch receptors in the GI tract) and
hormonal and metabolic signals.9 During the gastric phase
the brain receives signals concerning the volume of food
ingested and data about its nutrient content.9 Endocrine
cells in the stomach produce ghrelin that stimulates appetite4; ghrelin levels are high when the stomach is empty
and fall after eating.4,10 Emptying of the stomach also influences the neural control of appetite with gastric distention
signaling via the vagus nerve to decrease appetite.10
The intestinal phase is communicated by a variety of
signaling peptides that are released into the circulation.
These peptides act to decrease appetite and are released in
proportion to the amount of various nutrients ingested.4
These include peptide YY, glucagon-like peptide 1, oxyntomodulin, cholecystokinin, and pancreatic polypeptide.4 A
variety of other peptides may influence appetite but these
await confirmatory studies.
The hypothalamus integrates all of these signals to
regulate appetite. The heightened appetite drive that occurs
in pediatric patients that increases the caloric intake for
growth is not well understood. This drive may derive from
programming within the hypothalamus itself or from
signals indicating increased nutrient needs due to growth.
Mastication/Dentition
An important part of digestion is the initial homogenization

of food that takes place in the mouth. Mastication, or the act
of chewing, depends on the teeth to make foods a uniform
consistency. Human beings are born toothless, which necessitates a reliance on liquid feedings. The muscles used in
mastication are the temporalis, the masseter, and the medial
and lateral pterygoids. The trigeminal nerve is the primary
nerve involved in mastication. The act of chewing involves
two sets of teeth, the anterior teeth (incisors and canines)
and the posterior teeth (premolars and molars). The anatomy
of the incisors and canines with their single cusps and their
anterior position in the mouth allow themto tear food. The
anatomy of the premolars and molars with multiple cusps
and their posterior position in the mouth allow them to
grind and chew food, preparing it for swallowing.13
The primary dentition, or development and eruption of
teeth, consists of 20 teeth, all of which begin development
between 13 to 20 weeks in utero. Teething, the act of tooth
eruption, may cause infants malaise, with increased drooling
plus stomach or bowel changes, but it is not associated with
MECHANICS OF NUTRIENT INTAKE
fevers. The mandibular central incisors are the first teeth

to erupt between ages 6 to 10 months. The next teeth to
erupt are the maxillary central incisors between ages 8 to 12
months. Over the next 2 years the other primary teeth come
in as shown in Table 1-1.
Table 1-1 Primary Teeth by Age of Eruption
Primary Teeth
Age of Eruption
Mandibular central incisors

Maxillary central incisors
Maxillary lateral incisors
Mandibular lateral incisors
Maxillary first molars
Mandibular first molars
Maxillary canines
Mandibular canines
Second molars
610 mo
812 mo
913 mo
1016 mo
1319 mo
1418 mo
1622 mo
1723 mo
23 y
The primary dentition stays intact until ages 5 to 7 years

when the permanent dentition begins to erupt. As the root
end of the permanent tooth develops in the bone, it causes
the crown of the tooth to emerge, which resorbs the root of
the primary tooth leaving only the crown. The crown of the
primary tooth is then shed, allowing the permanent tooth
to erupt. The mandibular central incisors and mandibular
and maxillary first molars are the first permanent teeth to
erupt between ages 6 and 7 years. Their hard tissue formation begins shortly after birth. The subsequent progression
of permanent tooth acquisition is shown in Table 1-2.
Table 1-2 Permanent Teeth by Age of Eruption
Permanent Teeth
Age of Eruption
Mandibular central incisors

Mandibular first molars
Maxillary first molars
Maxillary central incisors
Mandibular lateral incisors
Maxillary lateral incisors
Mandibular canines
Maxillary premolars
Mandibular premolars
Maxillary second premolars
Mandibular second premolars
Maxillary canines
67 y
67 y
67 y
78 y
78 y
89 y
910 y
1011 y
1012 y
1012 y
1112 y
1112 y
The permanent third molars, or wisdom teeth, are the most

common missing teeth and normally erupt between ages 17
and 21 years.14
Feeding Development
Swallowing
The process of swallowing is divided into 3 distinct
physiological phases. These phases are the oral phase, the
pharyngeal phase, and the esophageal phase. Each phase
depends on the correct anatomy and neurophysiology of
the muscles for feeding and appropriate ventilation.
The oral phase consists of the preparatory stage and the
movement of food being propelled to the back of the mouth.
Infants take most liquids into the mouth already on the
back third of the tongue; this changes as they develop more
skill in the front of the mouth (tongue, jaw, and lips), and
develop teeth. Purees and solids are propelled to the back of
the mouth by the tongue. (Later in infant development the
lips are used for assisting with eating during the oral phase.
Skills such as taking purees off a spoon or drinking through
a straw will occur in the last half of the first year.)
The pharyngeal phase consists of the liquid or food
coming to the back of the mouth, the pharynx, and reflexively being swallowed. The soft palate and uvula lift so that
liquid or food will not pass into the nasopharynx. The larynx
closes by muscle contractions and the downward movement
of the epiglottis. Respiration ceases briefly (deglutition
apnea) and, after the food has started its descent, expiration
then inspiration will occur. In the infant, the swallow can
occur at any part of the respiratory cycle and it is variable.15
The upper esophageal sphincter relaxes so that the food
can enter the esophagus in the beginning of the esophageal
phase. The cricopharyngeus muscle relaxes at the upper
end of the esophagus and food travels to the stomach by
peristalsis. Successful swallowing depends on all of these
structures, muscles, and neurological and respiratory
systems working in coordinated millisecond timing.16,17
Anatomical or physiological abnormalities with these
systems will affect feeding effectiveness and efficiency.
Feeding Skills in the First Year

The typical newborn is ready to feed shortly after birth.
The reflexive root allows the infant to open the mouth,
turn toward the food source, latch, and begin to suck. The
newborn will suck, swallow, and breathe in a rhythmic
sequence. This pattern is established with the help of the
early reflexes and behaviors that are developed in utero
and improves by the third day of life.18 The rooting reflex
is among the most important and is activated by a light
touch on or near the infants mouth. Once latched onto the
nipple, the infants tongue and jaw work together to stroke
the nipple and express milk.19 The infant will feed in a burst 2010 A.S.P.E.N. www.nutritioncare.org
pause pattern that is usually quite regular, with the bursts

being suck-swallow-and-breathe cycles and the pauses
being brief and regular rest periods. Bursts of 8 sucks or
more are seen in the typical newborn. 20 Sensing changes in
the nipple, the infant can vary the suck pressure quite easily
to control the flow of milk. During early infancy, the infant
will increase the rate of expression per minute with age.
Studies have varied on the changes in the volume of expression; however, it ranges from 0.26 to 0.4 mL per suck. 21,22
In a typical newborn, one suck-swallow-breathe cycle
including all 3 phases lasts approximately 1 second. 21 As the
infants oromotor skills develop, the increase in control and
efficiency of intake allows the older infant to take more milk
in less time.
Pacifier sucking differs from feeding. In pacifier sucking
(non-nutritive sucking), the suck rate is twice as fast as nutritive sucking.20 Only the oral phase is seen in non-nutritive
sucking. The swallow-and-breathe phases of feeding are not
coordinated. This is why many non-feeding infants can nonnutritively suck but have difficulty when liquid is introduced
by a nipple.
Readiness for transitioning to spoon feeding has been
debated, and recommendations have changed over the
years. Brain growth and neural pathway maturation support
development of a larger variety of oromotor movements. The
tongue no longer moves in a forward-backward patterned
response. The infants tongue is able to stay in the mouth, not
thrust out, and move side to side in response to stimulation,
such as mouthing his or her fingers or hand. The infant no
longer has a single oral response of suck-swallow-breathe, or
bursts of sucking without swallowing as in pacifier sucking.
At 5 to 6 months of age an infant typically has some sitting
balance and wants to feed in an upright position. The infant
can anticipate the food and will open his or her mouth for
the spoon. The lips will close on the spoon to pull the food
off.23 The food is moved all around in the mouth, not strictly
kept over the center of the tongue for propulsion back for
swallowing. The tongue and the jaw no longer work only as
a single unit. The gag is diminished to allow for non-liquids
and will continue to be modulated as the experience with
textures continues.24
When infants begin to pick up objects, at age 6 to 7
months, they naturally put them into their mouths. As the
tongue can move in multiple directions and mouth objects,
the parent introduces meltable solids and foods with greater
texture (lumps) for the infant to handle. In late infancy, the
infant begins to munch or use an up-down motion of the
jaw to begin mastication of foods. This chewing increases
in efficiency with age.25 Soft solid foods are then provided
with small single bite-size pieces for the infant to move

around in the mouth and eventually swallow. There is less
rhythm to this feeding as compared to nutritive sucking.
The movements are volitional and no longer directed by
reflex. Early reflexes are fading between 4 to 8 months and
volitional patterns of oromotor skills are the norm. 26 By 9
months of age, with the development of the fine motor skills
of reach, grasp, and release, self-feeding is established. Now
the infant is skillful at watching others, communicating
interests in foods and eating. Cup and straw drinking begin
as the infant is guided by a parent. The infant will not gum
the cup, but opens his or her mouth to accept liquids from
the cup that is guided by the parent. At this age, both breastfeeding and bottle feeding begin to diminish as the infant
takes in a greater proportion of liquids by cup and solids by
spoon or hand.24
Problems in Infant Feeding Skills
Infant feeding difficulties can be broadly related to problems with anatomy, neurodevelopment, or respiration.
Anatomical abnormalities of the head and neck are typically congenital and may affect the muscles of feeding as
well as the physiological timing and efficiency of feeding,
and lead to poor efficiency of intake. In the extreme,
dysphagia (or swallowing dysfunction) can be seen. Classically, cranial nerve abnormalities cause dysphagia, and it
is being recognized earlier along with the subtle effects of
muscle tone and posture on feeding. Neurodevelopmental
problems, such as an infant with muscle tone abnormalities,
persistence of early reflexes, or abnormal oral reflexes, can
also lead to dysphagia.27 Infants with hypotonia (as may
be seen in infants with Down syndrome) may have significant oromotor dysfunction, dysphagia, and aspiration.28
Even infants with normal development can have difficulty
feeding if they have abnormal respirations or gastroesophageal reflux. They may tire easily and self-limit their intake,
or they may have difficulty with the suck-swallow-breathe
sequence and self-limit due to aspiration, which is passage
of liquid or solids into the airway during swallowing.29
Premature infants frequently have feeding difficulties
because of either, or both, respiratory problems and neurodevelopmental problems. Early birth does not allow for the
typical developmental sequence of oral skills. Poor growth,
of especially the youngest gestational age infants, may not
allow for maturation of neural pathways. Many premature
infants have difficulty with newborn skills when they are
at a term-adjusted age and may have significant feeding
problems. Premature infants with bronchopulmonary
dysplasia have been seen to have abnormal development of
suck patterns. 30 Some infants, who had significant limitations in oral feeding attempts due to a high level of illness
or respiratory disorders, can display aversion to attempts at
oral feeding. In others, a persistent rapid breathing rate can
interfere with establishing an efficient feeding rhythm.
Evaluation of the infant who is not feeding appropriately can be performed by a physician, nurse, occupational
therapist, or speech therapist trained in, and experienced
with, infant feeding. The evaluation will include a medical
history, developmental history, and a neurological examination as well as an oromotor assessment including feeding or
feeding attempt. A multidisciplinary approach is required.
Pediatric specialists in gastroenterology, neurology, rehabilitation, development, and others may be needed. The
evaluation, under the direction of a physician, may include
radiological testing such as a feeding study, esophagram, or
studies for reflux or gastric emptying. Neurological studies
of the central nervous system may be needed for the diagnosis of neurodevelopmental abnormalities. Studies of
respiratory function and sufficiency of ventilation may be
needed to provide optimal respiratory support for feeding.
It is important to determine the safety of feeding and
ensure that the infant is not aspirating as a result of the
underlyingproblems. 31
Sometimes, despite extensive evaluations, the etiology
of the feeding difficulties is never discovered. There is also a
belief that in some situations the initiating organic cause has
resolved but the resulting behavior has become established.
Once the cause and extent of poor feeding is understood,
a treatment plan can be undertaken to work on oral feedings, and/or to provide supplemental feedings for the safety
and growth of the infant. Supplemental feedings can consist
of nasogastric feedings or feedings into the jejunum. Such
treatment plans should be drafted with the parents and a
team of medical and therapy providers.
period, chewing improves and changes from the up-down

munching motion to the rotary chewing that allows the
toddler to grind meat fibers by age 3 years. The toddler will
increase chewing efficiency to 5 years of age. 33 Through trial
and error, carefully, the parents will supply the toddler with
small bites of their own foods and expand the toddlers diet.
Meltable solids will be exchanged for non-meltable solids
that require biting off and chewing as the parent sees the
child is ready for the single bite. Gradually, the diet will
reach that of the preschooler.
The toddler may initially allow the parent to assist with
providing bites, but this will diminish and, by 18 months, the
child will insist on exclusive self-feeding. The use of utensils
can start as early as 15 months, but is generally not perfected
until much later. Initially, sticky foods will be given to help
with self-spoon feeding; later the child will learn to spear
with a fork as well, particularly soft foods. Eating with his
or her fingers to assist the utensil feeding will continue until
the preschool age. Also, the child can now drink independently from an open cup.24
Behavior during mealtimes can be challenging as the
toddler will seek to exert control over this environment
as well. How the parents model and reinforce appropriate
behavior to diminish unwanted behavior can affect not only
eating but also sleeping habits and play interactions. Routine
meals and snacks that are eaten with the child are the best
times to teach a child appropriate mealtime behavior. As the
toddlers ability to understand language increases, the parents
need to demonstrate and explain appropriate behavior at
mealtimes. Praise for sitting and eating with the family is
necessary, as well as repetitive teaching of appropriate behaviors. Watching the toddlers cues is important, as throwing or
playing with food may signal that the child is full. As with all
behaviors, routine and consistency will teach both the easy as
well as the difficultfeeder.
Feeding Skills in the Second Year
Problems with the Toddler Feeder

Problems that affected an infants feeding may still be
present when that child reaches toddlerhood. Medical
problems of anatomical anomalies, neurodevelopmental
problems, or cardio-respiratory concerns require ongoing
medical and therapeutic intervention. However, those
toddlers who had normal feeding skills in their first year
may have new behaviors affecting feedings, or have aversion to advancing on to a variety of flavors and textures. In
one population study, parents described 20% of toddlers as
having feeding problems. 34 At times a sentinel event can be
recalled (he had his tonsils out and couldnt eat); other
times, subtle problems with advancing textures in infancy
Toddlers typically need to expand their acceptance of foods

and master self-feeding, including biting and chewing. This
is a tall order as they are also developing independence and
have the ability to make choices and affect their environment. The majority of toddlers (from 1 to 3 years of age)
enter this stage eating table foods. They have successfully transitioned to some of the foods their families eat
by their first birthday. 32 Due to their immature oromotor
skills, toddlers need their foods diced, chopped, or cut into
small bite-sized pieces. This continues until their ability to
bite a single mouthful of food becomes skillful. Only then
can a parent rely on the toddler not to choke. During this
were present and not well recognized. Still other problems

include the toddler with behavioral problems that are now
more evident at this age, such as short attention span, oppositionality, or slow learning. Sometimes the organic process
that caused a feeding problem will resolve but the inappropriate feeding behavior persists.
Evaluating new feeding problems in the toddler begins
with a thorough feeding history of who, what, when, where,
how, and how much the child is fed. Often through this
history, the initial therapeutic interventions can be determined. Review of the anthropometric measures since birth
will identify growth failure, and a physical examination will
determine the need for additional cardiac, respiratory, or GI
evaluation. The neurological and developmental examination can determine the need forfeeding studies, or further
psychological or developmental evaluation.
Most therapeutic plans include a mealtime routine and
appropriate modeling of eating behavior by parents and
caregivers. Choosing a nutritious variety of foods to serve
at meals and as snacks will expand the feeding experience
of the toddler and decrease pickiness. 3537 It is important
to ascertain the toddlers baseline abilities with oromotor
function, fine motor development, and cognitive function
to determine the level at which to begin. Identification of
the problem(s) as well as the parents goals for feeding will
direct the therapists plans, dietary plans, and home intervention. In toddlers with weight loss, worsening feeding
problems, or significant family stress, referral to a feeding
team can be helpful. The toddler with feeding problems may
need such a team approach, including a psychologist, occupational and speech therapists, and dietitian, to provide
behavioral plans, therapy, and dietary advice.
Dysphagia
Neuromotor impairment in swallowing can also be termed

dysphagia. In the infant and young child, feeding proceeds in
the developmental sequence mentioned, and abnormalities
in feeding abilities need to be evaluated for a neurological
cause. This diagnosis is made by history, a neurological
examination by a physician, and a feeding observation.
Feeding studies, in which the infant or child is fed using the
observation of video fluoroscopy, can identify neuromotor
problems of pharyngeal pooling, nasopharyngeal reflux, or
laryngeal aspiration. During a swallow/feeding study, the
infant or child is fed liquids, purees, or solids laced with
barium so that the ingested substance is visible under video
fluoroscopy. At some institutions, feeding studies can be
done with pulse oximetry to see the effect of respiratory
effort or deglutition apnea on the total saturation of oxygen.
The real-time images are observed by the therapist or other

personnel performing the study, and are further reviewed
by a radiologist. When a child aspirates, the feeding plan
is modified to avoid liquids or textures that the child is not
able to eat safely. Further neurological diagnosis as to the
cause of dysphagia should be investigated by the physician.
Therapeutic interventions can include:
physical, occupational, and speech therapy to advance
skills;
modifications of liquids or foods offered;
adaptation of cups and utensils for feeding;
positioning assistance to provide a flexed and upright
position for feeding;
dietitian adaptation of the diet to meet caloric, nutrition, and volume goals;
nutrition support through gastrostomy feedings;
diagnosis and treatment of gastroesophageal reflux;
medications to normalize tone and posture; and
repeated feeding studies.
The goals of therapy will be to normalize tone and
posture, particularly around head control and seating for
feeding. Other goals will be to foster feeding development
in the typical sequence as determined by the childs level
of function and the safety of the feeding. For example, an
infant who has had brain damage from meningitis may be
seen to have dysphagia. Methods that lead to relaxation
may need to be used on the infant to decrease hypertonicity
and foster normal positioning. This infant may require a
feeder seat for good positioning, and may need to be offered
purees only, because liquids are aspirated. This infant may
need dietary assistance with increased caloric density to
decrease the volume of intake needed by tube feeding; or he
may need to have small and frequent feedings if intolerant
of large gastrostomy feeding volumes. Once again, a team
approach is needed in the feeding care of the infant or child
who has dysphagia. 38
Feeding Teams
Pediatric institutions that form feeding teams draw from

the professional expertise at their organizations. With that
in mind, each team will determine the problems they feel
are appropriate in their setting and for their population. The
usual team members include:
child and parents;
a physician, who may be a developmental pediatrician,
gastroenterologist, general pediatrician, or a pediatric
physiatrist;
a coordinator, who may be in social work, psychology,
or nursing;
a child psychologist;
a speech and/or occupational therapist;
a dietitian; and
a social worker.
For the feeding team to be successful, the parents must
clearly identify their goals and be willing to make changes,
and to work with the team members. Each professional
must also be willing to work with team members and to
support the parents and patient during the process. Setting
clear goals with the team and reviewing those goals is an
important part of a feeding team program.
For example, Abby is a young toddler who has
aversiveness to eating because of severe respiratory problems caused by prematurity. Her respiratory status has
significantly improved and she needs only occasional bronchodilators. She is gastrostomy fed and is very sensitive to
the rate of feedings. Her mother has cut back on her feedings so Abby is also failing to thrive. There are many goals
for the team members, and progress may vary in these goals.
The family hopes to shorten feeding times and increase
Abbys oral feedings so she can eventually stop gastrostomy
feedings. These are appropriate goals for the child and the
team members; however, these are long-term goals and the
progress is incremental and variable. The parents, with the
teams help, determine the daily schedule for feeding, and
continue in the routine of feedings. The physician and dietitian may work on a short-term goal of improving Abbys
weight gain while trying to shorten her feeding times. The
therapists may start by improving her ability to stay at the
table at mealtime and touch food for short time periods.
The dietitian and therapists may use a chaining technique
to select foods that are similar to foods Abby likes so as to
slowly broaden her food choices. At each follow-up visit
with the team, the goals are reassessed and the plan of care is
revised based on the childs progress. 39 Referral to a feeding
team is generally made by the childs primary care provider
and reviewed by the coordinator for appropriateness to the
team.
Test Your Knowledge Questions
1. Appetite is suppressed by:

A. Sensory stimulus before eating
B. Ghrelin release by the stomach
C. Intestinal release of glucagon-like peptide 1
D. Low leptin levels
2. An abnormal swallow contains:
A. Lift of the soft palate and uvula
B. Continued respirations
C. Closure of the epiglottis
D. Opening of the upper esophageal sphincter
3. Chewing that allows the intake of higher texture foods
requires:
A. Rotary chewing
B. Forward-backward patterning
C. Suck-swallow-and breathe cycles
D. Up-down motion of the jaw
See p. 487 for answers.
References
1. Winkler MF. American Society for Parenteral and Enteral

Nutrition presidential address: food for thought: its more
than nutrition. J Parenter Enteral Nutr. 2007;31(4):334340.
2. Harris G. Development of taste and food preferences in
children. Curr Opin Clin Nutr Metab Care. 2008;11(3):
315319.
3. Lupton D. Food, The Body and the Self. Thousand Oaks, CA:
Sage Publications; 1996.
4. Druce M, Bloom SR. The regulation of appetite. Arch Dis
Child. 2006;91:183187.
5. Scaglioni S, Salvioni M, Galimberti C. Influence of parental
attitudes in the development of children eating behaviour. Br J
Nutr. 2008;99(Suppl 1):S22S25.
6. Birch LL, Fisher JO. Development of eating behaviors
among children and adolescents. Pediatrics. 1998;101(3)
(Suppl):539549.
7. Northstone K, Emmett P, Nethersole F. The effect of
age of introduction to lumpy solids on foods eaten and
reported difficulties at 6 and 15 months. J Hum Nutr Dietet.
2001;14(1):4354.
8. Erlanson-Albertsson C. Appetite regulation and energy
balance. Acta Paediatr. 2005;94(6)(Suppl):4041.
9. Blundell JE. The control of appetite: Basic concepts
and practical implications. Schweiz Med Wochenschr.
1999;129(5):182188.
10. Inui A, Asakawa A, Bowers CY, Mantovani G, Laviano A,
Meguid MM, et al. Ghrelin, appetite, and gastric motility: the
emerging role of the stomach as an endocrine organ. FASEB J.
2004;18:439456.
11. Pavlov IP. The centrifugal (efferent) nerves to the gastric
glands and the pancreas. In: Thompson WH, ed. The Work
of the Digestive Glands. Philadelphia, PA: Charles Griffin and
Co; 1910:4859.
10
12. Mattes RD. Physiologic responses to sensory stimulation by food: nutritional implications. J Am Diet Assoc.
1997;97(4):406413.
13. McDonald RE, Avery DR, Dean JA. Dentistry for the Child and
Adolescent. 8th ed. St. Louis, MO: Mosby; 2004:176178.
14. Kronfeld R, Schour I. Chronology of the human dentition. J
Am Dent Assoc. 1939;26:1832.
15. Kelly BN, Huckabee ML, Jones RD, Frampton CMA. The
first year of human life: Coordinating respiration and nutritive swallowing. Dysphagia. 2007; 22(1):3743.
16. Bosma JF. Development of feeding. Clin Nutr. 1986;5(5):
210218.
17. Derkay SD, Schechter GL. Anatomy and physiology of
pediatric swallowing disorders. Otolaryngol Clin North Am.
1998;31(3):397404.
18. Weber F, Wollridge MW, Baum JD. An ultrasonographic study
of the organisation of sucking and swallowing by newborn
infants. Dev Med Child Neurol. 1986;28(1)1924.
19. Tamura Y, Horikawa Y, Yoshida S. Co-ordination of tongue
movements and peri-oral muscle activities during nutritive
sucking. Dev Med Child Neurol. 1996;38(6):503510.
20. Wolff PH. The serial organization of sucking in the young
infant. Pediatrics. 1968;42(6):943956.
21. Qureshi MA, Vice FL, Taciak VL, Bosma JF, Gewolb IH.
Changes in rhythmic suckle feeding patterns in term infants
in the first month of life. Dev Med Child Neurol. 2002;44(1):
3439.
22. McGowan JS, Marsh RR, Fowler SM, Levy SE, Stallings VA.
Developmental patterns of normal nutritive sucking in infants.
Dev Med Child Neurol. 1991;33(10):891897.
23. Ayano R, Tamura F, Ohtsuka Y, Mukai Y. The development
of normal feeding and swallowing: Showa University study of
the feeding function. Int J Orofacial Myology. 2000;26:2432.
24. Gesell A, Ilg FL. Feeding Behavior in Infants. A Pediatric
Approach to the Mental Hygiene of Early Life. Philadelphia, PA:
J.B. Lippincott Co; 1937.
25. Gisel EG. Effect of food texture on the development of chewing
of children between six months and two years of age. Dev Med
Child Neurol. 1991;33(1):6979.
26. Sheppard JJ, Mysak ED. Ontogeny of infantile oral refluxes
and emerging chewing. Child Dev. 1984;55(3):831843.
27. Arvedson JC. Dysphagia in pediatric patients with neurologic

damage. Semin Neurol. 1996;16(4):371385.
28. Frazier JB, Friedman B. Swallow function in children with
Down syndrome: A retrospective study. Dev Med Child Neurol.
1996;38(8):695703.
29. Mercado-Deane MG, Burton EM, Harlow SA, et al. Swallowing dysfunction in infants less than 1 year of age. Pediatr
Radiol. 2001;31(6):423428.
30. Gewolb IH, Bosma JF, Taciak VL, Vice FL. Abnormal developmental patterns of suck and swallow rhythms during
feeding in preterm infants with bronchopulmonary dysplasia.
31. Arvedson J, Rogers B, Buck G, Smart P, Msall M. Silent aspiration prominent in children with dysphagia. Inter J Pediatr
Otorhinolaryngol. 1994;28(23):173181.
32. Briefel RR, Reidy K, Karwe V, Jankowski L, Hendricks
K. Toddlers transition to table foods: Impact on nutrient
intakes and food patterns. J Am Diet Assoc. 2004;104(1)(Suppl
1):S3844.
33. Gisel EG. Chewing cycles in 2- to 8-year-old normal children:
A developmental profile. Am J Occup Ther. 1988;41(1):4046.
34. Wright CM, Parkinson KN, Shipton D, Drewett RF.
How do toddler eating problems relate to their eating
behavior, food preferences, and growth? Pediatrics.
2007;120(4):e1069e1075.
35. Gidding SS, Dennison BA, Birch LL, Daniels SR. Dietary
recommendations for children and adolescents: A guide for
practitioners. Pediatrics. 2006;17(2)544559.
36. Satter E. How to Get Your Kid to Eat: But Not Too Much.
Boulder, CO: Bull Publishing Co; 1987.
37. Jana L, Shu J. Food Fights: Winning the Nutritional Challenges of
Parenthood Armed with Insight, Humor, and a Bottle of Ketchup.
Washington, DC: American Academy of Pediatrics; 2008.
38. Dusick AM. Investigation and management of dysphagia.
Semin Pediatr Neurol. 2003;10(4):255264.
39. Fraker C, Fishbein M, Cox S, Walbert L. Food Chaining: The
Proven 6-Step Plan to Stop Picky Eating, Solve Feeding Problems, and Expand Your Childs Diet. New York, NY: Marlowe
& Co; 2007.
Gross Digestion Principles: Gastric

Grinding and Gastrointestinal Motility
Jane P. Balint, MD
CONTENTS
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Gastric Motility. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12
Small Bowel Motility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Effect of Intake on Motor Activity. . . . . . . . . . . . . . . . . . . . 13
Consistency
Nutrient Content
Caloric Density
Osmolarity
Altered Patterns of Motility and Potential Interventions . 13

Delayed Gastric Emptying
Dumping
Slow Intestinal Transit
Rapid Intestinal Transit
Learning Objectives
1. Describe the normal response of the stomach to

nutrientintake.
2. Explain the different motor patterns of the smallintestine in the fasting and fed states.
3. Predict the response of the intestinal tract to different
types of nutrients.
4. Develop management strategies for altered gastrointestinal motility.
Background
Gastrointestinal (GI) motility is necessary for the movement

of nutrients from the stomach through the intestinal tract as
well as for the breakdown and mixing of these nutrients with
digestive enzymes, which in turn allows for digestion and
absorption. An elementary understanding of these processes
is helpful in planning and managing nutrition support.
The motor activity of the GI tract is regulated by the
enteric nervous system (ENS), which consists of two nerve
plexuses. The myenteric plexus (Auerbachs plexus) lies
between the outer longitudinal muscle layer and the inner
circular muscle layer. This plexus is key to the motility of the
GI tract, including regulation of the normal motor patterns
seen in the GI tract described below. The submucosal plexus
(Meissners plexus), found between the muscularis mucosa
and the circular muscle layer, affects absorption, secretion,
and blood flow. While the ENS can act independently, it
receives input from the parasympathetic nervous system
(primarily the vagus nerve), the sympathetic nervous
system, and sensory nerves in the intestine, as well as from
mast cells, paracrine signals, and endocrine signals. In addition, the ENS has multiple neurotransmitters for signaling,
including acetylcholine, norepinephrine, serotonin,
11
12
vasoactive intestinal peptide, nitric oxide, somatostatin,

and tachykinins.14
Integral to the functioning of the GI tract are the interstitial cells of Cajal (ICC). There are two types: those around
the myenteric plexus that generate and propagate electrical
slow waves (pacemakers), and those between neural fibers
and smooth muscle cells providing communication between
the two. The ICC help to coordinate peristaltic movement
of the GI tract. 5,6 Slow waves have variable frequency in
different parts of the GI tract. In the stomach, the slow-wave
rhythm is 3 cycles per minute. In the proximal small bowel
the rhythm is 11 to 12 cycles per minute, decreasing to 7 to
9 cycles per minute in the distal ileum. Slow waves do not
generate contractions but dictate the frequency at which
they can occur.4,7
Gastric Motility
The gastric fundus, which is the uppermost portion of the

stomach, acts as a reservoir for ingested food. It is in the
antrum and body of the stomach where food is ground into
small particles prior to passage into the small intestine. With
swallowing at the onset of a feeding or meal, vagally mediated
relaxation of the fundus occurs. As food enters the stomach,
there is further relaxation of the proximal stomach to provide
a reservoir for nutrients. This receptive relaxation/gastric
accommodation allows for an initial increase in the volume
of the stomach without an increase in pressure. However,
ultimately the pressure will increase, leading to a tonic
contraction that then pushes the gastric contents toward
the antrum. With this there is the start of regular phasic
contractions at 3 cycles per minute that both mix and grind
(triturate) the gastric contents. During the churning process,
the food bolus is first pushed toward the antrum where some
grinding takes place. Distention of the antrum results in
fundic relaxation and in turn retropulsion of contents back to
the body of the stomach. Grinding is important for creating
small particles, less than 1 to 2 mm in size, that will pass into
the duodenum through the pylorus. Mixing with gastric
acid and pepsin begins the chemical digestion of food. This
initial phase of mixing and grinding is the lag phase in gastric
emptying that occurs after ingestion of nutrients.1,4,811
Once the ingested nutrients are appropriately mixed
and solid material is ground into small particles, antral
contractions accompanied by pyloric relaxation allow small
aliquots of this chyme to empty into the duodenum. This
begins the second or linear gastric emptying phase. The time
for gastric emptying is variable, and depends upon a variety
of factors as discussed below, but is generally complete by 4
hours.1,4,7,8,10,11
The preterm infant has an immature pattern of GI

motility affecting both gastric emptying and small bowel
motility, which impacts feeding. The normal electrical activity of the stomach, with a slow wave frequency of 3 cycles
per minute, does not develop until 32 weeks gestation and
does not become the dominant pattern until 35 weeks gestation. This results in slower gastric emptying in these more
premature infants in comparison to the term infant.4,12,13
Small Bowel Motility
Motor activity of the small intestine serves a number of

important functions, including mixing chyme with intestinal secretions for further digestion, enhancing contact
between enteric contents and the mucosa for absorption,
moving ingested contents distally, and clearing the intestinal tract by powerful contractions that propagate in an
aboral direction.14
In the fasting state, or interdigestive period, there are 3
phases of the migrating motor complex (MMC). Phase I is a
quiescent phase. In phase II there are intermittent, irregular
contractions. Phase III is characterized by strong, propagating contractions that begin almost simultaneously in the
stomach and duodenum and travel through the small bowel.
This phase III of the MMC provides the housekeeping function of intestinal motility, sweeping material through the
small bowel. It occurs at irregular intervals, ranging from
18 to 145 minutes with an average occurrence of every 80
minutes, and lasts from 2 to 14 minutes.1,4,1416
In the fed state, there is a combination of mixing and
propulsion of intestinal contents. In general, there are
random bursts of activity, primarily resulting in mixing.
When a contraction occurs, intestinal contents move. If the
contraction in one region of the small intestine occurs in a
coordinated manner with proximal and distal bowel, then
the intestinal contents will be propelled downstream. If
the contraction is not coordinated with activity of adjacent
areas, then the intestinal contents moves both retrograde
and antegrade in the intestine, resulting in mixing. 3,15
As noted above, the premature infant has not developed
a normal pattern of intestinal motility. The fasting pattern of
premature infants is characterized by short bursts of activity
called clusters that do not progress aborally as a mature
phase III MMC does. The nature of these clusters is different
depending upon the gestational age. The length of a cluster
increases with gestational age from less than 90 seconds
in the 27- to 28-week gestation infant to 5 to 6 minutes at
36 weeks gestation. At the same time the frequency with
which the clusters occur decreases. The fed pattern also
differs in the premature infant with most demonstrating
GROSS DIGESTION PRINCIPLES: GASTRIC GRINDING AND GASTROINTESTINAL MOTILITY
an abrupt cessation of intestinal contractions after a bolus

feeding. Not surprisingly, intestinal transit is slower in the
preterm infant. There is some evidence that feeding premature infants, even small amounts, can promote maturation
of intestinal motility.12,1719
Effect of Intake on Motor Activity
Gastric emptying can be affected by a variety of characteristics of the ingested material as well as the rapidity of
transit through the GI tract. With this, the time for gastric
emptying can vary from 1 to 4 hours. The effect of nutrient
composition on motor activity has been more clearly delineated for the stomach than the small bowel.
Consistency
Liquids will empty from the stomach more quickly than
solids. In turn, clear liquids will empty more rapidly than
full liquids, with non-nutritive liquids emptying the fastest,
leaving the stomach in about 20 minutes.11,20 The viscosity
of the feeds will also affect the speed of gastric emptying,
with lower viscosity material emptying more rapidly. Thus
both soluble and insoluble fibers mixed with the feedings
will slow emptying.21,22 In addition to delaying gastric
emptying, soluble fibers can prolong transit through the GI
tract by prolonging the duration of the fed pattern of small
bowel motor activity.22
Nutrient Content
The response to the type of nutrient ingested is complex.
There are both hormonal and neural responses to food that
regulate motor activity of the stomach and small intestine.
These are interrelated in that neural activity can affect
the release of some GI hormones. Once chyme starts to
pass through the pylorus, there is feedback via vagal afferents from receptors in the duodenum that regulate gastric
emptying. These receptors include those that detect fat,
amino acids, glucose, pH, and osmolarity.23 A component
of the response is mediated by release of gastrin, cholecystokinin, pancreatic polypeptide, glucagon-like peptide 1,
and peptide YY.4,24,25 It has been demonstrated that carbohydrates will empty from the stomach before proteins, with
fats emptying the most slowly.4,26,27 Fats reaching the distal
ileum inhibit both gastric emptying and small intestinal
motility, a mechanism known as the ileal brake.28 Complex
carbohydrates that reach the distal small intestine can
also stimulate the ileal brake.1 In addition to the actual
nutrient content, the pH will affect gastric emptying as well
with more acidic material emptying more slowly from the
stomach.29
13
Caloric Density
Increased calorie content of the ingested food or liquid will
result in slower emptying from the stomach.21,30 It has also
been demonstrated that a higher calorie content meal will
result in a longer fed pattern in the small bowel leading to a
longer transit time through the small intestine. 31
Osmolarity
Finally, solutions that have a higher osmolarity will empty
more slowly from the stomach than those that are lower in
osmolarity.27
While each of these factors individually can influence
gastric emptying in the older infant, child, and adult, the
same has not been found to be true in premature infants.
In one study of 25 to 30 weeks gestation infants, it was
demonstrated that altering osmolality, caloric density, or
the volume of the feeding separately did not change gastric
emptying. However, when the volume of the feeding was
increased in combination with decreasing the osmolality,
gastric emptying was more rapid. 32 Additionally, across age
groups in clinical practice, these factors can clearly overlap
as nutrient content is closely tied to caloric density. For
example, a meal or formula higher in fat will likely be higher
in calories.
Altered Patterns of Motility

and Potential Interventions
Disordered motility in any part of the GI tract can impact

feeding tolerance.
Delayed Gastric Emptying

As noted above, slower gastric emptying occurs in the premature infant and may impair feeding advancement. Premature
infants who require tube feedings due to immature suck
and swallow may benefit from a slower intermittent infusion over as long as 2 hours, rather than a 15-minute bolus,
as this slower infusion has been demonstrated to result both
in improved gastric emptying and a more mature duodenal
motor pattern. 33,34 In the older infant or child, delayed
emptying may occur during or following a viral illness,
associated with a significant systemic illness, as well as after
surgery, resulting in fullness, bloating, decreased appetite,
and emesis. 35 Management strategies depend on the degree
of the problem and how the child was being fed prior to the
onset of the problem. If the child was eating a regular diet,
smaller more frequent meals that are lower in fat, in fiber,
and in caloric density may empty better from the stomach. 36
As liquids empty more readily than solids, increasing the
liquid content of the meal may help. If the child is unable to
14
tolerate any solids, a trial of liquid nutritional supplements

is warranted. If the child was tube fed prior to the onset of
the delayed gastric emptying, then adjusting the formula or
the manner of delivery may be necessary. The osmolarity,
caloric content, fat content, and fiber content of the formula
should be evaluated and a determination made as to whether
a change is possible, as the higher each of these are, the
slower emptying will be even under normal circumstances.
Drip feedings, rather than bolus feedings, may need to be
considered. There are few pharmacologic options available
currently. Erythromycin, which acts as a motilin receptor
agonist, can accelerate gastric emptying. 37 If the problem is
severe enough, continuous transpyloric or jejunal feedings
may be necessary, at least temporarily.
Dumping
Very rapid gastric emptying, or dumping, is relatively
uncommon in pediatrics. 35 It can occur as a result of surgery,
particularly involving the pylorus, or with damage to the
vagal nerve such as during a fundoplication or cardiac
surgery. Symptoms include nausea, abdominal distention,
cramping, diarrhea, and vasomotor changes associated with
swings in glucose. Some management strategies are the opposite of those suggested for use in delayed emptying. One can
try to take advantage of normal physiology by increasing the
fat and protein content of the diet and increasing the fiber
content of the diet, including the addition of pectin and guar
gum.36 Rather than mixing liquids with the meal, liquids
should be taken separately from solids. On the other hand,
some of the same strategies recommended for treatment of
delayed gastric emptying may also be helpful in too rapid
emptying, specifically smaller more frequent meals as well
as continuous drip or post-pyloric feedings. Pharmacologic
therapeutic options are limited. Acarbose, an alpha-glucosidase inhibitor, has been used to treat dumping syndrome
as it delays the hydrolysis of carbohydrates with resultant
delayed absorption of glucose38,39 Octreotide, an analogue of
somatostatin, can be beneficial as one of its specific actions is
to delay gastric emptying.40,41
Slow Intestinal Transit

Slow intestinal transit may occur following surgery (postoperative ileus), following a viral illness or other systemic
illness, as a side effect of many drugs, or as part of a significant motility disorder, the most extreme being chronic
intestinal pseudoobstruction. There is no clear evidence or
consensus opinion upon which to make recommendations
in terms of nutrition interventions that may be beneficial
in these circumstances. Currently, there are also a paucity
of drugs available to help promote motility of the small
bowel. There are some data to indicate that amoxicillinclavulonic acid may promote small bowel motility.42 In
more severe cases, octreotide may be beneficial. This somatostatin analogue has a wide range of effects on the GI tract,
including induction of phase III MMC when given in small
doses subcutaneously.43
Rapid Intestinal Transit

Rapid intestinal transit may occur following a systemic
illness or due to surgery on the GI tract. This can result in
malabsorption of nutrients and diarrhea. Feeding strategies
will be discussed in detail in later chapters, including those
on GI disease and intestinal failure. However, one approach
that may be beneficial, regardless of the feeding selected
or route of delivery, is the addition of soluble fiber such
as pectin or guar gum to the feeding as these will prolong
intestinal transit time.22,44 Various drugs can be used in an
effort to slow transit through the small bowel. Loperamide,
a peripherally acting opioid analogue, inhibits both small
bowel and colonic motility. Anticholinergic agents, such as
hyoscyamine, can also help to slow intestinal transit.
While it is important to consider the impact of gastric
and intestinal motility on feeding, this is only one of many
factors that must be taken into account as will be discussed
in subsequent chapters.
1. Gastric emptying can be slowed by all of the following

except:
A. Soluble fibers
B. Fats
C. Liquids
D. Protein
2. In the fed state, small bowel motor activity is characterized by:
A. A quiescent phase
B. Random bursts of activity
C. Intermittent, irregular contractions
D. Strong, propagating contractions
3. Which of the following is true for the premature
infant?
A. Bolus feeds will promote normal small bowel motor
activity.
B. Transit through the small bowel is shorter than in the
older infant.
C. Gastric emptying is more rapid than in the older
infant.
D. Feeding can promote the development of intestinal
motility.
GROSS DIGESTION PRINCIPLES: GASTRIC GRINDING AND GASTROINTESTINAL MOTILITY
References
1. Camilleri M. Integrated upper gastrointestinal response to

food intake. Gastroenterology. 2006;131:640658.
2. Costa M, Brookes SJH, Hennig GW. Anatomy and physiology of the enteric nervous system. Gut. 2000;47(Suppl IV):
iv15iv19.
3. Leger G. Basic physiology of motility, absorption and secretion. In: Langnas AN, Goulet O, Quigley EMM, Tappenden
KA, eds. Intestinal Failure: Diagnosis, Management and Transplantation. Malden, MA: Blackwell Publishing; 2008:2032.
4. Saps M, Di Lorenzo C. Gastric motility: normal motility and
development of the gastric neuroenteric system. In: Kleinman
RE, Sanderson IR, Goulet O, Sherman PM, Mieli-Vergani
G, Shneider BL, eds. Walkers Pediatric Gastrointestinal
Disease. Vol 1. 5th ed. Hamilton, Ontario: BC Decker, Inc;
2008:187193.
5. Rolle U, Piaseczna-Piotrowska A, Puri P. Interstitial cells of
Cajal in the normal gut and in intestinal motility disorders of
childhood. Pediatr Surg Int. 2007;23:11391152.
6. Sanders KM, Koh SD, Ward SM. Interstitial cells of Cajal as
pacemakers in the gastrointestinal tract. Annu Rev Physiol.
2006;68:307343.
7. Altaf MA, Sood MR. The nervous system and gastrointestinal
function. Dev Disabil Res Rev. 2008;14:8795.
8. Cuomo R, Sarnelli G. Food intake and gastrointestinal
motility. A complex interplay. Nutr Metab Cardiovasc Dis.
2004;14:173179.
9. Hennig GW, Brookes SJH, Costa M. Excitatory and inhibitory
motor reflexes in the isolated guinea-pig stomach. J Physiol.
1997;501:197212.
10. Lacy BE, Koch KL, Crowell MD. The stomach: normal function and clinical disorders. Manometry. In: Schuster MM,
Crowell MD, Koch KL, eds. Schuster Atlas of Gastrointestinal
Motility in Health and Disease. 2nd ed. Hamilton, Ontario: BC
Decker, Inc; 2002:135150.
11. Siegel JA, Urbain J-L, Adler LP, et al. Biphasic nature of gastric
emptying. Gut. 1988;29:8589.
12. Berseth CL. Assessment in intestinal motility as a guide
in the feeding management of the newborn. Clin Perinatol.
1999;26:10071015.
13. Riezzo G, Indrio F, Montagna O, et al. Gastric electrical
activity and gastric emptying in term and preterm newborns.
Neurogastroenterol Motil. 2000;12:223229.
14. Kellow JE. Small intestine: normal function and clinical
disorders. Manometry. In: Schuster MM, Crowell MD, Koch
KL, eds. Schuster Atlas of Gastrointestinal Motility in Health
and Disease. 2nd ed. Hamilton, Ontario: BC Decker, Inc;
2002:219236.
15. Boccia G, Staiano A. Intestinal motility: normal motility
and development of the intestinal neuroenteric system. In:
Kleinman RE, Sanderson IR, Goulet O, Sherman PM, MieliVergani G, Shneider BL, eds. Walkers Pediatric Gastrointestinal
Disease. Vol 1. 5th ed. Hamilton, Ontario: BC Decker, Inc;
2008:665674.
16. Scott SM, Knowles CH, Wang D, et al. The nocturnal jejunal
migrating motor complex: defining normal ranges by study of
51 healthy adult volunteers and meta-analysis. Neurogastroenterol Motil. 2006;18:927935.
15
17. Berseth CL Effect of early feeding on maturation of the

preterm infants small intestine. J Pediatr. 1992;120:947953.
18. Commare CE, Tappenden KA. Development of the infant
intestine: implications for nutrition support. Nutr Clin Pract.
2007;22:159173.
19. McClure RJ, Newell SJ. Randomised controlled trial of
trophic feeding and gut motility. Arch Dis Child Fetal Neonatal
Ed. 1999;80:F54F58.
20. Collins PJ, Houghton LA, Read NW, et al. Role of the proximal
and distal stomach in a mixed solid and liquid meal emptying.
Gut. 1991;32:615619.
21. Marciani L, Gowland PA, Spiller RC, et al. Effect of meal
viscosity and nutrients on satiety, intragastric dilution, and
emptying assessed by MRI. Am J Physiol Gastrointest Liver
Physiol. 2001;280:G1227G1233.
22. Schnfeld J, Evans DF, Wingate DL. Effect of viscous fiber
(guar) on postprandial motor activity in human small bowel.
Dig Dis Sci. 1997;42:16131617.
23. Schwartz GJ, Moran TH. Duodenal nutrient exposure elicits
nutrient-specific gut motility and vagal afferent signals
in rat. Am J Physiol Regulatory Integrative Comp Physiol.
1998;274:R1236R1242.
24. MacIntosh CG, Andrews JM, Jones KL, et al. Effects of age
on concentrations of plasma cholecystokinin, glucagon-like
peptide 1, and peptide YY and their relation to appetite and
pyloric motility. Am J Clin Nutr. 1999;69:9991006.
25. Feinle C, ODonovan D, Doran S, et al. Effects of fat digestion
on appetite, APD motility, and gut hormones in response to
duodenal fat infusions in humans. Am J Physiol Gastrointest
Liver Physiol. 2003;284:G798G807.
26. Houghton LA, Mangnall YF, Read NW. Effect of incorp
orating fat into a liquid test meal on the relation between
intragastric distribution and gastric emptying in human
volunteers. Gut. 1990;31:12261229.
27. Paraskevopoulos JA, Houghton LA, Eyre-Brooke I, Johnson
AG, and Read NW. Effect of composition of gastric contents
on resistance to emptying of liquids from stomach in humans.
Dig Dis Sci. 1988;33:914918.
28. Ohtani N, Sasaki I, Naito H, Shibata C, Matsuno S. Mediators
for fat-induced ileal brake are different between stomach and
proximal small intestine in conscious dogs. J Gastrointest Surg.
2001;5:377382.
29. Chaw CS, Yazaki E, Evans DF. The effect of pH change on the
gastric emptying of liquids measured by electrical impedance
tomography and pH-sensitive radiotelemetry capsule. Int J
Pharm. 2001;227:167175.
30. Boulby P, Moore R, Gowland P, Spiller RC. Fat delays
emptying but increases forward and backward antral flow
as assessed by flow-sensitive magnetic resonance imaging.
Neurogastroenterol Motil. 1999;11:2736.
31. Schnfeld J, Evans DF, Wingate DL. Daytime and night time
motor activity of the small bowel after solid meals of different
caloric value in humans. Gut. 1997;40:614618.
32. Ramirez A, Wong WW, Shulman RJ. Factors regulating gastric
emptying in preterm infants. J Pediatr. 2006;149:475479.
33. Baker JH, Berseth CL. Duodenal motor responses in preterm
infants fed with formula with varying concentrations and
rates of infusion. Pediatr Res. 1997;42:618622.
16
34. De Ville K, Knapp E, Al-Tawil Y, Berseth CL. Slow infusion feedings enhance duodenal motor responses and gastric emptying
in preterm infants. Am J Clin Nutr. 1998;68:103108.
35. Di Lorenzo C, Ciamarra P. Pediatric gastrointestinal motility.
In: Schuster MM, Crowell MD, Koch KL, eds. Schuster Atlas
of Gastrointestinal Motility in Health and Disease. 2nd ed.
Hamilton, Ontario: BC Decker, Inc; 2002:411428.
36. Karamanolis G, Tack J. Nutrition and motility disorders. Best
Pract Res Clin Gastroenterol. 2006;20:485505.
37. Karamanolis G, Tack J. Promotility medications now and
in the future. Dig Dis. 2006;24:297307.
38. Ng DD, Ferry RJ, Kelly A, et al. Acarbose treatment of
postprandial hypoglycemia in children after Nissen fundoplication. J Pediatr. 2001;139:877879.
39. Zung A, Zadik Z. Acarbose treatment of infant dumping
syndrome: extensive study of glucose dynamics and long-term
follow-up. J Pediatr Endocrinol Metab. 2003;16:905915.
40. Lamers CB, Bijlstra AM, Harris AG. Octreotide, a

long-acting somatostatin analog, in the management of
post-operative dumping syndrome. An update. Dig Dis Sci.
1993;38:359364.
41. Scarpignato C. The place of octreotide in the medical management of the dumping syndrome. Digestion. 1996;57(Suppl
1):114118.
42. Caron F, Ducrotte P, Lerebours E, et al. Effects of amoxicillin-clavulanate combination on the motility of the small
intestine in human beings. Antimicrob Agents Chemother.
1991;35:10851088.
43. Di Lorenzo C, Lucanto C, Flores AF, Idries S, Hyman PE.
Effect of octreotide on gastrointestinal motility in children
with functional gastrointestinal symptoms. J Pediatr Gastroenterol Nutr. 1998;27:508512.
44. Finkel Y, Brown G, Smith HL, et al. The effects of a pectinsupplemented elemental diet in a boy with short bowel
syndrome. Acta Paediatr Scand. 1990;79:983986.
Carbohydrates: Changes with Development

Seema Mehta, MD and Robert J. Shulman, MD
Contents
Digestion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Lactose
Starch
Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Malabsorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Learning Objectives
1. Describe the structure and classification of carbo

hydrates.
2. Describe the process of carbohydrate digestion and
absorption.
3. Identify diseases related to carbohydrate malab
sorption.
Digestion
Carbohydrates supply 50% of the bodys total energy

requirement. Dietary carbohydrates consist of sugars
and starches. Sugars include both monosaccharides (ie,
glucose, galactose, and fructose) and disaccharides (ie,
lactose, sucrose, maltose, and trehalose). Starches, also
known as storage carbohydrates, consist of large chains of
sugars linked together.1 Complex carbohydrate is another
term used for starch. It commonly refers to starch used in
formulas (ie, corn syrup solids, glucose polymers) and is a
smaller carbohydrate molecule than those found in other
food starches (ie, potato, corn). Small-chain starches,
generally 3 to 10 glucose units in length, are referred to as
oligosaccharides whereas long-chain starches are referred
to as polysaccharides.
Lactose
Lactose is the primary carbohydrate present in human
milk and most infant formulas.2 Lactose is hydrolyzed by
the enzyme lactase into the monosaccharides glucose and
galactose (Figure 3-1).
17
18
Figure 3-1 Digestion of Carbohydrates

Overall schema of complex carbohydrate digestion.5
Reprinted from Shulman RJ. Intraluminal digestion and absorption in

the small intestine. In: Gluckman PD, Heymann MA. Pediatrics and
Perinatology: The Scientific Basis. 2nd ed. New York, NY: Oxford University
Press; 1996. Reproduced by permission of Edward Arnold (Publishers) Ltd.
Lactase, the sole enzyme responsible for the hydrolysis of

lactose, is located along the brush border of the enterocytes
lining the villi of the small intestine. The optimum pH for
lactase activity is 6.0. Activity peaks in the jejunum and
progressively decreases toward the ileum. This gradient
is established by 11 weeks gestation. Antenatally, lactase
activity increases until term with the greatest increase
occurring during the third trimester. At the beginning of
the third trimester, lactase activity is approximately 25%
of that at term. 3,4 Early in fetal life, some lactase activity is
demonstrable in the colon, but by 28 weeks gestation it is
undetectable. 5
In preterm infants, it has been suggested that incomplete digestion of lactose may be linked to the pathogenesis
of necrotizing enterocolitis (NEC), thereby resulting in
a reluctance to feed preterm infants lactose.6 The time to
reach full enteral feedings was found to be inversely related
to lactase activity (Figure 3-2).2 Offsetting the apprehension
for complications related to early feedings are the potential
benefits. It has been demonstrated that early enteral feedings in preterm infants promote the development of lactase
activity (Figure 3-3). Infants fed human milk were found to
have greater lactase activity than those fed formula.
Figure 3-2 Age at Full Feedings versus Lactase Activity

There is a negative relationship between the time full enteral feedings are
achieved and lactase activity.2
Reprinted from Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN,

Smith EO. Early feeding, feeding tolerance, and lactase activity in preterm
infants. J Pediatr. 1998;133(5):645-649 with permission from Elsevier.
Figure 3-3 Lactase Development with Age and Type of Feeding

Lactase activity increases with age but the increase is greater in the early
fed group when compared with the standard group (p < 0.01).2 Lactase
activity in the early fed group is greater than that in the standard group at
10 and 28 days of age (p = 0.004) but not at 50 days of age (p > 0.5).2
Reprinted from Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN,

Smith EO. Early feeding, feeding tolerance, and lactase activity in preterm
infants. J Pediatr. 1998;133(5):645-649 with permission from Elsevier.
In many individuals, lactase activity begins to decline

with advancing age. This genetically predetermined
process, also known as primary lactase deficiency or
CARBOHYDRATES: CHANGES WITH DEVELOPMENT
primary hypolactasia, starts between 3 to 5 years of age and

continues into adulthood.4 The prevalence of hypolactasia
varies amongst individuals of different ethnic backgrounds
ranging from 90% amongst Asians, 80% for AfricanAmericans, followed by 53% for Hispanics, and 15% to
25% for non-Hispanic whites.7 In contrast to the adult-type
hypolactasia, congenital lactase deficiency, also a primary
lactase deficiency, is an extremely rare autosomal recessive disorder associated with a complete absence of lactase
expression.8 Symptoms in these patients manifest at birth
with the introduction of a lactose-containing diet.
Secondary lactase deficiency results as a consequence
of mucosal injury to the small intestine. It occurs most
commonly in infants with an infectious gastroenteritis and
generally resolves with the resolution of the illness.8 Many
otherwise healthy infants may demonstrate no signs or
symptoms of lactose intolerance during the course of their
illness.9 Other infants with either a poor nutrition status or
more prolonged illness may show clinical signs of lactose
intolerance and benefit from a lactose-free formula until
their symptoms resolve.10
Starch
Formula-fed infants are exposed to a variety of other carbohydrates in infancy including starches. The simplest form
of starch is amylose, a linear polymer of glucose molecules
linked by -1,4 glycosidic bonds. Amylopectin, a plant
starch, is the major form of carbohydrate in the diet. Structurally it is similar to amylose, but for every 20 to 30 glucose
units there are -1,6 branch points.11
Digestion of starch begins with intraluminal digestion
by salivary and then pancreatic amylases. Amylase hydrolyzes starch at the internal -1,4 bonds (Figure 3-1). It is not
active against those bonds located next to the -1,6 bonds or
those at the reducing end of the starch molecule. Amylase
cleaves amylose and amylopectin into maltotriose, maltose,
and -limit dextrans (Figure 3-1).12
Salivary amylase, secreted by the salivary glands, is
present in preterm infants. Amylase activity increases with
gestational age, rising rapidly after birth and approaching
adult values by 6 months to 1 year of age. Salivary amylase
is inactivated at pH < 4.5 In newborns, however, salivary
amylase tends to remain active because they have poorly
acidified stomachs.13 Pancreatic amylase, secreted by the
pancreas, is present at low levels in preterm and full-term
infants. Activity begins to increase at 4 to 6 months of age and
reaches adult values by 1 to 2 years of age (Figure 3-4).2
19
Figure 3-4: Development Profile of Pancreatic and Salivary Amylase

There is little pancreatic amylase activity prior to birth but salivary amylase
demonstrates some activity prior to 40 weeks gestation.20
Reprinted from McClean P, Weaver LT. Ontogeny of human pancreatic

exocrine function. Arch Dis Child. 1993;68:62-65, with permission from
BMJ Publishing Group Ltd.
Further digestion of the disaccharides and oligosaccharides occurs at the level of enterocytes. Glucoamylase, like
lactase, is located in the brush border of the small intestine.
It cleaves -1,4 bonds of primarily non-branching glucose
polymers (ie, amylose) and non-reducing ends of polysaccharides (Figure 3-1). Short chains (ie, < 10 glucose units)
are more easily digested by glucoamylase than longer-chain
units.14
Glucoamylase activity is detectable by 20 weeks gestation. At the beginning of the third trimester, the activity
level is about half that at 36 to 38 weeks gestation. 5 In addition, it is also present in low levels in the colon only early
in fetal life. 5 Therefore, in newborn infants, glucoamylase
is the primary enzyme for complex carbohydrate digestion
since pancreatic amylase activity is low. Young infants and
older children have similar glucoamylase activity levels
which are approximately half those in adults.15
Sucrase-isomaltase is a disaccharidase also found in the
brush border of the small intestine. At 20 weeks gestation,
sucrase-isomaltase activity is almost half to three-quarters that of term newborns and adults. 5 Similar to lactase,
sucrase-isomaltase activity is highest in the proximal small
intestine. Activity remains high over the course of an individuals life. Sucrase-isomaltase is cleaved into sucrase and
isomaltase by pancreatic proteases. 5 Sucrase hydrolyzes
sucrose into the monosaccharides glucose and fructose
(Figure 3-1). Isomaltase cleaves the -1,6 glycosidic bonds
of amylopectin (Figure 3-1). 5 A genetic deficiency of
sucrase-isomaltase known as congenital sucrase-isomaltase
deficiency is an autosomal recessive disorder. All patients
with this deficiency lack sucrase and have varying degrees
of isomaltase activity.16
20
Absorption
Dietary carbohydrates are absorbed in the form of the monosaccharides glucose, galactose, and fructose. Active transport
of glucose and galactose is present by 10 weeks gestation. 5
The absorption rate of glucose increases through gestation
and continues to increase postnatally into adulthood. Galactose absorption rate reaches adult values between 4 to 8 years
of age.8
Access into enterocytes occurs via carrier molecules.
Glucose and galactose are actively transported via the
sodium-glucose linked transporter (SGLT1) located at the
brush border. Glucose and galactose entry is coupled to the
entry of sodium along its electrochemical gradient. This
electrochemical gradient is maintained via the sodium-potassium-adenosine triphosphatase (Na+-K+ ATPase) located
at the basolateral surface. SGLT1 has binding sites for both
glucose and sodium. Two sodium molecules are absorbed
for every glucose molecule. Once both sites are occupied, the
transporter translocates across the brush border membrane
and releases the glucose and sodium into the enterocyte.11
The sodium-linked transport of glucose provides the basis
for adding glucose or starches to oral rehydration solutions.
Passive absorption of glucose also can occur across the brush
border.8
Fructose transport across the brush border membrane
occurs passively down its concentration gradient. The
fructose transporter, GLUT5, is not sodium dependent.
Transport of glucose, galactose, and fructose across the
basolateral membrane also occurs by facilitated transport
via the sodium-independent transporter, GLUT2.11 Recently
GLUT2 has been recognized in the brush border membrane,
and glucose transported by SGLT1 promotes the activation
of GLUT2 already in the apical membrane and rapid insertion of GLUT2 from vesicles.17 This observation explains the
enhancement of fructose absorption in the proximal intestine
in the presence of equimolar amounts ofglucose.17
Malabsorption
Incomplete digestion and absorption of carbohydrates can

occur in the small intestine. The remaining mono- , di- ,
and oligosaccharides create an osmotic gradient that drives
water into the lumen. Upon reaching the colon, these carbohydrates are fermented by colonic bacteria to short-chain
fatty acids which then are absorbed by the colon.18 If the
rate of malabsorption of carbohydrates exceeds their ability
to be fermented and absorbed as short-chain fatty acids,
osmotic diarrhea can result.
Carbohydrate malabsorption can be detected by testing
stool pH, stool-reducing substances, and/or a hydrogen
breath test. Stool pH of < 5.5 is indicative of short-chain

fatty acids in the stool, whereas stool-reducing substances
present in the stool denote the presence (ie, malabsorption)
of sugars, usually glucose. A positive breath hydrogen test
reflects the passage of carbohydrate into the colon and its
fermentation but interpretation depends on the carbohydrate. A significant rise in breath hydrogen would be
expected after ingestion of a starch such as corn but not
after sucrose. Disorders of carbohydrate absorption can
be congenital or acquired (Table 3-1).12,19 Treatment varies
because it is dependent on the clinical entity causing carbohydrate malabsorption. Treatment options include special
diets and formulas (eg, gluten-free diet for patients with
celiac disease) and enzyme supplements (eg, pancreatic
enzymes for patients with cystic fibrosis).12,19
Table 3-1 Disorders Associated with Carbohydrate Malabsorption
Sucrase-isomaltase deficiency
Glucose-galactose malabsorption
Congenital lactase deficiency
Congenital trehalase deficiency
Fructose malabsorption
Adult-type hypolactasia
Cystic fibrosis
Shwachman-Diamond syndrome
Congenital microvillus atrophy
Tufting enteropathy
Autoimmune enteropathy
Celiac disease
Postviral enteritis
Postradiation enteritis
Metabolism
Glucose is the most abundant carbohydrate in humans.

Dietary carbohydrates are converted into glucose and then
metabolized for energy. Starting soon after birth, gluconeogenesis contributes 30% to 70% of the bodys glucose.
Glucose that is not immediately utilized is stored in the
form of glycogen (ie, a storage carbohydrate).1 Insulin is the
hormone responsible for glycogenesis (glycogen synthesis),
while glucagon is the hormone responsible for glycogenolysis (glycogen degradation).
1. Which one of the following is a polysaccharide?

A. Lactose
B. Sucrose
C. Maltose
D. Amylose
CARBOHYDRATES: CHANGES WITH DEVELOPMENT
2. Lactose is hydrolyzed by the enzyme lactase into the

monosaccharides
and
.
A. Glucose; glucose
B. Galactose; glucose
C. Glucose; fructose
D. Galactose; fructose
3. Which enzyme is present in the lowest amount in
preterm infants compared with term infants?
A. Glucoamylase
B. Lactase
C. Sucrase
D. Salivary amylase
4. Which ethnic group has the lowest prevalence of
primary hypolactasia?
A. Asians
B. African-Americans
C. Hispanics
D. Non-Hispanic whites
References
1. American Academy of Pediatrics, Committee on Nutrition.

Carbohydrate and dietary fiber. In: Kleinman RE, ed. Pediatric
Nutrition Handbook. 5th ed. Elk Grove Village, IL: American
Academy of Pediatrics; 2004:247253.
2. Shulman RJ, Schanler RJ, Lau C, Heitkemper M, Ou CN,
Smith EO. Early feeding, feeding tolerance, and lactase
activity in preterm infants. J Pediatr. 1998;133(5):645649.
3. Antonowicz I, Chang SK, Grand RJ. Development and distribution of lysosomal enzymes and disaccharidases in human
fetal intestine. Gastroenterology. 1974;67:5158.
4. Raul F, Lacroix B, Aprahamian M. Longitudinal distribution of brush border hydrolases and morphological
maturation in the intestine of the preterm infant. Early Hum
Dev. 1986;13:225234.
5. Shulman RJ. Intraluminal digestion and absorption in the
small intestine. In: Gluckman PD, Heymann MA. Pediatrics
and Perinatology: The Scientific Basis. 2nd ed. New York, NY:
Oxford University Press; 1996:630637.
21
6. Kliegman RM. Neonatal necrotizing enterocolitis:

Bridging the basic science with the clinical disease. J Pediatr.
1990;117:833835.
7. Sahi T. Genetics and epidemiology of adult-type hypolactasia.
Scand J Gastroenterol. 1994;202(suppl):720.
Infant nutrition and the development of gastrointestinal function. In: Kleinman RE, ed. Pediatric Nutrition Handbook. 5th
ed. Elk Grove Village, IL: American Academy of Pediatrics;
2004:47.
9. Brown KH, Peerson JM, Fontaine O. Use of nonhuman
milks in the dietary management of young children with
acute diarrhea: a meta-analysis of clinical trials. Pediatrics.
1994;93:1727.
10. Caballero B, Solomons NW. Lactose-reduced formulas
for the treatment of persistent diarrhea. Pediatrics.
1990;86:645646.
11. Johnson LR. Digestion and absorption. In: Johnson LR, ed.
Gastrointestinal Physiology. 6th ed. St. Louis, MO: Mosby;
2001:122127.
12. Schmitz J. Maldigestion and malabsorption. In: Walker AW,
et al., eds. Pediatric Gastrointestinal Diseases. 4th ed. Hamilton,
Ontario: BC Decker Inc; 2004:820.
13. Hodge C, Lebenthal E, Lee PC, Topper W. Amylase in the
saliva and in the gastric aspirates of premature infants: Its
potential role in glucose polymer hydrolysis. Pediatr Res.
1983;12:9981001.
14. Shulman RJ, Kerzner B, Sloan HR, et al. Absorption and
oxidation of glucose polymers of different lengths in young
infants. Pediatr Res. 1986;20(8):740743.
15. Lebenthal E, Lee PC. Glucoamylase and disaccharidase activities in normal subjects and in patients with mucosal injury of
the small intestine. J Pediatr. 1980;97:389393.
16. Savilahti E, Launiala K, Kuitunen P. Congenital lactase
deficiency: A clinical study on 16 patients. Arch Dis Child.
1983;58:246252.
17. Kellett GL, Brot-Laroche E. Apical GLUT2: A major pathway
of intestinal sugar absorption. Diabetes. 2005;54:30563062.
18. Cummings JH, Macfarlane GT. Colonic microflora: Nutrition
and health. Nutrition. 1997;13:476478.
19. Montalto M, Santoro L, DOnofrio F, et al. Classification of
malabsorption syndromes. Dig Dis. 2008;26(2):104111.
20. McClean P, Weaver LT. Ontogeny of human pancreatic
exocrine function. Arch Dis Child. 1993;68:6265.
Fats
Peggy R. Borum, PhD
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Different Types of Fat
Essential Fatty Acids
Different Functions of Adipose Tissue
Importance of Dietary Fat in Infants
Digestion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Absorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Metabolism During Normal Physiology. . . . . . . . . . . . . . . . 26
Synthesis of Fatty Acids
Beta-Oxidation of Long-Chain Fatty Acids inMitochondria
Beta-Oxidation of Medium-Chain Fatty Acids inMitochondria
Steps of Beta-Oxidation
Beta-Oxidation of Very Long-Chain Fatty Acids inPeroxisomes
Omega-Oxidation of Fatty Acids
Metabolism During Pathophysiologies. . . . . . . . . . . . . . . . 27

Fat As Fuel for Preterm Infants
Lipid Emulsions Containing Fish Oils
As Fuel forParenteral Nutrition In Pediatrics
To Esterify or To Oxidize: That Is the Cells Question
Learning Objectives
1. List the different types of fatty acids.

2. Contrast the different fatty acid oxidation pathways.
3. Relate different pathological conditions to altered fat
metabolism.
Introduction
Lipids are one of three macronutrients in the diet, the other

two being carbohydrates and protein. Triglycerides (lipids
containing 3 fatty acids) are one of the main storage forms
of metabolic energy in the body. Since fatty acids are highly
reduced hydrocarbons, they are calorically dense, providing
more metabolic energy per gram than the other dietary
macronutrients. This characteristic is advantageous when a
patient has a limited stomach capacity or is fluid-restricted
and yet needs additional calories for rapid growth or due to
critical illness. Fat is often viewed negatively by the public
as a nutrient that should be reduced in the diet. However
the problem may not be excess fat, but rather excess calories.
Once the diet provides appropriate calories, careful attention should be given to the types of fatty acids included in
the diet.
Different Types of Fat

Fats are extraordinarily diverse in structure but they have in
common poor solubility in water. Triglycerides are the major
dietary form of lipid and, as noted above, consist of 3 fatty
acids joined by a glycerol backbone. Typical fatty acids are
carboxylic acids with hydrocarbon chains ranging from 4 to
24 carbons (Figure 4-1). The chains are often unbranched,
but can contain a variety of substituents including rings,
hydroxyl groups, and methyl groups. The chain can be
saturated (no double bonds), monounsaturated (1 double
22
FATS
bond), or polyunsaturated (2 or more double bonds).1 As

diagrammed in Figure 4-2, fatty acids can be classified
according to degree of chain saturation as well as chain
length. Although there is no consensus definition for the
general terms of short chain (26 carbons), medium chain
(812 carbons), and long chain (14 carbons or more), the
chain lengths of the fatty acids will contribute to both the
physical characteristics of the food and the metabolism of
the fat once it enters the body via ingestion, tube feeding,
or parenteral nutrition. The shorter the chain and the more
unsaturated the chain, the lower the melting point of fat
with the result that the fat is more likely to be liquid at room
temperature. Thus, an animal product with a significant
amount of stearic acid (18 carbons, no double bonds) (Figure
4-1) is solid at room temperature, whereas a medium-chain
triglyceride oil (812 carbons) with a significant amount of
saturated fatty acids is liquid at room temperature. Olive oil,
with a higher percentage of monounsaturated oleic acid (18
carbons, 1 double bond), is a liquid at room temperature.1
23
concentration of polyunsaturated fatty acids (PUFAs)

in the membrane increases membrane susceptibility to
oxidation and peroxidation. Because vitamin E is a major
antioxidant in the membrane, an increase in dietary PUFAs
should always be accompanied by a careful evaluation of
adequate vitamin E intake. Since the fatty acid composition
of the membrane reflects the fatty acid composition of the
diet, careful attention to the type of fatty acid in the diet is
warranted.2 Optimizing the dietary fatty acid profile can
alter membrane structure which in turn can possibly alter
cell signaling associated with clinical symptomatology.
Figure 4-2 Classification of Fatty Acids
Figure 4-1 Structural Representation of a Saturated Fatty Acid
Membrane fluidity is important in the function of many

cell types and is greatly influenced by the degree of saturation of the fatty acids in the membrane phospholipids.1 A
three-dimensional view of saturated fatty acids reveals that
the hydrocarbon chains are straight and thus can be packed
very tightly in membrane phospholipids. Most physiological
unsaturated fatty acids have cis double bonds (ie, the chains
on the same side of the double bond). Every cis double bond
puts a kink into the hydrocarbon chain. The result is that
the trans-fatty acid (where chains are on the opposite side
of the double bond) is a straight hydrocarbon and can be
packed very tightly in membranes, reducing membrane
fluidity. Phospholipids containing unsaturated fatty acids
cannot be packed as tightly, resulting in a membrane with
increased fluidity.
In the food industry, trans-fatty acids are made from
unsaturated fatty acids to both change the consistency of the
fat product to a less liquid-like product at room temperature
and to increase shelf life by reducing the double bonds that
make the fat product susceptible to rancidity. An increased
Essential Fatty Acids

There are two different methods to number the carbons
of a fatty acid. The chemist usually begins the numbering
with the carboxylic acid carbon. In the field of nutrition,
the numbering usually begins with the methyl carbon
or omega carbon () which is at the opposite end of the
molecule from the carboxylic acid (Figure 4-1). Using the
system of numbering, an omega-3 (-3) fatty acid has its
first double bond between C3 and C4 from the carbon, an
omega-6 (-6) fatty acid has its first double bond between
C6 and C7 from the carbon, and an omega-9 (-9) fatty
acid has its first double bond between C9 and C10 from
the carbon. Humans cannot synthesize -3 or -6 fatty
acids, but many physiological processes are dependent on
these fatty acids and their myriad products. Therefore -3
24
2
and -6 fatty acids are required in the human diet and are
termed essential fatty acids (EFAs).1 The simplest -6 fatty
acid is linoleic acid (LA). Humans can convert LA to arachidonic acid (ARA). The simplest -3 fatty acid is -linolenic
acid (-LA). Humans can convert -LA to eicosapentaeonic
acid (EPA), and EPA very slowly to docosahexaenoic acid
(DHA). The same enzyme pool is used to metabolize LA and
-LA to their respective longer-chain metabolites. The more
prevalent fatty acid is metabolized preferentially. Thus a diet
high in the -6 fatty acid LA will preferentially metabolize
it over the -3 fatty acid -LA. ARA (20-carbon polyunsaturated -6) and EPA (20-carbon polyunsaturated -3)
are released from membranes and further metabolized to a
cascade of eicosanoids. Although it is not quite that simple,
eicosanoids from -6 fatty acids generally are considered
pro-inflammatory and those from -3 fatty acids are considered weakly anti-inflammatory. The docosanoid products
of DHA also have anti-inflammatory actions. 3 Fatty acids
and eicosanoids can change the abundance of transcription
factors which in turn regulate gene expression. Thus, the
fatty acid composition of the diet influences the composition of the cell membranes which influences the availability
of appropriate substrate to make either pro- or anti-inflammatory fatty acid products. Traditionally low intake of -3
and -6 fatty acids associated with an increase in an -9
fatty acid known as Mead acid in plasma has been used
to diagnose EFA deficiency. A more recent method uses
red blood cells and measures two additional parameters.4
The emerging field of investigation known as lipidomics
measures all small molecular weight lipids in a sample and
will likely provide the nutrition community with improved
methods for specific EFA evaluation.
With the industrialization of Western society, dietary
intake of EFAs has changed, reflecting the trend away from
grains to more processed foods high in fat. Intake of LA
relative to -LA has increased significantly. Currently the
ratio of LA to -LA in the diet is 14:1 in contrast to the 2:1
or 1:1 ratio that is usually recommended.2 Interestingly,
the change in dietary fat intake follows a similar temporal
pattern to the increase in inflammatory bowel disease incidence in the pediatric population. 5
Different Functions of Adipose Tissue

Storage of a metabolic fuel source and structural elements
of membranes are the most generally recognized functions of fats. However, a long list of other functions for fat
is now recognized (Figure 4-3). Adipose tissue maintains
a balance between clearance of plasma triglycerides and
release of fatty acids. Excess dietary energy cannot be
excreted. Diets with excess calories are frequently high in

fat because dietary fat is highly palatable and calorically
dense. Excess dietary energy from any of the macronutrients is converted to fatty acids and stored as triglycerides in
adipocytes. Therefore, surplus dietary calories will increase
adipose depots.
Figure 4-3 The Different Functions of Fat
Adipose tissue is not simply a place for the body to store

fat. Adipose tissue is a complex organ with many different
cell types containing receptors sensitive to inflammatory
signals. Thus, changing the size of adipose tissue has farreaching effects. When stimulated, adipose tissue releases
more than 20 diverse molecules known as adipokines that
have a wide range of metabolic effects both during health
and disease. Fat deposits can be found in subcutaneous,
intramuscular, and intrathoracic depots that differ in fatty
acid composition, adipokine secretion, and storage capacity.
Macrophage content of adipose tissue can increase from
the usual 5% to 10% to as much as 60% during obesity and
secrete an increasing amount of inflammatory cytokines.
Taken together, obesity can have a striking effect not only
on the size but also on the metabolism of the body.2
Importance of Dietary Fat in Infants

The percent of total body weight that is adipose tissue
dramatically increases during human gestation. Fetal white
adipose tissue increases at a rate of about 67 mg/d during
FATS
the last trimester, and most of that is DHA. The brain also
grows rapidly during the last trimester and requires a large
amount of DHA for the synthesis of myelin. At birth, the
brain of the human is at about 50% of its adult size and
continues to grow rapidly until it reaches near adult size
at about 2 years of age. Thus, the extremely preterm infant
born at 24 or 25 weeks gestation requires a large amount of
EFAs, and -3 fatty acids in particular, to achieve the type
of growth usually experienced by a fetus in utero during the
same period postconception.6,7
Regulation of gene expression by nutrients is critically
important in preterm neonates. Regulation of gene expression by -3 fatty acids involves multiple complex processes
including regulation of the transcription factors sterol regulatory element-binding proteins (SREBPs) and peroxisome
proliferator-activated receptors (PPARs) that modulate
many critical steps in metabolism.8,9
The two most abundant long-chain PUFAs in the brain
are DHA and ARA. DHA is concentrated in the prefrontal
cortex and in some retinal cells.10 Inadequate intake of -3
fatty acids not only results in decreased brain DHA but also
increased brain -6 fatty acid concentration.11,12 Worldwide
there are a variety of enteral products that vary in their
supply of -3 fatty acids and in DHA in particular. However
none of them provide the amount of EFAs that would accumulate in the fetal brain during the last trimester of gestation
without additional supplementation. Thus, the current diet
provided to these infants appears to be deficient in DHA.
Although it is not known how these infants would develop
if fed to sufficiency, preterm infants fed increased amounts
of DHA have been reported to have improved visual acuity
and mental development.13,14 A recent multicenter prospective, randomized, double-blind placebo-controlled trial
in Italy compared 580 healthy term neonates receiving
20mg of liquid DHA to 580 healthy term infants receiving
placebo with a focus on developmental milestones. The
infants receiving DHA were able to sit without support
1week earlier, but there was no difference between groups
for hands-and-knees crawling, standing alone, and walking
alone.15 It is unclear how these data from healthy term
neonates relate to preterm neonates. In infants being fed
parenterally, the challenge to provide adequate DHA and
ARA is even greater with currently available lipid emulsions
approved for use in this population.
Digestion
Because dietary lipids are hydrophobic, they must be hydrolyzed and emulsified to very small micelles before they can
be absorbed by the intestine. Lingual and gastric lipases
25
hydrolyze triglycerides to diglycerides and free fatty acids.

After activation by colipase, pancreatic lipase hydrolyzes
dietary fat to 2-monoglycerides which are poor substrates
for continued hydrolysis.16 Gastric lipolysis is incomplete in
adults, being responsible for 30% or less of dietary fat lipolysis.17 Since neonates have limited expression of pancreatic
enzymes needed for fat digestion in the intestine, it has
been assumed that gastric lipolysis has a more important
role in neonates.18 Supplementation of infant formula with
medium-chain triglycerides (MCTs) has been reported to
have conflicting effects on intragastric lipolysis in infants
(no effect versus decreased lipolysis).19 This may be related
to differences in the MCT concentration of the formula
studied.20
The pH increases as the acidic stomach contents move
to the intestine. The free fatty acid products of gastric
lipase are ionized and become oriented to the outside of
the oil droplets, surrounding the oil droplet with charge
and stabilizing the emulsion. Some of the free fatty acids
dissociate from thedroplet and interact with the intestinal
epithelium. These fatty acids are potent stimuli of cholecystokinin (CCK) release. CCK stimulates an increase in
pancreatic enzymes, relaxes the sphincter of Oddi which
allows the pancreatic juice to flow into the intestinal lumen,
and contracts the gallbladder to provide a bolus of concentrated bile needed to form micelles.17 Secreted bile contains
bile salts made in the liver that emulsify the products of lipid
digestion. The resulting micelles transport the digested fat
products through the aqueous intestinal lumen making
close contact with the brush border of the mucosal cells.
Bile salts continue to the ileum where they are absorbed
into the enterohepatic circulation.16
Phospholipase A 2 from the pancreas cleaves the fatty
acid in the 2 position of dietary phospholipids. Pancreatic
juice also contains cholesterol esterase that hydrolyzes
cholesterol esters, esters of vitamins A, D, and E, and all
3 fatty acids in triglycerides.17 Cystic fibrosis (CF) affects
many aspects of metabolism, including adequate secretion
of pancreatic enzymes for dietary fat absorption. Administration of pancreatic enzyme supplements can assist with
the problem. Careful monitoring is required to assure that
children with CF do not develop EFA deficiency or deficiency in fat-soluble vitamins. Breast milk lipase produced
by the mammary gland of lactating females is similar to
cholesterol esterase. Breast milk lipase also has broad specificity and may predigest the lipid components of breast
milk and thus increase the efficiency of theiruptake.17,19
26
Absorption
Bile acids play an important role in solubilizing the products of lumenal lipolysis and facilitating their transfer to
the absorptive epithelium. Fatty acids and monoglycerides
have enough solubility in the lumenal contents that they
can diffuse to the brush border and be absorbed.16
The intestinal epithelium is the site of significant
metabolic activities. The absorbed 2-monoglycerides are
re-acylated to triglycerides. Some 1-monoglycerides in the
emulsion are absorbed and hydrolyzed to fatty acids and
glycerol. The glycerol released within the intestinal epithelium is reutilized for triglyceride synthesis. Long-chain fatty
acids (LCFAs) are esterified to triglycerides, secreted into
the lymphatics as chylomicrons, and enter the blood via the
thoracic duct. Free short- and medium-chain fatty acids are
absorbed into the hepatic portal vein.16
Metabolism During Normal Physiology
Dietary fat can enter a diverse set of metabolic pathways

intricately controlled and coordinated to meet the needs of
the body. The cell can either oxidize fatty acids for immediate metabolic energy or synthesize fatty acids from other
dietary components and store them for later use.
Synthesis of Fatty Acids

Excess calories in the form of protein, carbohydrate, or
fat cannot be eliminated from the body once ingested or
administered and must be stored in the form of fatty acids.
Six cytosolic enzymes plus an acyl carrier protein (ACP)
are needed for fatty acid synthesis from acetyl-coenzyme A
(acetyl-CoA). In the first step, malonyl-CoA is formed from
acetyl-CoA which has been shuttled out of the mitochondria. This reaction-forming malonyl-CoA is the regulatory
step for fatty acid synthesis. The sequence of reactions that
follows is a condensation, a reduction, a dehydration, and
a second reduction. Both reduction reactions use nicotinamide adenine dinucleotide phosphate (NADPH) as the
electron donor. The sequence of reactions adds 2 carbons
at a time and is repeated until a chain length of about 16
carbons is made and released from the ACP.1
As discussed in the Essential Fatty Acids section,
humans cannot synthesize LA or LA. Although humans
have the necessary enzymes to make EPA from -LA and
DHA from EPA, the capacity to do so is very low.21 Only
about 5% of -LA can be converted to EPA and less than
0.5% of -LA can be converted to DHA. There is also a low
capacity to convert LA to ARA. Thus, although only LA
and -LA are termed EFAs, the administration of only LA
or -LA often has only a negligible effect on plasma ARA,
EPA, and DHA.22,23 The optimal ratio of preformed EPA

and DHA has not been established, but ratios of 1:2 to 2:1
are expected to be effective.24
Beta-Oxidation of Long-Chain Fatty Acids

inMitochondria
Lipoprotein lipase in the capillary endothelium releases free
fatty acids delivered to tissues by chylomicrons. Hormonesensitive lipase mobilizes triglycerides from adipose tissue
when needed. The fatty acids are carried in the blood bound
to albumin and delivered to the tissues to use for fuel. When
fatty acids are to be used for fuel, they are activated to the
fatty acyl-CoA at the outer mitochondrial membrane. Fatty
acyl-CoA is the correct high-energy state for beta-oxidation
(-oxidation), but the enzymes for -oxidation are located
within the mitochondrial matrix (Figure 4-4) and the fatty
acyl-CoA cannot cross the inner membrane of the mitochondria to reach these enzymes. In order to use LCFAs for
metabolic energy, fatty acyl-CoA is converted to fatty acylcarnitine via carnitine palmitoyltransferase 1, transported
across the inner mitochondrial membrane via carnitineacylcarnitine translocase in exchange for free carnitine,
and reconverted to fatty acyl-CoA in the matrix of the
mitochondria via carnitine palmitoyltransferase 2. The end
result is that the high-energy fatty acyl-CoA is now in the
same location as the metabolic machinery for -oxidation.
Fatty acid oxidation and fatty acid synthesis do not occur at
the same time because malonyl-CoA (an early intermediate
in fatty acid synthesis) inhibits carnitine palmitoyltransferase1 and thus prevents the fatty acyl-CoA from reaching
the site of -oxidation.1,25
Figure 4-4 Sites of Fatty Acid Oxidation
FATS
27
Patients with high plasma levels of triglycerides are sometimes given heparin (assuming that it will stimulate lipolysis
of triglycerides) and carnitine (assuming it will stimulate
-oxidation of the released fatty acids). Definitive data to
confirm these assumptions in patients on special nutrition
support are yet to be obtained. In addition, it should be
remembered that supplemented heparin and carnitine each
have a variety of effects on the bodys metabolism.
shortened fatty acyl-CoA and acetyl-CoA. When the fatty

acyl-CoA is a medium-chain fatty acyl-CoA, the oxidation
sequence stops. Acetyl-CoA and the medium-chain fatty
acyl-CoA must be transported out of the peroxisome via a
carnitine shuttle. The medium-chain fatty acyl carnitine is
transported into mitochondria to complete the oxidation to
acetyl-CoA.1
Beta-Oxidation of Medium-Chain Fatty Acids

inMitochondria
In liver cells, medium-chain fatty acids (MCFAs) are transported into mitochondria (Figure 4-4) as free fatty acids
and then activated to medium-chain fatty acyl-CoA. Therefore, oxidation of MCFAs is carnitine independent in the
liver. However, other tissues activate MCFAs to mediumchain fatty acyl-CoA on the cytoplasmic side of the inner
mitochondrial membrane and require the carnitine shuttle
for -oxidation.26,27 Thus, if dietary MCFAs are provided
in quantities where they are expected to be a fuel substrate
for skeletal muscle, carnitine will be required for their
oxidation.
Omega-oxidation of fatty acids occurs in the endoplasmic

reticulum in the cytoplasm (Figure 4-4). The omega carbon
is first converted to an alcohol by a cytochrome P450
mixed function oxidase which requires both oxygen and
NADPH. Alcohol dehydrogenase and aldehyde dehydrogenase convert the alcohol to a carboxylic acid on the omega
carbon. Thus, the fatty acid is converted to a dicarboxylic
acid which can be esterified to carnitine and transported to
the mitochondrial matrix. There it can enter the -oxidation
pathway to be shortened at both ends of the molecule at
the same time. Omega-oxidation of fatty acids is normally
a minor pathway. Dysfunctional -oxidation in the mitochondria will increase omega-oxidation.28
Steps of Beta-Oxidation
Metabolism During Pathophysiologies
In mitochondria, 4 repeating reactions (dehydrogenation

requiring flavin adenine dinucleotide (FAD), hydration,
dehydrogenation requiring nicotinamide adenine dinucleo
tide (NAD), and cleavage requiring CoA) produce a fatty
acyl-CoA shortened by 2 carbons and acetyl-CoA. The
shortened fatty acyl-CoA reenters the sequence and the
acetyl-CoA is oxidized to carbon dioxide in the citric acid
cycle. The citric acid cycle coupled to the oxidative phosphorylation pathway yields metabolic energy as adenosine
triphosphate (ATP). Oxidation of unsaturated fatty acids
requires 2 additional enzymes in the mitochondria to
oxidize the double bonds.1
Beta-Oxidation of Very Long-Chain Fatty Acids

inPeroxisomes
Peroxisomes are subcellular organelles in the cytoplasm
that carry out -oxidation in 4 repeating steps similar to
those in the mitochondria. The difference is that the first
reaction transfers electrons directly to oxygen-producing
hydrogen peroxide. Peroxisomes oxidize very LCFAs
(Figure 4-4) and branched fatty acids. Fatty acids enter the
peroxisome before they are esterified to fatty acyl-CoA,
so the carnitine shuttle is not needed to deliver the fatty
acids to the peroxisomes. The very LCFAs are shortened
by 2 carbons during each reaction sequence producing the
Omega-Oxidation of Fatty Acids
Many chronic pathological conditions, including type 2

diabetes, hypertension, atherosclerosis, and obesity, are
associated with altered fat metabolism. In some situations,
inappropriate dietary fat quantity and/or composition
contribute to the observed pathology.
Fat As Fuel for Preterm Infants

Early introduction of lipid emulsions to preterm neonates
has not been shown to increase complications, 29 but also has
not been shown to improve short-term growth or prevent
morbidity and mortality. 30 An emulsion with a mixture
of medium-chain and long-chain fatty acids appears to be
superior to an emulsion containing only LCFAs in terms of
incorporation of EFAs and long-chain PUFAs into circulating lipids. 31 Adequate energy intake during the first days
of life is associated with improved brain function. A recent
study of 148 extremely low-birth-weight survivors showed
that every 42 kJ (10 kcal)/kg/d provided during the first
postnatal week is associated with a 4.6 point increase inthe
Mental Development Index. 32
Lipid Emulsions Containing Fish Oils As Fuel

forParenteral Nutrition In Pediatrics
As discussed earlier, -3 fatty acids including EPA and DHA
(sometimes called fish oils) have several important functions
28
in the body both during health and disease. Twelve children with pediatric short bowel syndrome who developed
parenteral nutrition-associated liver disease received parenteral -3 fatty acids while awaiting liver transplant. They
showed restoration of liver function to the point that 9 of
the children were no longer considered for liver transplant.
The remaining 3 children received a liver transplant with no
complications attributable to the -3 emulsion. 33 In another
study, 18 infants who developed cholestasis while receiving
a parenteral emulsion high in -6 fatty acids were switched
to an emulsion high in -3 fatty acids and compared to
21 historical controls who had similar symptoms and had
been maintained on the -6 fatty acid emulsion. Patients
receiving the -3 fatty acids experienced a reversal of
cholestasis 6.8 times faster when the data were adjusted for
baseline bilirubin concentration, gestational age, and diagnosis of necrotizing enterocolitis. The -3 fatty acid cohort
had had 2 deaths and no liver transplants and the historical
control cohort had 7 deaths and 2 liver transplantations. 34
Parenteral lipid emulsions containing fish oil are still
not approved for use in children or available in the United
States and Canada.
fatty acid catabolism, resulting in a situat ion some have

termed glucolipotoxicity.23 Intake of excess carbohydrate
increases cellular malonyl-CoA concentrations which
in turn inhibits carnitine palmitoyltransferase 1 activity,
impairing -oxidation of fatty acids. Insulin resistance is
associated not only with the intake of excess calories but also
with high intakes of saturated fat. Substituting saturated fat
with unsaturated fat seems to improve insulin sensitivity. 35
Figure 4-5 Path to Lipid Overload or Lipotoxicity
To Esterify or To Oxidize: That Is the Cells Question

The ability to synthesize or to oxidize fatty acids allows the
cell to store excess calories as fat and to mobilize the stored
fatty acids for metabolic fuel which is a life-saving adaptation during times of starvation. When products of digested
macronutrients enter the cell during normal physiological
situations, the cell responds to metabolic signals indicating
the metabolic fuel status of the cell and either uses the fuel
substrates to produce needed metabolic energy or stores the
fuel substrate as fatty acids in triglycerides. If excess calories
are chronically delivered to the cell, however, the ability of
adipose tissue to serve as a sink and protect non-adipose
tissues from fatty acid spillover appears to become saturated. As diagrammed in Figure 4-5, the result is lipid
overload or lipotoxicity that overwhelms the abilities of both
the endoplasmic reticulum and mitochondria to maintain
cellular homeostasis and results in systemic release of both
free fatty acids and inflammatory cytokines. Accumulation
of fatty acids in skeletal muscle, heart, liver, and pancreas
is likely the underlying factor during the development of
insulin resistance, cardiomyopathy, liver steatosis, and
type 2 diabetes. During normal physiological conditions,
there is intricate coordination of the use of fatty acids for
energy and the use of glucose for energy. Likewise during
chronic intake of excess calories, excess lipids inhibit the
utilization of glucose and hyperglycemia interferes with
Metabolism of dietary fat is altered in overweight patients.

For example, overweight patients with a fatty liver have a
higher postprandial triglyceride response and an increased
production of large very low-density lipoproteins after a fat
load compared to control subjects. 36 When providing nutrition support, it is important not only to provide appropriate
calories for the specific patient, but to carefully evaluate
how the patients current metabolic status may impact the
bodys metabolism of the nutritional fat substrate provided.
FATS
1. In order to maintain health and prevent a home parenteral nutrition patient from becoming overweight, the
optimal nutrition support prescription:
A. Restricts fat to an absolute minimum while
providing a generous amount of glucose.
B. Provides adequate calories including a fatty acid
blend with appropriate chain length, chain saturation, and ratios of LA, -LA, ARA, EPA, and DHA.
C. Provides 80% of the calories recommended for oral
intake.
D. Provides all the fat calories as the essential fatty
acids LA and -LA.
2. The cellular site(s) for fatty acid oxidation in the body
is (are):
A. Mitochondria
B. Peroxisomes
C. Cytoplasm
D. Mitochondria, peroxisomes, and cytoplasm
3. The essential fatty acid needs of a critically ill 24-week
neonate in the neonatal intensive-care unit requires
dietary:
A. LA and -LA
B. -LA and DHA
C. LA and ARA
D. LA, -LA, ARA, and DHA
References
1. Nelson DL, Cox MM. Lehniger Principles of Biochemistry. 5th

ed. New York, NY: W.H. Freeman and Co; 2008.
2. Innis SM. Dietary lipids in early development: relevance to
obesity, immune and inflammatory disorders. Curr Opin
Endocrinol Diabetes Obes. 2007;14(5):359364.
3. Fritsche K. Fatty acids as modulators of the immune response.
Annu Rev Nutr. 2006;26:4573.
4. Fokkema MR, Smit EN, Martini IA, Woltil HA, Boersma ER,
Muskiet FAJ. Assessment of essential fatty acid and omega
3-fatty acid status by measurement of erythrocyte 20:39
(Mead acid), 22:56/20:46 and 22:56/22:63. Prostaglandins Leukot Essent Fatty Acids. 2002;67(5):345356.
5. Innis SM, Jacobson K. Dietary lipids in early development
and intestinal inflammatory disease. Nutr Rev. 2007;65(12)
(pt 2):S188S193.
6. Marszalek JR, Lodish HF. Docosahexaenoic acid, fatty
acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu Rev Cell Dev Biol.
2005;21:633657.
7. Heird WC, Lapillonne A. The role of essential fatty acids in
development. Annu Rev Nutr. 2005;25:549571.
8. Deckelbaum RJ, Worgall TS, Seo T. n-3 fatty acids and gene
expression. Am J Clin Nutr. 2006;83(6):1520S1525S.
29
9. Sampath H, Ntambi JM. Polyunsaturated fatty acid

regulation of genes of lipid metabolism. Annu Rev Nutr.
2005;25:317340.
10. Agostoni C. Role of long-chain polyunsaturated fatty acids in
the first year of life. J Pediatr Gastroenterol Nutr. 2008;47(suppl
2):S41S44.
11. Innis SM. Dietary omega 3 fatty acids and the developing
brain. Brain Res. 2008;1237:3543.
12. Novak EM, Dyer RA, Innis SM. High dietary omega-6 fatty
acids contribute to reduced docosahexaenoic acid in the
developing brain and inhibit secondary neurite growth. Brain
Res. 2008;1237:136145.
13. Hay WW Jr. Strategies for feeding the preterm infant. Neonatology. 2008;94(4):245254.
14. Innis SM. Omega-3 Fatty acids and neural development to 2
years of age: do we know enough for dietary recommendations?
J Pediatr Gastroenterol Nutr. 2009;48 (Suppl 1):S16S24.
15. Agostoni C, Zuccotti GV, Radaelli G et al. Docosahexaenoic
acid supplementation and time at achievement of gross
motor milestones in healthy infants: a randomized, prospective, double-blind, placebo-controlled trial. Am J Clin Nutr.
2009;89(1):6470.
16. Bender DA, Mayes PA. Nutrition, digestion, & absorption. In:
Murray RK, Granner DK, Rodwell VW, eds. Harpers Illustrated Biochemistry. 27th ed. New York, NY: McGraw-Hill;
2006.
17. Barrett KE. Lipid assimilation. In: Barrett KE, ed. Gastrointestinal Physiology. New York, NY: McGraw-Hill; 2006.
18. Hamosh M. Digestion in the newborn. Clin Perinatol.
1996;23(2):191209.
19. Hernell O, Blackberg L. Human milk bile salt-stimulated
lipase: functional and molecular aspects. J Pediatr. 1994;125(5)
(pt 2):S56S61.
20. Hamosh M, Bitman J, Liao TH, et al. Gastric lipolysis and
fat absorption in preterm infants: effect of medium-chain
triglyceride or long-chain triglyceride-containing formulas.
Pediatrics. 1989;83(1):8692.
21. Russo GL. Dietary n-6 and n-3 polyunsaturated fatty acids:
from biochemistry to clinical implications in cardiovascular
prevention. Biochem Pharmacol. 2009;77(6):937946.
22. Plourde M, Cunnane SC. Extremely limited synthesis of long
chain polyunsaturates in adults: implications for their dietary
essentiality and use as supplements. Appl Physiol Nutr Metab.
2007;32(4):619634.
23. Brenna JT, Salem N Jr, Sinclair AJ, Cunnane SC. alpha-Linolenic acid supplementation and conversion to n-3 long-chain
polyunsaturated fatty acids in humans. Prostaglandins Leukot
Essent Fatty Acids 2009;80(2-3):8591.
24. Harris WS, Mozaffarian D, Lefevre M, et al. Towards establishing dietary reference intakes for eicosapentaenoic and
docosahexaenoic acids. J Nutr. 2009;139(4):804S819S.
25. Rasmussen BB, Wolfe RR. Regulation of fatty acid oxidation
in skeletal muscle. Annu Rev Nutr. 1999;19:463484.
26. Groot PHE, Hulsmann WC. The activation and oxidation of
octanoate and palmitate by rat skeletal muscle mitochondria.
Biochim Biophys Acta. 1973;316:124135.
27. Rssle C, Carpentier YA, Richelle M, et al. Medium-chain
triglycerides induce alterations in carnitine metabolism. Am J
Physiol Endocrinol Metab. 1990;258:E944E947.
30
28. Croston G. BioCarta omega oxidation pathway. http://www.

biocarta.com/pathfiles/omegaoxidationPathway.asp. 2009.
Accessed July 1, 2009.
29. Drenckpohl D, McConnell C, Gaffney S, Niehaus M, Macwan
KS. Randomized trial of very low birth weight infants receiving
higher rates of infusion of intravenous fat emulsions during
the first week of life. Pediatrics. 2008;122(4):743751.
30. Simmer K, Rao SC. Early introduction of lipids to parenterally-fed preterm infants. Cochrane Database Syst Rev.
2005;(2);CD005256.
31. Krohn K, Koletzko B. Parenteral lipid emulsions in paediatrics. Curr Opin Clin Nutr Metab Care. 2006;9(3):319323.
32. Stephens BE, Walden RV, Gargus RA, et al. First-week protein
and energy intakes are associated with 18-month developmental outcomes in extremely low birth weight infants.
Pediatrics. 2009;123(5):13371343.
33. Diamond IR, Sterescu A, Pencharz PB, Kim JH, Wales PW.
Changing the paradigm: omegaven for the treatment of liver
failure in pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr. 2009;48(2):209215.
34. Gura KM, Lee S, Valim C, et al. Safety and efficacy of
a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics.
2008;121(3):e678e686.
35. Riserus U. Fatty acids and insulin sensitivity. Curr Opin Clin
Nutr Metab Care. 2008;11(2):100105.
36. Assy N, Nassar F, Nasser G, Grosovski M. Olive oil consumption and non-alcoholic fatty liver disease. World J Gastroenterol.
2009;15(15):18091815.
Protein Digestion, Absorption,

andMetabolism
Richard A. Helms, PharmD, Emma M. Tillman, PharmD, Anup J. Patel, MD, and John A. Kerner, MD
Learning Objectives
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Ontogeny of the Gastrointestinal Tract
inRelation to Protein. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Protein Digestion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Protein Absorption. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Digestion and Absorption of Whey and Casein . . . . . . . . .
Amino Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
31
31
32
33
34
35
Conditionally Essential Amino Acids

Amino Acids of the Urea Cycle
Useful Classification of Amino Acids for the Clinician
Liver and Kidney: Roles in Amino AcidMetabolism. . . . . . 38

Functions of Amino Acids and Proteins . . . . . . . . . . . . . . . 39
Protein Requirements and
Protein-Energy Ratio DuringGrowth. . . . . . . . . . . . . . . . . . 40
Assessment of Protein Status
Monitoring Plasma Amino Acids
Case Presentation and Discussion. . . . . . . . . . . . . . . . . . . 41
1. Explain how protein metabolism and physiology is

profoundly affected by the ontogeny of the gastrointestinal tract.
2. Describe the roles of the liver and kidney in amino acid
metabolism.
3. Understand the functions of amino acids and proteins,
protein requirements for age, and protein energy ratios
during growth.
4. Discuss protein turnover, assessment of plasma amino
acids, and nitrogen balance.
Introduction
There is an extraordinary range of knowledge related to

protein in human nutrition. The basics of protein in adult
nutrition have been nicely reviewed in The A.S.P.E.N. Nutrition Support Core Curriculum, and materials covered in that
publication will not be extensively revisited here.1 Because
this chapter is restricted to protein in pediatrics, it will focus
particularly on the rapidly developing neonate and infant.
Ontogenic events relating to protein metabolism and physiology render the small child as much different than the
older child and adult. This chapter will review aspects of
digestion, absorption, and metabolism of protein focusing
on these differences.
Ontogeny of the Gastrointestinal Tract

inRelation to Protein
The gastrointestinal (GI) tract has been described as the

largest endocrine organ. It produces numerous regulatory
gut peptides that are involved in GI tract development,
growth, absorption, secretion, and gut motility. They
function in classic endocrine, autocrine, paracrine, and
31
32
neurocrine pathways.2,3 Selected gastrointestinal regulatory peptides involved with the ontogeny of the GI tract as
it relates to proteins are outlined in Table 5-1. All of these
peptides are present by the end of the first trimester in the
fetus, but adult levels may not be present until term.4 These
peptides that function as hormones are released in response
to feeding. The release of some of these hormones is limited
in the newborn compared to the adult.4,5
There are significant differences in the ontogeny of
the two main enzymes secreted by the gastric mucosa. In
the human, even though both pepsin and gastric lipase are
located at the same site (ie, in the chief cells of the gastric
mucosa), the enzymes have different developmental
patterns.6 Pepsin activity and output are much lower in
infants than adults.7,8 In contrast, gastric lipase activity and
output are equal in infants and adults.7,8
The ontogeny of the brush border amino-oligopeptidases as well as the dipeptide and amino acid transport
systems parallel that of the carbohydrate enzymes. Aminooligopeptidases are first detected immunohistochemically
by 10 to 16 weeks gestation. By 28 to 30 weeks gestation,
enzyme levels are approximately one-half of the values
found in term infants. Therefore, all aspects of intestinal
proteolysis and transport are relatively intact, even in the

preterm infant.9
Protein Digestion
Initial protein digestion occurs in the stomach, where

proteins are exposed to hydrochloric acid (HCl) and pepsin.
Gastric acid produces an acidic environment in the stomach,
and denatures protein.10,11 Although protein digestive
activity within the GI tract has been identified as early as 16
weeks gestation, there are relatively low amounts of gastric
acid secretion and consequently less protein denaturation
in both preterm and term infants. In fact, there is relatively
minimal functional protein digestion in the stomach in the
first few weeks of life. It is not until about 2 years of age that
adult levels of gastric acid secretion are reached.9
Chief cells secrete proenzymes (pepsinogen 1 and 2)
into the stomach, which undergo auto-activation to form
pepsins in the acidic milieu.12 This acidic environment is
critical for pepsin function as evidenced by its inactivity
in the duodenum, where the pH is neutral.13 These pepsins
function as endopeptidases; they hydrolyze internal bonds
of the polypeptides to primarily form shorter polypeptides, oligopeptides, and some free amino acids.9,11 Gastrin
Table 5-1 Gastrointestinal Regulatory Peptides2

Regulatory Peptide
Sources
Mechanisms
Actions
Epidermal Growth Factor
Salivary glands
Brunner glands
Paneth cells
Hormone
Paracrine
Stimulates mucosal proliferation and differentiation

Regulates gastrointestinal secretion
Has cytoprotective/ulcer-healing effects
Insulin-like Growth Factor
Gastrointestinal tract
Liver
Hormone
Autocrine
Paracrine
Stimulates crypt cell proliferation and enterocyte differentiation

Promotes intestinal adaptation
Enteroglucagon
Ileum
Colon
Hormone
Stimulates gut mucosal growth

Regulates gut motility
Neurotensin
Ileum
Central nervous system
Hormone
Neurocrine
Inhibits gastric emptying and acid secretion
Vasoactive Intestinal
Polypeptide
All tissues
Neurocrine
Promotes secretomotor, vasodilatation, and smooth

musclerelaxation
Pancreatic Polypeptide
Pancreas
Hormone
Inhibits pancreatic enzyme secretion and gallbladder

contraction
Motilin
Proximal small intestine
Hormone
Stimulates gastrointestinal motility
Peptide YY
Gastrointestinal tract
Central nervous system
Hormone
Paracrine
Neurocrine
Inhibits gastric acid secretion and gut motility
Reprinted from Gilger MA. Normal gastrointestinal function. Table 342-1. In: McMillan JA, Feigin RD, DeAngelis C, Jones MD, eds. Oskis Pediatrics. 4th ed.
Copyright 2006 with permission from Lippincott Williams & Wilkins.
PROTEIN DIGESTION, ABSORPTION, ANDMETABOLISM
stimulates both gastric acid and pepsin production and secretion, which initiates protein digestion in the stomach.10
The protein denaturation within the stomach does not
appear to be critical because patients with a more neutral
gastric pH do not have impaired protein digestion. However,
the amino acids that are produced from protein digestion in
the stomach do assist in releasing cholecystokinin (CCK)
or pancreozymin.12 CCK has a role in protein digestion by
helping to release pancreatic digestive enzymes, stimulate
gallbladder contraction, and relax the sphincter of Oddi.11,12
In contrast, the hormone secretin promotes pancreatic
secretion of bicarbonate-rich fluid to help establish a favorable pH.10
The pancreatic digestive enzymes are secreted in their
inactive proenzyme form, similar to the secretion of pepsin
as pepsinogen in the stomach. The pancreas secretes both
endopeptidases (trypsinogen, chymotrypsinogen, and
proelastase) and exopeptidases (procarboxypeptidase A
and B) into the proximal small intestine.11 The activated
endo- and exopeptidases hydrolyze the proteins at peptide
bonds within the polypeptide chains to form oligopeptides
and at the carboxyl terminal to form single amino acids,
respectively.911
Bile acids and trypsinogen together cause the release
of enterokinase, a brush border enzyme, which converts
trypsinogen into its active form trypsin. Trypsin then
converts the remaining pancreatic peptidases into their
respective active forms (chymotrypsin, elastase, and
carboxypeptidase A and B), and assists in forming more
trypsin from trypsinogen (see Figure 5-1).9,10,13 Overall, the
products of lumenal protein digestion are about 70% oligopeptides and 30% free amino acids.9
Enterokinase and trypsin have been detected at 26
and 28 weeks gestation, respectively. Enterokinase levels at
time of birth are about 10% of adult levels except in those
rare infants with congenital enterokinase deficiency.9,14
Trypsin activity in duodenal juice of the premature infant
is slightly less than in the full-term infant but does increase
in response to food as it does in full-term infants. Infants
have been found to have decreased trypsin activity in
duodenal fluid compared to older children.15 This reduced
trypsin activity has been demonstrated to increase over the
first 4 months of life, possibly resulting from their relative
increased enteral protein intake.9 However, the significance
of these differences is unclear given that protein digestion
and absorption is fairly efficient even in preterm infants. It
is estimated that term infants digest and absorb about 80%
to 85% of lumenal proteins while estimates for adults range
from 95% to 98%.9,11
33
Figure 5-1 Pancreatic Enzyme Activation10
Reprinted from Wahbeh GT, Christie DL. Basic aspects of digestion and
absorption. In: Wyllie R, Hyams JS, eds. Pediatric Gastrointestinal and Liver
Disease: Pathophysiology, Diagnosis, Management. 3rd ed.
Copyright 2006 with permission from Elsevier.
Protein Absorption
Normal protein absorption involves lumenal processing,

absorption into the intestinal mucosa, and transport into
the circulation.12 At the brush border of enterocytes, there
are different types of peptidases, including oligopeptidases, that further hydrolyze the partially digested proteins
into amino acids, dipeptides, and tripeptides (see Figure
5-2).9,10,12,16 Oligopeptidases have been detected as early as
10 to 16 weeks gestation, and they increase to nearly half of
full-term levels by 28 to 30 weeks gestation.9
Absorption into the enterocyte involves both sodiumdependent and -independent transport systems.9 The
sodium-dependent amino acid transporters are driven
by a low intracellular sodium concentration and negative
intracellular potential resulting from the sodium-potassium-adenosine triphosphatase (Na+-K+ ATPase) pump.12
There are many different transporters including those for
neutral, acidic, and basic amino acids with narrow substrate
specificity, and for di- and tripeptides with a broad substrate
specificity (see Figure 5-3).9,10,12,16
Once the amino acids are transported into the cytoplasm, there is additional processing by cytoplasmic
peptidases, mostly dipeptidases and tripeptidases, which
convert the di- and tripeptides into free amino acids.10,12,13
Although most of these amino acids are transported into the
blood stream, it is estimated that about 10% of amino acids,
particularly glutamine and glutamic acid, are used directly
by the enterocyte.10,13 This coincides with the observation
that animals receiving total parenteral nutrition without
enteral feeds have developed mucosal atrophy.10
Some of the sodium-independent amino acid transporters are located on the basolateral surface of the
enterocyte, and function to transport amino acids into the
34
Figure 5-2 Overview of Protein Digestion and Absorption
Reprinted from Roy CC, Silverman A, Alagille D. Pediatric Clinical Gastroenterology. Malabsorption syndrome. p. 307. (Modified and published with
permission from Ahnen DJ. Protein digestion and assimilation. In Yamada T, et al. Textbook of Gastroenterology, Philadelphia. 1991. Lippincott.)
portal vein.9 Although a significant majority of the protein

that enters the portal circulation is in the form of free amino
acids, there are small amounts of di- and tripeptides that
enter the blood stream intact through normal transport
systems.10
Studies have shown that an infants intestine may have
a higher capacity for absorption of macromolecules than
the adult intestine.17 Thus, among susceptible infants, for
example infants who sustain severe post-infectious villous
injury, the early introduction of specific foods of increased
antigenic potential may increase their risk of protein
sensitization.18,19
Given the broad substrate specificity for di- and tripeptidases at the brush border, it is not surprising that clinically
significant deficiencies resulting from specific amino acid
transport abnormalities are uncommon. Two of the more
well-known inherited defects of protein absorption include
Hartnup syndrome and cystinuria. In Hartnup syndrome,
neutral amino acid transport is defective and patients
present with pellagra-like skin eruptions. In cystinuria
(see Chapter 24), there is a defect in cystine reabsorption
resulting in excessive cystine in the urine and subsequent
renal stone formation. In contrast, acquired defects of
protein absorption, including exocrine pancreatic insufficiency and transient brush border enzyme deficiency from
gastroenteritis, are more common.8
Figure 5-3 The Transport of Amino Acids
Reprinted from Roy CC, Silverman A, Alagille D. Pediatric Clinical

Gastroenterology. 4th ed. Copyright 1995 with permission from Elsevier.
Digestion and Absorption of Whey and Casein
The major proteins in milk are whey and casein. Unmodified cows milk is approximately 18% whey and 82% casein.
When this unheated casein-predominant protein enters
the acidic environment of the stomach, it forms a relatively
hard curd of casein and minerals that can be difficult to
digest. In contrast, human milk protein is approximately
60% to 70% whey and 30% to 40% casein.20,21 Human milk
forms a very small, soft curd in acid. Some infant formula
companies have developed whey-predominant formulas by
combining equal amounts of demineralized whey protein
and skim milk protein to yield a formula with 60% whey

and 40%casein.
There are other important differences between these two
types of proteins. Whey results in a faster gastric emptying
time, and is overall more easily digested. In contrast, casein
is less soluble and has a slower rate of digestion, which
results in an extended release of amino acids into the circulation. In human studies, casein-predominant formulas
result in lower zinc bioavailability than whey-predominant
formulas, presumably because of less complete digestion of
casein.22
Other types of human whey proteins include secretory
IgA and lactoferrin.21 Secretory IgA attaches to the lining
of the GI tract and prevents potential pathogenic microorganisms from adhering.9 Lactoferrin is an iron-binding
protein that limits the ability of bacteria to thrive in the
intestines. Because this protein is biochemically similar to
transferrin, it is suggested that it may have a significant role
in iron absorption. However, in vivo studies do not definitively establish this role.23 Also, there is some evidence that
suggests that lactoferrin has a role in stimulating intestinal
mucosa growth.24 These two proteins found in human milk,
secretory IgA and lactoferrin, and the main protease inhibitors, alpha 1-antitrypsin and alpha 1-antichymotrypsin, are
not well-digested in early infancy.24,25 In fact, it has been
estimated that about 10% of intact milk proteins have been
found in infant stools prior to 1 month of age while this
decreases to about 3% at 4 months of age.24 In vitro studies
suggest that alpha 1-antitrypsin resists proteolysis by pepsin
and pancreatic enzymes.24,26 Alpha 1-antitrypsin has been
found in considerable quantities in both human milk and
in the stool of infants fed human milk; therefore it should
not be used to ascertain enteric protein loss in breastfed
infants.26
Overall, infant formulas traditionally contain more
protein than human milk due to the concern that proteins
found in infant formulas are less digestible. This is supported
by the observation that formula-fed infants have higher
blood urea nitrogen (BUN) levels due to the higher exposure
to proteins. These formulas also have a higher proportion of
whey, which should increase their digestibility. In addition,
it is important to note that heat treatment of milk proteins
does affect their digestibility. It has been observed that
protein digestibility in powdered formulas is increased in
comparison to identical liquid solutions. The heat treatment
for powdered formulas is less intense than liquid formulas
with a lower maximum temperature and shorter duration.
As a result, protein digestibility is increased with less intense
heat treatment.24
35
Amino Acids
There are literally hundreds of amino acids found in nature,

but only 20 are considered relevant in human nutrition.
Lafayette B. Mendel (1872-1935) demonstrated for the first
time that some amino acids cannot be synthesized in rats,
and, hence, defined them as essential amino acids required
in their diet. In an amazing series of experiments completed
in the 1940s and 1950s, William C. Rose (1887-1985, who
completed his training under Mendel) and co-investigators determined the amino acid requirements of normal
adults.27 These experiments revealed 8 amino acids that
resulted in negative nitrogen balance when excluded from
the diet. Upon resumption of these amino acids in adequate
amounts, there was a complete reversal of the negative
nitrogen balance. These 8 amino acids are isoleucine,
leucine, valine, lysine, methionine, phenylalanine, threonine, and tryptophan (Table 5-2). Other amino acids could
be withheld without appreciable effect on nitrogen balance.
Studies have confirmed these findings in infants and schoolage children.
Table 5-2 Essential, Non-Essential, and Conditionally Essential Amino
Acids in the Human Nutrition
Essential
Conditionally Essential
Non-Essential
Histidine*
Cyst(e)ine
Alanine
Isoleucine
Taurine
Aspartic Acid
Leucine
Tyrosine
Asparagine
Lysine
Glutamic Acid
Methionine
Glutamine
Phenylalanine
Glycine
Threonine
Proline
Tryptophan
Serine
Valine
Arginine
Cyst(e)ine = sum of cysteine and cystine. Glycine and Serine carbon

skeletons can be readily synthesized by neonates and infants, but the
rate of transamination is low.
* Not initially identified by Rose as being an essential amino acid.
Laidlaw-Kopple classification as acquired indispensible (see Table 5-4).
Amino acids are capable of existing in two isomeric

forms. The L-amino acids are utilized in humans and most
animals. The stereoselectivity is related to enzymes that
only recognize and utilize the L isomer. Amino acids do
exist as D isomers, but only D-methionine can be converted
to L-methionine by some animals, but not humans. For
the rest of this chapter the authors will not identify amino
acids as the L isomer; one can assume the L isomer is being
discussed.
36
Conditionally Essential Amino Acids

Investigations that followed Roses extraordinary work
generated questions as to whether other amino acids may
be required in the diet under certain conditions of immaturity, metabolic imbalance, organ failure, disease, and highly
defined diets such as parenteral nutrition (PN).
Histidine is now considered essential in the human
diet. While the original exclusion studies by Rose did not
demonstrate negative nitrogen balance, Nasset was able
to demonstrate that the hemoglobin of Roses subjects fell
while on histidine-free diets.28 These investigators calculated that the loss of hemoglobin was sufficient to supply
the subjects with 240 mg/d of histidine. Histidine stores
are particularly high in hemoglobin and in carnosine
(found in large quantities in muscle). Observations by
Kopple confirmed these findings.29,30 It is widely accepted
that histidine is the ninth essential amino acid in humans
(Table 5-2). Snyderman established histidine intake
requirements in infants of 24 mg/kg/d, which is generally
less than other essential amino acids. 31 In studies by Heird,
the histidine requirements in neonates and infants on PN
were greater than demonstrated by these earlier studies and
than predicted from older child and adult requirements
(adjusted by kilogram of weight). 32,33 The Guidelines for the
Use of Parenteral and Enteral Nutrition in Adult and Pediatric
Patients34 states that histidine is a conditionally essential
amino acid for neonates and infants up to 6 months of age.
Sulfur amino acid requirements of infants and children have been an area of intense research. The sulfur amino
acids include methionine (defined as essential by Rose) and
cysteine and taurine (both defined as nonessential in adults
by Rose). Cysteine contains a free sulfhydryl group, and is
oxidized with another cysteine moiety to form the dimer
cystine. After cysteine is incorporated into newly synthesized protein, the formation of cystine dimers aid in proper
protein folding and stability. Cysteine is metabolized from
methionine, and can replace 50% to 80% of methionine
intake. Because it can reduce the intake of an essential amino
acid, it has been classified as a conditionally essential amino
acid by Jackson. 35 Snyderman36 defined intakes of cysteine
in infants at 85 mg/kg/d, similar to many of the essential
amino acids. Pohlandt37 discovered that the requirement for
cysteine continues in diet into infancy, perhaps to 5 months
of age.
Most of the metabolic machinery for the metabolism
of methionine and cysteine resides in liver parenchymal
tissue near the portal vein. The transsulfuration pathway
for methionine metabolism is a complex series of enzymatic
steps leading to cysteine and taurine production (Figure
5-4). Many investigators have shown that multiple enzymes

in this pathway have lower or no activity in the fetal liver,
or in the livers of infants of various gestational ages who
died from non-liver-related causes. 38,39 -cystathionase and
cystathionine -synthase were found to be absent or to have
activity of less than half of the older child or adult. Zlotkin40
demonstrated that -cystathionase in liver of premature and
term infants did not reach adult activity until 6 to 9 months
postnatal age. This may be the reason that human milk is
relatively rich in cysteine content. This renders cysteine as
conditionally essential in neonates and infants.
Figure 5-4 The Transsulfuration Pathway in the Metabolism of Methionine
Cysteine is gradually oxidized to the dimer cystine

in aqueous solution at neutral pH. Therefore, for PN solutions containing cysteine, cysteine is added at the time of
preparation. The commonly used intravenous additive
is provided as the cysteine hydrochloride salt. The pediatric daily requirement for cysteine has been studied by
Helms et al.41,42 These investigators found that a dose of
77.4 mg/kg/d, close to that of Snyderman, appears to be
required for ideal nitrogen retention, nitrogen balance, and
growth in infants on PN. 36 Problems of acidosis occasionally occur in very low birth-weight (VLBW) infants, and
require the substitution of acetate for chloride in PN solutions. For every 160mg of cysteine HCl that is infused as
part of PN, 1 mmol of HCl is given to the pediatric patient.
For the preterm infant and neonate, the prescriber should
consider substitution of 1 mmol of acetate for 1 mmol of
additional chloride given as part of cysteine HCl.
37
Taurine is one of the most abundant free amino acids

in humans. It is not incorporated into protein in that no
aminoacyl tRNA synthetase recognizing taurine has been
identified. Taurine is actually a sulfonic acid (rare in nature)
and does not contain a carboxyl group as do other amino
acids. It has a host of important biological functions (Table
5-3). It is essential in the feline diet, and its absence results
in retinal degeneration and blindness. In children on home
parenteral nutrition (HPN) with no added taurine, degenerative changes in electroretinograms were observed.43
Cysteine sulfinic acid decarboxylase is key to production of
taurine from cysteine (Figure 5-4). The enzyme has much
lower overall activity in humans than in rats and cats, but its
activity is even lower in human fetal liver.44 Taurine is found
in high concentrations in human milk when compared
to cows milk.45 Formulas made from cows milk protein
require taurine supplementation, and taurine deficiency
may occur in synthetic formulas not containing taurine.
In neonates and premature infants these infants continue
to renally waste taurine even in the presence of low serum
taurine.46
kg/d in preterm infants. 36 Classic phenylketonuria (PKU),

the absence of the enzyme phenylalanine hydroxylase,
results in extreme elevations in phenylalanine concentration, and a requirement for tyrosine in diet. PKU can lead
to brain damage and possibly death if untreated. Tyrosine
may be conditionally essential in patients with liver disease,
and is the precursor for the neurotransmitter, dopamine.
Tyrosine content in parenteral amino acid solutions
is restricted because of poor solubility. Christensen found
that N-acetyl-tyrosine (NAT), an aqueously soluble form
of tyrosine with good stability in solution, was a reasonable
intravenous source of tyrosine in older infants.48 However,
clearance and non-renal clearance was significantly
decreased in younger infants of lower postconceptional
age, suggesting NAT may not be the ideal tyrosine source
in VLBW neonates. This investigative group was unable to
normalize plasma tyrosine concentrations in most infants
at a dose of approximately 50 mg/kg/d. Van Goudoever
was able to normalize plasma tyrosine levels with NAT
intake of 162 mg/kg/d.49
Table 5-3 Taurine Functions

Neurotransmitter
Bile acid conjugation
Brain and central nervous system development
Osmoregulation
Immunoregulation
Antioxidant
Retinal physiology
Platelet function
Mitochondrial function
The amino acids of the urea cycle are considered nonessential (Figure 5-5). Snyderman50 found no evidence that
arginine is essential in preterm infants. However, early
amino acid solutions with relatively lower concentrations of
arginine resulted in hyperammonemia in infants receiving
these formulas as part of PN. 51 Higher concentrations of
arginine reversed the finding of hyperammonemia. 52 Acute
renal failure patients given large doses of protein with
little supplemental arginine also present with hyperammonemia, and can be reversed with the supplementation
of arginine. 53 Treatment of urea cycle disorders generally
involves the supplementation of low-dose essential amino
acids, andarginine.
Taurine is added to crystalline amino acid formulas

designed for infants. Helms et al. described plasma amino
acid concentrations in preterm infants, and in long-term
home parenteral nutrition (PN) patients receiving a
pediatric-designed amino acid formula as part of their
PN.42,47 For infants, these investigators demonstrated that
concentrations of the sulfur amino acids remain within
age-related norms with the use of one of the commercially
available formulas with L-cysteine HCl supplementation.
Interestingly, even older children on home PN required
cysteine supplementation to normalize plasma taurine
concentrations.47
Tyrosine is exclusively metabolized from phenyla
lanine. Tyrosine, like cysteine for methionine, can spare
dietary requirement for phenylalanine. Snyderman demonstrated a dietary need for tyrosine of approximately 50 mg/
Amino Acids of the Urea Cycle
38
Figure 5-5 Urea Cycle With Enzymes and Substrates
CPS = carbamyl phosphate synthetase, OTC = ornithine transcarbamylase,

ASAS = argininosuccinic acid synthetase, AS = argininosuccinase,
A = arginase
Useful Classification of Amino Acids for the Clinician

Laidlaw and Kopple offer an alternative approach to the
Jacksonian35 classification of essential and nonessential
amino acids. 54 These 5 classifications enable the clinician
to better understand the requirement of amino acids in diet
(Table 5-4).
Table 5-4 Modification of Amino Acid Classification in Humans54
1.
Totally indispensable amino acids. No metabolic precursor or
product can be substituted. Lysine and threonine.
2.
Carbon-skeleton indispensable. Ketoacid analogue or
hydroxyacid analogue can be substituted. Histidine, isoleucine,
leucine, methionine, phenylalanine, tryptophan, and valine.
3.
Conditionally indispensable. Reduce requirement for
indispensable, and become indispensable in the absence
of precursor in diet. Tyrosine, cysteine, taurine, and possibly
orthnithine, and citrulline.
4.
Acquired indispensable. Become indispensable in states of
metabolic disorders, immaturity, severe stress. Cysteine, taurine,
tyrosine, arginine, citrulline, glycine, serine, and proline.
5.
Dispensible. Alanine, glutamate, aspartate.
Liver and Kidney: Roles in Amino

AcidMetabolism
The liver is important in synthesis of transport and other

constituent and functional proteins, metabolism of amino
acids, gluconeogenesis, and urea formation. 55,56 Major
plasma proteins derived from liver, such as albumin,
transthyretin (TTR) (also known as prealbumin for its
migration pattern during electrophoresis), and retinolbinding protein (RBP) are present at early stages of
development. Most liver-derived plasma proteins are at
lower concentrations in plasma in premature infants. Lipoprotein concentrations rise rapidly after birth in response
to high dietary fat intake, while albumin and TTR increase
toward adult values in the first months to year of life. Acute
phase proteins, such as C-reactive protein (CRP), appear to
be induceable even in prematurity, and are used to monitor
inflammatory response to infection or metabolic stress.
Reduction in visceral protein occurs in preterm infants,
and response to protein and energy intake can be assessed
through monitoring changes in serum concentrations of
albumin, TTR, and RBP. 57
The production of glutathione in the liver is essential;
however, other tissues can produce the tripeptide. Glutathione is an important sulfhydryl-reducing agent that
protects cells from oxygen free radicals. 58 It is synthesized
from glutamate, cysteine, and glycine, and studies have
shown cysteine is the rate-limiting substrate in glutathione
production. It is dependent in two distinct steps on cysteine
production via the transsulfuration pathway (principally in
the liver), or from dietary intake. The tripeptide also appears
to be important in the transport of amino acids, and in the
synthesis of leukotrienes via the enzyme gamma-glutamyl
transpeptidase. 59,60
The metabolism of amino acids is an important function of the liver. Several enzymes and enzyme systems, such
as the transsulfuration pathway and phenylalanine hydroxylase, both predominantly located in the liver, are responsible
for the metabolism of the essential amino acids methionine
and phenylalanine, respectively. Enzyme activity is reduced
in prematurity and early infancy, rendering the products
of these enzyme systems as conditionally essential amino
acids.
Approximately one-third of amino acids entering the
liver from portal blood are used for protein synthesis.61 The
remainder may be used in energy production, or gluconeogenesis, with perhaps only a third of dietary amino acids
entering to the peripheral blood. This explains why plasma
amino acids do not fluctuate substantially in the postprandial period. One group of amino acids that are released at
higher relative concentrations from the liver in the postprandial period are the branched-chain amino acids.62 These
are leucine, isoleucine, and valine. The branched-chain
amino acids are preferentially metabolized in the periphery
as these amino acids and arginine stimulate insulin release
and muscle protein synthesis.63 All is reversed in the postabsorptive period. As insulin concentrations fall, the
muscle then provides the principal gluconeogenic substrate,
alanine, to the liver for production of glucose in the fasting
period.
In parenterally fed neonates and infants, Heird found

that the branched-chain amino acid needs of infants was
increased even with their relatively lower muscle mass. 32,33
This would suggest that the shuttling of amino acids between
the periphery and the small infant liver is actually higher
than in the adult. Increased requirement of amino acids and
energy for synthesis may be the likely explanation.
The urea cycle is the principal mechanism for nitrogen
disposal (Figure 5-5). The catabolism of proteins, and their
component amino acids, results in ammonia production.
The liver will hydrolyze arginine to form urea and ornithine
under the enzymatic control of arginase. Urea then is delivered to the kidney for excretion. In neonates and infants,
the quantity of amino acids that enter into urea production
is small, presumably due to substantial need of amino acids
for growth; therefore, BUN will be low.64
The kidney plays a minor role in amino acid and protein
metabolism. Ninety percent of dietary protein nitrogen is
incorporated into new tissue, and therefore never requires
formation of urea in the liver, and excretion by the kidney.
In premature infants and neonates, excretion of nitrogen is
limited for the first months of life. Tubular reabsorption of
amino acids is reduced in premature infants and neonates,
39
and may explain increased amino acid needs in these

patients when compared to older children, or adults.65,66
Functions of Amino Acids and Proteins
Protein has multiple functions; it is essential for cell structure, maturation, remodeling, and growth. Besides being
utilized for energy, amino acids and proteins serve as precursors that are essential for many biological processes.67
When protein is consumed, it is extensively broken
down in the GI tract to amino acids, which can then enter
cells or continue to circulate in plasma. Once in the cell,
amino acids can be combined by peptide linkages to form
small peptides (such as glutathione), they can be substrates
for protein synthesis, or they can function as individual
amino acids in the urea cycle. Specific amino acids can act
as substrates, regulators, transporters, and precursors to
neurotransmitters and hormones.67
In the cell, protein can be utilized for energy or it can be
stored. There is a continuous flux of proteins being broken
down. The carbon chain of the amino acids can be utilized
for energy, and free amino acids can be released back into the
plasma to maintain plasma amino acid concentrations. 67
After synthesis within the cell, many proteins are
Table 5-5 Functions of Amino Acids and Protein67

Function
Amino acids
Substrates for protein synthesis
Regulators of protein turnover
Regulators of enzyme activity (allosteric)
Precursor of signal transducer
Methylation reactions
Neurotransmitters
Ion fluxes
Precursor of physiologic molecules
Nitrogen transport
Oxidation and reduction
Precursor of conditionally indispensable amino acids
Gluconeogenic substrate and fuel
Proteins
Enzymatic catalysis
Transport
Messenger / signals
Movement
Structure
Storage / sequestration
Immunity
Growth; differentiation; gene expression
Example
Amino acids with a codon

Leucine, arginine
Arginine and NAG synthetase, Phe and PAH activation
Arginine and nitric oxide
Methionine
Tryptophan (serotonin); glutamate, glycine, GABA
Taurine; glutamate
Arginine (creatinine); glutamine
Alanine; glutamine
Cystine; glutathione
Methionine (cys); phe (thy)
Alanine; serine; glutamine
BCKADH
B-12 binding proteins; ceruloplasmin; apolipoproteins
Insulin; growth hormones
Kinesin; actin
Collagens; elastin
Ferritin; metallothionein
Antibodies; TNF; interleukins
EGF; IGFs; transcription factors
40
released into the plasma. The three major types of plasma

proteins are albumin, globulin, and fibrinogen. Albumins
role is to maintain osmotic pressure in the plasma. Globulins are involved in enzymatic activity in the plasma, as well
as playing a vital role in natural and acquired immunity.
Fibrinogen is essential for coagulation, both in blood clotting and repair of blood vessels.67 For specific examples of
the functions of amino acids and protein refer to Table 5-5.
Protein Requirements and Protein-Energy

Ratio DuringGrowth
Protein requirements (similar to total caloric requirements)

are greater for VLBW neonates and gradually decrease with
increased age.28 VLBW neonates have the highest protein
requirements, often requiring 3 to 4 g/kg/d, while term
neonates require 2 to 2.5 g/kg/d. Protein requirements
in term infants are based on studies in freely breastfed
infants.68 Protein is essential for growth, and its requirement
increases during periods of rapid growth and decreases with
slowed growth. In infancy, 55% of daily protein is dedicated
for growth while 45% is for maintenance. This ratio gradually decreases and by 4 years of age only about 10% of total
protein requirement is utilized for growth and the remaining
90% is used for daily maintenance.69 Refer to Table 5-6 for
age-based protein requirements.
Table 5-6: Protein Requirements68
Protein (g/kg/d)
Very Low Birth Weight

Preterm
Infant / neonate
Infant
Preschool / School age
Adolescent
34
2.53
22.5
1.52
11.5
0.81.5
Many studies have demonstrated that adequate protein

may be more critical for nutritional status and growth than
total caloric requirements in preterm neonates and sick children.18 Protein requirements can be increased by as much as
20% to 50% in critical illness, thermal injury, and catch-up
growth.70
Early initiation of protein has been shown to be beneficial in extremely low birth-weight infants. Poindexter et al.
concluded that early amino acid administration was significant for better growth outcomes and neurodevelopment
when evaluated at 36 weeks postmenstrual age and again at
18 months follow-up.71
Assessment of Protein Status

Besides monitoring of visceral proteins (ie, albumin, TTR)
and acute phase proteins (ie, CRP), nitrogen balance can
be a useful tool in monitoring protein repletion and depletion in pediatric patients receiving specialized nutrition
support. Nitrogen balance is an estimate of nitrogen intake
minus nitrogen excretion. In adults, urinary urea nitrogen
(UUN in g/L 1.2 to yield total urinary nitrogen (TUN))
multiplied by the urine volume (L/d) plus 2 to 4 g nitrogen
(to reflect all other unmeasured nitrogen lost) results in
nitrogen balance. The method for collection and calculation
of nitrogen balance is altered in pediatric patients.
Urine collections in neonates and infants are problematic, but not impossible. The use of urine bags with attentive
clinician support, or collection of diapers with elution of
all urinary and stool nitrogen, has been used successfully
in the clinical arena to assess nitrogen output in children.72
While 24-hour urine collections have been considered the
standard, there is published experience using 6-hour collection in pediatrics.73 These authors are more comfortable
using 24-hour urine collections to predict actual nitrogen
balance over the period of observation.
Nitrogen balance has been reviewed nicely in the
Protein chapter of The A.S.P.E.N. Nutrition Support Core
Curriculum,1 but several issues should be considered when
completing nitrogen balance studies in pediatrics. Helms
characterized nitrogen excretion in stressed pediatric
intensive care unit patients and sick neonates.74 Urea as
a percentage of total nitrogen output was in the range of
40% to 60%, distinctly different from the 80% excretion as
urea assumed in adults. Because the percentage of nitrogen
excreted as urea is substantially different than the adult
patient and varies with clinical condition, it is recommended
that TUN be used to increase accuracy and reliability for
both children and adults.
Monitoring Plasma Amino Acids

Plasma amino acids have been widely reported in pediatric patients. Storm75 reviewed the hypothesis regarding
normalization of plasma amino acids, and its validation
as a predictive tool in understanding outcome in neonates
and infants receiving PN. This led to a number of investigations suggesting normalization results in improved
growth, nitrogen balance, increased calcium and phosphorus intakes, and improved liver health.7680 It is likely
that plasma amino acids will continue to be a benchmark
for efficacy of newly developed pediatric amino acid formulations. It is unclear whether plasma amino acid assessment
will ultimately migrate to the clinical environment as a

useful tool for evaluating efficacy in the individual pediatric
patient; this will require less expensive and more accessible
analytical technologies than those currently used in clinical
research.
Case Presentation and Discussion
A 2-month-old female was admitted to the hospital today

after having been seen by her primary care physician for a
well baby visit. She was born at 38 weeks gestation with a
birth weight of 3.4 kg. Her weight in the clinic today was
3.1 kg. The mother reports that she had to return to work
2 weeks ago and transitioned her daughter from breast
milk to an infant formula. Since then, the infant has had
increased fussiness, crying, spitting up, and small specks of
blood in the stool. The infant was admitted with a diagnosis
of feeding intolerance and failure to thrive. The nutrition
team was consulted to evaluate the infants nutrition needs.
Question: Explain how the infants symptoms could
be associated with the change from breast milk to an infant
formula.
Comment: Human milk has an increased whey content
that is more easily digestible and promotes gastric emptying.
Bovine milk is composed of beta-lactoglobulin, which is
associated with protein allergy, feeding intolerance, and
colic.
Question: What are your recommendations for this
infants nutrition?
Comment: Since this patient has demonstrated feeding
intolerance after switching from human milk to this infant
formula, it would be prudent to change her to an infant
formula that is easier to digest. A hydrolyzed or amino acidbased formula should be considered for this infant.
Question: What is the estimated protein requirement
for this infant?
Comment: Infants require approximately 2 g/kg/d of
protein. Because this infant has lost weight from her birth
weight, protein should be dosed based on the birth weight
of 3.4 kg. This corresponds to a total protein dose of approximately 7 g/d.
Question: What is the best nethod of monitoring nutrition status in this patient?
Comment: The best method for evaluation of protein
and overall nutrition status in this patient would be daily
weights. At this time there is no indication that this infant
has higher than normal protein or caloric requirements. If
the infant does not gain weight with appropriate protein
and calories, further evaluation may be necessary.
41
1. All of the following are functions of taurine EXCEPT:

A. Antioxidant
B. CNS development
C. Nitrogen transport
D. Bile acid conjugation
E. Immunoregulation
2. Which of the following is an advantage of human milk
over bovine milk?
A. Human milk contains IgA which is important in
host defense.
B. Human milk has a decreased whey content that
promotes rapid gastric emptying.
C. Human milk has an increased caloric density as
compared to bovine milk.
D. Human milk prevents children from developing
colic.
E. All of the above are advantages of human milk.
3. Protein digestion:
A. Occurs mostly in the small intestine.
B. Is dependent on hydrochloric acid and pepsin to
denature protein.
C. Has been identified as early as 16 weeks gestation,
but gastric acid secretion does not reach adult levels
until 38 weeks gestation.
D. Products include approximately 30% oligopeptides
and 70% amino acids.
4. Which of the following is TRUE regarding nitrogen
balance?
A. Nitrogen balance is not an accurate way to assess
protein needs in a pediatric patient.
B. In order to estimate a nitrogen balance, you must do
a 24-hour urine collection.
C. Total urinary nitrogen (TUN) is a better estimate of
urinary losses as compared to urinary urea nitrogen
(UUN).
D. Nitrogen balance is an estimate of nitrogen intake
divided by nitrogen excreted.
References
1. Young LS, Kearns LR, Schoepfel SL. Protein. In: Gottschlich

MM, DeLegge MH, Mattox T, Mueller C, Worthington
P, eds. The A.S.P.E.N. Nutrition Support Core Curriculum:
A Case-Based Approach The Adult Patient. Silver Spring,
MD: American Society for Parenteral and Enteral Nutrition;
2007:7187.
42
2. Gilger MA. Normal gastrointestinal function. In: McMillan

JA, Feigin RD, DeAngelis C, Jones MD, eds. Oskis Pediatrics.
4th ed. Philadelphia, PA: Lippincott Williams & Wilkins;
2006:19151921.
3. Berseth CL. Overview of the development of the gastrointestinal tract. UpToDate Web site. http://www.uptodate.com/
home/index.html. October 11, 2005. Accessed December 19,
2008.
4. Lucas A, Bloom SR, Aynsley-Green A. Development of gut
hormone responses to feeding in neonates. Arch Dis Child.
1980;55(9):678682.
5. Berseth CL, Nordyke CK, Valdes MG, Furlow BL, Go VL.
Responses of gastrointestinal peptides and motor activity to
milk and water feedings in preterm and term infants. Pediatr
Res. 1992;31(6):587590.
6. Moreau H, Bernadac A, Gargouri Y, Benkouka F, Laugier
R, Verger R. Immunocytolocalization of human gastric
lipase in chief cells of the fundic mucosa. Histochemistry.
1989;91(5):419423.
7. Armand M, Hamosh M, Mehta NR, et al. Effect of human
milk or formula on gastric function and fat digestion in the
premature infant. Pediatr Res. 1996;40(3):429437.
8. Armand M, Hamosh M, DiPalma JS, et al. Dietary fat modulates gastric lipase activity in healthy humans. Am J Clin Nutr.
1995;62(1):7480.
9. Rudolph CD. Structure and development of the gastrointestinal tract. In: Rudolph CD, Rudolph AM, Hostetter MK,
Lister GE, Siegel NJ, eds. Rudolphs Pediatrics. 21st ed. New
York, NY: McGraw-Hill; 2003.
10. Wahbeh GT, Christie DL. Basic aspects of digestion and
absorption. In: Wyllie R, Hyams JS, eds. Pediatric Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management.
3rd ed. Netherlands: Saunders Elsevier; 2006:1123.
11. Colaizzo-Anas T. Nutrient intake, digestion, absorption,
and excretion. In: Gottschlich MM, DeLegge MH, Mattox
T, Mueller C, Worthington P, eds. The A.S.P.E.N. Nutrition
Support Core Curriculum: A Case-based Approach The Adult
Patient. Silver Spring, MD: American Society for Parenteral
and Enteral Nutrition; 2007:318.
12. Mason JB. Mechanisms of nutrient absorption and malabsorption. UpToDate Web site. http://www.uptodate.com/
home/index.html. October 18, 2007. Accessed December 19,
2008.
13. DeLegge MH, Ridley C. Nutrient digestion, absorption, and
excretion. In: Gottschlich, MM, Fuhrman MP, Hammond
KA, Holcombe BJ, Seidner DL, eds. The Science and Practice of
Nutrition Support: A Case-Based Core Curriculum. Dubuque,
IA: Kendall/Hunt Publishing Co; 2001:116.
14. Hadorn B, Tarlow MJ, Lloyd JK, Wolff OH. Intestinal enterokinase deficiency. Lancet. 1969;1(7599):812813.
15. Johnson TR, Moore WM, Jeffries JE. Developmental Physiology.
2nd ed. Columbus, OH: Ross Laboratories; 1978:150152.
16. Roy CC, Silverman A, Alagille D. Pediatric Clinical Gastroenterology. 4th ed. St. Louis, MO: Mosby-Year Book, Inc;
1995:307309.
17. Axelsson I, Jakobsson I, Lindberg T, Polberger S, Benediktsson B, Rih NC. Macromolecular absorption in preterm
and term infants. Acta Paediatr Scand. 1989;78(4):532537.
18. Motil KJ. Meeting protein needs. In: Tsang RC, Zlotkin SH,
Nichols BL, Hansen JW, eds. Nutrition During Infancy: Principles and Practice. 2nd ed. Cincinnati, OH: Digital Education
Publishing, Inc; 1997:83103.
19. Philipps AF, Sherman MP. Neonatal nutrition and gastrointestinal function. In: Rudolph CD, Rudolph AM, Hostetter
MK, Lister GE, Siegel NJ, eds. Rudolphs Pediatrics. 21st ed.
New York, NY: McGraw-Hill; 2003.
20. Hansen JW, Boettcher JA. Human milk substitutes. In: Tsang
RC, Zlotkin SH, Nichols BL, Hansen JW, eds. Nutrition
During Infancy: Principles and Practice. 2nd ed. Cincinnati,
OH: Digital Education Publishing, Inc; 1997:441466.
21. Schanler, RJ. Nutritional composition of human milk and
preterm formula for the premature infant. UpToDate Web site.
http://www.uptodate.com/home/index.html. September 7,
2007. Accessed December 19, 2008.
22. Lnnerdal B, Cederblad A, Davidsson L, Sandstrm B.
The effect of individual components of soy formula and
cows milk formula on zinc bioavailability. Am J Clin Nutr.
1984;40(5):10641070.
23. Brock, JH. Lactoferrin in human milk: its role in iron absorption and protection against enteric infection in the newborn
infant. Arch Dis Child. 1980 Jun;55(6):417421.
24. Lnnerdal B. Digestibility and absorption of protein in
infants. In: Rih NC, ed. Protein Metabolism During Infancy.
New York, NY: Raven Press; 1994:5365.
25. Lindberg T, Ohlsson K, Westrm B. Protease inhibitors and
their relation to protease activity in human milk. Pediatr Res.
1982 Jun;16(6):479483.
26. Davidson LA, Lonnerdal B. Fecal alpha 1-antitrypsin
in breast-fed infants is derived from human milk and is
not indicative of enteric protein loss. Acta Paediatr Scand.
1990;79(2):137141.
27. Rose WC. The amino acid requirements of adult man. Nutr
Abstr Rev. 1957;27:631647.
28. Nasset ES, Gatewood VH. Nitrogen balance and hemoglobin
of adult rats fed amino acid diets low in L- and D-histidine. J
Nutr. 1956;53:163176.
29. Kopple JD, Swendseid ME. Evidence that histidine is an
essential amino acid in normal and chronically uremic man.
J Clin Invest. 1975;55:881891.
30. Kopple JD, Swendseid ME. Effect of histidine intake on plasma
and urine histidine levels, nitrogen balance and N-methylhistidine excretion in normal and chronically uremic men. J Nutr.
1981;111:931942.
31. Snyderman SE, Boyer A, Roitman E, Holt LE Jr, Prose
PH. The histidine requirement of the infant. Pediatrics.
1963;31:786801.
32. Heird WC, Dell RB, Helms RA, et al. Evaluation of an amino
acid mixture designed to maintain normal plasma amino acid
patterns in infants and children requiring parenteral nutrition.
Pediatrics. 1987;80:401408.
33. Heird WC, Hay W, Helms RA, Storm MC, Kashyap S, Dell,
RB. Pediatric parenteral amino acid mixture in low birth
weight infants. Pediatrics. 1988;81(1):4150.
34. Anonymous. Practice guidelines: protein requirements.

In: Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients. J Parenter Enteral Nutr.
2002;26:27SA28SA.
35. Jackson AA. Amino acids: essential and non-essential? Lancet.
1983;1:10341037.
36. Snyderman SE. The protein and amino acid requirements of
the premature infant. In: Ionxix JHP, Visser HKA, Troelstra
JD, eds. Metabolic Processes in the Fetus and Newborn Infant.
Leiden: HE Stenfert Kroesse NV; 1971:128141.
37. Pohlandt F. Cystine: a semi-essential amino acid in the
newborn infant. Acta Pediatr Scand. 1974;63:801804.
38. Gaull G, Sturman JA, Raiha NCR. Development of mammalian sulfur metabolism: absence of cystathionase in human
fetal tissues. Pediatr Res. 1972;6:538547.
39. Sturman JA, Gaull G, Raiha NCR. Absence of cystathionase in human fetal liver: is cystine essential? Science.
1970;169:7476.
40. Zlotkin SH, Anderson GH. Sulfur balances in intravenously
fed infants: effects of cysteine supplementation. Am J Clin
Nutr. 1982;36: 862867.
41. Helms RA, Chesney RW, Storm MC. Sulfur amino acid
metabolism in infants on parenteral nutrition. Clin Nutr.
1995;14:381387.
42. Helms RA, Christensen ML, Storm MC, Chesney RW.
Adequacy of sulfur amino acid intake in infants receiving
parenteral nutrition. Nutr Biochem. 1995;6:462466.
43. Vinton NE, Ament ME, Heckenlively JR, et.al. Visual function in patients in patients undergoing home total parenteral
nutrient. Am J Clin Nutr. 1986;43:689.
44. Sturman JA, Hayes KC. The biology of taurine in nutrition
and development. In: Draper HH, ed. Advances in Nutrition Research. Vol. 3. New York, NY: Plenum Publishing Co;
1980:231299.
45. Rassin DK, Sturman JA, Gaull GE. Taurine and other free
amino acids in milk of man and other mammals. Early Hum
Dev. 1978;2:113.
46. Zelikovic I, Chesney RW, Freidman AL, Ahlfors CE. Taurine
depletion in very low birth weight infants receiving prolonged
total parenteral nutrition: Role of renal immaturity. J Pediatr.
1990;116:301306.
47. Helms RA, Storm MC, Christensen ML, Hak EB, Chesney
RW. Cysteine supplementation results in normalization of
plasma taurine concentrations in children receiving home
parenteral nutrition. J Pediatr. 1999; 134:358361.
48. Christensen ML, Helms RA, Veal DF, Boehm KA, Storm MC.
Clearance of N-acetyl-L-tyrosine in infants receiving a pediatric amino acid solution. Clin Pharm. 1993;12:606609.
49. Van Goudoever JB, Sulkers EJ, Timmerman M, et al. Amino
acid solutions for premature neonates during the first week of
life: the role of N-acety-L-cysteine and N-acetyl-L-tyrosine. J
Parenter Enteral Nutr. 1994;18:404408.
50. Snyderman SE, Boyer A, Holt LE Jr. The arginine requirement
of the infant. AMA J Dis Child. 1959;97:192195.
51. Heird WC, Nicholson JF, Driscoll JM Jr, Schullinger JN,
Winters RW. Hyperammonemia resulting from intravenous
alimentation using a mixture of synthetic L-amino acids: a
preliminary report. J Pediatr. 1972;81:162167.
43
52. Thomas DW, Sinatra FR, Hack SL, Smith TM, Platzker ACG,
Merritt RJ. Hyperammonemia in neonates receiving intravenous nutrition. J Parenter Enteral Nutr. 1982;6:503506.
53. Motil KJ, Harmon WE, Grupe WE. Complications of essential amino acid hyperalimentation in children with acute renal
failure. J Parenter Enteral Nutr. 1980;4:3235.
54. Laidlaw SA, Kopple JD. Newer concepts of the indispensable
amino acids. Am J Clin Nutr. 1987;46:593605.
55. Raiha NCR, Suihkonen J. Development of urea-synthesizing enzymes in human liver. Acta Pediatr Scand.
1968;57:121124.
56. Raiha NCR, Lindros KO. Development of some enzymes
involved in gluconeogenesis in human liver. Ann Med Exp
Biol. 1969;47:146150.
57. Helms RA, Dickerson RN, Ebbert ML, Christensen ML,
Herrod HG. Retinol-binding protein and prealbumin: useful
measures of protein repletion in critically ill, malnourished
infants. J Pediatr Gastroenteral Nutr. 1986;5:586592.
58. Beutler E. Nutritional and metabolic aspects of glutathione.
Annu Rev Nutr. 1989;9:287302.
59. Meister A. On the enzymology of amino acid transport.
Science. 1973;180:3339.
60. Svartz J, Hallin E, Soderstorm M, Hammarstrom S. Identification of regions of leukotriene C4 synthase which direct the
enzyme to its nuclear envelope localization. J Cell Biochem.
2006;98;15171527.
61. Yamamoto H, Aikawa T, Matsutaka H, Okuda O, Ishikawa
E. Interorganal relationships of amino acid metabolism in fed
rats. Am J Physiol. 1974;226;14281433.
62. Munro HN. Fifth annual Jonathan E. Rhoads lecture. Metabolic integration of organs in health and disease. J Parenter
Enteral Nutr. 1982;6:271.
63. Rocha DM, Falona GR, Unger RH. Glucagon-stimulating activity of 20 amino acids in dogs. J Clin Invest.
1972;51:2346.
64. Raiha NCR, Kekomaki MP. Studies on the development of
ornithine-keto acid amino transferase activity in the liver.
Biochem J. 1968;108:521524.
65. Edelman CM, Wolfish NM. Dietary influence on renal maturation in premature infants. Pediatr Res. 1968;2:421422.
66. Brodehl J, Gellissen K. Endogenous renal transport of
free amino acids in infancy and childhood. Pediatrics.
1968;42:395404.
67. Protein metabolism. In: Guyton AC, ed. Textbook of
Medical Physiology. Philadelphia, PA: W.B. Saunders Co;
1991:765770.
68. Wu PYK, Edwards N, Storm MC. The plasma amino
acid pattern of normal term breast-fed infants. J Pediatr.
1986;109:347349.
Protein. In: Kleinman RE. Pediatric Nutrition Handbook. 6th
2009:325341.
70. Scrimshaw NS. Effect of infection on nutritional status. Proc
Natl Sci Counc Repub China B. 1992;16:4664.
44
71. Poindexter BB, Langer JC, Dusick AM, Ehrenkranz RA. Early
provision of parenteral amino acids in extremely low birth
weight infants: relation to growth and neurodevelopmental
outcome. J Pediatr. 2006;148:300305.
72. Boehm KA, et al. Assessing the validity of adjusted urinary
urea nitrogen as an estimate of total urinary nitrogen
in three pediatric populations. J Parenter Enteral Nutr.
1994;18(2):172176.
73. Lopez et al. Estimation of nitrogen balance based on a sixhour urine collection in infants. J Parenter Enteral Nutr.
1986;10(5):517518.
74. Helms RA, Mowatt-Larssen CA, Boehm KA, et al. Urinary
nitrogen constituents in the postsurgical preterm neonate
receiving parenteral nutrition. J Parenter Enteral Nutr.
1993;17:6872.
75. Strom MC, Helms RA. Normalizing plasma amino acid levels
in pediatric patients requiring parenteral nutrition. Nutr Clin
Pract. 2007;22:194203.
76. Helms RA, Christensen ML, Muer EC, Storm MC. Comparison of a pediatric versus standard amino acid formulation
in preterm neonates requiring parenteral nutrition. J Pediatr.
1987;110:466470.
77. Beck R. Use of a pediatric parenteral amino acid mixture in a
population of extremely low birth weight neonates: frequency
and spectrum of direct bilirubinemia. Am J Perinatol. 1990
Jan;7(1):8486.
78. Forchielli ML, Gura KM, Sandler R, Lo C. Aminosyn PF
or TrophAmine: which provides more protection from
cholestasis associated with total parenteral nutrition? J Pediatr
Gastroenterol Nutr. 1995;21:374382.
79. Pratt CA, Garcia MG, Poole RL, Kerner JA. Life-long total
parenteral nutrition versus intestinal transplantation in children with microvillus inclusion disease. J Pediatr Pharmacol
Ther. 2001;6:498503.
80. Fitzgerald KA, MacKay MW. Calcium and phosphate solubility in neonatal parenteral nutrient solutions containing
TrophAmine. Am J Hosp Pharm. 1986 Jan;43(1):8893.
Minerals
Winston Koo, MBBS, FACN, CNS, Mirjana Lulic-Botica, BSc, BCPS, May Saba, PharmD, BCNSP, and Letitia Warren, RD, CSP
CONTENTS
Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Biochemistry and Physiology
Sources
Dietary Requirements
Absorption and Excretion
Metabolism
Deficiency States
Excess Intake and Adverse Effects
Calcium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Sources
Absorption, Excretion, and Metabolism
Deficiency States
Phosphorus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Sources
Deficiency States
Magnesium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Sources
Deficiency States
Learning Objectives
1. Understand the physiological basis for the functions

of and requirements for calcium, phosphorus, and
magnesium.
2. Understand the common risk factors for the development of deficiency in these nutrients.
3. Understand the common manifestations of deficiency
states for these nutrients.
4. Understand the potential risks with excessive intake of
these nutrients.
Overview
Calcium (Ca) is the most abundant mineral in the body and
together with phosphorus (P) forms the major inorganic
constituent of bone. Magnesium (Mg) is the fourth most
abundant cation and is the second most common intracellular electrolyte in the body. The total body content of
Ca, P, and Mg in the skeleton is about 99%, 85%, and 60%,
respectively.
Less than 1% of the total body content of Ca, P, and
Mg is in the circulation. However, disturbances in serum
concentrations of these minerals are associated with disturbances of physiological function. These are manifested by
numerous clinical symptoms and signs. Acute changes in
the serum concentrations likely reflect adaptive changes and
do not reflect the state of tissue store, although chronic and
severely lowered serum concentrations of these minerals
usually reflect the presence of a deficiency state.
From a clinical perspective, the skeleton has the dual
function of providing both structural and mechanical
support as well as being a reservoir to maintain mineral
45
46
homeostasis. Deficiency of Ca and/or vitamin D and in the

case of small preterm infants, deficiency of P, can result in
osteopenia and rickets in infants and children.1 In addition, numerous physiological functions of all organs are
dependent on the maintenance of normal circulating
concentrations of Ca, P, and Mg, and the integrity of the
skeleton.
Sources
Natural foods and a variety of foods and beverages fortified
with Ca are good sources for these minerals. Any food that
provides 20% or more of the daily recommended intake per
serving for a specific nutrient is considered to be high in
that nutrient.2 Dietary sources of minerals, including Ca
fortified foods and beverages, are preferred to the use of
supplements alone because the range of nutrients and the
establishment of good dietary habits are enhanced by the
use of dietary sources. Nutrient interactions also may be
less and tolerance may be greater for minerals provided by
food sources.
Mineral supplements are freely available. However, use
of supplements does not compensate for poor food choices
and inadequate diet. Furthermore, the Food and Drug
Administration (FDA) regulates dietary supplements under
a different set of regulations than drug products (prescription and over-the-counter). As a result, specific contents of
dietary supplements and contaminants are not as rigorously
monitored. 3
Table 6-1 Dietary Reference Intakes for Calcium, Phosphorus and

Magnesium2,5
Life Stage
Calcium*
mg/d
Phosphorus
mg/d
Magnesium
mg/d
06 mo*
712 mo*
13 y
48 y
Males
913 y
1418 y
Females
913 y
1418 y
Pregnancy
1418 y
Lactation
1418 y
UL
210
270
500 (2500)
800 (2500)
100
275
460 (3000)
500 (3000)
30
75
80 (65)
130 (110)
1300 (2500)
1300 (2500)
1250 (4000)
1250 (4000)
240 (350)
410 (350)
1300 (2500)
1300 (2500)
1250 (4000)
1250 (4000)
240 (350)
360 (350)
1300 (2500)
1250 (3500)
400 (350)
1300 (2500)
1250 (4000)
360 (350)
* Adequate intake (AI) = observed or experimentally determined estimates

of nutrient intake by a group or groups of healthy people. AI is the only
reference level provided for infants < 12 mo.
Recommended dietary allowance (RDA) = average daily dietary intake
sufficient to meet the requirement of 97% to 98% of healthy individuals
in a life stage and gender group.
Tolerable upper intake level (UL) = highest level of daily nutrient intake
that is likely to pose no risk of adverse health effects to almost all
individuals in the general population.
Upper limit for each life stage is indicated in parenthesis. For
magnesium, applies to non-food sources only.
Dietary Requirements
Absorption and Excretion
Mineral requirements depend on the needs for tissue

synthesis in growing children and the balance among
dietary supply, intestinal absorption, renal excretion, and
bone exchange for these minerals. There are a number of
unique challenges in maintaining mineral homeostasis
during infancy, childhood, and adolescence. All neonates
must adapt successfully to extrauterine life when the
continuous supply of these minerals from the placenta is
interrupted at birth. This adaptation is usually achieved
with appropriate nutrition support, even in critically ill
and preterm neonates.4 Nutrition requirements for these
minerals remain high until completion of skeletal growth.
Infants and adolescents have the greatest requirements
because of their high growth rates. The average gain in
skeletal growth over 1 year is > 25 cm for an infant and is
even greater for the preterm infant. The peak height gain is
about 7 to 10 cm per year during adolescence. The recommended dietary reference intakes (DRIs) for Ca, P, and Mg
are shown in Table 6-1.
Intestinal absorption of these minerals involves a passive

paracellular concentration-dependent process as well as
a saturable active transcellular process. Vitamin D has
some influence on the active intestinal transport but its
role under normal circumstances appears to be much less
than the passive diet-dependent process in the growing
child. Renal reabsorption of these minerals also has passive
and active transport components. It is highly efficient but
an excessive intake can overwhelm the renal reabsorption
capacity, leading to elevated circulating levels for each of
these minerals. Conversely, during deficient states, especially if there is abnormal loss from the gastrointestinal
(GI) tract or the kidney, renal conservation alone is unable
to prevent the development of abnormally low circulating
concentrations. Normally, the growing child has net bone
(and soft tissue) accretion of these minerals. Some exchange
of these minerals occurs normally with bone modeling.
The exchangeable portion may be increased during
periods of stress and increased turnover. During extreme
MINERALS
circumstances (eg, severe Ca or P deficiency in infants) it is

not possible to protect the skeleton or to maintain mineral
homeostasis.
Metabolism
Maintaining mineral homeostasis requires a complex interaction of hormonal and non-hormonal factors; adequate
functioning of various body systems, in particular the
renal, gastrointestinal, skeletal, and endocrine systems; and
adequate dietary intake. When assessing changes in serum
concentrations of these minerals, it is vital to understand
there is an interrelationship among them. For example,
hypomagnesemia may cause hypocalcemia, due to the
decreased action of parathyroid hormone (PTH). Serum
Ca and P have a reciprocal relationship, and hypoalbuminemia can cause hypocalcemia secondary to decreased Ca
binding, while ionized calcium (unbound calcium) concentration remains normal.
At the intestine-kidney-bone axis, intake of minerals
may interact with other nutrients including protein, sodium,
potassium, vitamin D, iron, zinc, and copper. There may be
significant effects on intestinal absorption, renal excretion,
or metabolism of the minerals or on these other nutrients.
Direct regulation on this axis by PTH, 1,25-dihydroxyvitamin D, and fibroblast growth factor-23, and indirect
regulation by growth-regulating hormones including sex
hormones, also significantly affect growth and mineralization of the skeleton, and maintenance of normal circulating
concentrations of these minerals. A negative effect on
mineral metabolism is possible, particularly if minerals and
other nutrients stated above are ingested in large amounts
as dietary supplements. Thus, it is vital to manage the cause
of the abnormalities in addition to providing symptomatic
treatment to the abnormal circulating concentration of the
minerals.
Deficiency States
Low dietary intake for Ca is common in older children. Less
than 40% of boys and < 30% of girls 6 years or older receive
the recommended daily adequate intake for Ca. Preoccupation with being thin is common in adolescents, especially
among females, as is the misconception that all dairy foods
are fattening. Many children and adults are unaware that
low-fat milk contains at least as much Ca as does whole
milk. A list of foods relatively high in Ca is shown in Table
6-2. Low Ca intake places children at risk for fractures, and
both Ca and vitamin D deficiency are factors in the development of rickets in infants and young children. 8,9
47
Table 6-2 Dietary Sources of Calcium57

Dietary calcium (mg)
Calciumenriched food (mg)
Milk 240 mL (285302)
Fortified orange and other fruit

juices 180 mL (200260)
Instant drink mix with 240 mL
water (105250)
Ready-to-eat cereals 1 cup
(1001,000)
Breads/English muffins 30 g (30)
Yogurt 240 g (245415)

Cheese single-wrapped oz
(120), others (140210/oz)
Chocolate pudding made with
120 mL 2% milk (153)
Sardines with bones 90 g (270)
Salmon 90 g (181)
Chinese cabbage 1 cup shredded
and boiled (158)
Broccoli chopped 1 cup (100)
Kale 1 cup (90)
Tortilla corn one 6 diameter

(1.2 oz) (40)
Tortilla flour one 6 diameter
(1.75 oz) (58)
Tofu 3 oz (60150)
Several servings of certain foods with less bioavailable calcium (eg,

vegetables) are needed to achieve the same amount of calcium absorbed
from 1 serving (240 mL) of milk.
Risks for mineral deficiency escalate with increased

requirement, decreased absorption or increased losses
through the GI tract or the kidney, or disturbed metabolism. All rapidly growing infants, especially extremely low
birth weight (< 1 kg) preterm infants, are at risk for mineral
deficiency because of increased requirement, intolerance to
multiple nutrients during acute illness, and interference with
mineral retention or metabolism from therapies. Critically
ill neonates or children who require parenteral nutrition
(PN) are often intolerant to increased nutrient intake,
especially the energy load. Thus, it is unrealistic to expect
any critically ill child to achieve normal growth (ie, normal
anabolic state). In critically ill preterm neonates, growth
rarely reaches the in utero rate, thus the needs for minerals
are correspondingly less compared to stable and growing
patients. There is no convincing evidence of mineral deficiency in the stable small preterm infant who is receiving
adequate volumes (> 150 mL/kg/d) of high-energy preterm
infant formula or mothers milk with commercial human
milk fortifier containing energy and high mineral contents
and is not receiving any medications that might interfere
with mineral absorption, excretion, or metabolism.
Malabsorption states, chronic therapy with loop
diuretics and gastric acid inhibitors, or heritable disorders
of mineral metabolism are associated with abnormalities in
mineral retention and/or metabolism.1,5 In disease states,
deficiency involving multiple minerals and additional
nutrients may be unmasked during therapy. This is best
represented by the development of hypophosphatemia,
48
hypomagnesemia, and hypokalemia simultaneously during

refeeding of severely malnourished individuals.

The most common risk factor for excessive intake of
minerals is associated with increased parenteral intake of
minerals from the unrealistic expectation of normal growth
in the critically ill child. Minerals delivered via parenteral
routes can exceed the excretory capacity, resulting most
commonly in hyperphosphatemia and hypermagnesemia
with associated hypocalcemia.1,4 These findings may in part
reflect shifts in minerals among various compartments
but they also suggest that delivery of minerals can occur in
excess of the bodys needs.
Adverse effects from excess dietary intake of minerals
occur rarely in normal pediatric ages. However, it is possible
that some healthy infants may develop hyperphosphatemia
and secondary hypocalcemia from feeding of standard
infant formula. This is the result of a combination of higher
intake of P from infant formulas relative to breast milk, and
the inability to eliminate the excess P because of immature kidney and parathyroid gland function.1,4 Most of the
adverse effects of excess mineral intake are due to excessive
intake of supplements in pharmacologic doses and may
result in serious morbidity and even mortality. The derivation of the current recommendation for the upper level of
intake of Mg is based on the amount of supplement. 2
Calcium
(1 mmol = 40 mg)

Calcium is the most abundant mineral in the human
body and accounts for about 1% to 2% of adult human
body weight. More than 99% of total body Ca is stored
in the bones and teeth where it functions to support their
structure. Thus, calcium is critical for normal growth and
development of the skeleton and teeth.10 The remaining 1%
is found throughout the body in blood, muscle, and other
tissues and is critical to numerous physiological functions.
In the circulation, ~50% of Ca is ionized and the rest is
bound to albumin or complexed to small anions such as
citrate, bicarbonate, and phosphorate.
Optimal bodily function depends on maintaining
the circulating total and especially ionized Ca concentration within a narrow range. Calcium exerts its effect
either through a membrane-bound Ca sensing receptor
(a member of the G protein-coupled receptor (GPCR)
family, expressed on numerous organs and tissues) or at
the cellular level through the action of ionized Ca, which

functions both as extra- and intracellular messenger. Its
role as a secondary messenger is critical to numerous
bodily functions including muscle contraction, blood vessel
contraction and expansion, the secretion of hormones and
enzymes, and message relay through the nervous system. 2
In 1993 the FDA authorized placement of a health claim
on food labels that states adequate Ca intake throughout
life is linked to reduced risk of osteoporosis through the
mechanism of optimizing peak bone mass during adolescence and early adulthood and decreasing bone loss later in
life, and the addition of vitamin D to this claim is currently
being considered.11 Calcium may contribute among other
nutrition factors to the prevention of chronic diseases such
ashypertension.12
Sources
Calcium is present in many dietary sources with dairy
products having the best bioavailability (Table 6-2) and
accounting for > 70% of dietary Ca intake in the United
States.2,5 Non-fat and reduced fat dairy products contain the
same amount of Ca as regular dairy products. Some food
sources (eg, fruit juices, fruit drinks, tofu, and cereals) are
fortified with various Ca compounds that are well absorbed.
Calcium is present in human milk in relatively constant
amounts between 200 to 250 mg/L. Various Ca salts are
added to cows milk formulas for term infants to provide
at least 60 mg/100 kcal. This is about twofold higher than
the Ca density in human milk.13 Calcium fortification of
formulas for small preterm infants may be four- to sixfold
higher than human milk.
Oral supplements such as calcium compounds
containing carbonate and citrate are the most common
although preparations containing other anions are available.
Naturally occurring products (eg, oyster shell marketed as
calcium supplement) contain high levels of lead, mercury,
and other potentially toxic contaminants.14 Common
parenteral supplements include calcium gluconate and
calcium chloride but other compounds also are available.
The proportion of elemental calcium by weight varies with
the calcium compound and is 40% for carbonate, 38% for
tribasic calcium phosphate, 21% for citrate, 13% for lactate,
9% for gluconate, and 6.4% for glubionate.14,15

Gastric acid aids in the digestion of natural or Ca fortified
food or drink. Some Ca compounds such as calcium citrate
are better absorbed in those individuals who have decreased
gastric acid when compared to calcium carbonate. About
MINERALS
90% of the Ca absorbed is through the small intestine and

< 10% is absorbed through the large intestine. Paracellular
absorption takes place throughout the small intestine and is
dependent on concentration gradient. Transcellular absorption takes place largely in the duodenum and is dependent
on 1,25-dihydroxyvitamin D.
The efficiency of Ca absorption decreases with increased
amounts of Ca consumed and with the presence of non-Ca
components of the diet. The latter include the type and
content of carbohydrate, phytic acid (whole grain bread,
wheat bran, beans, seeds, nuts, grains, and soy isolates),
and/or oxalic acid (spinach, collard greens, sweet potatoes,
rhubarb, and beans) that may bind to Ca and prevent its
optimal absorption. These plant substances do not appear
to interfere with Ca absorption from other foods.
Calcium is excreted through feces, urine, and sweat.
Calcium excretion can be increased by many factors
including high intake of dietary sodium, protein, and
caffeine. High potassium intake lowers urinary Ca thereby
affecting the net Ca absorption. 2,16 The effect of dietary P on
Ca and bone metabolism is limited if Ca intake is adequate. 5
The detrimental effects of consuming foods high in phosphate such as carbonated soft drinks is probably due to the
replacement of milk with soda rather than the phosphate
level itself.17 Chronic use of Mg antacids and potent loop
diuretics such as furosemide can increase urinary Ca excretion. Aluminum antacids should not be used, especially for
those with limited renal function such as infants, because
of potential aluminum toxicity.18 Chronic therapy with a
proton pump inhibitor raises risks for fractures.19
Retention of Ca generally reflects the bodys need. It is
usually higher in individuals undergoing rapid growth and
may be > 60% of dietary intake. Adequate intakes of Ca that
meet or exceed the amount needed to maintain a nutritional
state of adequacy in nearly all members of a specific age and
gender group are shown in Table 6-1. The pregnant and
lactating adolescent theoretically could have an increased
need for Ca because of the need to support the bone mineralization of the mother and the fetus. Limited data indicate
there is a compensatory increase in Ca absorption and any
decrease in bone mass is replenished upon return of ovarian
function and no additional increase in dietary Ca intake is
recommended.2 However, pregnant women with adequate
diets except for very low Ca intake can lower the fetal bone
mineral content. This is prevented by an adequate Ca intake
from diet or from Ca supplementation. 20 At all ages,21 particularly in young children, dietary Ca absorption is primarily
regulated by Ca 22 rather than vitamin23 intake.
Calcium homeostasis is maintained by a combination of
49
dietary intake and hormonal control of PTH and the active

vitamin D metabolite, 1,25-dihydroxyvitamin D, with additional modulation by other factors.1 Classic target organs
critical to Ca homeostasis include the GI tract, kidney, and
bone. In pediatrics, the gut and kidney act primarily in the
capacity of retaining Ca for the growth needs of the bone,
hence there is always a positive Ca balance during growth.
Dietary Ca, physical activity, and pubertal stage have independent effects on the rate of bone mineralization. 24,25
Maintenance Ca intake generally should be in the form
of foods because of the range of other nutrients present in
various foods. Foods fortified with Ca have increased the
choices of Ca rich foods in the diet. 5
Deficiency States
Risk factors for a deficient state include increased need, such
as the rapidly growing infant, or the presence of disease
states that affect Ca digestion, absorption, or metabolism.
Physically active females, particularly those with secondary
menstrual disorders, may have lower Ca absorption and
decreased bone formation, and adequate Ca intake is important to their bone health.26 Lactose-intolerant individuals
may be at risk for Ca deficiency, not due to an inability to
absorb Ca, but rather from the avoidance of dairy products. 2
Drinking milk with a meal and other dietary options (eg,
choosing aged cheeses (such as Cheddar and Swiss) which
contain little lactose, yogurt which contains live active
cultures that aid in lactose digestion, or lactose-reduced
and lactose-free milk) may allow increased Ca intake. Strict
vegans27 should include adequate amounts of non-dairy
sources of Ca in their daily diets or likely will need a Ca
supplement to meet the recommended Ca intake.
Dietary Ca deficiency is a risk factor for fractures8
although it is usually not associated with clinical or biochemical manifestations unless the Ca intake is extremely low.
Hypocalcemia does not usually occur due to low Ca intake
alone but occurs with concomitant deficiency of vitamin
D or Mg or associated medical problems. Severe hypocalcemia may result in clinical signs and symptoms that may
be subtle and vary with maturity of the individuals. Preterm
infants often manifest with non-specific symptomatology
that may include irritability, jitteriness or lethargy, feeding
poorly with and without feeding intolerance, abdominal
distention, apnea, cyanosis, and seizures. These features
may be confused with manifestations of hypoglycemia,
sepsis, meningitis, anoxia, intracranial bleeding, and
narcotic withdrawal. The degree of irritability of the infant
does not appear to correlate with serum Ca values. In more
mature individuals, other symptoms and signs may include
50
tetany from peripheral hyperexcitability of motor nerves.

In chronic deficient states, Ca is mobilized from the skeleton to maintain Ca levels in the blood and predisposes to
suboptimal bone accretion. In young children, both Ca and
vitamin D deficiency have a key role in the development of
rickets.9 Resolution of hypocalcemia may not be possible
until the underlying cause has been corrected. For example,
hypocalcemia secondary to Mg deficit may not be correctable until Mg replacement therapy is initiated.

Excess Ca intake can result in hypercalcemia (serum or
plasma total Ca > 11 mg/dL or ionized Ca > 5.6 mg/dL,
respectively) and its complications of polyuria and polydipsia, renal calculi, and metastatic calcification. High
dietary Ca intakes and routine Ca supplementation generally do not cause hypercalcemia. However, high Ca intake
has the potential to interfere with the absorption of other
minerals such as iron, zinc, Mg, and P. Calcium supplements
have the potential to interact with several prescription
and over-the-counter medications. 28,29 Calcium decreases
absorption of digoxin, fluroquinolones, levothyroxine,
tetracycline, tiludronate disodium, phenytoin, and mineral
oil or stimulant laxatives when taken simultaneously with
these drugs. Thiazide diuretics can interact with calcium
carbonate and vitamin D supplements to increase the risk
for hypercalcemia and hypercalciuria. Calcium supplements from natural products such as oyster shell should be
avoided because of possible toxic contaminants.
Hypercalcemia may be a manifestation of P deficiency
(see Phosphorus section). Metastatic deposits of calcium
precipitate in the infusion delivery system, in kidneys,
and in other organs with an increased mortality have been
reported in neonates who received ceftriaxone simultaneously with parenteral solutions containing calcium. 30
Phosphorus
(1 mmol = 31 mg)

Phosphorus as phosphate is an essential constituent of all
known protoplasm. The terms phosphorus and phosphate
are often used interchangeably, but the term phosphate
actually means the inorganic freely available form. This
measurable component is generally referred to as phosphorus (P).
Tissue P increases from ~0.5% of the body weight in the
neonate to ~1% in the adult from an increase in bone and soft
tissue mass. Structurally, P is incorporated in mineralized
tissues of the skeleton and teeth, in biological membranes

as phospholipids, and in cells as nucleotides and nucleic
acids. About 85% of P is in the skeleton, primarily in the
form of hydroxyapatite. Of the remainder, 14% is intracellular (primarily in the soft tissues) and 1% is extracellular
in the circulation and interstitial fluid. Of the extracellular
P, 70% is organic and contained within phospholipids, and
30% is inorganic. 31 At pH of 7.4, the mono- and di-hydrogen
form is in a ratio of about 4:1. For that reason, P is usually
expressed in mmol rather than mEq/L.
The serum or plasma P concentration is ~1 to 2 mmol/L
(3.16.2 mg/dL) and is higher at younger ages. Plasma P
concentrations of preterm infants is about 0.5 mmol higher
but may be as high as 2.81 mmol/L (8.7 mg/dL) without
affecting plasma Ca concentration.1 This minute compartment of P is the major source of exchange of P associated
with dietary uptake and absorption, renal excretion and
reabsorption, and bone modeling and remodeling. This
compartment is also the primary source of P for structural and high-energy phosphate in the cells of all tissues.
When extracellular fluid P concentrations are low, cellular
dysfunction follows.
A normal level of P in the extracellular fluid is necessary
for cellular function and skeletal mineralization. The physiological functions include the maintenance of mineral and
acid- base homeostasis, the temporary storage of the transfer
of energy derived from metabolic fuels, and the activation of
many catalytic proteins through phosphorylation. 32 Most of
these processes involve the recycling of P. Thus, the function of dietary P is to support tissue growth and to replace
excretory and cellular and dermal losses.2
Sources
Phosphorus is ubiquitous in natural foods and is present
in both organic and inorganic forms. Various phosphate
salts used in food processing for non-nutritive functions
(eg, moisture retention, smoothness, and binding) provide
significant contributions to dietary P intake. Cola soft
drinks contain phosphoric acid as the acidulant and provide
about 50 mg of P per 12 oz serving.2 Phosphorus intake
fromsoft drinks can be substantial when multiple beverages
are consumed.
Dairy and meat products have high P density. Plants,
nuts, and seeds also are significant sources of P. Animal or
synthetic protein has more bioavailable phosphorus than
soy or grain-based protein. Phosphorus in plants (beans,
peas, cereals, nuts) is present in the poorly digestible
phytic acid. However, some phytate P is absorbed from the
combined effect of food phytases, colonic bacteria enzymes,
MINERALS
51
and yeast products.2 Human milk has low P content, which

decreases further with prolonged lactation, although the
P bioavailability is higher than all other milks for infants.
Compared to human milk, P content is higher in cows milk
by five- to sixfold, standard cow milk-based infant formula
by about twofold, and soy-based infant formula by about
threefold. The Ca:P ratio varies widely in natural foods.
However, both the Ca:P ratio and absolute quantities of
these minerals are important to optimize mineral accretion in bone and soft tissue. P supplements are available as
mono- and dibasic-phosphates, in both oral and parenteral
forms. They are usually used for medical indications such as
inherited metabolic defects.
hormone and thyroid hormone. Renal P reabsorption is

increased with 1,25-dihydroxyvitamin D.
The kidney can increase or decrease its P resorptive
capacity to accommodate P needs. 32,33 In infants and children, lower glomerular filtration rate is probably the main
determinant of the higher serum P because P resorptive
capacity is high even in the small preterm infant.1 Healthy
infants have lower serum P when breastfed compared to
those fed infant formula.1,34 The least renal excretory work
to maintain normal P homeostasis during the first year is
achieved with human milk as the major source of minerals.
In deficient states, renal retention of filtered phosphate is
almost complete even in the preterm infant.1
Deficiency States
Net absorption of P ranges from 55% to 70% in adults and

65% to 90% in children and infants. The fractional P absorption is virtually constant across a broad range of intake. The
bulk of P absorption is passive (paracellular) and concentration-dependent. A saturable, active transcellular sodium
(Na+)-dependent involving the type IIb Na+/phosphate
cotransporter and facilitated by 1,25-dihydroxyvitamin D
also exists. P is not absorbed in the stomach but is absorbed
throughout the small bowel. The fractional absorption of P
and other minerals is lower from infant formulas compared
to human milk although the absolute amounts of each
mineral absorbed from infant formulas are higher because
of the much higher mineral content in infant formulas.
Medications or foods that bind P (antacids, phosphate
binders, and calcium) can decrease the net amount of P
absorbed by decreasing the free phosphate for absorption.
Unabsorbed Ca complexes with phytic acid can interfere with bacterial hydrolysis of phytate and decreases P
absorption.2
The kidney is a major regulator of P homeostasis. Renal
P is reabsorbed primarily at proximal tubular cells (70%
80%). The remaining is reabsorbed in the distal tubules.
Serum P increases as the total P intake and absorption
exceeds the renal tubular maximum transport for P. Renal
P reabsorption is modulated by changes in basolateral
basement membrane abundance of type IIa Na/phosphate
cotransporter (Npt2a) protein and requires the interaction
of Npt2a with various scaffolding and regulatory proteins. 33
Renal P reabsorption is decreased (ie, excretion is increased)
by a decrease in renal Npt2a, an increase in dietary P intake,
PTH, or fibroblast growth factor-23, or a loss of Phex function. Although the effects are more minor, renal P excretion
is also increased by volume expansion, metabolic acidosis,
glucocorticoids, and calcitonin. It is decreased by growth
Cellular storage of phosphate and the portion of P that

can be mobilized from bone are limited. Thus, dietary P
is required to maintain extracellular fluid P, which is the
source of P for the tissue metabolic phosphate. Normally,
because P is ubiquitous in foods, dietary P deficiency rarely
occurs unless the individual is subjected to near total starvation. However, small preterm infants with chronically low
P intake from prolonged exclusive feeding of non-supplemented mothers milk; infants and children with poorly
managed PN with inadequate P content, inappropriate
administration of fluid and electrolyte therapy that causes
excessive renal P loss; or rapid refeeding in the setting of
diabetic ketoacidosis or severe malnourishment, especially
if accompanied by diarrhea, are at risk for hypophosphatemia in addition to other electrolyte abnormalities.1,2,35
Individuals with chronic aluminum antacid therapy and
heritable defects of P metabolism also can manifest P deficiency. Chronic diuretic therapy that increases urine P can
exacerbate the P deficit.
Clinical manifestations of P deficiency include
anorexia, general debility, anemia, muscle weakness
including respiratory compromise, bone pain, rickets
and osteomalacia, increased susceptibility to infection,
paresthesia, ataxia, confusion, and even death. 36 These
severe manifestations usually occur when the extracellular
fluid P is < 0.3 mmol/L (0.9 mg/dL). Plasma Ca may be
elevated simultaneously, particularly in infants.1

Essentially all the adverse effects of excess P intake from any
source are the result of hyperphosphatemia. These include
adjustments in the hormonal control system regulating
Ca homeostasis and may be complicated by hypocalcemia
and its adverse effects, ectopic (metastatic) calcification,
52
particularly of the kidney, and possibly decreases in the

intestinal absorption of Ca, iron, zinc, and copper but
without documented clinical adverse effects. Hyperphosphatemia usually occurs in the setting of kidney disease and
rarely occurs under normal circumstances. One exception
is the development of hyperphosphatemia and secondary
hypocalcemia in some healthy infants from the use of standard infant formulas. This is the result of a combination of
higher intake of P from infant formulas relative to breast
milk, and the inability to eliminate excess P because of
immature renal and parathyroid functions. Clinically, this
is exacerbated by the early introduction of solids or whole
cows milk to the infant.1
Magnesium
(1 mmol = 24 mg)

Magnesium (Mg) is the fourth most abundant cation in the
body and is the second most abundant intracellular cation.
Total body Mg content is ~25 g (1000 mmol), of which
~60% resides in bone. About one-third of the skeletal Mg
is exchangeable and serves as a reservoir for maintaining
extracellular Mg concentration. The rest of the Mg is in soft
tissues such as muscle and organs, and ~1% is in extracellular fluid. Cellular Mg content is 6 to 9 mmol/kg net weight,
and most of this Mg is localized in membrane structures
(eg, microsome, mitochondria, plasma membrane). 37,38
The much smaller pool of free Mg in the cell is maintained
at ~1 mmol/L and is in an exchanging equilibrium with
membrane-bound Mg. This unbound intracellular Mg has a
critical role in cellular physiology. 39 Intracellular Mg usually
remains stable despite wide fluctuations in serum Mg. In
Mg-deficient states, however, the intracellular content
of Mg can be low despite normal serum concentrations.
Serum Mg has a protein-bound (~30%) and an ultrafiltrable
(~70%) portion. Of the latter, 70% to 80% is in ionic form.
The remainder is complexed to anions, particularly phosphate, citrate, and oxalate.
Magnesium is a required cofactor for > 300 enzyme
systems. It is critical for normal ATP function and glucose
metabolism and is necessary for both aerobic and anaerobic
metabolism. It is important in cellular cytoskeleton contraction and at the myoneural junction, and therefore can alter
skeletal and cardiac muscle function. It catalyzes enzymatic
processes concerned with the transfer, storage, and use of
energy; regulation of movement of potassium and Ca across
the cell membranes; and numerous other cell functions.
Abnormalities in circulating Mg concentrations are associated with widespread cellular effects.
Sources
Magnesium is ubiquitous in foods but the Mg content of
foods varies substantially. Green leafy vegetables are rich
in Mg because chlorophyll is the Mg chelate of porphyrin.
Unpolished grains and nuts also have high Mg content,
whereas meats and milk have intermediate levels. Refined
foods generally have the lowest Mg content.40,41 Water is a
variable source of Mg depending on the source of ground
water. Typically, hard water has higher concentrations
of Mg salts.2,41 Human milk contains adequate amounts of
Mg and infant formulas are mandated to contain at least
6mg/100 kcal.13 Supplements containing various Mg salts
are freely available in oral forms. The proportion of elemental
magnesium by weight is 60.3% for oxide; 28% for carbonate;
16% for citrate; ~12% for chloride, acetate, and lactate;
9.7% for sulfate; 6.8% for phosphate; 6.4% for ascorbate;
and 5.4%for gluconate.15 Magnesium sulfate is available in
parenteral form. Mg supplements may contribute a substantial portion of daily intake and are used as a basis for the
derivation of tolerable upper intake levels.2

The net absorption of Mg is about 40% to 60%. Fractional intestinal absorption is inversely proportional to
the amount of Mg ingested. Intestinal absorption is via
a passive gradient-dependent paracellular and an active
saturable vitamin D-dependent transcellular mechanism.
Magnesium is absorbed throughout the entire intestinal
tract with maximal absorption at the distal jejunum and
ileum.2 Magnesium absorption is not significantly affected
by other nutrients at the usual dietary intake. It is lowered
with high P intake, particularly if there is an associated high
fiber and phytate intake, and at low protein intake.2,42
The kidney plays an important role in the homeostasis
of divalent ions. Most of the ionized forms of Ca and Mg are
reabsorbed at the proximal tubules and the thick ascending
limb of Henles loop via a passive paracellular pathway. It
is dependent on salt and water reabsorption and rate of
fluid flow. At the level of the distal convolute tubule and
the connecting tubule, ionized Ca and ionized Mg are reabsorbed via an active transcellular transport.
Renal Mg transport also is affected by both hormonal
(parathyroid hormone, calcitonin, glucagon, arginine vasopressin, 17 beta estradiol) and non-hormonal factors. High
intake of glucose, sodium, Ca, and Mg, chronic excessive
MINERALS
alcohol intake, as well as elevated serum Mg or Ca, depletion of potassium and phosphate, and metabolic acidosis
inhibit Mg and Ca reabsorption, leading to increased urine
excretion of both cations.43
Deficiency States
Magnesium deficiency is usually associated with malabsorption, increased losses from the gut or kidney, or during
refeeding of severe and chronically malnourished individuals. Chronic therapy with loop diuretics, cisplatin, and
tacrolimus are among the increasing list of medications
that result in increased renal Mg excretion and predisposition to Mg deficiency.43 There are also increasing reports of
patients with heritable defects of Mg transport that lead to
Mg wasting and deficiency states.44
The typical deficit required to produce symptomatic hypomagnesemia is approximately 0.5 to 1 mmol
(1224 mg)/kg of body weight.45 Hypomagnesemia is
usually associated with a significant Mg deficit. These
individuals often are at risk for concurrent hypocalcemia,
hypokalemia, hypophosphatemia, and possible disturbance of acid-base status. The loss of other nutrients such
as zinc from the gastrointestinal secretion also may be
considerable. Symptoms and signs of hypomagnesemia,
which often coexists with hypocalcemia, may be indistinguishable. Prolonged dietary Mg deprivation in human
adults leads to personality change, tremor, muscle fasciculations, spontaneous carpopedal spasm, and generalized
spasticity as well as hypomagnesemia, hypocalcemia, and
hypokalemia.45 In infants, acute complications associated with clinical manifestations include seizure, apnea,
cyanosis and hypoxia, electrocardiographic changes,
bradycardia, and hypotension.

Ingestion of Mg from natural foods has not been shown to
exert any adverse effects. However, adverse effects of excess
Mg intake have been reported from non-food sources such
as various Mg salts for pharmacologic purposes, particularly in patients with renal dysfunction. The amount of Mg
supplement is the basis from which the current upper limit
of Mg intake is derived.2 The primary initial manifestation
of excessive Mg intake from non-food sources is diarrhea
(probably from its osmotic effect), and may be accompanied by nausea and abdominal cramping. Clinical signs of
neuromuscular depression with floppiness and lethargy, and
respiratory depression are frequent manifestations of severe
neonatal hypermagnesemia in infants born to mothers who
53
received Mg therapy prior to delivery.1 Acute hypotonia,

apnea, hypotension, and refractory bradycardia mimicking
septic shock syndrome has been reported in premature
infants accidentally overdosed with Mg in PN.46 In adults
with hypermagnesemia, hypotension and urinary retention
occur at serum Mg concentrations of 1.67 to 2.5 mmol/L
(46 mg/dL); central nervous system depression, hyporeflexia, and electrocardiographic abnormalities (ie, increased
atrioventricular and ventricular conduction time) at 2.5 to 5
mmol/L (612 mg/dL); and respiratory depression, coma,
and cardiac arrest above 5 mmol/L (12 mg/dL).47
1. Which of the following statements on bioavailability of

calcium is incorrect?
A. Highest in dairy products in the diet
B. Presence of phytate in plants can decrease calcium
availability
C. Calcium supplement from natural sources such
as oyster shells may be contaminated with toxic
metals
D. Vitamin D status is one of the determinants of
calcium bioavailability
E. Low-fat dairy products have low calcium content
2. Which of the following statements on calcium absorption is incorrect?
A. Inversely related to dietary content of calcium
B. Lowest in pediatric ages
C. Is diminished with steatorrhea
D. Varies with type of food consumed
E. Dietary zinc decreases calcium absorption
3. Which of the following statements about phosphorus
is incorrect?
A. It is ubiquitous in natural foods
B. Dietary intake of phosphorus is increased with
increased consumption of processed foods
C. Calcium phosphorus ratio of natural foods varies
widely
D. Phosphorus deficiency can result in hypercalcemia
E. None of the above
4. Extracellular fluid (and serum) inorganic phosphate is
regulated by:
A. Renal function
B. Parathyroid hormone
C. Fibroblast growth factor-23
D. All of the above
E. None of the above
54
5. All of the following statements associated with magnesium deficit are correct except for:
A. May be associated with chronic gastrointestinal
losses
B. May result in fecal fat loss
C. May be associated with deficiency of other
nutrients
D. May result in hypocalcemia
E. May be asymptomatic
6. Which of the following statements about hypermagnesemia is incorrect?
A. Can occur with drinking hard water
B. Can result in cardiac arrhythmia
C. Can cause respiratory failure
D. Usually occurs only with pharmacologic doses of
magnesium
E. Can decrease muscle tone
References
1. Koo WWK. Neonatal calcium, magnesium and phosphorus

disorders. In: Lifshitz F, ed. Pediatric Endocrinology: A
Clinical Guide. 5th ed. New York, NY: Marcel Dekker Inc;
2007:497529.
2. Food and Nutrition Board, Institute of Medicine. Dietary
Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin
D and Fluoride. Washington, DC: National Academy Press;
1997.
3. U.S. Food and Drug Administration. Dietary supplements.
http://www.fda.gov/Food/DietarySupplements/default.
htm. Accessed November 20, 2009.
4. Koo WWK, McLaughlin K, Saba M. Nutrition support for
the neonatal intensive care patients. In: Merritt R, ed. The
A.S.P.E.N. Nutrition Support Practice Manual. 2nd ed. Silver
Spring, MD: American Society for Parenteral and Enteral
Nutrition; 2005:301314.
5. National Institutes of Health. Office of Dietary Supplements.
Dietary supplement fact sheet: Calcium. http://ods.od.nih.
gov/factsheets/calcium.asp. Accessed August 14, 2009.
6. Pennington JAT, ed. Bowes & Churchs Food Values of Portions
Commonly Used. 18th ed. Philadelphia, PA: J. B. Lippincott;
2005.
7. Calcium content in foods. CalorieKing for Food Awareness
Web site. http://www.calorieking.com. Accessed November
25, 2009.
8. Greer FR, Krebs NF, Committee on Nutrition. Optimizing
bone health and calcium intakes of infants, children, and
adolescents. Pediatrics. 2006;117:578585.
9. Fischer PR, Thacher TD, Pettifor JM. Pediatric vitamin D and
calcium nutrition in developing countries. Rev Endocr Metab
Disord. 2008;9:181192.
10. U.S. Department of Health and Human Services. Office of the

Surgeon General. Bone Health and Osteoporosis: A Report of
the Surgeon General. 2004. http://www.surgeongeneral.gov/
library/bonehealth/content.html. Accessed March 20, 2009.
11. U.S. Food and Drug Administration. Guidance for Industry:
Food Labeling: Health Claims; Calcium and Osteoporosis, and
Calcium, Vitamin D, and Osteoporosis. http://www.fda.gov/
Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/ucm152626.htm.
Accessed August 24, 2009.
12. National Heart Lung and Blood Institute, National Institutes
of Health. Your guide to lowering your blood pressure with
DASH.http://www.nhlbi.nih.gov/health/public/heart/
hbp/dash/index.htm. Accessed August 16, 2009.
13. U.S. Food and Drug Administration. Code of Federal Regulations Title 21. Infant formula nutrient specifications.
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFR Search.cfm?fr=107.100&SearchTerm=infant%20
formula. Accessed August 2, 2009.
14. Levenson D, Bockman R. A review of calcium preparations.
Nutr Rev. 1994;52:221232.
15. Drug Facts and Comparisons 2009. St. Louis, MO: Wolters
Kluwer Health.
16. Standing Committee on the Scientific Evaluation of Dietary
Reference Intakes, Food and Nutrition Board, Institute of
Medicine. Dietary Reference Intakes for Water, Potassium,
Sodium, Chloride, and Sulfate. Washington, DC: National
Academy Press; 2004.
17. Heaney RP, Rafferty K. Carbonated beverages and urinary
calcium excretion. Am J Clin Nutr. 2001;74:343347.
18. Koo WWK, Kaplan LA. Aluminum and bone disorders: with
specific reference to aluminum contamination of infant nutrients. J Amer Coll Nutr. 1988;7:199214.
19. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton
pump inhibitor therapy and risk of hip fracture. JAMA
2006;296:29472953.
20. Koo WWK, Walters JC, Esterlitz J, Levine RJ, Bush AJ, Sibai
B. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol. 1999;94:577582.
21. Bronner F. Recent developments in intestinal calcium absorption. Nutr Rev. 2009;67:109113.
22. Oramasionwu GE, Thacher TD, Pam SD, Pettifor JM,
Abrams SA. Adaptation of calcium absorption during treatment of nutritional rickets in Nigerian children. Br J Nutr.
2008;100:387392.
23. Thacher TD, Obadofin MO, OBrien KO, Abrams SA. The
effect of vitamin D2 and vitamin D3 on intestinal calcium
absorption in Nigerian children with rickets. J Clin Endocrinol
Metab. 2009;94:3314-3321.
24. Slemenda CW, Reister TK, Hui SL, Miller JZ, Christian
JC, Johnston CC Jr. Influences on skeletal mineralization
in children and adolescents: evidence for varying effects
of sexual maturation and physical activity. J Pediatr.
1994;125:201207.
25. Specker BL. Evidence for an interaction between calcium
intake and physical activity on changes in bone mineral
density. J Bone Miner Res. 1996;11:15391544.
26. Nattiv A. Stress fractures and bone health in track and field
athletes. J Sci Med Sport. 2000;3:268279.
MINERALS
27. Key TJ, Appleby PN, Rosell MS. Health effects of vegetarian
and vegan diets. Proc Nutr Soc. 2006;65:3541.
28. Shannon MT, Wilson BA, Stang CL. Health Professionals Drug
Guide. Stamford, CT: Appleton & Lange; 2000.
29. Jellin JM, Gregory P, Batz F, Hitchens K. Pharmacists Letter/
Prescribers Letter Natural Medicines Comprehensive Database.
3rd ed. Stockton, CA: Therapeutic Research Facility; 2000.
30. U.S. Food and Drug Administration. Information for Healthcare Professionals: Ceftriaxone (marketed as Rocephin
and generics). http://www.fda.gov/Drugs/DrugSafety/
PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/
ucm084263.htm#main. Accessed November 20, 2009.
31. Nordin BEC. Phosphorus. J Food Nutr. 1988;45:6275.
32. Takeda E, Taketani Y, Sawada N, Sato T, Yamamoto H. The
regulation and function of phosphate in the human body.
Biofactors. 2004;21:345355.
33. Tenenhouse HS. Regulation of phosphorus homeostasis by
the type IIa Na/phosphate cotransporter. Annu Rev Nutr.
2005;25:197214.
34. Specker BL, Lichtenstein P, Mimouni F, Gormley C, Tsang
RC. Calcium-regulating hormones and minerals from birth
to 18 months of age: a cross-sectional study. II. Effects of sex,
race, age, season, and diet on serum minerals, parathyroid
hormone, and calcitonin. Pediatrics. 1986;77:891896.
35. Freiman I, Pettifor JM, Moodley GM. Serum phosphorus
in protein energy malnutrition. J Pediatr Gastroenterol Nutr.
1982;1:547550.
36. Lotz M, Zisman E, Bartter FC. Evidence for a
phosphorus-depletion syndrome in man. N Engl J Med.
1968;278:409415.
37. Elin RJ. Assessment of magnesium status. Clin Chem.
1987;33:19651970.
55
38. Reinhart RA. Magnesium metabolism: a review with special

reference to the relationship between intracellular content
and serum levels. Arch Intern Med. 1988;148:24152420.
39. Saris NE, Mervaala E, Karppanen H, Khawaja JA, Lewenstam
A. Magnesium. An update on physiological, clinical and
analytical aspects. Clin Chim Acta. 2000;294:126.
40. Egan SK, Tao SS, Pennington JA, Bolger PM. U.S. Food and
Drug Administrations Total Diet Study: intake of nutritional and toxic elements, 1991-96. Food Addit Contam.
2002;19:103125.
41. National Institutes of Health. Office of Dietary Supplements.
Magnesium. http://ods.od.nih.gov/factsheets/magnesium.
asp. Accessed August 14, 2009.
42. Schwartz R, Walker G, Linz MD, MacKellar I. Metabolic
responses of adolescent boys to two levels of dietary magnesium and protein. I. Magnesium and nitrogen retention. Am J
Clin Nutr. 1973;26:510518.
43. Quamme GA. Renal magnesium handling: new insights in
understanding old problems. Kidney Int. 1997;52:11801195.
44. OMIM - Online Mendelian Inheritance in Man. National
Center for Biotechnology Information. http://www.ncbi.
nlm.nih.gov/sites/entrez. Accessed August 20, 2009.
45. Shils ME. Experimental human magnesium depletion. Medicine. 1969;48:6185.
46. Ali A, Walentik C, Mantych GJ, Sadiq HF, Keenan WJ,
Noguchi A. Iatrogenic acute hypermagnesemia after total
parenteral nutrition infusion mimicking septic shock
syndrome: two case reports. Pediatrics. 2003;112:e7072.
47. Mordes JP, Wacker WE. Excess magnesium. Pharmacol Rev.
1978;29:273300.
Water-Soluble Essential Micronutrients
Winston Koo, MBBS, FACN, CNS, Judith Christie, RN, MSN, May Saba, PharmD, BCNSP,
Mirjana Lulic-Botica, BSc, BCPS, and LetitiaWarren, RD, CSP
CONTENTS
Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Digestion, Absorption, and Metabolism. . . . . . . . . . . . . . . 57
Dietary Reference Intake. . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Increased Demands and Predisposition toDeficiency
States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Management of Deficiency State andSupplementation . 59
Specific Nutrients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Thiamin (Vitamin B1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Riboflavin (Vitamin B2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Niacin (Vitamin B3) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Vitamin B6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
Folate (Vitamin B9). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Vitamin B12 (Cobalamin) . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Vitamin C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Pantothenic Acid (Vitamin B5) . . . . . . . . . . . . . . . . . . . . . . 69
Biotin (Vitamin B7). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Choline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
56
Learning Objectives
1. Understand the physiological basis for the function and

requirement common to the group or to the individual
water-soluble essential micronutrients.
2. Understand the common risk factors and special
considerations in the predisposition for the development of deficiency state for these nutrients.
3. Understand the common manifestations and diagnosis
of deficiency state for these micronutrients.
4. Understand the potential risks with excessive intake of
these micronutrients.
Overview
Water-soluble essential micronutrients include the 8

B-complex vitamins: thiamin (vitamin B1), riboflavin
(vitamin B2), niacin (vitamin B3), vitamin B6 (pyridoxine),
vitamin B12 , folate (vitamin B9), pantothenic acid (vitamin
B5), biotin (vitamin B7); and vitamin C and choline. These
micronutrients affect the function of all cells, and many
have interrelated transport mechanisms, metabolism, and
functions. In pediatric subjects, these cellular functions
additionally affect growth and development.
Some of these essential nutrients can be synthesized
de novo from other nutrients (eg, niacin from tryptophan,
choline from methylation of phosphatidylethanolamine) or
from intestinal bacteria (eg, riboflavin, pyridoxine, vitamin
B12 , pantothenic acid, and biotin), although in amounts
inadequate to meet physiological demands.
One or more of these micronutrients are used to fortify
many food and drink products, some nutrients such as
choline are added to foods as an emulsifying agent, and
all water-soluble micronutrients are available as individual
supplements or as part of multivitamin +/- multinutrient
WATER-SOLUBLE ESSENTIAL MICRONUTRIENTS
supplements.19 All are available as oral and parenteral

preparations except for choline, which is available in oral
form only. Multivitamin preparations used for parenteral
nutrition (PN) are shown in Table 7-1. Vitamin B12 is also
available in an intranasal form. 5,6,9
Dietary supplements in the form of multivitamins and
multiminerals are taken regularly by more than 30% of
children in the United States with the lowest use reported
among infants younger than 1 year (11.9%) and teenagers
14 to 18 years old (25.7%) and highest use among 4- to
8-year-old children (48.5%).10 Given such extensive use,
nutrient intakes from dietary supplements must be included
to obtain accurate estimates of overall nutrient intake in
children.
For healthy near-term or term infants, milk from
well-nourished mothers ingesting a varied diet should be
sufficient to provide all water-soluble essential micronutrients for their daily needs. Small preterm infants have greater
needs for these and other nutrients because of minimal or
absent reserves, and for catch-up growth. Human milk fortifier added to mothers milk raises the concentration of these
nutrients to multiple folds higher than what is naturally
present in human milk and should be sufficient for preterm
infants tolerating adequate volumes of enteral intake. 3 For
formula-fed infants, the use of commercial milk-based
formula designed for term and preterm infants is expected
to be adequate. 3 Beyond infancy, a culturally appropriate
57
varied diet assures the adequacy of intake at all life stages

because these essential nutrients are present in a wide range
of food products.13,7
Digestion, Absorption, and Metabolism
These dietary micronutrients are released with the digestion of foods and then absorbed in free form or as small
molecular complexes. Absorption is usually by active transport at low nutrient intake and by passive diffusion at high
intake. Absorption occurs mainly at the jejunum except for
cobalamin which is absorbed only at the ileum under physiological conditions. Some absorption occurs at the stomach
(niacin) and proximal colon (riboflavin, biotin).11 Postabsorptive transport usually occurs as an enzyme complex or
bound to proteins. Erythrocytes may serve both as transporter and storage source. Tissue uptake is usually specific
to each nutrient. Some of these essential nutrients have
interrelated metabolism and function. The bioavailability
of water-soluble vitamin supplements is generally similar to
or better than that from dietary sources when tested under
the same conditions.1,2,5,6,9
Dietary Reference Intake
The current dietary reference intake (DRI) values for

pediatric populations are provided in Table 7-2. However,
current reference values are subject to change with
increasing understanding of the relationship among various
Table 7-1 Content Per Unit Dose of Multivitamin Preparations for Use with Parenteral Nutrition*
Ingredient
M.V.I.
Pediatric
M.V.I. Adult
(for ages 11 y)
M.V.I. 12
(no vitamin K)
Unit dose volume (mL)

Fat-soluble vitamins
Vitamin A (retinol, mg)
Vitamin D (ergocalciferol, mcg)
Vitamin E (dl--tocopheryl acetate, mg)
Vitamin K (phytonadione, mcg)
Water-soluble vitamins
Vitamin B1 (thiamin, mg)
Vitamin B2 (riboflavin 5-phosphate sodium, mg)
Niacinamide (vitamin B3, mg)
Vitamin B6 (pyridoxine hydrochloride, mg)
Folic Acid (vitamin B9, mcg)
Vitamin B12 (cyanocobalamin, mcg)
Vitamin C (ascorbic acid, mg)
Dexpanthenol (d-pantothenyl alcohol, provitamin B5, mg)
Biotin (vitamin B7, mcg)
10
10
0.7
10
7
200
1
5
10
150
1
5
10
none
1.2
1.4
17
1
140
1
80
5
20
6
3.6
40
6
600
5
200
15
60
6
3.6
40
6
600
5
200
15
60
* Data from manufacturer product insert (Hospira, Inc., Lake Forest, IL).
Lyophilized powder reconstituted immediately prior to use.
Dual vial liquid formulation. Vial one or lower chamber of unit vial contains fat-soluble vitamins A, D, E, and K; and water-soluble vitamins B1, B2, B6, C,
niacinamide, and dexpanthenol. Vial two or upper chamber of unit vial contains: biotin, folic acid, and vitamin B12.
58
Table 7-2 Dietary Reference Intake of Water-Soluble Essential Micronutrients in Pediatric Populations1,2
Life
Stage
06 m*
712 m*
13 y
48 y
Males
913 y
1418 y
Females
913 y
1418 y
Pregnancy
1418 y
Lactation
1418 y
Highest
intake
UL
Thiamin
(B1) mg
Riboflavin
(B2) mg
Niacin
(B3) mg
B6
(Pyridoxine)
mg
Folate
(B9) mcg
B12
(cobalamin)
mcg
Vitamin
C mg
Pantothenic
acid (B5) mg*
Biotin
(B7) mcg*
Choline
mg*
0.2
0.3
0.5
0.6
0.3
0.4
0.5
0.6
2
4
6 (15)
8 (20)
0.1
0.3
0.5 (30)
0.6 (40)
65
80
150 (300)
200 (400)
0.4
0.4
0.9
1.2
40
50
15 (400)
25 (650)
0.2
0.2
2
3
0.7
0.7
8
12
125
150
200 (1000)
250 (1000)
0.9
1.2
0.9
1.3
12 (20)
16 (30)
1.0 (60)
1.3 (80)
300 (600)
400 (800)
1.8
2.4
45 (1200)
75 (1800)
4
5
20
25
375 (2000)
550 (3000)
0.9
1.0
0.9
1.0
12 (20)
14 (30)
1.0 (60)
1.2 (80)
300 (600)
400 (800)
1.8
2.4
45 (1200)
65 (1800)
4
5
20
25
375 (2000)
400 (3000)
1.2
1.4
18 (30)
1.9 (80)
600 (800)
2.6
80 (1800)
30
450 (3000)
1.4
1.6
17 (30)
2.0 (80)
500 (800)
2.8
35
550 (3000)
11 mg
at >
51 y
NA
11 mg
at
> 70 y
NA
77 mg
at
5170 y
3.9 mg
at
1930 y
625 mcg
at
5170 y
36.8 mcg
at
1455 y
NA
115
(1800)
656 mg at
5170 y
NA
NA
NA
NA
NA
* AI, Adequate intake = observed or experimentally determined estimates of nutrient intake by a group or groups of healthy people. AI is the only reference
level provided for infants < 12 months, and for pantothenic acid, biotin, and choline at all life stages and genders.
RDA, Recommended dietary allowance is calculated as + 2 standard deviations of the estimated average requirement or in its absence, a coefficient of
variation of 10% to 15% for each standard deviation is assumed for a life stage and gender group.
UL, Tolerable upper intake level = highest level of daily nutrient intake that is likely to pose no risk of adverse health effects to almost all individuals in the
general population.
Upper limit for each life stage is indicated in parenthesis.
NA = not available.
Highest intake = highest reported daily mean intake from both food and supplements at 95th percentile for any life stage or gender group.
nutrients and increasing data on the type and bioavailability of specific nutrients from naturally occurring dietary
sources, fortification of foods and drinks, and supplements.
For infants, DRI of each essential micronutrient is
based on adequate intake (AI): the average daily intake of
a specific nutrient in healthy infants fed principally human
milk during the first and second 6 months after birth. For
ages beyond 1 year, several sets of reference values are used
and include AI, estimated average requirement (EAR), and
recommended dietary allowance (RDA). Establishing AI
depends on the availability of the content of the specific
essential micronutrient in food-composition data, largescale epidemiologic studies to determine the dietary and
any supplement intake of the nutrient in group/s of healthy
people of both genders, and at the specific life stage. These
data in turn allow the determination of EAR which is a
daily nutrient intake value estimated to meet the requirement of half the healthy individuals, and RDA which is the
average daily dietary intake level that is sufficient to meet

the nutrient requirement of nearly all (97% to 98%) healthy
individuals. If sufficient data are available, dose response
risk assessment to high intakes and setting of upper tolerable levels of intake (UL) are made. The absence or limited
data in children and adolescents often necessitated the derivation of EAR, RDA, and UL in these life stages and gender
by extrapolation downwards from adult data, and rounded
up. AI is used when RDA cannot be determined.1,2
Increased Demands and Predisposition

toDeficiency States
Requirements for many water-soluble vitamins generally increase with growth, pregnancy, lactation, physical
exertion, fever, and conditions associated with increased
metabolic needs. Tobacco and alcohol also affect the needs
for these nutrients. More than 15% of in-school youths in the
United States are reported to be current cigarette smokers12
and there is an association between cigarette smoking and

dieting in adolescents even in non-overweight individuals.13
Smokers may have an increased need for antioxidant vitamins because of the oxidative stress from smoking.1 Also
there may be a concomitant decreased intake because of
inappropriate dieting.13 Alcohol is used by more young
people than tobacco and illicit drugs.14 Alcohol abuse is
often associated with poor dietary intake of many essential
nutrients. In addition, alcohol can directly or indirectly
interfere with the digestion, absorption, and metabolism of
multiple essential water-soluble micronutrients.1,2,1517
Table 7-3 Predispositions to Deficiency of Water-Soluble Essential
Micronutrients*
Limited body store particularly in infants and young children
Inadequate endogenous synthesis
Decreased intake
Parenteral nutrition without water-soluble vitamins
Food faddism or severe dietary restrictions
Food refusal
Anorexia nervosa
Decreased bioavailability
Cooking and storage of foods at high temperatures and
prolonged periods
Addition of baking soda to vegetables
Decreased absorption and/or increased loss
Celiac disease, Crohn disease, cystic fibrosis, gastrointestinal
bypass surgery, and any malabsorption states
Nutrient-nutrient and nutrient-drug interaction (see Table 7-4)
Mixed predispositions including some or all of above
Hyperemesis gravidarum
Chronic renal dialysis
Alcohol abuse
Human immunodeficiency virus infection
* There is usually more than one predisposition to the development of
deficiency state.
Occurs during production shortage of parenteral multivitamin
preparation.
Most deficient states are associated with deficiencies in

more than one water-soluble essential micronutrient. There
are many potential predispositions to the development of
deficiency states and multiple predisposing factors may be
present (Table 7-3). Deficiency of multiple micronutrients is
commonly associated with human immunodeficiency virus
(HIV) infection or acquired immunodeficiency syndrome
(AIDS). It is likely a complex interplay of primary dietary
deficiency, deficiencies secondary to antiretroviral-induced
or concomitant diarrheal diseases, and inflammationsuppressed circulating nutrient biomarkers. Micronutrient
supplementation probably provides some overall benefits with respect to growth in children and pregnancy
outcomes.18,19 However, not all children with HIV infection
59
have micronutrient deficiencies, 20 particularly in developed

countries, and it is at least theoretically possible that certain
micronutrients might exacerbate HIV infection.18,21 Certain
drugs including chronic diuretic therapy through its actions
on excretion or metabolism of certain nutrients also predisposes individuals to deficiency states (Table 7-4). Thus, the
management of deficiency states must take into account all
potential predisposing factors.13,22
Isolated water-soluble vitamin deficiency is rare.
However, biochemical deficiency of vitamin B12 as indicated
by increased urinary methylmalonic acid has been reported
in 2- to 14-month-old infants predominantly fed human
milk from vegan mothers.23 Thiamin deficiency with cardiac
failure and encephalopathy was reported during a shortage
of multivitamin preparation for patients requiring total
parenteral nutrition.24 Inborn errors of metabolism associated with various aspects of digestion, absorption, transport,
and metabolism of specific essential micronutrients also
may result in deficiency of the specific micronutrient. These
heritable predispositions to deficiency or dependency states
have been reported for niacin, vitamin B6, folate, vitamin
B12 , biotin, and vitamin C and the number of disorders is
expected to increase with improvements in molecular diagnostic techniques.
Clinical manifestations of deficiency states may overlap
and biochemical indicators of deficiency may be affected by
laboratory technique. Normal ranges of laboratory values
may vary with life stages and possibly other physiologic
factors such as gender. Thus, interpretation of nutrient
status must take into account these variables.
Management of Deficiency State

andSupplementation
Treatment of deficient state requires an understanding

of the primary cause, the possibility of deficiency of other
nutrients, and concomitant therapies that may interfere
with effective replacement therapy. The initial treatment
may require an amount of micronutrient that is 10- to
100-fold or greater than the daily requirement and delivered via a route that will ensure delivery to the tissues, for
example, parenteral or intranasal delivery rather than oral if
there is a significant malabsorption state. Correction of the
underlying cause if possible, continued monitoring for clinical response, and normalization of laboratory parameters
are warranted. Thus, management of deficient state should
be individualized taking into account the cause, concomitant diet, and non-nutritional therapy. Close monitoring of
patients requiring total parenteral nutritionparticularly
those patients with abnormal gastrointestinal losses, organ
60
Table 7-4 Characteristics of Water-Soluble Essential Micronutrients*

Adult
Tissue
Store
Biological
Half-life
Major
Interactions
with Other
Nutrients
Interactions
with Drugs
Deficiency
Major Clinical
Manifestations
DeficiencyBiochemical
Erythrocyte (RC), Blood
(WB), Plasma (P)
Toxicity
Thiamin (B1)
~30 mg
918 d
Not available
Excess alcohol
& caffeine,
diuretics
Beriberi: wet,
dry. Wernicky
Encephalopathy
RC or WB Thiamin
Rapid injection:
anaphylactoidlike reaction
Riboflavin
(B2)
Very low
Minutes
Folate,
pyridoxine,
niacin
Ariboflavinosis:
pharyngitis,
cheilosis, angular
stomatitis,
glossitis,
seborrheic
dermatitis
Niacin (B3)
Not
available
45 min
Riboflavin,
pyridoxine
Anticholinergic,
tricyclic
antidepressant,
phenothiazines,
phenytoin,
probenecid,
thiazide diuretics,
doxorubicin
Isoniazid
B6
(Pyridoxine)
160 mg
assume
muscle has
80%
1228 mg,
liver has
~50%
25 d
Riboflavin,
niacin, folate,
zinc
Isoniazid, L-dopa
Erythrocyte
~8 wk
B12
Antifolate
medications
B12
(cobalamin)
23 mg,
liver has
50%+
6d
Folate
Vitamin C
2g
840 d
Glutathione,
tocopherol,
flavanoid, iron,
copper
Not
available
Bile acid
sequestrants,
H2 receptor
antagonist,
proton pump
inhibitors
Aspirin, warfarin,
proton pump
inhibitors
Folate
Not
available
Not
available
Biotin
Not
available
2h
Avidin binds
(postingestion biotin
elimination)
Not
available
Choline
Not
available
43 h
Not
available
* Insufficient data to provide quantitative data in some cells.

Selected list. For updated list.9, 35
Pellegra: diarrhea, RC nicotinamide adenine

dementia,
dinucleotide:nicotinamide
dermatitis
adenine dinucleotide
phosphate ratio; 24 h U
niacin & its metabolites
Seizures
P pyridoxal phosphate,
RC Aspartate & alanine
transferase saturation
Pantothenic
acid
Folate
pyrophosphate (TPP);
RC transketolase activity
with TPP
RC Riboflavin; RC
erythrocyte glutathione
reductase activity
coefficient with FAD
stimulation; 24 h urine
riboflavin
Not
available
Seizures,
neuromotor
disorder,
developmental
delay,
megaloblastic
anemia
Macrocystic
megaloblastic
anemia,
Nervous system
involvement
Scurvy
Vasodilatory,
nausea &
vomiting,
hepatitis,
neurovisual
disturbance,
glucose
intolerance
Peripheral
sensory
neuropathy
RC folate, P
Homocysteine
Exacerbates
B12 deficient
neuropathy
P B12, P & U
Methylmalonic acid & P
Homocysteine
Cyanocobalamin
worsens Lebers
optic atrophy,
use hydroxy
cobalamin
P ascorbate < 0.2 mg/dL,

RC and leukocyte
Nausea,
abdominal
cramps, and
diarrhea
Not available
ascorbate
Gastrointestinal
and nervous
system
Seizures,
developmental
delay, rash,
alopecia
Non-specific
Photo-oxidation
of some amino
acids
No consistent changes in
RC, WB or P
U biotin,
3-hydroxyisovaleric acid
Not available
P, RC, and tissue choline
Hypotension,
cholinergic, fishy
odor
and phosphatidylcholine
failure, or pre-existing nutrient deficiencyis critical to the

clinical management. Fortification of selected nutrients,
such as folic acid in the diet, is effective in the improvement
of folate status of the population.
There is no evidence of adverse effect from the consumption of naturally occurring water-soluble nutrients in foods.
This is presumably in part the result of lowered fractional
absorption at high intakes. The increasing practice of
ingesting multinutrient supplements to provide an intake
similar to daily need has no documented long-term benefit
but is unlikely to result in any long-term side effects. Their
use does not compensate for poor food choices and inadequate diet. Furthermore, at high intakes of supplements
or if the individual has an underlying metabolic disorder
that enhances or interferes with the action of a specific
nutrient or the drug, clinical adverse effects may result from
nutrient-nutrient and drug-nutrient interactions (Table
7-4). Detailed descriptions of some of these interactions
may be obtained from multiple sources.1,2,5,6,9
There is limited understanding of the biochemical
and genetic mechanisms whereby impaired metabolism of
these essential micronutrients increases the risk for developmental anomalies and disease. Similarly, understanding
of the mechanisms whereby elevated intake of these nutrients protects against these pathologies is also limited.
Current initiatives to increase intake of some essential
nutrients such as folic acid in human populations to ameliorate developmental anomalies and prevent disease, while
effective, lack predictive value with respect to unintended
adverse outcomes. Systematic studies of excessive intake of
some water-soluble essential micronutrients for prolonged
periods are extremely limited.13 The lack of reported
adverse effects does not mean that there is no potential
for adverse effects from prolonged periods of high intakes.
Nevertheless sufficient data are available to set the upper
limit of intake for niacin, vitamin B6, folate, vitamin C, and
choline (Table7-2).
Specific Nutrients
Thiamin (Vitamin B1)
Chemically, thiamin consists of substituted pyrimidine and
thiazole rings linked by a methylene bridge. Thiamin exists
mainly in various interconvertible phosphorylated forms:
thiamin monophosphate (TMP), thiamin triphosphate
(TTP), and ~80% as thiamin pyrophosphate (TPP). TPP,
the coenzyme form of thiamin, is involved in 2 main types
61
of metabolic reactions: decarboxylation of -keto acids (eg,

pyruvate, -ketoglutarate, and branch-chain keto acids)
and transketolation (eg, among hexose and pentose phosphates). Thiamin requirement is a function of carbohydrate
intake and is critical to the metabolism of carbohydrates
and branched-chain amino acids, synthesis of neurotransmitters glutamate and -amino butyric acid, nicotinamide
adenine dinucleotide phosphate (NADPH), and the
pentose sugars deoxyribose and ribose.1 TPP is also present
in nerve membranes and activates a chloride channel for
nerve conduction.
Source
Thiamin in the diet includes free thiamin, phosphorylated
thiamin, and protein-phosphate complexes. Dietary sources
include enriched, fortified, or whole grain rice; pasta and
cereals; pork; eggs; yeast; legumes; and nuts. Thiamin is lost
during processing to white flour, from milling of brown rice,
and during cooking.
Thiamin in fortified foods and pharmaceutical preparations are usually thiamin salts: thiamin hydrochloride
and thiamin mononitrate. Thiamin supplement is available
in oral and injectable forms as thiamin salts or as part of
multivitamin preparations. Lipid-soluble thiamin derivatives called allithiamins are also available and may be better
absorbed at higher intakes.9
Absorption, Metabolism, and Excretion

Thiamin uptake by the small intestines and by cells within
various organs is mediated by a saturable, high-affinity
transport system. At high intake, absorption can occur
by passive diffusion. Following absorption mainly at the
jejunum, thiamin is transported by blood in both erythrocytes (~90%) and plasma. Non-phosphorylated thiamin is
weakly bound to plasma proteins. The liver appears to be
the major organ for phosphorylation of thiamin although
it can occur in all tissues. After an oral dose of thiamin,
peak urine excretion occurs in about 2 hours and is nearly
complete after 4 to 6 hours. However, the biological half-life
of the vitamin is much longer and estimated to be between
9 to 18 days. Total thiamin content in the adult human is
estimated to be ~30 mg.17
Deficiency State
Thiamin deficiency can occur with inadequate intake
particularly during PN without added water-soluble vitamins,24 or inadequate absorption, and excessive loss from
multiple causes. A state of severe depletion may occur in
less than 3 weeks from a strict thiamin-deficient diet but the
62
most common cause of thiamin deficiency in affluent countries is alcoholism.16,17 Alcohol abuse is often associated
with poor dietary intake of many essential nutrients, and
decreases the absorption and phosphorylation of thiamin.
Patients with end-stage organ failure especially of the liver
are at risk for deficiency of thiamin and multiple nutrients. A number of inborn errors of metabolism have been
described in which clinical improvements can be documented following administration of pharmacologic doses of
thiamin, such as thiamin-responsive megaloblastic anemia
with ringed sideroblasts. The latter is part of a clinical triad
including diabetes mellitus and sensorineural deafness,
associated with an autosomal recessive defect in thiamin
transporter.15
The classic clinical syndromes associated with
deficiency of thiamin include Beriberi or Wernickes
encephalopathy. Beriberi is traditionally classified as dry
or wet form. Dry beriberi is characterized by a symmet
rical peripheral neuropathy with progressive weakness,
muscle wasting, difficulty walking, and ataxia and is accompanied by paresthesia and loss of deep tendon reflex. Wet
beriberi is secondary to cardiomyopathic congestive cardiac
failure and edema. Infantile beriberi is characterized by
shock at 2 to 3 months in a breastfed child with or without
a preceding history of weak cry and poor feeding. It generally occurs in the exclusively breastfed infant whose mother
has a subclinical thiamin deficiency.25 Wernickes encephalopathy is characterized by altered consciousness as well
as the triad of ophthalmoplegia, nystagmus, and ataxia. It is
generally seen in adults with alcohol abuse and malnutrition
although it has been reported in infants and children. 25,26
Thiamin deficiency from feeding of unfortified soy
infant formula due to manufacturing error has been
reported.27, 28 Clinical presentation occurred between 2
and 12 months. Initial manifestations were non-specific
and included vomiting, lethargy, irritability, abdominal
distention, diarrhea, respiratory symptoms, developmental
delay, and failure to thrive. Respiratory and gastrointestinal
infections were noted in many of the reported cases. Classic
manifestation of ophthalmoplegia or death also occurred in
several infants.
Laboratory investigations include abnormal magnetic
resonance imaging at the frontal lobes, basal ganglia, periaqueductal region, thalami, and the mammillary bodies,
while magnetic resonance spectroscopy demonstrates
a characteristic lactate peak.28 Biochemical diagnosis of
thiamin deficiency is by low TPP in erythrocyte and whole
blood29 or by the transketolase activation test. 30 The latter
measures the whole blood or erythrocyte transketolase
activity at baseline which is increased after adding TPP if

the individual is deficient.
Acute symptomatic improvement occurs rapidly within
one day of treatment.27 However, neurodevelopmental
delay, particularly in receptive and expressive language, 31
and recurrent seizures32 have been noted up to 6 years of
follow up.
Supplementation
Prophylactic use of thiamin supplements may be warranted
in malabsorption disorders. Occasional reports of anaphylactic reaction with parenteral administration of thiamin
has been noted but toxic effects of thiamin excess have not
been studied systematically.1
Riboflavin (Vitamin B2)

Riboflavin (7,8-dimethyl-10-ribityl-isoalloxazine) is a
water-soluble, yellow, fluorescent compound. The primary
form of riboflavin is an integral component of the coenzymes flavin mononucleotide (FMN) and flavin adenine
dinucleotide (FAD), the predominant flavoenzyme in body
tissues. These coenzymes are involved in multiple oxidation-reduction reactions integral to carbohydrate, protein,
and fat metabolism, and are involved in the metabolism of
folate, pyridoxine, and niacin. Riboflavin-binding proteins
expressed in fetuses of different species are evidently essential to normal fetal development. 33
Source
More than 90% of dietary riboflavin is consumed as a
complex of food protein with FAD and FMN and lesser
amounts as free vitamin and traces of glycosides and esters.
Animal protein (meat, dairy, and eggs) as well as green
vegetables and fortified cereals are abundant sources.4 Riboflavin may be synthesized by colonic bacteria but the extent
of its contribution to human needs is not known. 33

FAD and FMN from dietary protein are released by gastric
acid digestion. They are then hydrolyzed to riboflavin by
non-specific pyrophosphatases and phosphatases in the
upper small intestine. Riboflavin absorption is relatively
poor compared to other water-soluble vitamins but is
increased when ingested along with other foods and in the
presence of bile salts. Some divalent cations, such as copper,
zinc, iron, and manganese, form chelates with riboflavin
and lower riboflavin absorption.
Most absorption occurs in the small intestine via an

active or facilitated transport system at low intakes and via
passive diffusion at high intakes. A small amount is absorbed
in the large intestine. 34 There is also a small component of
enterohepatic circulation.
Riboflavin is transported in the circulation bound to
albumin and immunoglobulins. It is phosphorylated to
FMN and FAD in most tissues, in particular, in the small
intestine, liver, kidney, and heart. Intracellular phosphorylation is regulated by thyroid hormone and production of
FAD is under negative feedback control. Very little riboflavin is stored in body tissues and the excess riboflavin is
excreted in the urine secondary to glomerular filtration and
active tubular secretion as riboflavin (~60% to 70%) and
as a variety of flavin-related products. Riboflavin is more
heat stable than thiamin but is very photosensitive. 34 It also
interacts with an extensive list of drugs35 (Table 7-4).
Deficiency State
Riboflavin deficiency is often accompanied by deficiencies of one or more of the other B vitamins. Chronically
limited dietary meat or dairy intake (including infants after
weaning) is a specific risk factor for riboflavin deficiency.
Riboflavin deficiency is also found in protein energy malnutrition states, such as Kwashiorkor and anorexia nervosa,
and in patients with other risk factors that are common to all
water-soluble micronutrients. Symptoms and signs of mild
deficient state can be non-specific. The more characteristic
features of severe deficiency state of ariboflavinosis include
pharyngitis, cheilosis, angular stomatitis, glossitis (magenta
tongue), and seborrheic dermatitis involving nasolabial
folds, flexural area of extremities, and the genital areas.
Diagnosis of riboflavin deficiency is by low erythrocyte riboflavin quantified by high-performance liquid
chromatography and low 24-hour excretion of riboflavin.
Erythrocyte glutathione reductase activity coefficient
from in vitro stimulation by FAD increased in the ranges of
>40%, 20% to 40%, and < 20% are considered as deficient,
low, and acceptable levels of riboflavin status. Biochemical
deficiency has been reported in infants receiving short-term
phototherapy. 36
Supplementation
Excess riboflavin turns urine yellow although there are no
demonstrated functional or structural adverse effects in
vivo after excess riboflavin intake. This is in part because of
the limited absorption of ingested riboflavin. Nevertheless,
it is theoretically possible that riboflavin increases photosensitivity to ultraviolet irradiation and excess riboflavin
63
will increase the photosensitized oxidation of amino

acids and proteins in infants receiving phototherapy for
hyperbilirubinemia.
Niacin (Vitamin B3)

Niacin refers to nicotinamide (nicotinic acid amide), nicotinic acid (pyridine-3-carboxylic acid), and derivatives that
exhibit the biological activity of nicotinamide. None of the
forms are related to the nicotine found in tobacco although
their names are similar. 37 The 2 major forms of niacin are
chemically modified in the mitochondria to form coenzymes nicotinamide adenine dinucleotide (NAD) and
nicotinamide adenine dinucleotide phosphate (NADP).
About 200 enzymes require the niacin coenzymes, NAD
and NADP, mainly to accept or donate electrons in the
energy-producing oxidation-reduction (redox) reactions.
NAD functions most often in energy-producing reactions during degradation (catabolism) of carbohydrate,
fat, protein, and alcohol. NADP functions more often in
biosynthetic (anabolic) reactions, such as in the synthesis of
macromolecules including fatty acids and cholesterol. Nonredox enzymatic reactions important to DNA repair, and
stress responses, cell signaling, transcription, regulation
or apoptosis, chromatin structure, and cell differentiation
require separation of the niacin moiety from NAD and integration of ADP-ribose in these functions.1,3,37
Source
Unlike most of the water-soluble vitamins, nicotinamide
can be synthesized in the liver and kidney from tryptophan. This process requires adequate amounts of riboflavin,
pyridoxine, and iron and is highly variable depending on
multiple other factors. For instance, tryptophan is used also
for protein synthesis which takes priority over NAD and
NADP synthesis. An estimated average of 60 mg of tryptophan produces 1 mg of niacin or niacin equivalent. However,
dietary intake of niacin is needed to meet the daily requirements. Good sources of niacin include yeast, meats, poultry,
red fish (eg, tuna and salmon), cereals (especially fortified
cereals), legumes, and seeds. Lesser amounts are found in
milk, green leafy vegetables, coffee, and tea. In corn and
wheat, niacin may be bound to sugar molecules as glycosides which significantly decrease niacin bioavailability. 38

Intestinal glycohydrolases catalyze the release of nicotinamide from NAD. Nicotinic acid and nicotinamide are
64
rapidly absorbed from the stomach and the intestine. They

enter cells by simple diffusion and also by sodium-dependent
facilitated transport across gut mucosa and erythrocytes.
The coenzymes NAD and NADP are synthesized in
all tissues. Extracellular nicotinamide appears to regulate
the tissue NAD but is itself under hepatic control. Hepatic
NAD is hydrolyzed to provide nicotinamide for tissues that
lack the ability to synthesize nicotinamide from tryptophan. Tissue store of niacin is in the form of NAD that is
not bound to enzymes or as nicotinamide adenine mononucleotide synthesized from tryptophan and nicotinic acid.
Excess niacin is methylated in the liver to N1-methyl-nicotinamide and excreted in the urine either unchanged or as its
2-pyridone derivative.
Deficiency State
Several conditions uniquely predispose to niacin deficiency.
These include carcinoid syndrome in which tryptophan is
preferentially oxidized to 5-hydroxytryptophan and serotonin; prolonged treatment with isoniazid which competes
with the pyridoxine-derived coenzyme required in the
tryptophan-niacin pathway; and Hartnups disease, an autosomal recessive disorder that interferes with the absorption
of tryptophan.
The classic manifestation of severe niacin deficiency is
pellagra, an Italian term meaning rough skin. It is characterized by the triad of diarrhea, dermatitis, and dementia. 39
Gastrointestinal manifestations include glossitis, angular
stomatitis, chelitis, and diarrhea in about 50% of patients.
Skin lesions begin as painful erythema in sun-exposed areas.
Vesicle or bullae formation may occur upon re-exposure to
sun and the skin eventually becomes rough, hard, and scaly.
Hair and nails tend to be spared. Neuropsychiatric manifestations include insomnia, fatigue, nervousness, irritability,
apathy, and memory impairment. Dementia and death may
occur in untreated cases.
Niacin status is determined by a decreased concentration of NAD relative to NADP in erythrocytes, and low
levels of excretion in 24-hour urine niacin and its metabolite N1-methyl-nicotinamide and its 2-pyridone derivative.
Supplementation
Niacin, as a supplement or pharmacologic agent used
primarily in the treatment of hyperlipidemia, can result
in clinical side effects. Both forms of niacin may result
in similar side effects although nicotinamide results in
less vasodilatory effects. Nicotinic acid as low as 30 mg
daily is associated with vasodilatory effects including
flushing, burning, tingling, and itching sensation, and
gastrointestinal effects of nausea and vomiting. Some

improvement may occur with gradual increase in dosage,
co-ingestion of food, or the slow-release form of supplement. Liver dysfunction is more common with slow-release
form. At high intakes of niacin, fulminant hepatitis and
encephalopathy, glucose intolerance, and ocular effects of
blurred vision, toxic amblyopia, macular edema, and cystic
maculopathy also may occur.1
Vitamin B6
Vitamin B6 comprises a group of 6 related compounds: pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM), and their
respective 5-phosphates (PLP, PNP, and PMP). The major
forms in animal tissues are PLP and PMP; plant-derived
foods contain primarily PN and PNP, sometimes in the
form of a glucoside.
PLP is a coenzyme for a multitude of enzymes involved
in amino acid metabolism including aminotransferases,
decarboxylases, racemases, and dehydratases. It is required
for the conversion of tryptophan to both niacin and the
neurotransmitter serotonin; from homocysteine to cysteine,
dopa to dopamine as well as the synthesis of the inhibitory
neurotransmitter gamma-aminobutyric acid. Pyridoxine
is a coenzyme for -aminolevulinate synthase, the ratelimiting first step in heme synthesis.
Source
Foods rich in pyridoxine include fruits and nuts (bananas,
cantaloupe, walnuts), plants (green leafy vegetables, broccoli, peas, carrots, rice husks, brown rice, maize, wheat germ,
yeast), and animal products (eggs, chicken, fish, beef), as
well as fortified cereals. Microbial synthesis of B6 is possible
but the extent to which its contribution to the physiological
need is not known.

Bioavailability of vitamin B6 in a mixed diet is ~75% with
nonphosphorylated B6 as the major form absorbed. Phosphatase-mediated hydrolysis of PLP and PMP precedes
absorption by a nonsaturable passive diffusion transport of
the non-phosphorylated form primarily at the jejunum and
ileum. Pyridoxine glucoside is absorbed after deconjugation
by a mucosal glucosidase and some is absorbed intact, then
hydrolyzed in various tissues. The unphosphorylated forms
of B6 are absorbed and then converted to 5-phosphate forms
by pyridoxal kinase primarily in the liver. PNP and PMP
are oxidized to PLP by PNP oxidase. PMP is also generated
from PLP via aminotransferase reactions. PLP is bound to

various proteins in tissues which protects it from the action
of phosphatases. Muscle, plasma, and erythrocyte (hemoglobin) have high capacity for PLP-protein binding.
When the capacity for protein binding is exceeded, free
PLP is rapidly hydrolyzed and non-phosphorylated forms of
B6 are released from the tissues into the circulation where
albumin is the major PLP-binding protein. Free PLP in the
circulation is dephosphorylated then reabsorbed or carried
in the erythrocyte. Vitamin B6 is found in various subcellular compartments but primarily in the mitochondria and
cytosol.
In humans, the major excretory form is 4-pyridoxic
acid which accounts for about half the B6 compounds in
the urine. At high doses of pyridoxine, much of the dose is
excreted unchanged. The bodys B6 content is estimated to
be about 167 mg based on muscle biopsy data and assuming
that muscle represents about 80% of the store. The overall
half-life of vitamin B6 is about 25 days but the muscle turnover for B6 is much slower.40
Deficiency State
Isolated deficiency of pyridoxine is rare because its metabolism is intimately involved with multiple other nutrients
including riboflavin, niacin, zinc, and folate. Special considerations for predisposition to lower plasma PLP may include
therapy with isoniazid and L-dopa (react with carbonyl
group of PLP); acetaldehyde but not ethanol decreases
net PLP formation and may compete with PLP for protein
binding. However, the extent to which these situations
increase B6 requirements is not known.
Clinical manifestations of the B6 deficient state
include seizures in infants fed milk formulas without
fortification by pyridoxine from error in the manufacturing41,42 and abnormal electroencephalogram in adults
from experimental B6 deficiency.43 Both are reversed with
reintroduction of B6. Intractable seizures during infancy
and childhood may respond to large doses of pyridoxine and
sometimes only to pyridoxal phosphate. The latter form may
be a result of mutations in the PNPO gene for pyridox(am)
ine 5-phosphate oxidase and present as neonatal epileptic
encephalopathy.44 Other clinical manifestations of B6 deficiency are non-specific and may include microcytic anemia,
glossitis, seborrheic dermatitis, and depression.
Plasma PLP is probably the best indicator of B6 status
because it appears to reflect tissue stores.45 Erythrocyte
aspartate and alanine aminotransferase saturation by PLP
or tryptophan metabolites is also a useful indicator of relative B6 status.
65
Supplementation
High-dose pyridoxine supplement of 2 to 6 g daily for 2 to
40 months46 or chronic intake even at doses < 500 mg/d47
may result in peripheral sensory neuropathy.
Folate (Vitamin B9)

Folate is a generic term for this water-soluble B-complex
vitamin. Most naturally occurring food folates are pteroyl
glutamates containing 1 to 6 glutamate molecules joined in
a peptide linkage to the -carboxyl of glutamate. Folic acid
(pteroylmonoglutamic acid) is the most oxidized and stable
form of folate. It consists of a p-aminobenzoic acid molecule
linked at one end to a pteridine ring and at the other end to
a glutamic acid molecule, and occurs rarely in food but is
the form used in vitamin supplements and in fortified food
products.
Folate is critical to the metabolism of nucleic and
amino acids and promotes cellular growth in general and
is necessary for the maturation of red cells. Folate is a
substrate (5-methyl-tetrahydrofolate) and vitamin B12 is
a coenzyme in the formation of 5,10-methylenetetrahydrofolate (MTHF) and thymidylate synthesis. In either a
folate or vitamin B12 deficiency, the megaloblastic changes
in bone marrow and other replicating cells result from lack
of MTHF. Onset of anemia is usually gradual, and clinical manifestation of anemia typically appears only at an
advanced stage of anemia but may be earlier in the elderly.
Folate and vitamin B12 deficiency are independent risk
factors for neurotube defects including anencephaly and
spina bifida.48
Source
Natural sources include fresh green vegetables, liver, yeast,
and some fruits. Folic acid is the only water-soluble vitamin
mandated as part of prenatal supplement for the prevention
of neurotube defects. The generally lower intake of vegetables
and fruits contributes to the potentially inadequate intake
of folate. Significantly improved folate status as indicated
by population survey of red cell and serum folate has been
reported since the Food and Drug Administration (FDA)
in 1998 required the addition of folic acid to all enriched
breads, cereals, flours, corn meal, pasta products, rice, and
other cereal grain products sold in the United States.49

Dietary folate equivalent has ~50% lower bioavailability
compared to folic acid. Food folates (polyglutamate
66
derivatives) are hydrolyzed by conjugase enzymes to monoglutamate forms, then enter various cells by membrane
carrier or folate-binding protein-mediated system. The folate
transporter derives from the SLC19 gene family of solute
carriers and shares structural homology with the thiamin
transporter.15 Monoglutamates, mainly 5-methyl-tetrahydrofolate, are metabolized in the liver and other tissues to
polyglutamate derivatives by the enzyme folylpolyglutamate synthetase. Polyglutamates are the forms retained in
various tissues or found in blood or bile and are the forms
needed for function as a coenzyme in single-carbon transfer
reactions.
Folate catabolism involves cleavage of intracellular and
circulatory polyglutamates to the monoglutamate form.
Approximately two-thirds of the folate in plasma is protein
bound and albumin accounts for ~50% of the bound folate.
Folates freely filter through the glomeruli, are secreted,
and reabsorbed by the renal tubules. The bulk of the urine
excretory products are folate cleavage products mainly
in the monoglutamate form. There is extensive enterohepatic circulation of folate. 50 The estimated total body folate
content is between 12 and 28 mg, of which ~50% is in the
liver.
Deficiency State
Patients receiving folate antagonists such as methotrexate
and other drugs that have antifolate activity including
pyrimethamine, trimethoprim, triamterene, trimetrexate,
and sulfasalazine require monitoring for folate status to
ensure adequate dietary intake or folate supplementation. Several inborn errors in folate metabolism (MTHF
reductase deficiency associated with mutations of alleles on
chromosome 1)51 as well as the presence of autoantibody to
folate receptor (cerebral folate deficiency)52 predispose the
affected individual to folate deficiency. Serum and red cell
folate concentration are low in the former and normal in
the latter. In cerebral folate deficiency, the transfer of folate
from plasma to cerebrospinal fluid is low and cerebrospinal
fluid MTHF concentration is low.
Clinical features of folate deficiency may begin during
infancy and include retarded psychomotor development,
poor social contact, decelerating head growth, hypotonia,
ataxia, dyskinesia, irritability, visual and hearing deficiency,
and seizures. Some neurological manifestations may be
reversible with folinic acid supplement. Symptomatology
from anemia may be present.
Deficiency states are confirmed with low red cell folate
which reflects tissue folate store. Plasma folate reflects
concurrent folate balance. Plasma total homocysteine
concentrations increase when folate status is inadequate to

convert homocysteine to methionine.
Supplementation
Excessive folate intake may precipitate or exacerbate
neuropathy in vitamin B12 deficient individuals.
Vitamin B12 (Cobalamin)

The term vitamin B12 is usually restricted to cyanocobalamin but can be used to refer to all potentially biologically
active cobalamins, a group of cobalt-containing compounds
(corrinoids) that contains the sugar ribose, phosphate,
and a base (5,6-dimethyl benzimidazole) attached to the
corrin ring. The cobalamin coenzymes active in human
metabolism exist as methylcobalamin and 5-deoxyadenosylcobalamin. Methylcobalamin is required for the methyl
transfer from MTHF to homocysteine to form methionine and tetrahydrofolate with the enzyme methionine
synthase. Adenosylcobalamin is required for isomerization
of L-methylmalonyl-CoA to succinyl-CoA with the enzyme
L-methylmalonyl-CoA mutase. An adequate supply of B12
is essential for normal blood formation and neurological
function.
Source
Cobalamin is found in animal foods including meat, fish,
poultry, cheese, milk, and eggs. Cereal and soy milks are
fortified with varied amounts of B12 . Vitamin B12 content
in breast milk is dependent on maternal diet and mature
milk has lower content than colostrum. In the United States
and Canada, both cyanocobalamin and hydroxocobalamin
are available commercially although cyanocobalamin is
most commonly used in supplements and pharmaceuticals.
Vitamin B12 can be synthesized by intestinal bacteria but
its contribution to body pool is not known but likely to be
limited.

Cobalamin absorption and cellular uptake require an
intact stomach, adequate transport proteins, pancreatic
sufficiency, and a normally functioning terminal ileum.11
Haptocorrin (HC), gastric intrinsic factor (IF) and transcobalamin (TC) are critical to B12 transport from food to cell.
IF and HC but not TC are glycosylated proteins. There is
increasing specificity for binding to cobalamin in the order
HC, TC, and IF. 53 Cobalamin released from food is bound
to salivary HC. After proteolysis of HC in the duodenum,
67
cobalamin is then bound to IF. The cobalamin-IF complex

is absorbed only in the ileum under physiological conditions via endocytosis mediated by a specific receptor. In
the enterocyte, the cobalamin-IF complex is degraded and
cobalamin is transported to the cells bound to TC and taken
up via endocytosis by a specific receptor on most cell types.
Vitamin B12 appears in circulation several hours after
ingestion. If the circulating B12 exceeds the B12 binding
capacity of the blood, the excess is excreted in the urine.
About 80% of circulating B12 is bound to the proteins
transcobalamin I (TCI) and the remainder to TCII or III.
TCII is the form that delivers B12 to the tissues (~50% taken
up by the liver) through specific receptors for TCII. HC in
the plasma cannot facilitate cellular uptake of cobalamin
except in hepatocytes.
There is an active enterohepatic circulation which
reabsorbs, in the presence of intrinsic factor, almost all B12
secreted into the bile. Unlike other water-soluble vitamins,
there is a large store of B12 primarily in the liver. The average
B12 content of liver is ~1 mcg/g in healthy adults. The average
total body pool of B12 is estimated to be 2 to 3 mg. Daily loss
of B12 is ~0.1 to 0.2% of the B12 pool regardless of the size of
the store, with the 0.2% value generally applicable to those
with pernicious anemia. 54
biochemical indicators of functional B12 deficiency state.

Plasma B12 is considered as a less sensitive indicator of B12
deficiency compared to other biochemical changes.
Deficiency State
Ascorbic acid is the enolic form of an -ketolactone

(2,3-didehydro-L-threo-hexano-1,4-lactone) and the 2
enolic hydrogen atoms give the compound its acidic character and provide electrons for its function as a reductant
and antioxidant. Vitamin C refers to both ascorbic acid
and dehydroascorbic acid. Ascorbic acid is the functional
and primary in vivo form of the vitamin. Ascorbate is the
free reduced form of ascorbic acid. Ascorbyl radical and
dehydroascorbic acid are the 1- or 2-electron oxidation
products which readily reduce back to ascorbic acid in vivo,
thus a relatively small amount of the vitamin is lost through
catabolism.
Vitamin C is known to be an electron donor for 8
human enzymes. Three enzymes participate in collagen
hydroxylation (also requires iron) and contribute to
the biosynthesis of other connective tissue components
including elastin, fibronectin, proteoglycans, bone matrix,
and elastin-associated fibrillin. Two enzymes along with
iron are required in carnitine synthesis; and 3 enzymes,
dopamine--hydroxylase, peptidyl-glycine monooxygenase,
and 4-hydroxyphenylpyruvatedioxygenase, are required in
hormone and amino acid biosynthesis.
Vitamin C is an effective antioxidant because of its
ability to donate electrons and its antioxidant effect operates
Breastfed infants of strict vegan mothers, children receiving

macrobiotic diets, and the elderly are at risk for B12 deficiency
as are individuals with the absence of intact stomach, ileum,
pancreatic exocrine function or intrinsic factor. 55 Chronic
use of proton pump inhibitors increases the risk for B12
deficiency by inhibition of intragastric proteolysis, thereby
inhibiting the release of B12 from food prior to binding
to haptocorrin and also inhibiting B12 binding to gastric
intrinsic factor. 56 Autoantibodies against parietal cell H+K+adenosine triphosphate causing loss of gastric parietal cells
or blocking the B12 binding site for intrinsic factor result
in B12 deficiency. Genetic defects that involve deletions
or defects of methylmalonic acid-CoA mutase, TCII, or
enzymes in the pathway of cobalamin adenosyllation have
been reported to be associated with B12 deficiency. 57
Clinical manifestations of B12 deficiency include macrocytic megaloblastic anemia and neurological problems. The
latter include ataxia, muscle weakness, spasticity, incontinence, vision problems, dementia, psychosis, and mood
disturbance. Impaired cognitive function has been demonstrated in adolescents with marginal cobalamin. 58
Decreased plasma B12 and elevated plasma and
urine methylmalonic acid and plasma homocysteine are
Supplementation
Short-term studies up to 4 months indicate that oral B12
supplement has similar efficacy to intramuscular treatment
for B12 deficiency. 59,60 B12 fortification of foods to improve
the populations B12 status55 has been advocated. Intranasal
delivery of B12 is possible but the bioavailability is ~10% of
intramuscular preparation. Periodic parenteral administration of high-dose B12 (1-5 mg) to patients with pernicious
anemia (lack of intrinsic factor) supports the lack of adverse
effects at high doses.
The use of cyanocobalamin is contraindicated in B12
deficient individuals at risk for Lebers optic atrophy, a
genetic disorder caused by chronic cyanide (present in
tobacco smoke, alcohol, and some plants) intoxication,
because the latter may increase the risk of irreversible optic
atrophy. Hydroxocobalamin, a cyanide antagonist, 61 can be
used instead of cyanocobalamin.1
Vitamin C
68
in the aqueous phase both intra- and extracellularly. It

participates in redox reactions with many other dietary and
physiological compounds including glutathione, tocopherol, flavonoids, and the trace metals iron and copper.
Antioxidation activities at the tissue level include protection of the eye, neutrophils, and sperm DNA among many
other tissues. In the circulation, it protects against oxidation of plasma low-density lipoprotein (LDL). Ascorbate
also provides antioxidant protection indirectly by regenerating other biological antioxidants such as glutathione
and -tocopherol back to their active state. Ascorbic acid
functions as a reducing agent for mixed function oxidases in
the microsomal drug-metabolizing system that inactivates
a wide variety of substrates, such as endogenous hormones
or xenobiotics including drugs, pesticides, or carcinogens
that are foreign to humans. The vitamin is involved in the
biosynthesis of corticosteroids and aldosterone and in the
microsomal hydroxylation of cholesterol to bile acids. 5 One
form of hereditary methemoglobinemia is reported to be
responsive to vitamin C.62
Source
Almost 90% of vitamin C in the typical diet comes from
fruits and vegetables. Citrus fruits, tomatoes, tomato juice,
and potatoes are major sources. Other sources include
brussel sprouts, cauliflower, broccoli, strawberries, cabbage,
and spinach. Vitamin C content of foods can vary with
growing condition, season, stage of maturity, cooking practice, and storage time prior to consumption. 22

Some 70% to 90% of usual dietary intake of ascorbic acid
is absorbed via a sodium-dependent active transport at low
gastrointestinal ascorbate concentrations, while passive
diffusion occurs at high concentrations. With large intakes
of vitamin C, unabsorbed ascorbate is degraded in the
intestine, a process that may account for the diarrhea and
intestinal discomfort. Dehydroascorbic acid is the form of
vitamin that primarily crosses the membranes of blood and
intestinal cells, after which it is reduced intracellularly to
ascorbic acid and localized mostly in the cytosol. Cellular
transport of ascorbic acid and dehydroascorbic acid is mediated by tissue-specific cellular transport systems which
allow for wide variation of tissue ascorbate concentrations.
High levels are maintained in the pituitary and adrenal
glands, leukocytes, eyes, and the brain, while low levels are
found in plasma and saliva.
Both intracellular and plasma vitamin C exist predominantly in the free reduced form as ascorbate monoanion.
Both the 1- and 2-electron oxidation products of the

vitamin are readily reduced back to ascorbic acid in vivo
chemically and enzymaticallyby glutathione, NADH,
and NADPH dependent reductases and relatively small
amounts of the vitamin are lost through catabolism.
Vitamin C is actively secreted in human gastric juice.
Proton pump inhibitor therapy lowers the concentration of
vitamin C in gastric juice and may reduce the bioavailability
of ingested vitamin C.
The kidney is capable of reabsorption of ascorbate but
renal excretion of ascorbate is greater with increased intake.
Aspirin may increase urinary ascorbate.6 Due to homeostatic regulation, the biological half-life of ascorbate varies
widely from 8 to 40 days and is inversely related to the
ascorbate body pool. A body pool of < 300 mg is associated
with scurvy while maximum body pools are estimated to be
about 2 g.
Deficiency State
In developed countries, population surveys show serum
vitamin C concentrations are significantly lower in smokers
and low-income persons, presumably reflecting the increased
oxidative stress of smokers and low dietary consumption of
vitamin C foods.63 Clinical manifestation of vitamin C deficiency is quite rare but has been reported in children with
severely restricted diets related to food faddism, psychiatric
or developmental problems, 64 or in children with end-stage
organ disease with severely compromised nutrition.65 It
also has been reported in young children who ingest only
well-cooked foods, few fruits and vegetables, and are supplemented with ultra heat-processed milk.66
The primary clinical manifestation of vitamin C deficiency is scurvy and reflects deterioration of elastic tissues.
Clinical features include follicular hyperkeratosis, petechiae, ecchymoses, coiled hairs, inflamed and bleeding
gums, perifollicular hemorrhages, and impaired wound
healing. Refusal to walk, with or without joint effusions and
arthralgia, dyspnoea, edema, weakness, fatigue, depression and Sjogren syndrome (dry eyes and mouth) also can
occur. In experimental subjects, gingival inflammation and
fatigue were among the most sensitive markers of deficiency
without being frankly scorbutic. Impaired bone growth,
disturbed ossification, and subperiosteal hemorrhage may
be present. Scurvy usually occurs at a plasma concentration
of < 0.2 mg/dL (11 mol/L) although leukocyte ascorbate concentration is considered a better measure of tissue
reserve than plasma ascorbate concentration and is the
preferred indicator of vitamin C status.67
Supplementation
Gastrointestinal disturbances such as nausea, abdominal
cramps, and diarrhea have been reported at vitamin C
intake of > 3 g/d probably as a result of the osmotic effect
of unabsorbed vitamin C.68 In vivo data do not clearly show
a causal relationship between excess vitamin C intake by
apparently healthy individuals and other adverse effects2
although increased urine oxalate excretion and development
of oxalate stones may be possible. However, individuals with
hemochromatosis, glucose-6-phosphate dehydrogenase
deficiency, and renal disorders may be more susceptible to
adverse effects of excess vitamin C intake, which include
excess iron absorption, pro-oxidant effects, and kidney
(oxalate) stone formation. There is also risk for reduced
vitamin B12 and copper levels, increased oxygen demand,
dental enamel erosion, allergic response,2 and blocking the
action of warfarin.6 Vitamin C intake of 250 mg/d or higher
has been associated with false negative result for stool and
gastric occult blood.69 High-dose vitamin C supplement
should be stopped before these laboratory tests.
69
pathway end products, CoA and acyl-CoA. CoA is hydrolyzed to pantothenic acid in a multiple-step reaction and is
excreted intact in the urine in proportion to dietary intake.
Deficiency State
Deficiency has been reported only with feeding semisynthetic diets70 or an antagonist to the vitamin, -methyl
pantothenic acid.71 Clinical manifestations may be nonspecific and include irritability, restlessness, fatigue, apathy,
malaise, sleep disturbances, nausea, vomiting and abdominal cramps, numbness, paresthesia, and staggering gait, and
increased sensitivity to insulin. Historically, pantothenic
acid was implicated in the burning feet syndrome that
affected prisoners of war in Asia during World War II.72
There are no data to support the use of whole blood,
plasma, or red cell concentrations as a marker of deficiency
state. Urinary excretion of pantothenic acid is strongly
dependent on dietary pantothenic acid.70
Supplementation
Pantothenic Acid (Vitamin B5)
There are no subgroups of population who are distinctly

susceptible to adverse effects of excess pantothenic acid.
Biotin (Vitamin B7)
Pantothenic acid is a component of coenzyme A (CoA)

which is involved in more than 70 enzymatic pathways.
CoA, in forms such as acetyl-CoA and succinyl-CoA, plays
an important role in the tricarboxylic acid cycle and in the
synthesis of fatty acids and membrane phospholipids, amino
acids, steroid hormones, vitamins A and D, porphyrin and
corrin rings, and neurotransmitters, and acetylation and
acylation of proteins and the synthesis of -tubulin.
Source
Pantothenic acid is widely distributed in foods and found
in high concentrations in organ meats, yeast, egg yolk, fresh
vegetables, whole grains, and legumes. Intestinal microflora can synthesize pantothenic acid but its contribution in
humans has not been quantified.

CoA in the diet is hydrolyzed in the intestinal lumen to
dephospho-CoA, phosphopantethine, and pantethine, with
the latter subsequently hydrolyzed to pantothenic acid.
Intestinal absorption of pantothenic acid occurs through a
saturable sodium-dependent active transport at low intakes,
while passive diffusion occurs at high intakes.
Tissue CoA synthesis is regulated primarily by panto
thenate kinase, an enzyme feedback inhibited by the

Biotin is a cofactor for 5 mammalian carboxylases. These
carboxylases catalyze the carboxylation of pyruvate to oxaloacetate which serves as an intermediate in the tricarboxylic
acid cycle, of propionyl-CoA to form D-methylmalonylCoA, then undergoes isomerization to succinyl-CoA and
enters into the tricarboxylic acid cycle, of acetyl-CoA to
malonyl-CoA, which serves as a substrate for fatty acid elongation; and in the degradation of leucine.
Source
Biotin is widely distributed in natural food stuffs but its
concentration varies substantially with liver having the
highest content; fruits and most meats contain small
amounts. The contribution of biotin synthesized by intestinal microflora to the bodys needs has not been defined.

Most dietary biotin is protein bound although it also exists
in free form. Biotinase releases the free vitamin from the
protein for absorption primarily in the proximal small
intestine but some occurs at the proximal colon. Absorption is by active transport at low concentrations and passive
diffusion at high concentrations. Avidin, a protein found
70
in appreciable amounts in raw egg white, binds to biotin

and prevents its absorption. Specific receptors are probably
involved in tissue uptake of biotin.
About half of biotin undergoes metabolism to bisnorbiotin and biotin sulfoxide before excretion. In human
urine and plasma, they are present in molar proportions
of ~3:2:1. Two additional minor metabolites, bisnorbiotin
methyl ketone and biotin sulfone, are also present in urine.
The urinary excretion and serum concentrations of biotin
and its metabolites increase roughly in the same proportion
in response to either intravenous or oral administration of
large doses of biotin.73
During normal breakdown of cellular proteins,
biotin-containing enzymes are degraded to biocytin
(-N-biotinyl-L-lysine) or short oligopeptides containing
biotin-linked lysyl residues. Biotin is released from these
oligopeptides by biotinidase and the biotin is reused.74
Deficiency State
Clinical deficiency of biotin is uncommon but has been
reported in individuals who consumed raw egg whites over
long periods75 or received total parenteral nutrition before
biotin supplementation.76 Infantile seizures either alone or
with other neurological or cutaneous findings, particularly
in the presence of ketolactic acidosis and organic aciduria,
are typical of biotinidase deficiency.77 Infants manifest
rash around the mouth, nose, and eyes as biotin deficiency
facies after several months of biotin-free total parenteral
nutrition. This rash may extend to ears and perineal orifices.
Alopecia totalis, hypotonia, lethargy, developmental delay,
and withdrawn behavior also may occur. Similar manifestations including ataxia and paresthesia may occur in older
children and adults. The list of inborn errors of metabolism
that result in biotin dependency and various degrees of
neurological and dermatologic abnormalities now extends
to holocarboxylase synthetase deficiency and a defect in
biotin transport.78
Biochemically, urine excretion of biotin is decreased
and 3-hydroxyisovaleric acid is increased.79 Plasma biotin
is not a sensitive indicator of inadequate biotin intake.
Reduced expression of SLC19A3, a potential biotin transporter, in leukocytes may prove to be a useful indicator of
marginal biotin deficiency.80
Biotinidase deficiency results in a relative biotin deficiency through lack of adequate digestion of protein-bound
biotin. It is treated with free (unbound) biotin at the estimated typical dietary intake of 50 to 150 mcg/d.81
Supplementation
Intakes of biotin at > 10 mg/d in a variety of subjects at
different life stages was not associated with documented
adverse effects.
Choline
Choline is the major source of methyl groups in the diet. It is
a precursor for acetylcholine, phospholipids, and the methyl
donor betaine. Functionally, it plays a critical role in the
structural integrity of cell membranes, methyl metabolism,
cholinergic neurotransmission, transmembrane signaling,
and lipid and cholesterol transport and metabolism.
Source
Choline in the diet is available as free choline or is bound as
water-soluble (phosphocholine, glycerophosphocholine) or
lipid soluble (sphingomyelin, phosphotidylcholine) esters.
It is widely distributed in foods with most in the form of
phosphatidylcholine in membranes. Foods especially rich
in choline compounds are milk, liver, eggs, and peanuts.
Lecithin, a phosphatidylcholine-rich fraction prepared
during commercial purification of phospholipids, is often
used interchangeably with phosphatidylcholine, and is
frequently added to food as an emulsifying agent and may
be a significant source of choline.
Endogenous synthesis of choline occurs via sequential
methylation of phosphatidylethanolamine catalyzed by the
enzyme phosphatidylethanolamine N-methyltransferase
and with S-adenosylmethionine as the methyl donor.
However, it is insufficient to compensate for the lack of
dietary choline.

Choline can be absorbed as lipid-soluble esters through the
lymph or as free choline into portal circulation. Pancreatic
enzymes can liberate choline from its ester forms. The
absorption through the small intestinal mucosa is by transporter proteins, which are probably unique for choline.
Some choline may be metabolized by intestinal bacteria to
form betaine (which may be absorbed and used as a methyl
donor) and methyl amines (which are not methyl donors).
Choline, folate, and B12 metabolism interactions are required
for methyl transfer from MTHF to homocysteine to form
methionine and tetrahydrofolate with the enzyme methionine synthase. Thus, the need for choline is modified by
methionine, folic acid, and vitamin B12 .
All tissues accumulate choline by diffusion and mediated transport and a specific carrier mechanism transports
free choline across the blood-brain barrier at a rate proportional to the serum choline concentration. The liver and
kidney also readily take up choline where a large proportion
is oxidized to betaine. The methyl groups of betaine can be
scavenged and reused in single-carbon metabolism.
Deficiency State
Though many foods contain choline, there is at least a
twofold variation in dietary intake in humans. When
deprived of dietary choline, most men and postmenopausal
women developed signs of organ dysfunction (fatty liver
or muscle damage), while less than half of premenopausal
women developed such signs.82 Individuals receiving
total parenteral nutrition devoid of choline but adequate
for methionine and folate developed hepatic steatosis
and elevated alanine aminotransferase. These abnormalities resolved in some individuals when a source of dietary
choline was provided.83 In addition to the gender influence,
there also appears to be genetic polymorphism and epigenetics influence for susceptibility to choline deficiency. 82
Fasting plasma, erythrocyte, and tissue content of choline
and phosphatidylcholine can be used as markers of choline
status.
Supplementation
The critical adverse effect from high intake of choline is
hypotension, with corroborative evidence on cholinergic
side effects (eg, sweating and diarrhea, and fishy body
odor).1
1. Bioavailability of water-soluble essential micronutrients is usually not affected by:

A. Temperature and duration of cooking
B. Storage
C. Exposure to light
D. Source from food or supplement
E. Maturity of the plant
2. Clinical status of water-soluble essential micronutrients may be affected by all of the following except:
A. Dietary intake
B. Intact pancreatic function
C. Intact stomach
D. Intact small bowel
E. Intact large bowel
71
3. Niacin can be synthesized from:

A. Valine
B. Threonine
C. Tryptophan
D. Methionine
E. Linoleic acid
4. Excess folate intake may exacerbate clinical manifestation of deficiency in:
A. Iron
B. Vitamin B6
C. Thiamin
D. Vitamin B12
E. Choline
5. Inherited metabolic defects in water-soluble essential
micronutrients may present in the neonate as:
A. Intractable seizures
B. Nutritional deficiency rickets
C. Bleeding tendency
D. Cataract
E. Blindness
References
1. Institute of Medicine, Food and Nutrition Board. Dietary

Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin
B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline.
Washington, DC: National Academy Press; 1998.
2. Institute of Medicine, Food and Nutrition Board. Dietary
Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press; 2000.
3. American Academy of Pediatrics Policy. In: Kleinman RE, ed.
Pediatric Nutrition Handbook. 6th ed. Elk Grove Village, IL:
American Academy of Pediatrics; 2009.
4. Northwestern University. Fact sheet: Nutrients and diet regimens. www.feinberg.northwestern.edu/nutrition. Accessed
May 28, 2009.
5. Drugs, Supplements, and Herbal Information, Medline Plus,
National Institutes of Health. http://www.nlm.nih.gov/
medlineplus/druginformation.html. Accessed June 25, 2009.
6. Micronutrient Information Center, Linus Pauling Institute,
Oregon State University. http://lpi.oregonstate.edu/infocenter/vitamins.html. Accessed May 28, 2009.
7. USDA Agriculture Research Service. Nutrient data laboratory.
http://www.nal.usda.gov/fnic/foodcomp/search/.
Accessed September 23, 2009.
8. Department of Health and Human Services. Food and Drug
Administration. Parenteral multivitamin products. Federal
Register. 2000;65:2120021201
9. Drug Facts and Comparisons 2009. St Louis, MO: Wolters
Kluwer Health.
72
10. Picciano MF, Dwyer JT, Radimer KL, et al. Dietary

supplement use among infants, children and adolescents
in the United States, 1999 2002. Arch Pediatr Adol Med.
2007;161:978985.
11. Basu TK, Donaldson D. Intestinal absorption in health and
disease: micronutrients. Best Pract Res Clin Gastroenterol.
2003;17:957979.
12. Rudatsikira E, Muula AS, Siziya S. Current cigarette smoking
among in-school American youth: results from the 2004
National Youth Tobacco Survey. Int J Equity Health. 2009 Apr
3;8:10
13. Seo DC, Jiang N. Associations between smoking and
extreme dieting among adolescents. J Youth Adolesc.
2009;38:13641373.
14. National Center for Chronic Disease Prevention and Health
Promotion. Healthy youth! Alcohol and drug use. http://
w w w.cdc.gov/HealthyYouth/alcoholdrug/index.htm.
15. Ganapathy V, Smith SB, Prasad PD.
SLC19: the folate/thiamine transporter family. Pflugers Arch. 2004;447:641646.
16. Singleton CK, Martin PR. Molecular mechanisms of thiamine utilization. Curr Mol Med. 2001;1:197207.
17. Ariaey-Nejad MR, Balaghi M, Baker EM, Sauberlich HE. Thiamin metabolism in man. Am J Clin Nutr.
1970;23:764778.
18. Mehta S, Fawzi W. Effects of vitamins, including vitamin A,
on HIV/AIDS patients. Vitam Horm. 2007;75:355383.
19. Allen LH, Peerson JM, Olney DK. Provision of multiple rather
than two or fewer micronutrients more effectively improves
growth and other outcomes in micronutrient-deficient children and adults. J Nutr. 2009;139:10221030.
20. Malik ZA, Abadi J, Sansary J, Rosenberg M. Elevated levels
of vitamin B12 and folate in vertically infected children with
HIV-1. AIDS. 2009;23:403407.
21. Nevado J, Tenbaum SP, Castillo AI, Snchez-Pacheco A,
Aranda A. Activation of the human immunodeficiency virus
type I long terminal repeat by 1 alpha, 25-dihydroxyvitamin
D3. J Mol Endocrinol. 2007;38:587601.
22. Ball GFM. Vitamins in Foods: Analysis, Bioavailability, and
Stability. Boca Raton, FL: Taylor and Francis; 2006.
23. Specker BL, Black A, Allen L, Morrow F. Vitamin B-12: low
milk concentrations are related to low serum concentrations
in vegetarian women and to methylmalonic aciduria in their
infants. Am J Clin Nutr. 1990;52:10731076.
24. Hahn JS, Berquist W, Alcorn DM, Chamberlain L, Bass D.
Wernicke encephalopathy and beriberi during total parenteral
nutrition attributable to multivitamin infusion shortage. Pediatrics. 1998;101:E10.
25. Luxemburger C, White NJ, ter Kuile F, et al. Beri-beri: the
major cause of infant mortality in Karen refugees. Trans R Soc
Trop Med Hyg. 2003;97:251255.
26. Davis RA, Wolf A. Infantile beriberi associated with
Wernickesencephalopathy. Pediatrics. 1958;21:409420.
27. Fattal-Valevski A, Kesler A, Sela BA, et al. Outbreak of
life-threatening thiamine deficiency in infants in Israel
caused by a defective soy-based formula. Pediatrics.
2005;115:e233e238.
28. Kornreich L, Bron-Harlev E, Hoffmann C, et al. Thiamine

deficiency in infants: MR findings in the brain. Am J Neuroradiol. 2005;26:16681674.
29. Talwar D, Davidson H, Cooney J, St JOReilly D. Vitamin
B(1) status assessed by direct measurement of thiamin
pyrophosphate in erythrocytes or whole blood by HPLC:
comparison with erythrocyte transketolase activation assay.
Clin Chem. 2000;46:704710.
30. Bayoumi RA, Rosalki SB. Evaluation of methods of coenzyme
activation of erythrocyte enzymes for detection of deficiency
of vitamins B1, B2, and B6. Clin Chem. 1976;22:327335.
31. Fattal-Valevski A, Azouri-Fattal I, Greenstein YJ, Guindy
M, Blau A, Zelnik N. Delayed language development due
to infantile thiamine deficiency. Dev Med Child Neurol.
2009;51:629634.
32. Fattal-Valevski A, Bloch-Mimouni A, Kivity S, et al. Epilepsy
in children with infantile thiamine deficiency. Neurology.
2009;73:828833.
33. Powers HJ. Riboflavin (vitamin B-2) and health. Am J Clin
Nutr. 2003;77:13521360.
34. Jusko WJ, Levy G. Absorption, metabolism, and excretion of
riboflavin-5-phosphate in man. J Pharm Sci. 1967;56:5862.
35. Erlich SD. Possible interactions with vitamin B2 (riboflavin).
(2007). www.umm.edu/altmed/articles/vitamin-b2-000989.
htm. Accessed May 28, 2009.
36. Amin HJ, Shukla AK, Snyder F, Fung E, Anderson NM,
Parsons HG. Significance
of phototherapy-induced riboflavin deficiency in the full-term neonate. Biol Neonate.

1992;61:7681.
37. Drake VJ, Jacobson EL (2007) Niacin. Micronutrient
Information Center, Linus Pauling Institute, Oregon State
University. http://lpi.oregonstate.edu/infocenter/vitamins/
niacin. Accessed May 28, 2009.
38. Gregory JF 3rd. Nutritional Properties and significance of
vitamin glycosides. Annu Rev Nutr. 1998;18:277296.
39. Hegyi J, Schwartz RA, Hegyi V. Pellagra: dermatitis,
dementia,and diarrhea. Int J Dermatol. 2004;43:15.
40. Coburn SP. Location and turnover of vitamin B6 pools and
vitamin B6 requirements of humans. Ann N Y Acad Sci.
1990;585:7685.
41. Coursin DB. Convulsive seizures in infants with pyridoxinedeficient diet. J Am Med Assoc. 1954;154:406408.
42. Bessey OA, Adam DJ, Hansen AE. Intake of vitamin B6 and
infantile convulsions: a first approximation of requirements of
pyridoxine in infants. Pediatrics. 1957;20:3344.
43. Kretsch MJ, Sauberlich HE, Newbrun E. Electroencephalographic changes and periodontal status during short-term
vitamin B-6 depletion of young, nonpregnant women. Am J
Clin Nutr. 1991;53:12661274.
44. Gospe SM Jr. Pyridoxine-dependent seizures: new genetic
and biochemical clues to help with diagnosis and treatment.
Curr Opin Neurol. 2006;19:148153.
45. Lui A, Lumeng L, Aronoff GR, Li TK. Relationship between
body store of vitamin B6 and plasma pyridoxal-P clearance: metabolic balance studies in humans. J Lab Clin Med.
1985;106:491497.
46. Schaumburg H, Kaplan J, Windebank A, et al. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N
Engl J Med. 1983;309:445448.
47. Parry GJ, Bredesen DE. Sensory neuropathy with low-dose

pyridoxine. Neurology. 1985;35:14661468.
48. Stover PJ. Physiology of folate and vitamin B12 in health and
disease. Nutr Rev. 2004;62:S3S12.
49. McDowell MA, Lacher DA, Pfeiffer CM, et al. Blood folate
levels: the latest NHANES results. NCHS Data Brief. 2008
May;(6):18.
50. Weir DG, McGing PG, Scott JM. Folate metabolism, the
enterohepatic circulation and alcohol. Biochem Pharmacol.
1985;34:17.
51. Tonetti C, Burtscher A, Bories D, Tulliez M, Zittoun J. Methylenetetrahydrofolate reductase deficiency in four siblings: a
clinical, biochemical, and molecular study of the family. Am J
Med Genet. 2000;91:363367.
52. Ramaekers VT, Rothenberg SP, Sequeira JM, et al. Autoantibodies to folate receptors in the cerebral folate deficiency
syndrome. N Engl J Med. 2005;352:19851991.
53. Wuerges J, Geremia S, Fedosov SN, Randaccio L. Vitamin
B12 transport proteins: crystallographic analysis of beta-axial
ligand substitutions in cobalamin bound to transcobalamin.
IUBMB Life. 2007; 59:722729.
54. Amin S, Spinks T, Ranicar A, Short MD, Hoffbrand AV.
Long-term clearance of [57Co]cyanocobalamin in vegans and
pernicious anaemia. Clin Sci (Lond). 1980;58:101103.
55. Allen LH. How common is vitamin B-12 deficiency? Am J Clin
Nutr. 2009;89:693S696S.
56. Termanini B, Gibril F, Sutliff VE, Yu F, Venzon DJ, Jensen
RT. Effect of long-term gastric acid suppressive therapy on
serum vitamin B12 levels in patients with Zollinger-Ellison
syndrome. Am J Med. 1998;104:422430.
57. Kapadia CR. Vitamin B12 in health and disease: part
I-inherited disorders of function, absorption, and transport.
Gastroenterologist. 1995;3:329344.
58. Louwman MW, van Dusseldorp M, van de Vijver FJ, et al. Signs
of impaired cognitive function in adolescents with marginal
cobalamin status. Am J Clin Nutr. 2000;72:762769.
59. Vidal-Alaball J, Butler CC, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12
deficiency. Cochrane Database Syst Rev. 2005;(3):CD004655.
60. Andrs E, Dali-Youcef N, Vogel T, Serraj K, Zimmer J. Oral
cobalamin (vitamin B12) treatment. An update. Int J Lab
Hematol. 2009;31:18.
61. Shepherd G, Velez LI. Role of hydroxocobalamin in acute
cyanide poisoning. Ann Pharmacother. 2008;42:661669.
62. Jamal A. Hereditary methemoglobinemia. J Coll Physicians
Surg Pak. 2006;16:157159.
63. Schleicher RL, Carroll MD, Ford ES, Lacher DA. Serum
vitamin C and the prevalence of vitamin C deficiency in the
United States: 2003-2004 National Health and Nutrition
Examination Survey (NHANES). Am J Clin Nutr. 2009; Aug
12 [Epub ahead of print].
64. Willmott NS, Bryan RA. Case report: scurvy in an epileptic
child on a ketogenic diet with oral complications. Eur Arch
Paediatr Dent. 2008;9:148152.
65. Samonte VA, Sherman PM, Taylor GP, et al. Scurvy diagnosed
in a pediatric liver transplant patient awaiting combined
kidney and liver retransplantation. Pediatr Transplant.
2008;12:363367.
73
66. Ratanachu-Ek S, Sukswai P, Jeerathanyasakun Y, Wongtapradit L. Scurvy in pediatric patients: a review of 28 cases. J
Med Assoc Thai. 2003;86:S734740.
67. Thurnham DI. Micronutrients and immune function: some
recent developments. J Clin Pathol. 1997;50:887891.
68. Wandzilak TR, DAndre SD, Davis PA, Williams HE. Effect
of high dose vitamin C on urinary oxalate levels. J Urol.
1994;151:834837.
69. Gogel HK, Tandberg D, Strickland RG. Substances
that interfere with guaiac card tests: implications for gastric aspirate
testing. Am J Emerg Med. 1989;7:474480.
70. Fry PC, Fox HM, Tao HG. Metabolic response to a pantothenic acid deficient diet in humans. J Nutr Sci Vitaminol (Tokyo).
1976;22:339346.
71. Hodges RE, Bean WB, Ohlson MA, Bleiler R. Human pantothenic acid deficiency produced by omega-methyl pantothenic
acid. J Clin Invest. 1959;38:14211425.
72. Glusman M. The syndrome of burning feet (nutritional
melagia) as a manifestation of nutritional deficiency. Am J
Med. 1947;3:211223.
73. Wolf B, Grier RE, Secor McVoy JR, Heard GS. Biotinidase
deficiency: a novel vitamin recycling defect. J Inherit Metab
Dis. 1985;8 (suppl 1):5358.
74. Mock DM, Heird GM. Urinary biotin analogs increase in
humans during chronic supplementation: the analogs are
biotin metabolites. Am J Physiol. 1997;272:E8385.
75. Baugh CM, Malone JH, Butterworth CE Jr. Human biotin
deficiency. A case history of biotin deficiency induced by
raw egg consumption in a cirrhotic patient. Am J Clin Nutr.
1968;21:173182.
76. Mock DM, Baswell DL, Baker H, Holman RT, Sweetman
L. Biotin deficiency complicating parenteral alimentation:
diagnosis, metabolic repercussions, and treatment. J Pediatr.
1985;106:762769.
77. Wolf B, Heard GS, Weissbecker KA, McVoy JR, Grier RE,
Leshner RT. Biotinidase deficiency: initial clinical features
and rapid diagnosis. Ann Neurol. 1985;18:614617.
78. Mardach R, Zempleni J, Wolf B, et al. Biotin dependency due to a
defect in biotin transport. J Clin Invest. 2002;109:16171623.
79. Mock NI, Malik MI, Stumbo PJ, Bishop WP, Mock DM.
Increased urinary excretion of 3-hydroxyisovaleric acid
and decreased urinary excretion of biotin are sensitive early
indicators of decreased biotin status in experimental biotin
deficiency. Am J Clin Nutr. 1997;65:951958.
80. Vlasova TI, Stratton SL, Wells AM, Mock NI, Mock DM.
Biotin deficiency reduces expression of SLC19A3, a potential
biotin transporter, in leukocytes from human blood. J Nutr.
2005;135:4247.
81. Wolf B, Heard GS, McVoy JR, Raetz HM. Biotinidase deficiency: the possible role of biotinidase in the processing of
dietary protein-bound biotin. J Inherit Metab Dis. 1984;7
(suppl 2):121122.
82. Zeisel SH. Gene response elements, genetic polymorphisms
and epigenetics influence the human dietary requirement for
choline. IUBMB Life. 2007;59:380387.
83. Buchman AL, Dubin MD, Moukarzel AA, et al. Choline
deficiency: a cause of hepatic steatosis during parenteral nutrition

that can be reversed with intravenous choline supplementation. Hepatology. 1995;22:13991403.
Fat-Soluble Vitamins
Winston Koo, MBBS, FACN, CNS, May Saba, PharmD, BCNSP, Mirjana Lulic-Botica, BSc, BCPS, and Judith Christie, RN, MSN
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Vitamin A. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .76
Sources
Absorption and Metabolism
Deficiency
Adverse Effects
Vitamin D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Sources
Deficiency
Adverse Effects
Vitamin E. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Sources
Deficiency
Adverse Effects
Vitamin K . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Sources
Deficiency
Adverse Effects
74
Learning Objectives
1. Understand the physiological basis for the function and

requirement for fat-soluble vitamins, as a group or for
each vitamin individually.
2. Understand the common risk factors and special
considerations in the predisposition to develop fatsoluble vitamin deficiency states.
3. Understand the common manifestations and diagnosis
of deficiency states for these fat-soluble vitamins.
4. Understand the potential risks of excessive intake of
fat-soluble vitamins.
Introduction
Achievement of adequate status for fat-soluble vitamins (A,

D, E, and K) depends on adequate intake, intestinal digestion
and absorption, cellular uptake, and metabolism. Vitamins
D and K are produced endogenously in substantial, but variable, amounts. Fortification of some vitamins (eg, vitamin
D) is widely practiced because of their limited distribution
in commonly consumed natural foods. However, a varied
dietary intake generally assures an adequate supply of fatsoluble vitamins meeting the dietary reference intake (DRI)
values in the normal population (Table 8-1).
Fat-soluble vitamins have metabolic interactions with
one another, and with other nutrients. These interactions
may affect the requirements for and biological actions of fatsoluble vitamins. For example, other antioxidants including
vitamin C, glutathione, and ubiquinols, can affect the regeneration of -tocopherol and the requirement for vitamin E;
zinc, energy, and protein metabolism affect vitamin A status
through their effect on production of retinol-binding protein
(RBP) and transthyretin; novel ligands (eg, secondary
bile acids and long-chain polyunsaturated fatty acids) can
FAT-SOLUBLE VITAMINS
activate vitamin D receptors leading to additional potential

biological function for vitamin D. Thus nutrient requirements and functions of fat-soluble vitamins should not be
considered in isolation; they must be considered as part of
total nutrition support.
Table 8-1 Dietary Reference Intake for Fat-Soluble Vitamins1-4
Life stage
Vitamin A
mcg RAE
(1 mcg = 3.3
IU)
VITAMIN D*
IU (1 mcg =
40 IU)
VITAMIN E
mg
VITAMIN K*
mcg
06 mo*
712 mo*
13 y
48 y
913 y
MALES
1418 y
FEMALES
1418 y
PREGNANCY
1418 y
LACTATION
1418 y
UL
400 (600)
500 (600)
300 (600)
400 (900)
600 (1700)
400 (1000)
400 (1000)
400 (2000)
400 (2000)
400 (2000)
4
5
6 (200)
7 (300)
11 (600)
2.0
2.5
30
55
60
900 (2800)
400 (2000)
15 (800)
75
700 (2800)
400 (2000)
15 (800)
75
750 (2800)
400 (2000)
15 (800)
75
1200 (2800) 400 (2000)
19 (800)
75
NA
For the individual:

* Adequate intake (AI) = observed or experimentally determined estimates
of nutrient intake by a group or groups of healthy people. Applicable for
all ages for vitamins D and K.
Recommended dietary allowance (RDA) = average daily dietary intake
sufficient to meet the requirement of 97% to 98% of healthy individuals
in a life stage and gender group. RDA = EAR + 2SDEAR or 1.2 EAR or 1.3
EAR.
For a group:
Estimated average requirement (EAR) = daily intake of a nutrient estimated
to meet the nutrient requirement of half of the healthy individuals in a life
stage and gender group.
Dose response assessment
UL = Upper limit for each life stage is indicated in parenthesis.
NA = not available
Consideration of special circumstances including the

effect of medication is warranted. Chronic glucocorticoid
and phenobarbital therapy affects vitamin D metabolism.
Alternately, marked alteration in vitamin K intake can
adversely affect coumarin anticoagulant therapy. Treatment
of extreme obesity with increasingly severe dietary restriction and bariatric surgery can result in decreased intake and
absorption of fat-soluble vitamins and other nutrients. The
use of bile salt or fat sequestrants, such as cholestyramine
and orlistat, as adjunct therapy for hypercholesterolemia,
hepatobiliary disorders, or extreme obesity has the potential
75
to decrease the absorption of all fat-soluble vitamins and

predisposes an individual to a deficiency state. Mineral oil
and other nonabsorbable lipids interfere with absorption
of fat-soluble vitamins. The adverse effects are potentially
greater during periods of increased metabolic demands (eg,
pediatric age ranges).
Certain groups of individuals are at risk for fat-soluble
vitamin deficiency. Individuals with any disease state that
impairs biliary and pancreatic secretions, intestinal mucosal
function, micelle formation, uptake into enterocytes,
and chylomicron secretion can impair the digestion and
absorption of all fat-soluble vitamins. Thus, severe hepatobiliary disorders, cystic fibrosis, and Whipples disease are
some of the diseases that predispose the individual to fatsoluble vitamin deficiency. Increasingly, inherited defects
in absorption or metabolism of various vitamins are documented to contribute to deficiency states in an individual.
Deficiency states from limited intake are more common
for vitamins A and D than for vitamins E and K. Restrictions
in the variety of foods due to limited financial resources or
fad diets is a risk factor for deficiency states. Concomitant
deficit in other nutrients is also common in these circumstances. The at-risk life stages include the very young and
adolescence. For example, prolonged exclusively breastfed
infants living at higher latitudes are at risk for vitamin D
deficiency. This is the result of lack of endogenous production from inadequate sunlight exposure and poor exogenous
intake because of the low vitamin D content of breast milk.
Pregnancy and lactation result in added demands to the
bodys nutritional requirements.
In certain disease states, supplementation of fat-soluble
vitamins under medical supervision is appropriate. Bioavailability of the enteral supplement may be improved with the
water miscible form or with alteration in the physical form, 5
although parenteral supplementation still may be needed
in some patients. In healthy populations, ingestion of fatsoluble vitamins, often in some combination of multiple
vitamins, is a common practice among adults and children.13,6 Supplementation in amounts similar to the daily
requirements (ie, doubling the intake to twice the daily
recommendation), is unlikely to result in any adverse effect,
although there is also no consistent benefit.
Adverse effects from consumption of fat-soluble vitamins naturally occurring in foods has been reported for
vitamin A.7 Chronic exposure to excess intake of vitamins
A and D is well known to have toxic effects affecting many
organ systems. In some cases, single exposure to large doses
of some fat-soluble vitamins may be toxic and occasionally
may be lethal. Certain individuals (eg, those with chronic
76
alcohol abuse and liver dysfunction) may be at greater risk

for adverse effects of excess intake or deficiency in fat-soluble
vitamins and other nutrients. Cigarette consumption
increases the demand on antioxidants in addition to its
other adverse effects.
Vitamin A
Vitamin A, or retinoids, refers to retinol and its derivatives
including synthetic analogs that have the same -ionone
ring and similar biological activities. They also include
provitamin A carotenoids that are the dietary precursor of
retinol. The all-trans isomer is the most common and stable
form although many cis isomers also exist.
Retinoids are critical to the maintenance of proper
vision in the signal transmission of images to the visual
cortex. They are necessary for cell differentiation and integrity of epithelial cells throughout the body including normal
differentiation of the cornea and conjunctival membranes,
as well as for the photoreceptor rod and cone cells of the
retina. Other critical functions include maintenance of
immune function, expression of various genes that encode
for structural- and extracellular matrix-proteins, enzymes,
RBPs and receptors, and embryonic development of hindbrain, eyes, ears, heart, and limbs. Provitamin A carotenoids
must be converted to retinoids to exert vitamin A function.
In addition, carotenoids are excellent antioxidants and may
have other biological properties unrelated to their vitamin
A activity.
Sources
Vitamin A is present in the diet as retinyl esters derived
almost exclusively from animal sources (liver and fish
liver oils, dairy products, kidney, and eggs). Most of the
vitamin A in breast milk is in the form of retinyl palmitate
in milk fat and is in greatest concentration in colostrum
and transition milk. The vitamin A content of breast milk
is generally lower in vitamin A deficient populations but is
still sufficient to prevent subclinical deficiency in exclusively
breastfed infants during the first 6 months. 8 Cows milk has
relatively lower vitamin A content than human milk and
averages ~40 International Units (IU)/g fat.9 The U.S. Food
and Drug Administration encourages dairy producers to
fortify reduced fat milk to 2000 IU/L.9 Infant formulas are
fortified with vitamin A at 250 to 750 IU/100 kcal.10 Hightemperature sterilization of milk increases isomerization
of trans- to cis-retinol by as much as 34%. 3 Provitamin A
carotenoids (mainly -carotene) are distributed widely in
green and yellow vegetables, oils, and fruits. Ripe, colored

fruits and cooked, yellow tuber vegetables are more efficiently converted to vitamin A compared to dark green
leafy vegetables. 3 Current estimates of vitamin A intake
from vegetable sources is about 26% to 34% based on retinol
activity equivalent (RAE). 3
Supplements are available as retinol, retinyl esters
(palmitate, acetate, and N-formyl aspartamate), retinaldehyde or -carotene, either alone or in a multivitamin, and in
oral and parenteral forms.11,12
Vitamin A activity is expressed as RAEs (1 mcg RAE
= 1 mcg all-trans-retinol = 2 mcg supplemental all-trans-carotene = 12 mcg dietary all-trans--carotene = 24 mcg
other dietary provitamin A carotenoids = 3.3 IU of vitamin
A activity). 3 The bioconversion of dietary provitamin carotenoids to RAE is estimated to be 12:1 (mcg:mcg) based
on the relative absorption efficiency of -carotene from
food and the functional carotene:retinol equivalency ratio.
One RAE for dietary provitamin A carotenoids other than
-carotene is lower and set at 24 mcg. 3 The use of mcg RAE
is preferred to mcg retinol equivalent (RE) or International
Units when calculating and reporting the amount of total
vitamin A in mixed foods or assessing the amount of dietary
and supplemental vitamin A consumed. RE was based on
the earlier erroneous two times higher estimate of bioconversion of dietary carotenoids. 3

The efficiency of absorption of preformed vitamin A is
about 70% to 90%. Vitamin A supplements, particularly
-carotene, are generally better absorbed than the dietary
vitamin sources. There may be a maturation lag in the ability
to absorb vitamin A in the preterm infant13 and the only
effective means to elevate plasma retinol concentrations
in preterm infants is via parenteral route.14 Dietary retinyl
esters are freed by acidic digestion and emulsified by bile
salts to form micelles. These micelles are transported to the
intestinal cells, where the retinyl ester is moved across the
mucosal membrane and hydrolyzed, re-esterified, and then
incorporated into chylomicrons within the cell and secreted
into lymph. At physiological concentrations, cellular uptake
and efflux of unesterified retinol by enterocytes is mediated by lipid transporters and saturable, whereas at high
pharmacological doses, the absorption of retinol is nonsaturable.15 Portal route of absorption is possible under
some circumstances.
Carotenoids are solubilized into micelles, from which
they are absorbed into duodenal mucosal cells. Absorption
of carotenoids is by passive diffusion and by a facilitated
process that requires, at least for lutein, the class B-type1

scavenger receptor (SR-B1).16 The intestine, liver, lung,
adipose, and other tissues possess ,-carotene 15,15
monooxygenase activity that allows the central cleavage of
the -carotene to form 2 molecules of retinal. The latter can
be converted to other retinoids. Eccentric cleavage of carotenoids by other enzymes is also possible. The absorption
efficiency of -carotene has wide inter-individual variation
and is usually < 20%. 3,16 It is higher in the presence of dietary
fat, from homogenized, juiced, or cooked vegetables which
allow the release of carotenoids, and during poor vitamin
A status. It is lower in the presence of intestinal infections
or infestations, and at high dietary carotenoid intake.17
-carotene significantly reduces lutein absorption when
given simultaneously. 3
Retinyl esters and carotenoids are transported to the
liver in chylomicron remnants. Apoprotein E and several
specific hepatic membrane receptors are required for the
uptake of chylomicron remnants by the liver. Retinyl esters
are hydrolyzed to retinol then bound to RBP for release
into the circulation. In the blood, holo-RBP associates with
transthyretin to form a trimolecular complex with retinol
in a 1:1:1 molar ratio for delivery to peripheral tissues.
Retinoic acid, nuclear retinoic acid receptor and retinoid X
receptors, cellular retinol, and retinoic acid binding proteins
I and II are critical to the function of retinoids. Carotenoids
are incorporated into very low density lipoproteins and
exported from the liver into the blood. They enter peripheral tissues via receptor uptake of lipoproteins and undergo
further metabolism.
Retinoids are stored in the liver and other tissues
including adipose tissue, bone marrow, lung, eye, kidney,
and other organs. When vitamin A intake is adequate,
>90% of total body vitamin A is present in the liver. Vitamin
A concentration of at least 20 mcg/g of liver in adults is
suggested as the minimal acceptable reserve.18 Regeneration of retinyl esters to form local storage pools (eg, in the
retinal pigment epithelium) also occurs.
Typically, the majority of vitamin A metabolites
are excreted in the urine and almost all of the excreted
metabolites are biologically inactive. Thus elevated plasma
concentrations of retinol, RBP, and transthyretin can occur
in chronic renal disease. Some retinoid metabolites are
conjugated with glucuronic acid or taurine in the liver for
excretion in bile.
Deficiency
Vitamin A deficiency is an endemic nutrition problem
throughout much of the developing world and affects the
77
health and survival of infants, young children, and pregnant and lactating women. These life-stage groups represent
periods when both nutrition stress is high and the diet is
likely to be chronically deficient in vitamin A. There are
numerous clinical effects of vitamin A deficiency (Table
8-2) but the most specific manifestation is xerophthalmia.
In developed countries, risk factors for vitamin A deficiency
include fat malabsorption conditions, strict vegan diets,
fad diets, and severely restricted preformed- or provitamin
A. Ethanol decreases liver vitamin A stores by increasing
release of hepatic retinol independent of dietary intake
and decreasing conversion of -carotene to retinol, thus
promoting vitamin A deficiency. 3
Table 8-2 Clinical Effects of Vitamin A Deficiency3,19,20
Xerophthalmia*
XN: Impaired dark adaptation (from slowed regeneration of
rhodopsin) to night blindness
XCj: Conjunctival dryness (xerosis), XB: keratinization (Bitots spot)
XCo: Corneal xerosis, XU/K: Corneal ulceration and/or keratomalacia
of any part, XSc: Corneal scar in central part, XSp: Corneal scar
in peripheral part
XF: Xerophthalmia fundus
Generalized dysfunction of cellular and humoral immunity
withincreased morbidity and mortality especially from
measlesanddiarrhea
Impairs iron mobilization from stores
Defects in lung function
Follicular hyperkeratosis
* Classification according to reference 19.
The level of retinol in the blood is under homeostatic

control over a broad range of body stores and reflects body
stores only when these are very low or very high. 8 In addition,
low plasma retinol concentration can result from an inadequate supply of dietary protein, energy, or zinc because of
decreased rate of synthesis of RBP; or from acute or chronic
infection because of decreases in the concentrations of the
negative acute phase proteins, RBP and transthyretin, even
when liver retinol is adequate. 3 Changes over time in plasma
retinol concentration distributions within a population can
be helpful to determine vitamin A status.8 Plasma retinol at
< 0.70 mol/L (1 mol/L = 28.6 mcg/dL) reflects vitamin
A inadequacy and at < 0.35 mol/L is considered as indicative of vitamin A deficiency.20 Simultaneous measurement
of plasma RBP is helpful to assess the vitamin A status.4
Other measures of vitamin A status such as the relative
dose response (RDR) and modified relative dose response
(MRDR), immune function tests, conjunctival impression cytology, dark adaptation test, pupillary response test,
78
and total liver reserve by isotope dilution, are abnormal in

clinical vitamin A deficiency. However, none of the above
measures have sufficient data relating to the usual dietary
intakes of individuals or populations to allow adequate
determination of the vitamin A status. Some of these tests
(eg, RDR and MRDR) are subjected to other factors such as
RBP production that can influence the outcome. 3,8,21
Night blindness significantly improved in a majority of
affected persons with vitamin A or -carotene supplementation.22 Vitamin A supplementation reduces the risk of
mortality among infants, young children, and pregnant and
postpartum women in developing countries. Intramuscular
vitamin A supplement has a modest effect on reduction in
oxygen requirement at 36 weeks postmenstrual age in those
with birth weights < 1 kg.14 Deficiency in other nutrients
also should be treated as they also may detrimentally affect
vitamin A status. For example, zinc deficiency decreases
the synthesis and secretion of RBP and transthyretin, and
synthesis of rhodopsin.
There is no evidence for a certain percentage of provitamin A carotenoids to meet the vitamin A requirement.
However, in view of the health benefits of consumption of
fruits and vegetables, 5 servings of fruits and vegetables
daily could provide 5.2 to 6 mg/d of provitamin A which is
~50% to 65% of the mens RDA for vitamin A. 3
Adverse Effects
There are substantial data on the adverse effects of high
vitamin A intake.18,23 Individuals with pre-existing liver
disease, hyperlipidemia, severe protein malnutrition, or
high alcohol intake, may be distinctly susceptible to the
adverse effects of preformed vitamin A intake. Short-term
large doses and even a single dose > 150,000 mcg in adults24
and proportionately lower in children can result in acute
toxicity characterized by nausea, vomiting, headache,
vertigo, blurred vision, muscular incoordination, and raised
intracranial pressure. In infants, there is also bulging of
fontanels.18,25 Animal studies demonstrated that a similarly
large single dose of vitamin A can be lethal.26
Chronic toxicity is usually associated with ingestion of
large doses > 30,000 mcg/day for months or years. Clinical
manifestations of chronic toxicity are varied and non-specific
and may include irritability, anorexia, skin desquamation,
and liver abnormalities including elevated liver enzymes,
fibrosis, and cirrhosis. In infants, additional non-hepatic
manifestations include bulging fontanel, craniotabes, and
laboratory findings of cortical hyperostosis, hypercalcemia,
and hyperphosphatemia, and metastatic calcifications may
occur at an intake between 5,500 to 6,750 mcg/d for 1 to
3 months. 3,25 In adults, there are inconsistent findings for

bone mineral loss and fractures. 3
Ethanol, while promoting a deficiency of vitamin A, also
enhances vitamin A hepatotoxicity.27 Care is needed with
vitamin A supplementation in patients with renal dysfunction to avoid vitamin A toxicity because the kidney is the
main route of excretion of vitamin A and its metabolites.
Both acute and chronic vitamin A toxicity are associated
with increased plasma retinyl ester concentrations. 28
In humans, teratogenic effects, particularly neural crest
defects, from naturally occurring metabolites of vitamin
A (trans-retinoic acid, 13-cis retinoic acid, and their oxoderivatives) are well documented in women exposed during
the first trimester. There are limited data to link teratogenic effects to high-dose preformed vitamin A (retinol
and retinyl esters) and insufficient data to determine the
presence of toxic non-teratogenic developmental effects. 29
Adolescents using vitamin A or derivatives for the treatment
of acne must be informed of the potential teratogenic effects
and counseled on the need to avoid pregnancy during this
therapy.
High -carotene intake has not been shown to cause
hypervitaminosis A but carotenodermia (a yellowish
discoloration of the skin from hypercarotenemia) has been
reported30,31 and is reversed when the intake is discontinued. Clinical intervention trial of -carotene supplement
based on its antioxidant activity has resulted in a significant
increase in the rate of lung cancer in smokers. This would
suggest that excessive intake of the provitamin A carotenoids may have unintended consequences on the complex
and intricately balanced natural antioxidant defense
system. 32 Also, the combination of excess -carotene and
ethanol may result in hepatotoxicity. 3
Vitamin D
Vitamin D (calciferol) refers to two fat-soluble seco-sterols:
cholecalciferol (vitamin D3) photosynthesized in the skin of
vertebrates, and ergocalciferol (vitamin D2) from the yeast
and plant sterol. The term vitamin D without the subscript
is frequently used generically to describe vitamins D2 and
D3 and, correspondingly, their metabolites. The parent
vitamin D compounds are biologically inert and require
two obligatory hydroxylation steps primarily in the liver
and kidney to 25 hydroxyvitamin D (25 OHD) and 1,25
dihydroxyvitamin D (1,25 (OH)2D), respectively. Quantitatively, 25 OHD is the major circulating metabolite. It is a
good marker of vitamin D status as it reflects the cumulative
effects of exposure to sunlight and dietary intake of vitamin

D. 33 At physiological concentrations, 1,25 (OH)2D is the
metabolite responsible for most, if not all, biological functions of vitamin D.
The classic actions of vitamin D include the maintenance of calcium homeostasis and bone mineralization in
the prevention of rickets in children and osteomalacia in
adults. These effects are mediated primarily through 1,25
(OH)2D binding of nuclear vitamin D receptor (VDR)
and from participation in various feedback loops involving
parathyroid hormone, calcitonin, and fibroblast growth
factor (FGF)-23. There is also 1,25 (OH)2D3 -mediated
gene regulation for several bone anabolic and resorbing
factors. VDR is widely distributed in numerous organ
systems and 1,25 (OH)2D3 -VDR effects at the local level
include immunomodulation, antimicrobial action, detoxification, cell proliferation, apoptosis regulation, insulin
secretion, skin integrity and -oxidation. 34 VDR stimulation independent of1,25 (OH)2D3 controls hair cycling and
brain development. Novel ligands other than 1,25 (OH)2D3
including lithocolic acid, curcumin, -tocotrienol, and
essential fatty acid derivatives may play additional specific
roles in physiological functions. 35 Despite the numerous
physiological functions mediated by VDR, the evidence for
major dysfunction from vitamin D deficiency other than
the classic actions of mineral homeostasis and bone mineralization islimited.
Biological activity of vitamin D is expressed in International Units based on bioassay using cholecalciferol. The
biological activity of 1 mcg of vitamin D is 40 IU and 1 mcg
25 OHD is 200 IU (ie, 5 times more potent than cholecalciferol).1 Both forms of vitamin D undergo the same metabolic
fate and function similarly at least for the classic actions
in the clinical prevention and treatment of rickets and
osteomalacia. 36,37 The role of vitamin D2 in other actions is
not well defined.
Sources
Endogenous synthesis of vitamin D3 requires exposure
to sunlight or irradiation in the ultraviolet B range. It is
extremely effective and a 10- to 15-minute whole-body
exposure to peak summer sun will generate and release up
to 20,000 IU vitamin D3 into the circulation. 38,39 However,
prolonged sunlight exposure increases the conversion of
previtamin D3 to inactive metabolites. Cutaneous production of vitamin D3 is substantially diminished by decreased
exposure to sunlight from seasonal changes, or time of day,
clouds, aerosols, thick ozone, higher latitude, aging, clothing,
sunscreen use, and melanin pigmentation.40 In dark-skinned
79
individuals, endogenous synthesis of vitamin D is possible

although the rate of production is lower than less pigmented
individuals. In any case, adequate endogenous production
of vitamin D3 is not assured for all populations because of
multiple factors that affect its endogenous synthesis.
Foods naturally rich in vitamin D are limited to the
flesh of fatty fish and fish liver oil, and the liver and fat from
aquatic mammals (eg, seals and polar bears). Thus, dietary
intake of vitamin D from foods comes primarily from fortified milk products and other fortified foods such as breakfast
cereals.41,42 The average intake of vitamin D is about 200 to
400 IU per day with children tending to have greater intake
than adults.41 Human milk and cows milk have very low
vitamin D content (< 50 IU/L). In the United States, a vast
majority of natural milk and all infant formulas are fortified
with vitamin D3 at 400 IU (10 mcg)/L9 and 40 to 100 IU/100
kcal,10 respectively. The amounts of vitamin D added to the
milk products were erratic during the early 1990s but more
recent testing of samples indicates that vitamin D fortification is more uniform.9
Vitamin D supplements as vitamin D2 or D3 are available
either alone or as multivitamins in oral preparations. The
parent vitamin D compound is available in parenteral form
only as part of a multivitamin. The more potent vitamin D
analog or hydroxylated vitamin D metabolites are available
in the oral and parenteral forms and are most often used as
part of the management of specific medical conditions. For
example, there are vitamin D analogs with minimal or no
calcemic effects that are used for their antiproliferative and
pro-differentiation actions.11,12

Intestinal absorption of vitamin D and its metabolites
requires normal bile and pancreatic secretions. Once
absorbed from the intestine, it is incorporated into chylomicrons and transported through the lymphatic system. Both
the endogenously synthesized and absorbed dietary vitamin
D and its metabolites are transported in the circulation
primarily by specific vitamin D binding protein and also
by albumin to the various tissues. Structural differences in
the parent vitamin D3 and vitamin D2 and their metabolites
alter their binding to the carrier protein vitamin D binding
protein (DBP) and their metabolism. Data on bioavailability
of vitamin D3 versus D2 is controversial with respect to the
maintenance of circulating 25 OHD concentrations.43,44
Circulating parent vitamin D is short-lived as it is either
stored in the fat or metabolized in the liver.45 In the hepatic
mitochondria, vitamin D 25 hydroxylase is regulated by
vitamin D and its metabolites. The half-life of circulating
80
25 OHD is 10 days to 3 weeks.46 Subsequent hydroxylation at the 1-carbon position to 1,25 (OH)2D in the kidney
is tightly regulated, principally through the action of parathyroid hormone in response to calcium and phosphorus
levels. The half-life of 1,25 (OH)2D is ~4 to 6 hours.47 It is
possible that activated macrophages, some lymphoma cells,
and cultured skin and bone cells also make 1,25 (OH)2D
and exert paracrine or autocrine actions. Excessive unregulated production of 1,25 (OH)2D by activated macrophages
and lymphoma cells is responsible for hypercalciuria and
hypercalcemia.
Enterohepatic circulation of vitamin D and its metabolites is present but probably has a limited role in their
conservation.48 Further hydroxylation at the 24-carbon of
25 OHD and 1,25 (OH)2D is the initial step in the metabolic degradation of these 2 vitamin D metabolites, with the
major metabolite (calcitroic acid) excreted in the urine.49
Deficiency
Clinical deficient states can result from lack of cutaneous
production of vitamin D3 with inadequate intake, impaired
absorption or metabolism of vitamin D to its active form
1,25 (OH)2D, or impaired recognition of 1,25 (OH)2D by
its receptor. Drugs such as glucocorticoids inhibit vitamin
D dependent calcium absorption. Phenobarbital and
phenytoin can alter the metabolism and circulating halflife of vitamin D metabolites. Chronic therapy with these
medications predisposes patients to the effects of vitamin
D deficiency.
Vitamin D deficiency results in inadequate mineralization, or demineralization, of the skeleton with occurrence
of rickets in the developing skeleton and osteomalacia in
adults. Rickets is characterized by widening at the ends of
long bones, rachitic rosary, deformations include bowed
legs and knock-knees, and frontal bossing of the skull.
In addition, secondary hyperparathyroidism occurs as a
homeostatic response to prevent a decrease in circulating
ionized calcium from vitamin D deficiency. Parathyroid
hormone mobilizes calcium from the skeleton resulting in
porotic bones, and conserves renal calcium but increases
phosphorus excretion as reflected by low or absent urine
calcium and increased urine phosphorus. Thus, vitamin D
deficiency is characterized by a low circulating concentration of 25 OHD, normal fasting circulating calcium with
low or low normal phosphorus, and elevated parathyroid
hormone, although hypocalcemia can occur in chronic
vitamin D deficiency. Increased bone turnover with
vitamin D deficiency is reflected by elevated bone alkaline
phosphatase, collagen, and non-collagenous bone proteins
including hydroxyproline, pyridinoline, deoxypyridinoline,

N- and C-teleopeptides, and osteocalcin in the circulation
and/or urine.
Based on the traditional Gaussian distribution, the
lower limit of serum or plasma 25 OHD is considered to be
in the range of 10 to 15 ng/mL (1 nmol/L = 0.4 ng/mL).
However, the lower limit in adults is recommended to be
~80 nmol/L (32 ng/mL) based on changes in biomarkers
such as parathyroid hormone, calcium absorption, and
bone mineral density38 and in children to be ~60 nmol/L
(24 ng/mL).4 Low circulating 25 OHD is common in children50 and adults.42 Non-calcium and non-bone related
clinical outcomes including cancer risk and immune defects
from population-based studies in vitamin D status are not
well defined. The widespread occurrence of low circulating
25OHD concentrations in children and the occasional clinical manifestation of rickets in non-supplemented infants
have prompted the recommendation to raise the daily
vitamin D intake to 400 IU.4 However, beneficial effects
of having values of serum or plasma 25 OHD concentrations higher than the current recommended levels remain
undefined.
Adverse Effects
Vitamin D toxicity from prolonged exposure to natural
sunlight has not been reported. Increased sunlight exposure
leads to a decrease in endogenous production of vitamin
D3 by conversion of previtamin D3 to inactive metabolites,
inhibition of 25-hydroxylase enzymes results in decreased
production of 25 OHD3, and stimulation of 24-hydroxylase enzyme results in increased metabolic degradation of
vitamin D metabolites. These processes contribute to the
prevention of hypervitaminosis D and vitamin D toxicity.
Excessive vitamin D intake from supplements can
result in hypervitaminosis D and is characterized by a
considerable increase in plasma 25 OHD in the range of
400 to 1250 mol/L (160500 ng/mL). 51,52 Other vitamin
D metabolites are also elevated although the increase in
1,25 (OH)2D is generally elevated to a much lower extent. 52
Clinical toxicity is manifested through hypercalcemia and
its multiple debilitating effects include polyuria, polydipsia,
depression, and metastatic calcification of soft tissues
including the kidney, blood vessels, heart, and lung. These
effects generally are seen with chronic supplementation in
excess of 20,000 IU daily53 although toxicity can occur at
lower doses. Toxicity from chronic intake of ergocalciferol
appears to require significantly higher doses. 54 It is possible
that this lower toxicity may be a result of its relatively low
bioactivity compared to cholecalciferol.
Vitamin E
There are 8 naturally occurring forms of vitamin E with
4 (-, -, -, and -) tocopherols, all in the RRR- form,
and 4 (-, -, -, and -) tocotrienols. The RRR- form of
-tocopherol is maintained in human plasma and occurs
naturally in foods. Eight different stereoisomers in equal
amounts are found in synthetic vitamin E (all rac-tocopherol): RRR-, RSR-, RRS-, RSS-, SRR-, SSR-, SRS-,
and SSS- forms with structural differences at the side chain
and at the ring/tail junction.
The various forms of vitamin E are not interconvertible in the human. The plasma concentration and biological
activity of different forms of vitamin E are dependent
primarily on the affinity of -tocopherol transfer protein
(-TTP) for them. RRR--tocopherol has the highest
affinity for -TTP. Other forms of vitamin E stereoisomers
have much lower binding affinity to -TTP.2 They may have
some biological functions55,56 and their intake are reported
as -tocopherol equivalent.2
Vitamin E functions primarily as a non-specific chainbreaking antioxidant acting as a peroxyl radical scavenger
that prevents the propagation of free radical reaction and
lipid peroxidation. 57 Vitamin E also may play important
roles in cell proliferation and differentiation, cell adhesion
and arachidonic acid cascade through inhibition of protein
kinase C activity, downregulating expression of intercellular cell adhesion molecule (ICAM-1) and vascular cell
adhesion molecule (VCAM-1), and upregulating expression of cytosolic phospholipase A 2 and cyclooxygenase-1.2
Current recommendations for vitamin E intake include
only the 2R-stereoisomeric forms of -tocopherol (RRR-,
RSR-, RRS-, RSS-) since they are maintained in human
plasma or tissue. Data on intakes from current surveys and
nutrient content of foods are presented as -tocopherol
equivalents (-TE) and include all 8 naturally occurring
forms of vitamin E, after adjustment for bioavailability
using previously determined equivalency. For example,
-tocopherol is estimated to have only 10% of the bioactivity of -tocopherol.
Based on the NHANES III (Third National Health and
Nutrition Examination Survey 1988 to 1994) data, ~80%
of the -TE from foods is contributed by foods containing
-tocopherol. Thus, the intake of -TE is usually greater
than the intake of -tocopherol alone.2 Milligrams of
-tocopherol in a meal including fortified food or multivitamins is based on the following conversion factors:
81
= mg -TE in a meal 0.8 and/or

= IU of the RRR--tocopherol compound 0.67
= IU of all rac--tocopherol compound 0.45
If diets vary considerably from what might be considered
typical in the United States or Canada, a conversion factor
other than 0.8 might be more appropriate.2
All forms of supplemental -tocopherol are used to
establish the tolerable upper intake level for vitamin E as all
forms of vitamin E are absorbed.2
Sources
The main dietary sources of vitamin E are edible vegetable
oils. All of the -tocopherol present in natural foods is in the
RRR--tocopherol form. Oils from wheat germ, sunflower,
safflower, canola, olive, and cottonseed contain > 50% of the
tocopherol as -tocopherol. Soybean and corn oils contain
~10 times as much -tocopherol as -tocopherol. Palm and
rice bran oils contain high proportions of -tocopherol,
as well as various tocotrienols. Meat, poultry, fish, dairy
products, nuts, grains and fruit, especially the oils or fatty
portions, are other sources of -tocopherol. 2 Colostrum and
breast milk are rich sources of vitamin E. 58 Infant formulas
are fortified with a minimum of 0.7 IU/100 kcal.10 Infant
formulas fortified with the natural form of -tocopherol have
better bioavailability compared to the synthetic forms. 59
Estimation of dietary intake of vitamin E is difficult
because the source of oil is not always known with certainty
and most nutrient databases, as well as nutrition labels, do
not distinguish among the different tocopherols in food.
Food preparation, such as deep frying using vegetable oil,
leads to chemical structure modification and may result
in functional discrepancy. 56 Vitamin E esters usually as
acetate of either natural RRR- or the synthetic mixture (all
rac-) of -tocopherol are used in food fortification, supplements, and pharmacological agents. Vitamin E supplements
are available alone or as multivitamins in oral preparation.
Vitamin E is available in parenteral form only as part of a
multivitamin.11 A water-miscible formulation of vitamin E,
tocopheryl polyethylene glycol succinate 1000 (TPGS), is
absorbed, metabolized, and reverses signs of vitamin E deficiency in children60 with severe fat malabsorption.

Reports of vitamin E absorption from the intestinal lumen
vary widely from 21% to 86%. In healthy humans, the esters
are hydrolyzed and absorbed as efficiently as -tocopherol.
The absorption of various forms of vitamin E is independent and shows similar apparent efficiency. 2 Efficiency of
82
absorption depends upon biliary and pancreatic secretions,

micelle formation, uptake into enterocytes, and chylomicron secretion. 2 Vitamin E absorption is facilitated by
dietary fat and is lowered following vitamin E supplementation.61 During chylomicron catabolism, some vitamin E
is distributed to all of the circulating lipoproteins. Chylomicron remnants, containing newly absorbed vitamin
E, are taken up by the liver. The high affinity of hepatic
-TTP to -tocopherol over all other vitamin E isomers is
responsible for the preferential secretion of -tocopherol
with very low-density lipoprotein from the liver, 62 which is
the main determinant of plasma vitamin E concentrations.
Adipose tissue and muscle are other major storage sites for
vitaminE.
Vitamin E rapidly transfers between lipoproteins and
between lipoproteins and cell membranes, which may
enrich cell membranes with vitamin E. The human plasma
phospholipid transfer protein accelerates this process.63 The
RRR-stereoisomer has roughly twice the availability of the
all-rac forms. Tissue -tocopherol concentrations largely
reflect changes in plasma concentrations of -tocopherol.64
The 4 tocopherols are ultimately degraded by omegaoxidation and subsequent beta-oxidations followed by the
elimination of the metabolites in the bile and in the urine.
Excess -tocopherol as well as forms of vitamin E not preferentially used is excreted unchanged in the stool and in bile.
The decreased intestinal absorption and increased excretion of urinary vitamin E metabolites may limit the rise in
plasma -tocopherol (~ threefold) and vitamin E supplements providing > 150 to 200 mg daily may not promote
higher tissue concentrations.65
When vitamin E intercepts a radical, -tocopherol is
oxidized to the tocopheryl radical, a 1-electron oxidation
product. A tocopherol radical can be reduced (ie, to regenerate -tocopherol) by other antioxidants including vitamin
C, glutathione, and ubiquinols. The tocopherol radical can
undergo further metabolism and is excreted in urine. It also
may act as a prooxidant in the absence of a water-soluble
antioxidant and oxidize other lipids in vitro. Whether this
occurs in vivo is inconclusive. Vitamin E compounds other
than RRR--tocopherol are preferentially metabolized and
excreted.2
Deficiency
Vitamin E requirements increase with increased intake of
polyunsaturated fatty acids, high-level physical activity, and
cigarette smoking. However, the extent of increased requirement and the compensatory effects of other antioxidants
are not defined. Intake of plant phenolic compounds and
flavonoids may add to the total antioxidant pool. Cellular

redox cycling is coupled to the energy status of the organism.
Thus dietary deficiencies of niacin or riboflavin might result
in insufficient reducing equivalents for recycling oxidized
products.2
Clinical deficiency from low dietary intake of vitamin E
in normal individuals without undue oxidative stresses has
not been reported.2 Clinical vitamin E deficiency occurs
with fat malabsorption syndromes or with genetic defect
in -TTP or abetalipoproteinemia where there is decreased
hepatic reserve and circulating vitamin E.
Vitamin E deficiency causes axonal degeneration of
the large myelinated axons and results in posterior column
and spinocerebellar symptoms. Peripheral neuropathy is
initially characterized by areflexia, with progression to
ataxic gait, and by decreased vibration and position sensations. Ophthalmoplegia, skeletal myopathy, and pigmented
retinopathy also may occur.60 Neurological symptoms
can progress if untreated and may be reversed if treated
early. Increased erythrocyte fragility in vitro and hemolytic anemia with vitamin E deficiency are reversible with
adequate replacement of vitamin E.
Plasma -tocopherol is decreased in vitamin E depleted
subjects and a level > 12 mol/L (0.5 mg/dL; 1 mol/L
= 0.042 mg/dL) is consistent with vitamin E adequacy. 2
In subjects with elevated serum lipids, for example in
cholestasis, a ratio of serum -tocopherol to serum total
lipids of < 0.6 mg/g indicates vitamin E deficiency regardless of serum -tocopherol concentrations. In subjects with
normal serum lipid concentrations (328573 mg/dL),
corrections are not necessary to assess whether -tocopherol
concentrations are within the normal range. 60,66 Hydrogen
peroxide induced hemolysis and lipid peroxidation
biomarkers in plasma, urine, or breath are elevated during
vitamin E depletion and are normalized upon vitamin E
repletion. However, these markers are non-specific and may
vary with intake of other antioxidants.
Routine supplementation of vitamin E is recommended
for specific disorders. However, there are no conclusive data
to support a high intake of vitamin E in the management
of chronic illnesses involving the cardiovascular system,
diabetes mellitus, cancer, central nervous system, cataracts,
or immune function.2
Adverse Effects
All forms of vitamin E are absorbed and could contribute
to vitamin E toxicity although not all forms are maintained
in plasma. Normal adults appear to tolerate oral tocopherol
intake of 100 to 800 mg/d67 but adverse effects from the
83
consumption of vitamin E as a supplement, food fortifier,

or pharmacological agent are possible. There are contradictory reports in humans on hemorrhagic complications
from high vitamin E intake. It is possible that individuals
deficient in vitamin K or on anticoagulant therapy are at
an increased risk for coagulation defects. 2 Preterm infants
with birth weights < 1.5 kg with elevated plasma vitaminE
at a mean of 5.1 mg/dL have an increased incidence of
sepsis and necrotizing enterocolitis.68 Plasma -tocopherol
concentrations are not informative for assessing adverse
effects because they plateau at ~3 to 4 times the values for
non-supplemented individuals. 2
prevalent in margarines, infant formulas, and prepared

foods. Long-chain menaquinones are produced in substantial amounts endogenously but are probably insufficient to
meet the daily requirement for vitamin K.72 Vitamin K is
present in low concentrations in breast milk (< 5 mcg/L).
Commercial infant formulas are fortified with vitamin K
(50100 mcg/L) based on a minimum of 4 mcg/100 kcal.10
Intravenous fat emulsions are another source of vitamin K
although the content varies with composition of the fat emulsion and manufacturing process.73 Vitamin K supplement is
available alone or as part of many, but not all, multivitamin
preparations in oral and parenteral forms.
Vitamin K

There are 2 naturally occurring compounds with vitamin
K activity: phylloquinone (vitamin K1) from plants and
long-chain menaquinones (vitamin K 2) synthesized from
intestinal bacteria. Menadione (vitamin K 3) is chemically synthesized and has better water solubility than the 2
natural forms. Structural differences in the isoprenoid side
chain govern many facets of the metabolism of K vitamins,
including the way they are transported, taken up by target
tissues, and subsequently excreted.69
Vitamin K in its reduced form is a cofactor for gammaglutamyl carboxylase enzymes responsible for the
posttranslational conversion of specific glutamic acid (Glu)
residues to -carboxyglutamyl (Gla) residues in a subclass
of proteins known as vitamin K dependent proteins (also
known as -carboxylated proteins or Gla-proteins). The
major Gla proteins include certain proteins of the blood
coagulation system: prothrombin (coagulation factor II),
factors VII, IX, and X, protein C, protein S, and protein Z;
and proteins expressed in mineralized tissues: osteocalcin
and matrix Gla-protein.70,71 Other putative non-cofactor
functions of vitamin K include suppressing inflammation,
preventing brain oxidative damage, and playing a role in
sphingolipid synthesis. 3,71
Sources
Vitamin K content in most foods is very low (< 10 mcg/
100 g), and the majority is obtained from a few leafy green
vegetables and 4 vegetable oils (soybean, cottonseed, canola,
and olive) that contain high amounts. Hydrogenation of
plant oils to form solid shortenings results in some conversion of phylloquinone to 2,3-dihydrophylloquinone but
it is uncertain whether these forms are metabolically and
functionally identical. These forms of vitamin K are most
Phylloquinone absorption in the jejunum is dependent

on the presence of bile and pancreatic secretions and is
enhanced by dietary fat. Free phylloquinone is almost
completely absorbed but absorption of vitamin K from food
sources is much lower and is generally < 20%. 3 Absorbed
phylloquinone is secreted into lymph and enters the circulation. In the postprandial state, phylloquinone is transported
mainly by triglyceride-rich lipoproteins (TRLs) and longchain menaquinones mainly by low-density lipoproteins.
Liver uptake and turnover of phylloquinone is rapid. TRLborne phylloquinone uptake by some extrahepatic tissues
(eg, osteoblasts) is an apoE-mediated process with the
LRP1 receptor playing a predominant role.
Both phylloquinone and menaquinones activate the
steroid and xenobiotic receptor that initiates their catabolism. Vitamin K is excreted primarily in bile and also in
urine after oxidative degradation of the phytyl side chain
followed by glucuronide conjugation. The liver has the
highest concentration of phylloquinone and significant
amounts are also present in the heart and other tissues.
Hepatic reserve is rapidly depleted from restricted dietary
intake.
Deficiency
Individuals at risk for vitamin K deficiency include those
with severe fat malabsorption conditions (eg, hepatobiliary
disorders) or after bariatric surgery, especially those with
severe diet restriction. Prolonged use of broad-spectrum
antibiotics may decrease vitamin K synthesis by intestinal
bacteria. Long-term differences in dietary vitamin K intake
modulate the response to coumarin anticoagulants, which
act by blocking the vitamin K recycling. Elevated intake of
vitamin E antagonizes vitamin K action probably through
its effect on vitamin K absorption and metabolism.2,74
The classic sign of vitamin K deficiency is an increase in
84
prothrombin time, and in severe cases, a hemorrhagic event.

Both abnormalities are responsive to vitamin K. However,
other than the exclusively breastfed infant without vitamin
K prophylaxis therapy, it is almost impossible to achieve this
level of deficiency by simple restriction of vitamin K intake
in any nutritionally adequate, self-selected diet in healthy
individuals. The role of vitamin K in matrix-Gla formation
would support its physiological activity in the metabolism
of multiple organ systems but to date its role in chronic
diseases such as osteoporosis and atherosclerosis remains
to be defined.
Prothrombin time, vitamin K dependent factors II, VII,
IX, and X, plasma phylloquinone and menaquinone concentrations, and proteins induced in vitamin K deficiency
such as under--carboxylated prothrombin (PIVKA-II)
and osteocalcin (ucOC), respond to alterations in dietary
vitamin K and are helpful to assess relative changes in
vitamin K status. However, prothrombin time is the only
indicator of vitamin K status associated with adverse clinical
effects. Vitamin K prophylaxis is recommended in newborn
infants75 and in conditions that predispose the patient to fatsoluble vitamin deficiency states.
Adverse Effects
Vitamin K toxicity is rare. Parenteral administration of a
large amount of water-soluble synthetic vitamin K (vitamin
K 3) has been associated with hemolytic anemia, hyperbilirubinemia, and kernicterus4 and with liver damage. 3 No
adverse effects associated with other vitamin K supplements
or from food have been reported in healthy individuals
although high dietary intake or supplemental vitamin K can
inhibit the anticoagulation effect of vitamin K antagonists.
1. Human milk is a good source of which fat-soluble

vitamins?
A. A and E
B. D and A
C. E and D
D. K and D
E. K and A
2. All of the following statements about vitamin A are
correct except:
A. Absorption increases with presence of dietary fat.
B. Vitamin A metabolizes into various forms with
biological action.
C. Vitamin A activity of carotenoids is mediated
through its conversion to retinoids.
D. Carotenoids have a different extent of vitamin A

activity.
E. Retinoids and carotenoids have similar potency for
bioactivity.
3. All of the following statements on endogenous synthesis
of vitamin D are correct except:
A. It occurs following exposure to sunlight.
B. A brief period of sunlight exposure can generate a
large amount of vitamin D.
C. Dark-skinned individuals cannot produce vitamin
D.
D. Vitamin D toxicity does not occur following chronic
sunlight exposure.
E. Sunscreen, clothing, and winter can decrease the
capacity to produce vitamin D.
4. Which of the following statements concerning vitamin
E is correct?
A. Various forms of vitamin E are interconvertible.
B. Natural RRR--tocopherol has similar biopotency to all other naturally occurring vitamin E
stereoisomers.
C. Synthetic (all-rac-tocopherol) vitamin E has greater
biopotency than the natural RRR--tocopherol.
D. Soybean and safflower oils have much higher
content of -tocopherol versus -tocopherol.
E. Vegetable oils are poor sources of vitamin E.
5. Which of the following may interfere with vitamin K
action?
A. Chronic antibiotic therapy
B. Cholestyramine
C. Orilstat
D. Coumarin
E. All of the above
References

Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin
D, and Fluoride. Washington, DC: National Academy Press;
1997.
Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press; 2000.
Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron,
Chromium, Copper, Iodine, Iron, Manganese, Molybdenum,
Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National
Academy Press; 2001.

Kleinman RE, ed. Pediatric Nutrition Handbook. 6th ed. Elk
Grove Village, IL: American Academy of Pediatrics; 2009.
5. Papas KA, Sontag MK, Pardee C, et al. A pilot study on the
safety and efficacy of a novel antioxidant rich formulation in
patients with cystic fibrosis. J Cyst Fibros. 2008;7:6067.
6. Picciano MF, Dwyer JT, Radimer KL, et al. Dietary
supplement use among infants, children and adolescents
in the United States, 1999 2002. Arch Pediatr Adol Med.
2007;161:978985.
7. Mahoney CP, Margolis MT, Knauss TA, Labbe RF. Chronic
vitamin A intoxication in infants fed chicken liver. Pediatrics.
1980;65:893897.
8. World Health Organization. Brown E, Akre J, eds. Indicators
for Assessing Vitamin A Deficiency and Their Application in Monitoring and Evaluating Intervention Programmes. Geneva: World
Health Organization; 1996. http://www.who.int/nutrition/
publications/micronutrients/vitamin_a_deficieny/WHO_
NUT_96.10/en/index.html. Accessed July 25, 2009.
9. Murphy SC, Whited LJ, Rosenberry LC, Hammond BH,
Bandler DK, Boor KJ. Fluid milk vitamin fortification compliance in New York state. J Dairy Sci. 2001;84:28132820.
10. U.S. Food and Drug Administration. Code of Federal Regulations Title 21. Infant formula nutrient specifications.
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFR Search.cfm?fr=107.100&SearchTerm=infant%20
formula. Accessed August 2, 2009.
11. Drug Facts and Comparisons 2009. St. Louis, MO: Wolters
Kluwer Health.
12. Drugs, Supplements, and Herbal Information. Medline Plus,
National Institutes of Health. http://www.nlm.nih.gov/
medlineplus/druginformation.html. Accessed June 25, 2009.
13. Koo WWK, Krug-Wispe S, Succop P, Tsang RC, Neylan M.
Effect of different vitamin A intakes in very low birth weight
infants. Am J Clin Nutr. 1995;62:12161220.
14. Darlow BA, Graham PJ. Vitamin A supplementation to
prevent mortality and short and long-term morbidity in
very low birthweight infants. Cochrane Database Syst Rev.
2007;4:CD000501.
15. Harrison EH. Mechanisms of digestion and absorption of
dietary vitamin A. Annu Rev Nutr. 2005;25:87103.
16. Borel P, Drai J, Faure H, et al.
Recent knowledge about intestinal absorption and cleavage of carotenoids. Ann Biol Clin.
(Paris) 2005;63:165177.
17. Tang G, Qin J, Dolnikowski GG, Russell RM. Vitamin A
equivalence of beta-carotene in a woman as determined by a
stable isotope reference method. Eur J Nutr. 2000;39:711.
18. Olsen JA. Adverse effects of large doses of vitamin A and retinoids. Semin Oncol. 1983;10:290293.
19. Singh K. Modified classification of xerophthalmia. Indian J
Ophthalmol. [serial online] 1991 [cited November 24, 2009];
39:105107. http://www.ijo.in/text.asp?1991/39/3/105/24460.
20. World Health Organization. Global prevalence of vitamin A
deficiency in populations at risk 19952005. WHO Global
Database on Vitamin A Deficiency. Geneva: World Health
Organization; 2009. http://whqlibdoc.who.int/publications/
2009/9789241598019_eng.pdf. Accessed July 25, 2009.
85
21. Wasantwisut E. Application of isotope dilution technique in vitamin A nutrition. Food Nutr Bull. 2002; 23(3
Suppl):103106.
22. World Health Organization, United Nations Childrens Fund,
VACG Task Force. Vitamin A Supplements: A Guide to Their
Use in the Treatment and Prevention of Vitamin A Deficiency and
Xerophthalmia. 2nd ed. Geneva: World Health Organization;
1997. http://www.who.int/nutrition/publications/micronutrients/vitamin_a_deficieny/9241545062/en/index.html.
23. Penniston KL, Tanumihardjo SA. The acute and chronic toxic
effects of vitamin A. Am J Clin Nutr. 2006;83:191201.
24. Bendich A, Langseth L. Safety of vitamin A. Am J Clin Nutr.
1989;49:358371.
25. Persson B, Tunell R, Ekengren K. Chronic vitamin A intoxication during the first half year of life; description of 5 cases.
Acta Paediatr Scand. 1965;54:4960.
26. Macapinlac MP, Olson JA. A lethal hypervitaminosis A
syndrome in young monkeys (Macacus fascicularis) following
a single intramuscular dose of a water-miscible preparation containing vitamins A, D2 and E. Int J Vitam Nutr Res.
1981;51:331341.
27. Leo MA, Lieber CS. Alcohol, vitamin A, and beta-carotene:
adverse interactions, including hepatotoxicity and carcinogenicity. Clin Nutr. 1999;69:10711085.
28. Krasinski SD, Russell RM, Otradovec CL, et al. Relationship
of vitamin A and vitamin E intake to fasting plasma retinol,
retinol-binding protein, retinyl esters, carotene, alpha-tocopherol, and cholesterol among elderly people and young adults:
increased plasma retinyl esters among vitamin A-supplement
users. Am J Clin Nutr. 1989;49:112120.
29. World Health Organization, The Micronutrient Initiative. Safe Vitamin A Dosage During Pregnancy and Lactation.
Geneva: World Health Organization; 1998. http://www.who.
int/nutrition/publications/micronutrients/vitamin_a_deficieny/WHO_NUT_98.4/en/index.html. Accessed July 25,
2009.
30. Lascari AD. Carotenemia. A review. Clin Pediatr.
1981;20:2529.
31. Bendich A. The safety of beta-carotene. Nutr Cancer.
1988;11:207214.
32. Black HS. Reassessment of a free radical theory of cancer with
emphasis on ultraviolet carcinogenesis. Integr Cancer Ther.
2004;3:279293.
33. Haddad JG Jr, Hahn TJ. Natural and synthetic sources
of circulating 25-hydroxyvitamin D in man. Nature.
1973;244:515517.
34. Jurutka PW, Bartik L, Whitfield GK, et al. Vitamin D receptor:
key roles in bone mineral pathophysiology, molecular mechanism of action, and novel nutritional ligands. J Bone Miner Res.
2007;22 Suppl 2:v210.
35. Haussler MR, Haussler CA, Bartik L, et al. Vitamin D receptor:
molecular signaling and actions of nutritional ligands in
disease prevention. Nutr Rev. 2008;66 (10 Suppl 2):S98112.
36. Gordon CM, Williams AL, Feldman HA, et al. Treatment of
hypovitaminosis D in infants and toddlers. J Clin Endocrinol
Metab. 2008;93:27162721.
86
37. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention

of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch
Intern Med. 2009;169:551561.
38. Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a
new effective dietary intake recommendation for vitamin D. J
Nutr. 2005;135:317322.
39. Lehmann B. The vitamin D3 pathway in human skin and its
role for regulation of biological processes. Photochem Photobiol. 2005;81:1246 1251.
40. Engelsen O, Brustad M, Aksnes L, Lund E. Daily duration of
vitamin D synthesis in human skin with relation to latitude,
total ozone, altitude, ground cover, aerosols and cloud thickness. Photochem Photobiol. 2005;81:12871290.
41. Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in
the United States and Canada: current status and data needs.
Am J Clin Nutr. 2004;80:1710S6S.
42. Yetley EA. Assessing the vitamin D status of the US population. Am J Clin Nutr. 2008;88:558S564S.
43. Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as
effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab.
2008;93:677681.
44. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less
effective than vitamin D3 in humans. J Clin Endocrinol Metab.
2004;89:53875391.
45. Mawer EB, Backhouse J, Holman CA, Lumb GA, Stanbury
SW. The distribution and storage of vitamin D and its metabolites in human tissues. Clin Sci. 1972;43:413431.
46. Mawer EB, Schaefer K, Lumb GA, Stanbury SW. The metabolism of isotopically labeled vitamin D3 in man: the influence of
the state of vitamin D nutrition. Clin Sci. 1971;40:3953.
47. Kumar R. The metabolism and mechanism of action of
1,25-dihydroxyvitamin D3 . Kidney Int. 1986;30:793803.
48. Clements MR, Chalmers TM, Fraser DR. Enterohepatic
circulation of vitamin D: a reappraisal of the hypothesis.
Lancet. 1984;1:13761379.
49. DeLuca HF. Evolution of our understanding of vitamin D.
Nutr Rev. 2008;66 (10 Suppl 2):S73S87.
50. Rovner AJ, OBrien KO. Hypovitaminosis D among healthy
children in the United States: a review of the current evidence.
Arch Pediatr Adolesc Med. 2008;162:513519.
51. Jacobus CH, Holick MF, Shao Q , et al. Hypervitaminosis D associated with drinking milk. N Engl J Med.
1992;326:11731177.
52. Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin
Nutr. 2008;88:582S586S.
53. Heaney RP. Vitamin D: criteria for safety and efficacy. Nutr
Rev. 2008;66 (10 Suppl 2):S178S181.
54. Stephenson DW, Peiris AN. The lack of vitamin D toxicity
with megadose of daily ergocalciferol (D2) therapy: a case
report and literature review. South Med J. 2009;102:765768.
55. Sen CK, Khanna S, Roy S. Tocotrienols: vitamin E beyond
tocopherols. Life Sci. 2006;78:20882098.
56. Cornwell DG, Ma J. Studies in vitamin E: biochemistry and
molecular biology of tocopherol quinones. Vitam Horm.
2007;76:99134.
57. Traber MG, Atkinson J. Vitamin E, antioxidant and nothing

more. Free Radic Biol Med. 2007;43:415.
58. Debier C. Vitamin E during pre- and postnatal periods. Vitam
Horm. 2007;76:357373.
59. Stone WL, LeClair I, Ponder T, Baggs G, Barrett Reis B.
Infants discriminate between natural and synthetic vitamin
E. Am J Clin Nutr. 2003;77:899906.
60. Sokol RJ, Butler-Simon N, Conner C, et al. Multicenter trial
of d-alpha-tocopheryl polyethylene glycol 1000 succinate for
treatment of vitamin E deficiency in children with chronic
cholestasis. Gastroenterology. 1993;104:17271735.
61. Lodge JK, Hall WL, Jeanes YM, Proteggente AR. Physiological factors influencing vitamin E biokinetics. Ann N Y Acad
Sci. 2004;1031:6073.
62. Traber MG, Burton GW, Hamilton RL. Vitamin E trafficking.
Ann N Y Acad Sci. 2004;1031:112.
63. Kostner GM, Oettl K, Jauhiainen M, Ehnholm C, Esterbauer
H, Dieplinger H. Human plasma phospholipid transfer protein
accelerates exchange/transfer of alpha-tocopherol between
lipoproteins and cells. Biochem J. 1995;305:659667.
64. Burton GW, Traber MG, Acuff RV, et al. Human plasma and
tissue alpha-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E.
Am J Clin Nutr. 1998; 67: 669684.
65. Schultz M, Leist M, Petrizika M, Gassmann B, BrigeliusFlohe R. A novel urinary metabolite of -tocopherol,
2,5,7,8-tetramethyl-2(2carboxyethyl)-6-hydroxychroman,
as an indicator of adequate vitamin E supply? Am J Clin Nutr.
1995;62:1527S1534S.
66. Sokol RJ, Heubi JE, Iannaccone ST, Bove KE, Balistreri WF.
Vitamin E deficiency with normal serum vitamin E concentrations in children with chronic cholestasis. N Engl J Med.
1984;310:12091212.
67. Farrell PM, Bieri JG. Megavitamin E supplementation in man.
Am J Clin Nutr. 1975;28:13811386.
68. Johnson L, Bowen FW Jr, Abbasi S, et al. Relationship
of prolonged pharmacologic serum levels of vitamin E
to incidence of sepsis and necrotizing enterocolitis in
infants with birth weight 1,500 grams or less. Pediatrics.
1985;75:619638.
69. Shearer MJ, Newman P. Metabolism and cell biology of
vitamin K. Thromb Haemost. 2008;100(4):530547.
70. Suttie JW. Synthesis of vitamin K dependent proteins. FASEB
J. 1993;7:445452.
71. Benzakour O. Vitamin K dependent proteins: functions in blood coagulation and beyond. Thromb Haemost.
2008;100:527529.
72. Booth SL, Suttie JW. Dietary intake and adequacy of vitamin
K. J Nutr. 1998;128:785788.
73. Chambrier C, Bannier E, Lauverjat M, Drai J, Bryssine S,
Boultreau P. Replacement of long-chain triglyceride with
medium-chain triglyceride/long-chain triglyceride lipid
emulsion in patients receiving long-term parenteral nutrition:
effects on essential fatty acid status and plasma vitamin K1
levels. J Parenter Enteral Nutr. 2004;28:712.
74. Traber MG. Vitamin E and K interactions a 50-year-old
problem. Nutr Rev. 2008;66:624629.
75. American Academy of Pediatrics Policy Statement. Committee
on Fetus and Newborn. Controversies concerning vitamin K
and the newborn. Pediatrics. 2003;112:191192.
Fluids and Electrolytes
CONTENTS
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Fluid Distribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Fluid Regulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Hypervolemia
Hypovolemia
Fluid Considerations/Requirements inChildren. . . . . . . . 89

Treatment of Fluid Imbalances. . . . . . . . . . . . . . . . . . . . . . 90
Electrolyte Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Sodium
Potassium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Hyperkalemia
Hypokalemia
Magnesium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Hypermagnesemia
Hypomagnesemia
Calcium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Hypercalcemia
Hypocalcemia
Phosphorus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Hyperphosphatemia
Hypophosphatemia
Learning Objectives
1. Describe factors that influence movement of fluid and

electrolytes between the intracellular and extracellular
fluid compartments.
2. Recommend appropriate treatments for fluid and electrolyte abnormalities.
3. Describe the differences in the treatment of acute and
chronic electrolyte abnormalities.
Background
Water is the most abundant and probably the most important substance in the body. It is essential for digestion,
absorption, transport, and utilization of nutrients as well as
the excretion of waste products. The regulation of fluids and
electrolyte balance is maintained by an elaborate system
of interrelated regulatory systems to ensure proper cell
function. Unfortunately, fluid and electrolyte imbalances
are common, and when severe, these imbalances can have
a detrimental effect on major organ systems. This chapter
will focus on fluid and electrolyte homeostasis as well as
commonly encountered fluid and electrolyte abnormalities
and the treatment of these disorders.
Fluid Distribution
Water, being the most abundant component of the body,

makes up a large portion of total body weight. The actual
percentage of total body water (TBW) varies depending on
age, weight, gender, and body fat percentage. Adipose tissue
is the least hydrated body tissue; therefore, obese patients
will have a lower percentage of TBW content.13 Water
accounts for about 80% of total body weight in premature
infants and this proportion decreases slowly to 55% to 60%
of total body weight by age 18 years.4,5 TBW is divided into
87
88
3 separate compartments: intracellular fluid (ICF) (32%

52% of total body weight), transcellular fluid (1.5%2.5% of
total body weight), and extracellular fluid (ECF) (16%26%
of total body weight). The ECF is further divided into the
interstitial space (12%19% of total body weight) and the
intravascular space (4%6% of total body weight).6 Relative
percentages in each compartment at various ages can be
found in Table 9-1.
The primary factor that determines the water distribution between the ICF and ECF compartments is osmotic
pressure. Sodium is the predominant extracellular osmotic
agent, and potassium is the predominant intracellular
osmotic agent. The sodium-potassium-adenosine triphosphatase (Na+-K+-ATPase) pump maintains the sodium
and potassium gradient in normal conditions by pumping
3 sodium ions extracellularly for every 2 potassium ions it
pumps intracellularly. A disruption in the function of the
Na+-K+-ATPase pump can have a significant effect on fluid
distribution between the compartments. 3
Fluid composition also plays an important role in fluid
dynamics between the ICF and ECF. For example, when
100 mL of 5% dextrose (a solute-free solution) is administered intravenously to a patient, the dextrose is metabolized
and the resultant water gets distributed proportionally to
all compartments. Approximately 65% of the fluid volume
(65 mL) would go into the ICF, 32% (32 mL) would remain
in the ECF, and 3% (3 mL) would go into the transcellular
fluid compartment. Of the 32 mL that remained in the ECF,
25% (8 mL) would remain in the intravascular space and
75% (24 mL) would be in the interstitial space. If 100 mL of
0.9% sodium chloride were given, all 100 mL would stay in
the ECF: 25% (25 mL) in the intravascular space and 75%
(75 mL) in the interstitial space.7,8 The administration of a
hypertonic solution (eg, 3% sodium chloride) has a different
effect on fluid distribution. The increased tonicity of the
3% sodium chloride would create an osmotic gradient,
pulling fluid into the ECF from the ICF. Thus, the ECF
volume would increase as would the ECF and ICF osmolality. However, the ICF volume would decrease due to the
fluid shift caused by the hypertonic fluid. The volume of the
ECF increase would be determined by the tonicity and the
volume of the hypertonic solution given.7
The balance between the ECF and ICF is important in
fluid homeostasis, but these are not the only compartments
that must be maintained. The ECF components, the intravascular space and the interstitial space, are maintained
by Starling forces. Starling forces consist of plasma oncotic
pressure and hydrostatic pressure. When fluid moves from
the plasma to the interstitial space, edema occurs.9 As
vascular permeability increases, albumin leaks from the
plasma to the interstitial space. This capillary leak causes a
reduction in plasma oncotic pressure which in turn causes
fluid to move from the plasma to the interstitial space. If this
happens quickly, and the plasma volume is not replaced,
intravascular volume depletion can occur resulting in
hypotension and poor perfusion.
Fluid Regulation
The primary source of fluid intake is usually the diet,

although some water will be generated from the oxidation
of carbohydrates, proteins, and fat. 3,10 The majority of fluid
losses are through urinary output, but fluid losses also occur
via the skin and the respiratory and gastrointestinal (GI)
tracts. Sodium and fluid balance are closely intertwined.
Disturbances of water balance lead to changes in plasma
osmolarity and sodium balance, and changes in sodium
balance result in changes in plasma osmolarity and fluid
volume. In order to maintain a relatively normal serum
osmolarity (290 5 mOsm/L), the sodium-to-TBW ratio
must be maintained in a relatively narrow range. When a
fluid deficit or excess occurs, physiological feedback mechanisms are activated to either increase or decrease renal
water excretion or to increase or decrease thirst, thereby
influencing fluid intake.1115 An abnormality in either of
Table 9-1 Distribution of Total Body Water as a Percent of Total Body Weight
Age/Life Stage
Total Body Water
Intracellular
Extracellular
Transcellular
Premature infant
80%
52%
2.5%
3-month-old infant
70%
46%
6-month-old infant
60%
39%
10- to 18-year-old child/adolescent
Male 59%
Female 57%
50%
38%
36%
32%
26% Intravascular 6%
Interstitial 19%
22% Intravascular 5.5%
Interstitial 16.5%
Interstitial 14%
18% Intravascular 4.5%
Interstitial 13.5%
Interstitial 12%
Elderly patient
2%
1.8%
1.7%
1.5%
FLUIDS AND ELECTROLYTES
these 2 mechanisms can have a significant effect on water

and sodium balance. The treatment of a fluid deficit or a
fluid excess requires the identification of the condition
that caused the abnormality and determination of the
time frame during which the abnormality occurred. Acute
disturbances, changes occurring in 48 hours or less, are
more frequently associated with signs and symptoms and
can be corrected acutely. Chronic disturbances developing
over a longer period of time are typically asymptomatic
and should be replaced less aggressively.16 When assessing
or treating fluid and electrolyte imbalances, the patients
volume status must be assessed to determine if he or she
is euvolemic, hypervolemic, or hypovolemic. Patients who
are euvolemic usually have the ability to self-regulate fluid
status and require little more than maintenance fluids and
electrolyte supplementation. Patients who are either hyperor hypovolemic require additional assessment and may
require additional treatment as well.
Hypervolemia
Hypervolemia, or increased TBW, causes a decreased
serum osmolarity resulting in dilute urine by suppressing
the levels of circulating antidiuretic hormone (ADH). The
precise mechanism by which plasma osmolarity suppresses
ADH is unclear, but it probably is related to specialized cells
that sense osmolarity changes and send messages to the
neuroendocrine cells located in the hypothalamus or the
organum vasculosum.17 In most cases, the thirst response
will be suppressed, ADH will be suppressed, and the excess
water will be excreted by the kidneys. However, in conditions where the low plasma osmolarity fails to inhibit
ADH secretion (such as in severe low-output congestive
heart failure), cell expansion, hypervolemia, and hyponatremia continue to progress.18 Symptoms include headache,
nausea, vomiting, muscle twitching, convulsion, and if
severe, death.19 Other conditions that may result in hypervolemia include kidney or liver failure with ascites, sepsis,
cardiac failure, and syndrome of inappropriate antidiuretic
hormone (SIADH).
Hypovolemia
Hypovolemia is a condition where TBW is decreased significantly enough to result in symptoms. The body can correct
the problem by stimulating the thirst response, increasing
ADH release, or both. When the plasma osmolarity is
increased or when the blood volume or pressure is reduced,
the thirst response is stimulated.17 In hypovolemia, the
serum osmolarity increases and the blood volume decreases,
which results in the release of ADH. The presence of ADH
89
increases the permeability of water in the collecting tubule,

resulting in water reabsorption in the collecting tubule
(ie, water retention). The resultant water retention will
result in a more concentrated urine.20,21 Signs and symptoms of hypovolemia include thirst, altered mental status,
weakness, fatigue, neuromuscular irritability, agitation,
seizures, and coma.22 Other conditions that may lead to
hypovolemia include GI hemorrhage, vomiting, diarrhea,
excessive sweating, burns, diabetes insipidus, and excessive
diuresis.23 The fluid deficit can be calculated by using the
following equation:
Fluid deficit = {(Patient serum sodium 140) body weight in
kilograms} 140
Fluid Considerations/Requirements
inChildren
Normal daily fluid requirements can be estimated in

a variety of ways. One of the most common ways, the
Holliday-Segar formula, is a weight-based method (Table
9-2).24,25 For example, using this method, a child weighing
27 kg would require a minimum of 1640 mL of fluid per day.
This method is commonly used to estimate fluid requirements; however, it does not address fluid requirements in
abnormal circumstances such as kidney failure or congestive heart failure.
Table 9-2 Calculating Estimated Fluid Requirements
(Holliday-Segar Formula)
Body Weight
Daily Fluid Requirement
Fluid Requirements
10 kg
> 10 kg to
20 kg
> 20 kg
100 mL/kg
1000 mL + 50 mL/kg for
wt > 10 kg
1500 mL + 20 mL/kg for
wt > 20 kg
4 mL/kg/h
40 mL/h + 2 mL/kg/h
> 10 kg
60 mL/h + 1 mL/kg
> 20 kg
There are a number of conditions that require adjustments in fluid intake in order to provide optimal care. After
birth, a contraction of the ECF compartment takes place due
to the loss of interstitial fluid, which results in a 5% to 10%
weight loss in healthy neonates, possibly more in premature
infants.2631 Prematurity affects fluid balance. Premature
infants may require as much as 200 mL/kg/d to maintain
fluid balance due to their large insensible fluid losses. These
losses are due partially to the large skin-to-body surface area
ratio and partially to the immaturity of the skin which leads
to increased evaporative fluid loss. 32,33 In addition, phototherapy and radiant warmers increase water losses, often as
much as 20 to 40 mL/kg/d. 3437 Insensible fluid losses may
remain greater than 100 mL/kg/d for weeks in neonates
90
weighing less than 750 g. In patients weighing between 750

g and 1000 g, insensible fluid losses can decrease to 60 mL/
kg over the first week of life, and in those neonates weighing
between 1001 g and 1250 g, insensible fluid losses usually
decrease to 35 mL/kg over the first week. 38 This decrease in
insensible fluid losses is due mainly to maturation and thickening of the skin shortly after birth. Antenatal steroids that
help progress lung maturation will also affect skin thickening, which reduces fluid losses via the skin. Therefore,
premature infants whose mothers did not receive antenatal
steroids prior to birth may have excessive fluid losses for an
extended period of time. 37 Other conditions that increase
insensible water loss include omphalocele, gastroschisis,
tachypnea, and administration of non-humidified oxygen.
Conditions that may require fluid restriction due to
decreased fluid losses include but are not limited to kidney
and lung dysfunction and heart failure.
One relatively simple way to assess fluid balance is by
assessing daily weights. It is important to use the same scale
and to make sure that the patient has the same equipment
attached to accurately assess daily weights. Rapid weight
changes typically reflect changes in water balance. Another
useful indicator for assessing fluid status is serum sodium
concentrations. An increase in the serum sodium concentration with little weight gain or weight loss typically indicates
dehydration, whereas a low serum sodium concentration
along with weight gain typically indicates fluid overload.
Treatment of Fluid Imbalances
Conditions that affect the serum sodium concentration will

affect fluid balance. Likewise, conditions that affect fluid
balance will have an effect on the serum sodium concentration. When addressing fluid issues, assessing trends in
the serum sodium concentration is essential to making the
appropriate adjustment. Whenever possible the underlying
cause of the electrolyte disturbance should be treated,
rather than just treating the serum sodium concentration.
Dilutional hyponatremia (one form of hypervolemia) can
occur from conditions where fluid accumulates, such as in
sepsis, and in kidney or liver dysfunction, especially when
ascites is present. 39 In general, chronic fluid disturbances
take longer than 48 hours to develop, and patients typically
do not exhibit signs and symptoms unless the fluid overload
is severe, resulting in a very low serum sodium concentration (typically less than 120 mEq/L). Overzealous diuresis
or administration of hypertonic saline can result in an
osmotic demyelination syndrome, causing brain injury
if serum sodium is increased (or decreased) faster than
0.5mEq/L/h or by more than 10 mEq/L in 24 hours.19 The
treatment of significant hypovolemia (dehydration) will be

covered in the Hypernatremia section of this chapter.
Electrolyte Assessment
Changes in the ECF compartment are responsible for the

signs and symptoms associated with fluid and electrolyte
imbalances. Therefore, it is the ECF compartment that must
be corrected to alleviate those signs and symptoms. There are
5 basic steps or criteria that are essential in the assessment
and treatment of fluid and electrolyte abnormalities (Table
9-3). The first step is to determine the cause of the electrolyte imbalance. For example, is the hypokalemia a result of
chronic diuretic therapy or is it the result of an intracellular
shift secondary to a large dextrose infusion? Once the cause
has been identified, the second step is to classify the event as
either acute or chronic. The prescriber can then determine
whether a supplemental infusion or a change in the maintenance solution (step 3) is a more appropriate intervention to
correct the abnormality. Acute problems should usually be
treated with supplemental infusions whereas chronic problems should usually be treated with maintenance solutions.
The next step is to determine the therapeutic index of the
electrolyte to be corrected. If treating a severe hypokalemia,
it is typically safer to administer a relatively moderate
potassium infusion and then recheck the serum potassium
concentration before repeating the dose rather than giving
one large potassium supplemental infusion. If the deficit
was inappropriately assessed and the single supplementation was too high, the patient could develop hyperkalemia
and its associated consequences. In a patient with severe
hypomagnesemia, overestimating the magnesium supplementation will have little clinical impact on the patient.
Therefore the prescriber can be more aggressive when
supplementing magnesium and phosphate versus potassium. The final step or criterion is to assess the acuity of the
electrolyte imbalance. If the serum electrolyte concentration is critical or life-threatening, then the problem should
be treated acutely. After initial treatment, then the maintenance solution can be adjusted, if necessary.
Table 9-3 Five Steps or Criteria for Correcting Electrolyte Abnormalities
1. Determine the cause of the electrolyte abnormality.
2. Classify the electrolyte abnormality as acute or chronic.
3. Determine whether a supplemental infusion (bolus) or an increase in
the maintenance infusion or intake is appropriate for treatment.
4. Determine the therapeutic index of the electrolyte.
5. If the serum electrolyte concentration is critical or life-threatening,
treat acutely, then determine if an adjustment is needed in the
maintenance fluid intake.
Reference values for normal serum electrolyte concentrations based on age appear at the beginning of each
electrolyte section below. These values are included to
illustrate the differences in electrolyte concentrations for
various age groups. Laboratory reference values will vary
from institution to institution, and practitioners should use
the reference values listed at their individual institutions for
adjusting serum electrolyte values.
Sodium
Preterm:
Older Infants:
Children and Adolescents:
130140 mEq/L
133146 mEq/L
135145 mEq/L
Sodium is the most abundant extracellular cation in the

body. It has 2 primary functions: fluid balance and maintenance of the membrane potential of cells. The body
maintains sodium homeostasis primarily by the reninangiotensin-aldosterone system and ADH secretion. Other
systems involved in sodium maintenance include the
sympathetic nervous system, atrial natriuretic peptide, the
kallikrein-kinin system, various intrarenal mechanisms,
and other factors that regulate renal and medullary blood
flow.40 The body maintains cell membrane potential by the
Na+-K+-ATPase pump. Three sodium ions are pumped out
of the cell for every 2 potassium ions that are pumped into
the cell, which produces the negative charge in the cells
necessary for normal functioning of nerves and muscle cells
and the active transport of nutrients, such as glucose and
amino acids.41
In normal situations the bodys sodium losses match
the bodys sodium intake. The kidney has the ability to
reabsorb up to 99% of the sodium presented to the renal
tubules, so in times of a sodium intake deficit, serum sodium
concentrations can be maintained. Daily sodium losses in
these instances may be only a few milliequivalents. Medications can also affect sodium balance. Lactulose, normal
saline, and hypertonic saline can cause hypernatremia, and
medications such as chlorpropamide, demeclocycline, and
91
loop diuretics can cause hyponatremia. Diuretics can also

cause sodium imbalances. Loop diuretics cause a hypo
volemic hypernatremia due to increased water loss relative
to sodium loss, and overzealous use of thiazide diuretics
causes a hypovolemic hyponatremia. Sodium requirements vary depending on age group and also vary from
patient to patient. In general, parenteral requirements for
sodium are about 2 to 5 mEq/kg in term infants, children,
and adolescents. In preterm infants, as little as 1 mEq/kg
of sodium may maintain sodium concentrations, but in
general 3to4mEq/kg is recommended for the first week of
life and then 3 to 6 mEq/kg in preterm infants less than 28
weeks gestation.42,43 Oral sodium requirements vary with
age (Table 9-4).
Hypernatremia
Hypernatremia is defined as serum sodium concentration
greater than 145 mEq/L. Hypernatremia usually develops
under conditions of low or normal total body sodium but
it can also develop with an increase in total body sodium.
Hypernatremia is typically a result of net water loss or hypotonic fluid loss. Causes of hypernatremia include lack of oral
hydration, diarrhea, vomiting, overzealous diuresis, fever,
and the inability to express a need for water (eg, infants,
children, or patients who have an altered mental status).
An algorithm for the evaluation and treatment of hypernatremia can be found in Figure 9-1. If the hypernatremia is
due to sodium intake, then intake must be decreased. If the
hypernatremia is associated with dehydration, then rehydration should be started immediately. If the dehydration is
mild and asymptomatic, then rehydration can be addressed
by simply altering the oral fluid intake. If the dehydration is
moderate to severe or if the patient is symptomatic, aggressive treatment should begin immediately.
In order to treat the patient appropriately, classifying dehydration as mild, moderate, or severe is helpful.
Mild dehydration can be identified by the presence of dry
mucous membranes with normal hemodynamic parameters. Moderate dehydration can be defined as the presence
Table 9-4 Oral Electrolyte Requirements by Age (mg)

Age
Sodium
Potassium
Age
Magnesium
Age
Calcium
Phosphorus
00.5 y
0.51 y
12 y
25 y
69 y
10 y or older
120
200
225
300
400
500
500
700
1000
1400
1600
2000
00.5 y
0.51 y
13 y
48 y
913 y
> 13 y (M)
> 13 y (F)
30
75
80
130
240
400
360
00.5 y
0.51 y
13 y
48 y
8 y or older
210
270
500
800
1300
100
275
460
500
1250
92
of changes in hemodynamic parameters suggesting intravascular depletion like tachycardia, mild hypotension, and
orthostasis. Severe volume depletion is defined by the presence of more profound hemodynamic compromise, such
as moderate to severe hypotension, tachycardia, and poor
perfusion. Clinical symptoms of mild, moderate, and severe
dehydration generally correspond to a 5%, 10%, and 15%
weight loss in infants, respectively, which can be detected
if pre- and post-dehydration weights are available. In teenagers, mild, moderate, and severe dehydration correspond
to a 3%, 5%, and 7% loss in body weight, respectively.44 Fluid
therapy must include replacement of the deficit as well as
provision of maintenance fluids.
There are various methods used for correcting volume
depletion, but 3 principles always apply: (1) the fluid deficit
must be replaced with an appropriate fluid; (2) maintenance fluids must be provided on an ongoing basis; and (3)
if there are continued ongoing losses (eg, gastric drainage,
vomiting, diarrhea), these losses must be replaced on an
ongoing basis to prevent further fluid deficits. For example,
an infant weighing 5 kg has a 500 mL (10%) fluid deficit.
Given the degree of fluid deficit (10% or more), an isotonic
fluid bolus (20 mL/kg or 2% of the patients body weight
= 100 mL) would be indicated initially. After this bolus,
the remaining deficit (8% or 400 mL) would be replaced as
follows: 50% (200 mL) over the next 8 hours and 50% (200
mL) over the subsequent 16 hours. In addition to the deficit
replacement, usual maintenance fluids (Column 3 in Table

9-2) must be administered. If severely volume depleted, the
patient will require more than one 20 mL/kg fluid bolus to
resolve the tachycardia, hypotension, and other symptoms.
Once the tachycardia and hypotension have resolved, the
fluid deficit and maintenance requirements can be calculated. In a teenager, the fluid deficit associated with mild,
moderate, and severe dehydration is generally about 50% of
that seen in an infant; therefore the initial bolus is generally
10 mL/kg rather than 20 mL/kg. Alternatively, as in adults,
a fluid bolus of 500 mL to 1000 mL is given initially and
repeated based on hemodynamic response.
Hypertonic dehydration (hypernatremia) must be
managed differently. In hypertonic dehydration, the fluid
from the ICF compartment is drawn into the intravascular
space. Rapid administration of fluid as described above may
cause rapid fluid shifts that can result in cerebral edema and
intracranial bleeding. In hypertonic dehydration, the fluid
volume deficit is calculated and gradually replaced (usually
over 48 hours).45 The need for a fluid bolus as described
above is based on hemodynamic parameters. If the patient
is hemodynamically compromised (hypotension, severe
tachycardia), then a 10 to 20 mL/kg bolus of an isotonic
fluid is imperative to restore perfusion and normalize hemodynamic parameters. When correcting severe symptomatic
hypovolemic hypernatremia, the underlying cause of the
hypernatremia should be treated. In general, to prevent
Figure 9-1 Hypernatremia
Adapted from Matarese LE, Gottschlich MM, eds. Contemporary Nutrition Support Practice: A Clinical Guide. Whitmire SJ. Fluids and electrolytes, p. 130.
cerebral edema, the serum sodium should not be corrected

at a rate that exceeds 0.5mEq/L/h or more than 10 mEq/L
in 24 hours.
Hyponatremia
Hyponatremia is defined as a serum sodium concentration less than 135 mEq/L. It is one of the most common
electrolyte disturbances found in the hospitalized patient.
Signs and symptoms include headache, nausea, vomiting,
muscle cramps, lethargy, restlessness, disorientation, and
depressed reflexes and are more commonly seen with an
acute decrease in the serum sodium concentration typically
93
below 125 mEq/L. Severe acute hyponatremia is life-threatening; fortunately the more common type of hyponatremia
seen in hospitalized patients is slow-developing and less
severe. The 2 most common causes of hyponatremia include
hypervolemic hyponatremia where the total body sodium is
normal to high and TBW is high, and hyponatremia due to
actual sodium and water losses. In kidney failure, liver failure
with ascites, hyperaldosteronism, and congestive heart
failure, the body accumulates sodium and fluid, resulting
in hypervolemic hyponatremia, sometimes referred to as
dilutional hyponatremia. Diarrhea and other GI losses such
as gastric suction, enterocutaneous fistulas, or necrotizing
Figure 9-2 Hyponatremia
Adapted from Matarese LE, Gottschlich MM, eds. Contemporary Nutrition Support Practice: A Clinical Guide. Whitmire SJ. Fluids and electrolytes, p. 129.
94
enterocolitis; thiazide diuretic-induced hyponatremia; and

salt-wasting nephropathy are examples of conditions that
cause hypovolemic hyponatremia. In premature neonates,
the salt-wasting nephropathy can be severe, often requiring
delivery of sodium equal to 6 mEq/kg or more daily to
maintain sodium and fluid balance.27 An algorithm for the
evaluation and treatment of hyponatremia can be found
in Figure 9-2. Treatment with hypertonic saline may be
indicated if the serum sodium concentration is below
125 mEq/L or if the patient is symptomatic. The sodium
deficit is calculated by using the equation:
sodium deficit (mEq) = TBW wt (Nadesired Naactual)
where TBW is the percentage of the body weight found in Table 9-1
divided by 100, and weight is in kg.
Typically no more than 50% of the sodium deficit should

be replaced over 12 hours. In general, the serum sodium
should not be corrected at a rate that exceeds 0.5 mEq/L/h
or more than 10 mEq/L in 24 hours in order to prevent the
development of central pontine myelinolysis.46
Potassium
Newborn:
Infant:
Children and Adolescents:
3.75.9 mEq/L
4.15.3 mEq/L
3.44.7 mEq/L
Potassium is the primary ICF cation. Potassium is essential

for cell metabolism and maintenance of resting membrane
potential. Intracellular potassium concentrations are
approximately 140 mEq/L (ICF potassium concentrations
equal ECF sodium concentrations due to the action of the
Na+-K+-ATPase pump).47 Other factors that affect potassium
distribution include those affecting the Na+-K+-ATPase
pump, such as insulin, catecholamines, and ECF pH;
exercise; and cell breakdown. 3,48,49 Potassium is primarily
excreted via the kidney. Potassium excretion varies based
on serum potassium concentrations and the release of
aldosterone and angiotensin II. A lack of aldosterone causes
potassium retention, whereas an excess causes potassium
depletion. 50 In times of a potassium deficit, urinary excretion drops significantly, but not entirely. If potassium intake
significantly increases, urinary potassium excretion will
increase as well as potassium excretion via non-renal mechanisms (GI tract), a process known as potassium adaptation.
In chronic kidney insufficiency, GI potassium losses may
increase to 30% to 50% of the ingested potassium. 5153 Medications that affect potassium concentrations can be found
in Table 9-5. Supplementation in parenteral nutrition (PN)
solutions or maintenance intravenous (IV) fluids should

start at about 2 to 4 mEq/kg and may increase depending
on kidney function, GI losses, and medication use.42, 44 Oral
potassium requirements vary with age (Table9-4).
Table 9-5 Medications Affecting Potassium and Magnesium
Hyperkalemia
Hypokalemia
Potassium-sparing diuretics
Nonsteroidal anti-inflammatory
drugs
Angiotensin converting enzyme
inhibitors
Angiotensin-II receptor blockers
Trimethoprim
Pentamidine
Cyclosporine
Tacrolimus
Heparin
Penicillin G potassium
-blockers
Succinylcholine
Loop diuretics
Thiazide diuretics
Fludrocortisones
High-dose glucocorticoids
High-dose penicillins
Phenolphthalein
Sodium polystyrene sulfonate
Sorbitol
2adrenergic agonists
Tocolytic agents
Theophylline
Caffeine
Insulin/dextrose
Hypermagnesemia
Hypomagnesemia
Tocolytic agents
Magnesium-containing antacids
Magnesium-containing enemas
Cisplatinum
Foscarnet
Amphotericin B
Aminoglycosides
Thiazide diuretics
Hyperkalemia
Hyperkalemia is defined as a serum potassium concentration greater than 4.7 to 5.9 mEq/L, depending on
the patients age. Signs and symptoms of hyperkalemia
include muscle twitching, cramping, weakness, ascending
paralysis, electrocardiogram (ECG) changes (eg, peaked
T-waves, prolonged PR interval), and dysrhythmias (eg,
bradyarrhythmias, ventricular fibrillation, and asystole).
Hyperkalemia is one of the most dangerous electrolyte
imbalances that develop in premature infants. The immaturity of the kidneys results in a reduced glomerular filtration
rate, urinary potassium excretion, acidosis, and immature
renal tubular response to aldosterone. 54 Hyperkalemia can
occur from excessive potassium intake in the presence of
altered kidney excretion or metabolic acidosis caused by
conditions such as diabetic ketoacidosis and renal tubular
acidosis. Metabolic acidosis causes hyperkalemia by causing
a shift of potassium from the ECF to the ICF in order to
balance the excess hydrogen ions that are moving into the
ICF. Clinically significant hyperkalemia can also develop as
a result of cell lysis (hemolysis) or tissue injury and death
(eg, burns, rhabdomyolysis) in vivo due to the release of the

ICF potassium into the serum.
Treatment of hyperkalemia depends on both the
severity and the cause. All sources of potassium intake
should be discontinued immediately and, if feasible, any
medication that may contribute to hyperkalemia should
be stopped or the dose reduced. If the potassium is significantly elevated or if the patient is symptomatic, IV calcium
chloride should be administered immediately to reduce the
excitability of the cardiac muscle. (Note: Calcium gluconate
is generally not recommended in emergency situations.)
There are two basic mechanisms used to treat hyperkalemia:
shifting potassium into the ICF and removing potassium from the body. Insulin in combination with glucose,
2-adrenergic agonists, and sodium bicarbonate will shift the
potassium into the ICF. Loop and thiazide diuretics (loop
to a greater extent than thiazide), cation exchange resins
like sodium polystyrene, and dialysis all reduce potassium
concentrations by directly removing potassium from the
body (exchange resins and dialysis) or by increasing renal
potassium excretion (diuretics). Serum potassium concentrations should be monitored frequently during treatment,
especially in patients being treated with dextrose and
insulin, 2-adrenergic agonists, and sodium bicarbonate
because once these therapies are discontinued, potassium
will shift back to the ECF compartment. Potassium concentrations should be monitored for at least 12hours after the
hyperkalemia has resolved to ensure that equilibration of
potassium between the ICF and ECF is complete. 3
Pseudohyperkalemia is common in infants and young
children and can occur when red blood cells break down
during the blood-drawing process. In other words, the serum
potassium detected in the sample is higher than the actual
serum potassium concentration due to hemolysis of the red
blood cells during the blood-drawing process or while in
the collection tube. This form of hyperkalemia is the most
common form detected in pediatric patients with normal
kidney function. If pseudohyperkalemia is suspected, and
if the patient is asymptomatic and has normal kidney function, the serum potassium concentration should be repeated
(avoiding rapid aspiration and use of narrow gauge needles
if possible) before starting any treatment for hyperkalemia.
Hypokalemia
Hypokalemia is defined as a serum potassium concentration
less than 3.4 mEq/L. It is a common electrolyte abnormality seen in clinical practice. Causes of hypokalemia
include medications, metabolic alkalosis, abnormal
GI losses, hyperaldosteronism, hypomagnesemia,
95
catecholamines, and inadequate intake. Signs and symptoms are non-specific but include dysrhythmias, paralysis,
muscle necrosis, and possibly death. The treatment of
hypokalemia depends on both the severity and the cause
of the hypokalemia. Oral potassium supplements are available as a variety of salts, and the choice of agent depends
on other concomitant electrolyte imbalances, cost, and
patient preference. In an asymptomatic patient with mild to
moderate hypokalemia, oral supplementation is preferred
because of safety reasons (eg, there is no risk for potassium extravasation). Oral supplementation also reduces the
risk of overcorrection causing hyperkalemia and too rapid
correction causing dysrhythmias. Oral potassium can be
irritating to the GI tract. For mild to moderate potassium
depletion, doses of 2 to 5 mEq/kg/d in divided doses, not
to exceed 1 to 2 mEq/kg as a single dose, taken with plenty
of water, are recommended. 55,56 Serum potassium should
be rechecked approximately 2 hours after the initial dose is
completed, and additional doses given, if needed.
The use of IV potassium supplementation should be
reserved for patients who are symptomatic, who have severe
hypokalemia, or when administration via the GI tract is
contraindicated. Dosages range from 0.5 to 1 mEq/kg
depending on the severity of the hypokalemia and kidney
function. Generally, infusion rates should not exceed
0.5 mEq/kg/h, unless continuous cardiac monitoring is
available. Potassium can be caustic to the vein, so to minimize
irritation, the concentration for administration through a
peripheral vein should not exceed 0.06mEq/mL. 56,57 When
administering IV potassium supplementation, co-administration with dextrose may worsen the hypokalemia by
stimulating insulin release, which promotes the intracellular shift of potassium. Concurrent hypomagnesemia may
result in refractory hypokalemia due to increased renal
potassium losses due to the kidneys attempt to conserve
magnesium and impairment of the Na+-K+-ATPase pump. 58
As such, it is important to correct a low magnesium level
while treating hypokalemia. Serum potassium should be
rechecked approximately 2 hours after the initial dose is
completed, and additional doses given, if needed.
Magnesium
All Age Groups:
1.62.3 mg/dL
Magnesium is an essential cofactor in more than 300

enzymatic reactions, including those involved in glucose
metabolism, fatty acid synthesis and breakdown, and DNA
and protein metabolism. Magnesium plays a critical role in
the functioning of the Na+-K+-ATPase pump, thus affecting
96
neuromuscular transmission, cardiovascular excitability,

vasomotor tone, and muscle contraction. Magnesium is also
an integral component of bone and parathyroid hormone
(PTH) secretion. 59,60 More than 50% of the magnesium in
the body resides in bone. Magnesium is found primarily
in the ICF with only about 2% of total body stores found
in the ECF. About 61% of serum magnesium is physiologically active in the ionized form, 33% protein bound, and 5%
complexed to phosphate, citrate, and other compounds.
Magnesium homeostasis is maintained and regulated by the GI tract, kidney, and bone via PTH. Healthy
individuals absorb between 30% and 40% of ingested
magnesium. Magnesium is absorbed in the distal jejunum
and ileum, and absorption is inversely proportional to the
magnesium intake. Magnesium is primarily excreted via the
kidneys with about 35% of ingested magnesium excreted in
the urine. In the presence of high magnesium intake, renal
excretion increases to maintain normal serum magnesium
concentrations. Very little magnesium (1%2%) is excreted
via the feces. Bone is very important to the homeostasis
of serum magnesium concentrations. If a patient becomes
magnesium depleted, the mineral is leached from the bone to
maintain ECF magnesium concentrations. ECF magnesium
is then sacrificed to the ICF to maintain normal metabolic
functions.61 Medications that affect magnesium concentrations are listed in Table 9-5. IV magnesium supplementation
in PN solutions ranges from 0.25 mEq/kg to 0.5mEq/kg
daily but may be higher in patients with abnormal magnesium losses. Oral magnesium requirements vary with age
(Table 9-4).
Hypermagnesemia
Hypermagnesemia is defined as serum magnesium greater
than 2.4 mg/dL. Hypermagnesemia is usually well tolerated but can affect neurological, neuromuscular, and
cardiac function when magnesium concentrations exceed
3 mg/dL.62,63 Physical findings include nausea, vomiting,
diaphoresis, flushing, depressed mental function, drowsiness, muscular weakness, hypotension, and bradycardia. If
patients with severe hypermagnesemia are symptomatic,
IV calcium chloride should be administered immediately
to reduce the excitability of the cardiac muscle. (Note:
Calcium gluconate is generally not recommended in emergency situations.) Hemodialysis may be required to reduce
the magnesium concentration to a safer value. Treatments
for hypermagnesemia in an asymptomatic patient include
dietary magnesium restriction, administration of a loop
diuretic, and possibly hemodialysis if kidney dysfunction is
present.64, 65
Hypermagnesemia occurs primarily in the setting

of kidney insufficiency in combination with continued
magnesium intake. In the premature infant, the most
common cause of hypermagnesemia results from placental
transfer of magnesium during the treatment of premature
labor contractions with magnesium sulfate. The effect that
hypermagnesemia has on the ability to relax smooth muscle
makes magnesium a viable treatment due to the low risk of
harm to the neonate. The neonate with hypermagnesemia
will have poor muscle tone, which will return to normal
as the serum magnesium concentration decreases over
approximately 2 to 5 days, depending on the severity of the
initial hypermagnesemia.66
Hypomagnesemia
Hypomagnesemia is defined as serum magnesium concentration less than 1.3 mg/dL. It is a common condition seen in
hospitalized patients. Signs and symptoms include apathy,
depression, psychosis, muscle weakness, vertigo, ataxia,
seizures, confusion, leg cramps, hyperactive tendon reflexes,
anorexia, nausea, vomiting, paresthesias, Chvosteks and
Trousseaus sign, spontaneous carpal-pedal spasm, and
cardiac complications including dysrhythmias.67 Hypomagnesemia can also cause other electrolyte abnormalities.
Hypomagnesemia may result in refractory hypokalemia
because of increased renal potassium losses due to the
kidneys attempt to conserve magnesium and impairment
of the Na+-K+-ATPase pump. 58 Hypomagnesemia may also
result in hypocalcemia. Magnesium deficiency can impair
parathyroid function, and hypomagnesemia accompanied
by hypoparathyroidism is a common cause of neonatal
hypocalcemia.68,69
Hypomagnesemia can be caused by decreased intake,
increased excretion, or intracellular shifts of magnesium.70
Excessive renal losses may occur in patients with acute
tubular necrosis, renal tubular acidosis, Bartter syndrome,
or hyperaldosteronism, or may be induced by medications
such as amphotericin, cisplatin, cyclosporine, aminoglycosides, and foscarnet.71 Intracellular shifts can be caused
by dextrose and/or insulin administration. Because only
about 1% to 2% of total body magnesium is found in the
ECF, serum concentrations are not a good reflection of total
body magnesium stores. Treatment of hypomagnesemia is
therefore empirical. The IV route is preferred in patients
with moderate to severe hypomagnesemia because of the
GI intolerance generally seen with large oral doses. Recommended doses are 0.2 to 0.4 mEq/kg (2550 mg/kg), up to
2 mEq (2 g) every 8 to 12 hours for 2 to 3 doses.72 There is
a renal magnesium threshold for magnesium reabsorption;
thus up to 50% of an individual magnesium dose can be

eliminated via the kidneys if the magnesium is not distributed intracellularly.73,74 In asymptomatic adults, a maximum
infusion rate of 1 g (8 mEq)/h is recommended. 3,75 This infusion rate would equate to about 0.1 mEq/kg/h in children.
Supplemental magnesium doses may be reduced by 50% in
patients with kidney dysfunction to lessen the risk of hypermagnesemia. However, reducing the dose by 50% may not
be necessary in all cases because, if only a one-time dose is
given, the magnesium will not continue to accumulate, and
mild hypermagnesemia is well tolerated. Serum magnesium
should be rechecked approximately 2 hours after the infusion is completed, and additional boluses given, if needed.
97
the calcium bound to albumin, and the free or ionized

calcium. Therefore, if the serum albumin is low, the serum
total calcium also will be low. Although not completely reliable in critically ill patients, serum calcium concentrations
can be corrected for the degree of hypoalbuminemia using
the equation:
Corrected calcium = measured total calcium (mg/dL) +
0.8 [4 albumin (g/dL)]
Age Group
Total Calcium
Age Group
Ionized (SI Units)
Preterm
Full Term
6.211 mg/dL
7.610.4 mg/dL
Preterm
Full Term
< 36 h
Full Term
3684 h
> 84 h
1.752 mmol/L
1.051.37 mmol/L
Alternatively, if the patients albumin is low, then the

serum ionized calcium should be checked as this is the most
accurate laboratory test for assessing the physiologically
active calcium status. The serum pH and the phosphorus
and albumin concentrations affect the amount of calcium
that is ionized.7779 Supplementation of calcium in PN solutions ranges from 1 to 4 mEq/kg. Oral calcium requirements
vary with age and can be found in Table 9-4.
1.11.42 mmol/L
Hypercalcemia
Calcium
10 d 2 y
212 y
> 12 y
911 mg/dL
8.810.8 mg/dL
8.610 mg/dL
1.21.38 mmol/L
Calcium is one of the most abundant ions in the body.

It accounts for 1% to 2% of total body weight. Calcium
is necessary for many physiological functions including
neuromuscular activity, preservation of the integrity of cell
membranes, regulation of endocrine secretory activities,
blood coagulation, activation of the complement system,
and bone metabolism. Serum calcium concentrations are
controlled by the parathyroid gland. When serum calcium
is low, PTH secretion is stimulated, which increases bone
resorption, augments renal calcium conservation, and activates vitamin D, which increases calcium absorption from
the GI tract. When serum calcium is increased, the thyroid
releases calcitonin, which acts to inhibit bone resorption and
increase renal calcium excretion. Generally, serum calcium
concentrations are maintained by either renal excretion of
excess calcium or leaching of calcium from the bone.76
About 99% of the bodys calcium is found in teeth and
bone, with only 1% found in the serum. There are 3 forms
of calcium in the body: complexed, protein-bound, and
ionized. Complexed calcium is that combined with nonprotein anions such as phosphate, carbonate, and citrate. It
is not available for physiological activity. Slightly less than
half of the serum calcium is bound to protein, primarily
albumin. The serum calcium measures total serum calcium,
Hypercalcemia is most often seen in patients with hyperparathyroidism or cancer with bone metastases. It can
also occur with toxic serum concentrations of vitamin A
or vitamin D, chronic ingestion of milk and/or calcium
carbonate-containing antacids in the setting of kidney
insufficiency, immobility, tuberculosis, and medications.
Clinical signs and symptoms include fatigue, nausea,
vomiting, constipation, anorexia, and confusion. In severe
cases, cardiac dysrhythmias may be present. Mild hypercalcemia typically responds to fluid and ambulation. In severe
hypercalcemia, immediate treatment should be started
to prevent acute kidney failure, obtundation, ventricular
dysrhythmias, coma, and death. If a loop diuretic and IV
fluid are used to treat hypercalcemia (eg, to increase calcium
excretion), IV hydration with 0.9% sodium chloride should
be started immediately to prevent dehydration. Hemodialysis may be necessary for patients with life-threatening
hypercalcemia or those with kidney failure. 80
Hypocalcemia
Measured hypocalcemia is commonly encountered in
patients with hypoalbuminemia but does not require treatment unless the corrected calcium or ionized calcium is
found to be low. Signs and symptoms of hypocalcemia
include hypotension, decreased myocardial contractility,
prolonged QT interval, paresthesias, Chvosteks and
Trousseaus signs, muscle cramps, tetany, and seizures.
Causes of hypocalcemia include vitamin D deficiency or
the inability to activate vitamin D, hyperphosphatemia,
98
pseudohypoparathyroidism, decreased PTH activity,

sepsis, rhabdomyolysis, and massive blood transfusions.81
Medications can also cause hypocalcemia. Of particular
importance to the premature infant are furosemide,
phenobarbital, and phenytoin. 82 Sulfur-containing amino
acids (eg, cysteine) also increase renal calcium excretion.
The increased renal calcium excretion seen with cysteine
supplementation in PN solutions is counterbalanced by the
increased solubility of calcium and phosphorus in PN solutions supplemented with cysteine hydrochloride due to the
lower pH of the solution after cysteine is added.83, 84
Patients with severe hypocalcemia or acute symptomatic hypocalcemia require immediate treatment. IV calcium
comes in two salt forms: chloride and gluconate. Calcium
chloride contains 13.6 mEq of elemental calcium per gram;
calcium gluconate contains 4.65 mEq of elemental calcium
per gram. Because there is 3 times the elemental calcium
in calcium chloride compared to calcium gluconate,
calcium chloride is associated with a higher incidence of
tissue necrosis if extravasation occurs. 85 For hypocalcemic
tetany, 0.5 to 1 mEq/kg of calcium chloride infused over
5 to 10 minutes may be used; this dose may be repeated
in 6 hours or followed with a continuous infusion with
2.5 mEq/kg/d of calcium chloride.86, 87 If hypomagnesemia
is present, magnesium supplementation should be given to
facilitate correction of hypocalcemia. In cases of hypocalcemia secondary to hyperphosphatemia, treating with a
phosphate binder should be considered prior to giving IV
calcium to prevent calcium/phosphate precipitation in soft
tissues.
Phosphorus
Newborn:
10 days2 years:
212 years:
> 12 years:
4.59 mg/dL
4.56.7 mg/dL
4.55.5 mg/dL
2.74.5 mg/dL
Phosphorus, mainly in the form of phosphate, is the primary

intracellular anion in the body. It has many important functions including bone and cell membrane composition,
maintenance of normal pH, and provision of energy-rich
bonds (adenosine triphosphate, or ATP), and it is needed
in all cellular functions that require energy. Phosphorus is
required for glucose utilization, glycolysis, 2,3-diphosphoglycerate synthesis, neurological function, and muscular
function.88-90 Phosphorus homeostasis is maintained by GI
absorption, renal excretion, PTH, and distribution between
the ICF and ECF. Glucose and insulin, catecholamines, and
alkalosis all cause intracellular shifts of phosphorus. Cell
destruction and acidosis cause a shift to the ECF.77 Intravenous phosphorus requirements are 1 to 2.5 mmol/kg in
premature infants and 0.5 to 1 mmol/kg/d in term infants
and children up to 18 years of age. Oral phosphorus requirements vary with age (Table 9-4).
Hyperphosphatemia
Hyperphosphatemia is defined as a serum phosphate
concentration greater than 4.5 to 9 mg/dL, depending on
the patients age. Most patients are asymptomatic, but signs
and symptoms may include anorexia, nausea, vomiting,
dehydration, and neuromuscular irritability. The biggest
concern with hyperphosphatemia is metastatic calcification from elevated serum concentrations of calcium and
phosphate.91 Although various equations for predicting
metastatic calcification are used, the equations are not
accurate because of the variety of factors that determine
in vivo calcium/phosphate solubility. Ionized calcium is
much more reactive than phosphate, so hypercalcemia
with a mild hyperphosphatemia has a higher probability of
causing metastatic calcification than hyperphosphatemia
with slightly increased serum calcium. With the newer
phosphate-binding agents available, aluminum-containing
antacids are no longer recommended for the treatment or
prevention of hyperphosphatemia in patients with kidney
insufficiency because of the anemia, osteomalacia, and
central nervous system toxicity experienced with the use of
aluminum-containing agents in this patient population.92
Hypophosphatemia
Hypophosphatemia can be defined as a serum phosphorus
concentration below 2.7 mg/dL to 4.5 mg/dL, depending
on the patients age.47 Hypophosphatemia is common in
critical illness, malnutrition, alkalosis, and in patients
receiving phosphate binders (eg, aluminum- , magnesium- ,
and calcium-containing products, sevelamer, or sucralfate).
Signs and symptoms of hypophosphatemia include neurological, neuromuscular, cardiopulmonary, and hematologic
dysfunction.8890 Primary causes of hypophosphatemia
include inadequate intake of phosphate or the administration of large amounts of dextrose solutions in malnourished
patients who are at risk for developing refeeding syndrome
(Chapter 19).
Treatment of hypophosphatemia varies, depending
on the serum phosphorus concentration and the presence
of signs and symptoms. Mild asymptomatic hypophosphatemia can be treated with oral phosphate supplements,
assuming that the GI tract is functional. However, oral
supplements are not well absorbed and often cause diarrhea.
Patients with symptomatic or moderate to severe hypophosphatemia should be treated with IV phosphate. Two
salt forms are available for replacing phosphate: sodium
phosphate and potassium phosphate. Sodium phosphate
provides 4 mEq sodium for every 3 mmol phosphate, and
potassium phosphate provides 4.4 mEq potassium for
every 3 mmol phosphate. When ordering phosphate, the
dose should be ordered in millimoles of phosphate rather
than milliequivalent of the sodium or potassium component of the salt. Common recommendations for replacing
phosphate provide up to 0.32 mmol/kg of phosphate for
serum phosphorus levels < 1.5 mg/dL. This dose is often
inadequate and may require multiple boluses to reach
normal phosphorus levels.93,94 Higher doses have been
recommended for phosphorus replacement in adults, and
the higher supplemental doses have been used successfully
in pediatric patients (Table 9-6). Serum phosphate levels
should be checked 2 hours after the infusion is completed
and the patient should be redosed if needed. Phosphate
should be replaced no faster than 0.1 to 0.2 mmol/kg/h
to allow the phosphate time to move intracellularly and to
prevent possible hypocalcemia.95 If potassium phosphate
is used to replace the phosphate, the infusion rate should
be based on the potassium infusion rate. ECG monitoring
should accompany infusion of individual doses greater than
0.5 mEq/kg/h. Sodium phosphate is the preferred salt for
phosphate supplementation.
Table 9-6 Phosphate Replacement in Adults
Mild Depletion (2.33 mg/dL)
Moderate Depletion (1.62.2 mg/dL)
Severe Depletion (< 1.5 mg/dL)
0.16 mmol/kg
0.32 mmol/kg
0.64 mmol/kg
1. The intravenous administration of 100 mL of 0.9%

sodium chloride to a patient will:
A. Increase the intracellular fluid (ICF) compartment
by 100 mL but will not increase the extracellular
fluid (ECF) compartment.
B. Increase the ECF compartment by 100 mL, with a
75 mL increase in intravascular volume.
C. Increase the ECF compartment by 100 mL, with a
25 mL increase in intravascular volume.
D. Increase the ICF compartment by 50 mL, with a
25mL increase in intravascular volume.
2. A 1340-g neonate is placed on IV fluids/nutrition at
160 mL/kg/d. Over the next 5 days the weight decreased
to 1250 g due to the contraction of the ECF seen after
99
birth. On day 7, the patients serum sodium concentration is 137 mEq/L. The patient continues to receive
160 mL/kg/d of IV fluids that contain 3 mEq/kg/d
of sodium. Over the next 3 days, the patients serum
sodium concentration has decreased to 129 mEq/L.
The patient does not appear to be fluid overloaded,
septic, or suffering from necrotizing enterocolitis. The
patients weight has remained around 1250 g. What is
the most appropriate way to correct the serum sodium
concentration?
A. Increase the sodium concentration in the IV solution
because the current sodium intake is inadequate to
keep up with the renal and GI sodium losses.
B. Decrease the maintenance IV fluid rate by 25%
because the decrease in the serum sodium concentration is probably due to fluid overload.
C. Give sodium chloride orally to replace the sodium
deficit.
D. Decrease the maintenance IV fluid by 25% and
give sodium chloride orally because the decrease
in the serum sodium concentration is probably due
to fluid overload, but the serum sodium concentration is a critical value; thus treatment must begin
immediately.
3. An 8-year-old child who weighs 27 kg is admitted for
nausea, vomiting, and failure to thrive. The patient is
started on maintenance IV fluids containing D5W/0.2
NaCl with 20 mEq KCl per liter. The following morning,
the serum phosphorus concentration is 1.2 mg/dL and
the serum potassium concentration is 3.4 mEq/L.
What is the most appropriate way to correct the serum
phosphorus concentration?
A. Add sodium phosphate 1 mmol/kg to the maintenance IV fluid.
B. Add potassium phosphate 1 mmol/kg to the maintenance IV fluid.
C. Give sodium phosphate 27 mmol (36 mEq sodium)
intravenously over 8 hours.
D. Give potassium phosphate 27 mmol (40 mEq potassium) intravenously over 8 hours.
References
1. Steijaert M, Deurenberg P, Van Gaal L, De Leeuw I. The use

of multi-frequency impedance to determine total body water
and extracellular water in obese and lean female individuals.
Int J Obes Relat Metab Disord. 1997;21(10):930934.
100
2. Sartorio A, Malavolti M, Agosti F, Marinone PG, Caiti O,

Bedogni G. Body water distribution in severe obesity and its
assessment from eight-polar bioelectrical impedance analysis.
Eur J Clin Nutr. 2005;59(2):155160.
3. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders. 5th ed. New York, NY: McGraw-Hill; 2001.
4. Whitmire SJ. Fluids and electrolytes. In: Gottschlich MM, ed.
Science and Practice of Nutritional Support: A Case-Based Core
Curriculum. Dubuque, IA: Kendall/Hunt; 2001:5384.
5. Bhatia J. Fluid and electrolyte management in the very low
birth weight neonate. J Perinatol. 2006;26(Suppl 1):S19S21.
6. Bakris GL, Stein JH. Sodium metabolism and maintenance of
extracellular fluid volume. In: Arieff AI, DeFronzo RA, eds.
Electrolyte and Acid-Base Disorders. 2nd ed. New York, NY:
Churchill Livingstone; 1995:2950.
7. Soheyl B, Klaus Z, Zoltan S, et al. Small-volume fluid resuscitation with hypertonic saline prevents inflammation but not
mortality in a rat model of hemorrhagic shock. Shock. 2006;
25(3):283289.
8. Mange K, Matsuura D, Cizman B, et al. Language guiding
therapy: the case of dehydration versus volume depletion. Ann
Int Med. 1997; 127(9):848853.
9. Hansen M. Fluid balance. In: Hansen M, ed. Pathophysiology:
Foundations of Disease and Clinical Intervention. Philadelphia,
PA: Saunders; 1998:160175.
10. Toney GM, Chen QH, Cato MJ, Stocker SD. Central osmotic
regulation of sympathetic nerve activity. Acta Physiol Scand.
2003; 177(1):4355.
11. Sutsch G, Bertel O, Rickenbacher P, et al. Regulation of aldosterone secretion in patients with chronic congestive heart
failure by endothelins. Am J Cardiol. 2000; 85(8):973976.
12. Quinn SJ, Williams GH. Regulation of aldosterone secretion.
Annu Rev Physiol. 1988; 50:409426.
13. Weber KT. Aldosterone in congestive heart failure. N Engl J
Med. 2001;345(23):16891697.
14. Thomson CJ, Bland J, Burd J, Baylis PH. The osmotic thresholds for thirst and vasopressin release are similar in healthy
man. Clin Sci. 1986;71:651656.
15. Robertson GL. Thirst and vasopressin function in normal
and disordered states of water balance. J Lab Clin Med.
1983;101(3):351371.
16. Langley G. Fluid, electrolytes, and acid-base disorders.
In: Gottschlich MM, DeLegge MH, Mattox T, Mueller C,
Worthington P, eds. The A.S.P.E.N. Nutrition Support Core
Curriculum: A Case-Based Approach The Adult Patient. Silver
Spring, MD: American Society for Parenteral and Enteral
Nutrition; 2007:104128.
17. Zimmerman EA, Ma LY, Nilaver G. Anatomical basis of thirst
and vasopressin secretion. Kidney Int. 1987; 21:S14S19.
18. Uretsky BF, Verbalis JG, Generalovich T, Valdes A,
Reddy PS. Plasma vasopressin response to osmotic and
hemodynamic stimuli in heart failure. Am J Physiol.
1985;248(3):H395H402.
19. Sterns RH, Spital A. Disorders of water balance. In: Kokko JP,
Tannen RL, eds. Fluids and Electrolytes, 2nd ed. Philadelphia,
PA: Saunders; 1990:139194.
20. Knepper MA, Rector CF. Urinary concentration and dilution. In: Brenner BM, Rector FC, eds. The Kidney. 4th ed. Vol
1. Philadelphia, PA: Saunders; 1991:445482.
21. Mange K, Matsuura D, Cizman B, et al. Language guiding
therapy: the case of dehydration versus volume depletion. Ann
Intern Med. 1997;127(9):848853.
22. Heitz U, Horne M. Pocket Guide to Fluid, Electrolytes, and AcidBase Balance. 5th ed. St Louis, MO: Mosby-Year Book; 2004.
23. Mirtallo J, Canada T, Johnson D, et al. Safe practices for parenteral nutrition. J Parenter Enteral Nutr. 2004;28(6):S39S70.
24. Holliday MA, Segar WE. The maintenance need for water in
parenteral fluid therapy. Pediatrics. 1957;19:823832.
25. Choong K, Bohn D. Maintenance parenteral fluids in the critically ill child. J Pediatr (Rio J). 2007;83(2 Suppl):S3S10.
26. Lorenz JM, Kleinman LI, Ahmed G, et al. Phases of fluid and
electrolyte homeostasis in the extremely low birth weight
infant. Pediatrics. 1995;96(3):484489.
27. Modi N. Sodium intake and preterm babies. Arch Dis Child.
1993;69:8791.
28. Bauer K, Bovermann G, Roithmaier A, Gotz M, Proiss A,
Versmold HT. Body composition, nutrition and fluid balance
during the first two weeks of life in preterm neonates weighing
less than 1500 grams. J Pediatr. 1991;118(4):615620.
29. Sankar MJ, Agarwal R, Mishra S, Deorari AK, Paul VK.
Feeding of low birth weight infants. Indian J Pediatr.
2008;75(5):459469.
30. Shaffer SG, Brandt SK, Hall RT. Postnatal changes in
total body water and extracellular volume in the preterm
infant with respiratory distress syndrome. J Pediatr.
1986;109(3):509514.
31. Tang W, Ridout D, Modi N. Influence of respiratory distress
syndrome on body composition after preterm birth. Arch Dis
Child Fetal Neonatal Ed. 1997;77(1):F28F31.
32. Rutter N, Hull D. Water loss from the skin of term and preterm
babies. Arch Dis Child. 1979;54(11):858868.
33. Costarino AT, Baumgart S. Modern fluid and electrolyte
management of the critically ill premature infant. Ped Clin
North Am. 1986;33(1):153178.
34. Kjartansson S, Hammarlund K, Sedin G. Insensible water
loss from the skin during phototherapy in term and preterm
infants. Acta Paediatr. 1992;81(10):764768.
35. Grunhagen DJ, de Boer MG, de Beaufort AJ, Walther FJ.
Transepidermal water loss during halogen spotlight therapy
in preterm infants. Pediatr Res. 2002;51(3):402405.
36. Maayan-Metzger A, Yosipovitch G, Hadad E, Sirota L. Trans
epidermal water loss and skin hydration in preterm infants
during phototherapy. Am J Perinatol. 2001;18(7):393396.
37. Hartnoll G. Basic principles and practical steps in the
management of fluid balance in the newborn. Semin Neonatal.
2003;8(4): 307313.
38. Davis ID, Avner ED. Neonatal-perinatal medicine: diseases of
the fetus and infant. In: Fanaraff AA, Martin RJ, eds. Fluid and
Electrolyte Management. 7th ed. St. Louis, MO: CV Mosby;
2002:619627.
39. Kumar V, Cotran RS, Robbins SL. Disorders of vascular flow
and shock. In: Kumar V, Cotran RS, Robbins SL, eds. Basic
Pathology. 5th ed. Philadelphia, PA: Saunders; 1992:6191.
40. Pincus MR, Preuss HG, Henry JB. Evaluation of renal function, water, electrolytes, acid-base balance and blood gasses.
In: Henry JB, ed. Clinical Diagnosis and Management by
Laboratory Methods. 19th ed. Philadelphia, PA: Saunders;
1996:139149.
41. Hwai-Ping S. Sodium, chloride, and potassium. In: Stipanuk
M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia, PA: Saunders; 2000:686710.
42. Wilkins BH. Renal function in sick very low birthweight
infants: 3. Sodium, potassium, and water excretion. Arch Dis
Child. 1992; 67(10):11541161.
43. Hartnoll G, Betremieux P, Modi N. Randomised controlled
trial of postnatal sodium supplementation on body composition in 25 to 30 week gestational age infants. Arch Dis Child
Fetal Neonatal Ed. 2000;82(1):F24F28.
44. Roberts KB. Fluids and electrolytes: parenteral fluid therapy.
Pediatr Rev. 2001;22(11):380387.
45. Finberg L. Hypernatremic (hypertonic) dehydration in
infants. N Engl J Med. 1973;289(4):823832.
46. Holliday MA, Kalayci MN, Harrah J. Factors that limit brain
volume changes in response to acute and sustained hyper- and
hyponatremia. J Clin Invest. 1968;47(8):19161928.
47. Robertson J. Blood chemistries and body fluids. In: Robertson
J, Shilkofski N, eds. The Harriet Lane Handbook. 7th ed. Philadelphia, PA: Elsevier Mosby; 2006:661672.
48. Horisberger J, Lemas V, Kraehenbuhl J, Rossier BC. Structure-function relationship of Na,K-ATPase. Annu Rev Physiol.
1991;53:565584.
49. Rodriguez-Soriano J. Potassium homeostasis and its disturbance in children. Pediatr Nephrol. 1995;9(3):364374.
50. Ganguly A. Primary aldosteronism. N Engl J Med.
1998;339(25):18281834.
51. Kelvay LM, Bogden JD, Aladjem M, et al. Renal and gastrointestinal potassium excretion in humans: new insight based on
new data and review and analysis of published studies. J Am
Coll Nutr. 2007;26(2):103110.
52. Mathialahan T, Sandle GI. Dietary potassium and laxatives as
regulators of colonic potassium secretion in end-stage renal
disease. Nephrol Dial Transplant. 2003;18(2):341347.
53. Brown RS. Extrarenal potassium homeostasis. Kidney Int.
1986;30(1):116127.
54. Subramanian S, Agarwal R, Deorari AK, Paul VK,
Bagga A. Acute renal failure in neonates. Indian J Pediatr.
2008;75(4):385391.
55. Strom BL, Carson JL, Schinnar R, et al. Upper gastrointestinal
tract bleeding from oral potassium chloride. Comparative risk
from microencapsulated vs wax matrix formulations. Arch
Intern Med. 1987;147(5):954957.
56. Potassium chloride. In: Taketomo CK, Hodding JH, Kraus
DM, eds. Pediatric Dosage Handbook. 15th ed. Hudson, OH:
Lexi-Comp; 2008:14321435.
57. Potassium chloride. In: Phelps SJ, Hak EB, Crill CM, eds. The
Teddy Bear Book: Pediatric Injectable Drugs. 8th ed. Bethesda,
MD: American Society of Health-System Pharmacists;
2007:368369.
101
58. Whang R, Whang DD, Ryan MP. Refractory potassium repletion. A consequence of magnesium deficiency. Arch Intern
Med. 1992;152(1):4045.
59. Reinhart RA. Magnesium metabolism. A review with special
and serum levels. Arch Intern Med. 1988;148(11):24152420.
60. Zaloga GP, Roberts PR. Calcium, phosphorus, and magnesium disorders. In: Ayres SM, Grenvik NA, Holbrook PR,
Shoemaker WC, eds. Textbook of Critical Care. 4th ed. Philadelphia, PA: Saunders; 2000:905928.
61. Quamme GA. Laboratory evaluation of magnesium status.
Renal function and free intracellular magnesium concentration. Clin Lab Med. 1993;13(1):209223.
62. Teng RJ, Wu TJ, Sharma R, Garrison RD, Hudak ML. Early
neonatal hypotension in premature infants born to preeclamptic mothers. J Perinatol. 2006;26(8):471475.
63. Whang R, Ryder KW. Frequency of hypomagnesemia and
hypermagnesemia. Requested vs routine. JAMA. 1990;
263(22):30633064.
64. Reinhart RA. Magnesium metabolism. A review with special
and serum levels. Arch Intern Med. 1988;148:(11)24152420.
65. Van Hook JW. Endocrine crises. Hypermagnesemia. Crit Care
Clin. 1991;7(1):215223.
66. Ramsey PS, Rouse DJ. Magnesium sulfate as a Tocolytic
agent. Semin Perinatol. 2002;25(4):236247.
67. Weisinger JR, Bellorin-Font E. Magnesium and phosphorus.
Lancet. 1998;352(9125):391396.
68. Lee CT, Tsai WY, Tung YC, Tsau YK. Transient
pseudohypoparathyroidism as a cause of late-onset
hypocalcemia in neonates and infants. J Formos Med Assoc.
2008;107(10):806810.
69. Desai TK, Carlson RW, Geheb MA. Prevalence and
clinical implications of hypocalcemia in acutely ill
patients in a medical intensive care setting. Am J Med.
1988;84(2):209214.
70. Ryzen E, Wagers PW, Singer FR, Rude RK. Magnesium
deficiency in a medical ICU population. Crit Care Med.
1985;13(1):1921.
71. Dacey MJ. Hypomagnesemic disorders. Crit Care Clin.
2001;17(1):155173, viii.
72. Magnesium sulfate. In: Taketomo CK, Hodding JH, Kraus
Lexi-Comp; 2008:10901092.
73. Topf MJ, Murray PT. Hypomagnesemia and hypermagnesemia. Rev Endocr Metab Disord. 2003;4(2):195206.
74. Oster JR, Epstein M. Management of magnesium depletion.
Am J Nephrol. 1988;8(5):349354.
75. Herbert P, Mehta N, Wang J, Hindmarsh T, Jones G, Cardinal
P. Functional magnesium deficiency in critically ill patients
identified using a magnesium-loading test. Crit Care Med.
1997;25(5):749755.
76. Chattopadhyay N, Mithal A, Brown EM. The calciumsensing receptor: a window into the physiology and
pathophysiology of mineral ion metabolism. Endocrinol Rev.
1996;17(5):289307.
102
77. Popovtzer MM. Disorders of calcium, phosphorus, vitamin D,

and parathyroid hormone activity. In: Schrier RW, ed. Renal
and Electrolyte Disorders. 6th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2003:216277.
78. Jain A, Agarwal R, Sankar MJ, Deorari AK, Paul VK. Hypocalcemia in the newborn. Indian J Pediatr. 2008;75(2):165169.
79. Bushinsky DA, Monk RD. Electrolyte quintet: Calcium.
Lancet. 1998; 352(9124):306311.
80. Zivin JR, Gooley T, Zager RA, Ryan MJ. Hypocalcemia: a
pervasive metabolic abnormality in the critically ill. Am J
Kidney Dis. 2001;37(4):689698.
81. Guise TA, Mundy GR. Clinical review 69: Evaluation of
hypocalcemia in children and adults. J Clin Endocrinol Metab.
1995;80(5):14731478.
82. Schmidt GL, Baumgartner TG, Fischlschweiger W, Sitren
HS, Thakker KM, Cerda JJ. Cost containment using cysteine
HCl acidification to increase calcium/phosphate solubility
in hyperalimentation solutions. J Parenter Enteral Nutr.
1986;10(2):203207.
83. Wood RJ, Sitrin MD, Cusson GJ, Rosenberg IH. Reduction
of total parenteral nutrition-induced urinary calcium loss by
increasing the phosphorus in the total parenteral nutrition
prescription. J Parenter Enteral Nutr. 1986;10(2):188190.
84. Semple P, Booth C. Calcium chloride; a reminder. Anaesthesia.
1996;51(1):93.
85. Calcium chloride. In: Phelps SJ, Hak EB, Crill CM, eds. The
Teddy Bear Book: Pediatric Injectable Drugs. 8th ed. Bethesda,
MD: American Society of Health-System Pharmacists;
2007:7071.
86. Calcium chloride. In: Taketomo CK, Hodding JH, Kraus
Lexi-Comp; 2008:290291.
87. Davis KD, Attie MF. Management of severe hypercalcemia.

Crit Care Clin. 1991;7(1):175190.
88. Peppers MP, Geheb M, Desai T. Endocrine crises. Hypophosphatemia and hyperphosphatemia. Crit Care Clin.
1991;7(1):201214.
89. Knochel JP. The pathophysiology and clinical characteristics of severe hypophosphatemia. Arch Intern Med.
1977;137(2):203220.
90. Worley G, Claerhout SJ, Combs SP. Hypophosphatemia
in malnourished children during refeeding. Clin Pediatr.
1998;37(6):347352.
91. Clark Cl, Sacks GS, Dickerson RN, Kudsk KA, Brown RO.
Treatment of nutrition support using a graduated dosing
scheme: results from a prospective clinical trial. Crit Care
Med. 1995;23(9):15041511.
92. Sperschneider H, Gunther K, Marzoll I, Kirchner E, Stein G.
Calcium carbonate (CaCO3): an efficient and safe phosphate
binder in haemodialysis patients? A 3-year study. Nephrol Dial
Transplant. 1993;8(6):530534.
93. Potassium phosphate. In: Phelps SJ, Hak EB, Crill CM,
eds. The Teddy Bear Book: Pediatric Injectable Drugs. 8th ed.
Bethesda, MD: American Society of Health-System Pharmacists; 2007:370371.
94. Goodman WG, Goldin J, Kuzion BD, et al. Coronaryartery calcification in young adults with end-stage renal
disease who are undergoing dialysis. N Engl J Med.
2000;342(20):14781483.
95. Ritz E. The clinical management of hyperphosphatemia. J
Nephrol. 2005;18(3):221228.
PART II
AGE-SPECIFIC NUTRITION FOR

GROWTH AND DEVELOPMENT
10. Nutrition and Early Development. . . . . . . . . . . . . . 105

11. Human Milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
12. Infant Formulas and Complementary Feeding. . . . 129
Kelly Green Corkins, MS, RD, CNSD
13. Growth Assessment and Monitoring . . . . . . . . . . . 143
14. Obesity and Metabolic Disorders. . . . . . . . . . . . . . 149
Robert Murray, MD
15. Lipid Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Shirley Huang, MD
16. Use of Fad and Popular Diets. . . . . . . . . . . . . . . . . 169
17. Sports Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Nutrition and Early Development
10
Russell J. Merritt, MD, PhD, FAAP, Barbara Marriage, PhD, RD, and Ricardo Rueda, MD, PhD
Learning Objectives
CONTENTS
Nutrition Physiology of Pregnancy . . . . . . . . . . . . . . . . . . 105
Impact of Maternal Dietary Deficiencies onthe Fetus. . 107
Macronutrients
Calcium
Iron
Folic Acid and Vitamin B12
Vitamin E
Multiple Micronutrients
Impact of Nutrition and Other Stresses on Fetal

Metabolism, Organ Growth, andDevelopment . . . . . . . . 109
History and Epidemiology of the Fetal
Originsof Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
Hypothesis
Expansion to Postnatal Growth Period
Integration of Pre- and Postnatal

Programming Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
Early Programming in the Premature Infant
Animal Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

Animal Models of Dietary Manipulation
Animal Models Induced by Glucocorticoid Exposure
Animal Models Induced by Surgical Manipulation
Third and Future Generation Effects . . . . . . . . . . . . . . . .

Implications for Future Health . . . . . . . . . . . . . . . . . . . . .
Implications for Current Practice. . . . . . . . . . . . . . . . . . .
Future Research Needs. . . . . . . . . . . . . . . . . . . . . . . . . . .
114
115
115
116
1. Achieve familiarity with the normal physiology and

metabolism of the fetus and know nutrient deficiencies
associated with adverse pregnancy outcomes.
2. Know common late adverse manifestations of early
programming observed in epidemiologic and animal
studies.
3. Be aware of potential mechanisms involved in late and
transgenerational effects of early life programming.
Nutrition Physiology of Pregnancy
Pregnancy proceeds from fertilization to implantation

through development and maturation of the placenta (of
fetal origin) and the fetus. A healthy pregnancy is dependent on maternal nutrition status at conception, adequate
oxygen delivery (blood-flow dependent) to the placenta
and fetus, and the availability of appropriate amounts of
nutritional substrates in the hormonal matrix that facilitates development of the placenta and the fetus. Early in
gestation, placental mass is high relative to that of the fetus,
and in later gestation this ratio declines. Initially, placental
transport is largely dependent on increases in placental size,
but later in pregnancy, both placental transport function
and placental size must increase to meet the needs of the
rapidly growing fetus.
The uterus and placenta are perfused by the maternal
uterine arteries, and the placenta transfers nutrients and
gasses bi-directionally across the microvillous maternalfacing membranes and fetal-facing baso-lateral membranes
of the syncytiotrophoblast and into the fetal venous
circulation. The placenta has a relatively higher glucose
requirement than the fetus to perform its important functions of substrate regulation, transport, and hormone
105
106
secretion. In intrauterine growth restriction (IUGR) pregnancies, placental weight is reduced more than fetal weight.
In contrast, the placenta may be increased in mass in gestational diabetes.1
Much of what we know about fetal substrate metabolism comes from extensive studies of the late gestation
ovine fetus initiated by Battaglia and many other investigators associated with the Perinatal Research Center at the
University of Colorado School of Medicine.28 The umbilical
vein transports oxygen and nutrients to the fetus toward the
fetal liver and ductus venosus, which variably shunts blood
around the liver to the fetal heart and brain. Until the time
of birth, when the lungs expand and pulmonary artery
resistance increases, the lungs are also partly bypassed. This
increases oxygenated blood flow to the fetal brain via the
ductus arteriosus that connects the pulmonary artery and
the aorta. Blood containing amino acids, metabolites, and
carbon dioxide (CO2) returns to the placenta by way of the
2 umbilical arteries.
The major energy source for the fetus is glucose, which
normally all comes from maternal transport to the fetus and
placenta.2 It also uses lactate produced in the placenta and
endogenously.9 Glucose uptake by placental and fetal tissues
and fetal growth are proportional to glucose delivery. 2 The
fetal pancreas secretes insulin by mid-gestation and responds
to variations in the glucose delivery rate. Normally the fetal
liver is not active in gluconeogenesis. Fetal tissue glucose
transporters and intracellular downstream metabolic regulators are modulated by glucose and insulin levels in the
fetus. Insulin-responsive fetal tissues include the heart,
liver, skeletal muscle, and adipose tissue. Placental glucose
uptake is not regulated by insulin. When fetal glucose supply
is limited, fetal glucose oxidation is maintained by virtue of
increased uterine artery/umbilical vein glucose gradient
and gluconeogenesis from amino acids in the fetus: the
fetus develops with mechanisms that tend to keep its energy
metabolism relatively constant, while growth is, at times of
deficient energy supply, expendable.3
Amino acids are the second most important macronutrient in the fetus with at least 14 complex amino acid
transporter systems on both of the syncytiotrophoblast
membranes.10 The large neutral and branched-chain amino
acids are transported most directly proportional to their
maternal concentration. 5 Because of shared transporters
and competition among amino acids for specific transporters, an increase in delivery of multiple amino acids
sharing the same transporter to the uterine artery may have
a different effect than an increase of a single amino acid on
the uptake and transport of a specific amino acid. All amino
acids except tryptophan are in much higher concentration

in the placenta than in maternal blood. Leucine appears to
have specific trophic effects on the placenta and the fetus,
possibly because of its impact on mammalian target of
rapamycin (mTOR), which is a critical regulator of protein
synthesis. IUGR fetuses have reduced fetal enrichment of
leucine relative to the maternal circulation.4 Other specific
amino acids such as arginine have not only nutrient, but,
similarly, regulatory and developmental effects.10 The fetal
liver makes glutamate (largely from glutamine), aspartate, and serine; the flux of glutamate and serine is in the
direction of the placenta, where they are metabolized, the
glutamate oxidized to CO2 . Serine is important to the onecarbon pool for nucleotide biosynthesis and as a precursor
for glycine and gluconeogenesis. 5
When there is reduced oxygen, glucose, and amino
acid availability to the fetus by virtue of reduced umbilical
vein blood flow (associated with placental transport insufficiency), fetal weight gain slows. There are compensatory
increases in fetal amino acid catabolism such that changes
in fetal blood amino acid concentrations are minimized.
This situation is associated with altered substrate distribution and changes in relative organ growth. When glucose
(and other substrate) supply is limited and the fetus is
relatively hypoglycemic, growth of the brain, kidney, and
adrenals is relatively maintained. Growth of the spleen,
liver, pancreas, and lung are reduced in excess of the
(primate) body weight decrement.11 More blood is shunted
through the ductus venosus, reducing splanchnic substrate
availability. This leads to slower growth and altered fetal
liver metabolism and reduced pancreatic beta cell mass or
function, depending on the stage of pregnancy. The most
common cause of IUGR is placental transport insufficiency
(oxygen, glucose, amino acids), which may be related to
local uterine factors, maternal malnutrition, advanced
maternal diabetes, hypertension, or other maternal or
placental pathology.12,13
Central metabolic mediators for regulatory hormone
and metabolic changes in the fetus are fetal insulin, cortisol
(increased levels of which are associated with reduced
glucose uptake, increased gluconeogenesis, and slower fetal
growth),14 and insulin-like growth factors (IGFs), which are
critical for placental development and function and protein
synthesis in fetal tissues.15,16 The increased insulin levels
seen in response to acute hyperglycemia (in sheep) diminish
with sustained hyperglycemia, and glucose transporters
in liver, muscle, and adipose tissue decline, although total
fetal glucose uptake remains elevated. The liver volume may
beincreased. Many of these fetal adaptations may persist,
NUTRITION AND EARLY DEVELOPMENT
alter postnatal substrate metabolism, and determine the

metabolic response to postnatal and later diet.
Specific common metabolic/hormonal derangements
that influence organ growth and metabolic development of
the fetus include hypoglycemia, hyperglycemia, maternal
or gestational diabetes, and activation of the fetal hypothalamic-pituitary-adrenal (HPA) axis (summarized by
McMillen17) by a variety of intrauterine insults. The fetus
and its uteroplacental support system are highly adaptive
to their vascular supply, oxygenation state, and metabolic
substrate availability. In this formative stage of life, thousands of responses at the fetal, organ, tissue, membrane,
cytosolic, and nuclear levels determine the survival, health,
and function of the fetus. These responses are regulated at
the enzyme substrate level, others at the level of messenger
ribonucleic acid (mRNA) transcription, and some at the
nuclear level by way of epigenetic modification. Some of
these adaptations are transient and others, particularly with
prolonged exposure, appear to be permanent. Epigenetic
changes involve gene regulation effects that are inherited
from one cell generation to the next. These gene expression modifications do not change the deoxyribonucleic acid
(DNA) sequence.18 Examples of epigenetic mechanisms
include DNA methylation, histone modification, and alterations in noncoding RNAs.19 Epigenetic modifications of
cells in specific organs help determine the final metabolic
phenotype, which is a product of both genetic inheritance
and developmental environmental influences on gene
expression. Vulnerability to environmental and dietary
influences appears to continue well past the time of birth.
Fetal and early postnatal plasticity allows survival, but may
also set the stage for later maladaptive metabolic responses,
particularly to metabolic environments different from that
experienced early in development (eg, food surfeits versus
scarcity).20
Impact of Maternal Dietary Deficiencies

onthe Fetus
Maternal nutrition during pregnancy can exert long-lasting

effects on the health of the offspring.21 These effects may
be due to undernutrition or deficit of specific nutrients, or
to an excess of energy or nutrients. Epidemiological and
animal studies suggest that fetal adaptive responses to the
intrauterine environment, including maternal malnutrition,
overnutrition, or diabetes, may increase the risk of many
chronic diseases in adulthood, including Type 2 diabetes and
coronary heart disease (CHD).22 Animal studies also show
that both maternal undernutrition and overnutrition reduce
placental-fetal blood flow and slow fetal growth. Impaired
107
placental synthesis of nitric oxide, a major vasodilator and

angiogenesis factor, and polyamines, key regulators of DNA
and protein synthesis, may provide an explanation for IUGR
in response to the 2 extremes of nutrition problems with
the same pregnancy outcome. Placental and fetal growth
is most vulnerable to maternal nutrition status during the
peri-implantation period and the period of rapid placental
development (the first trimester of gestation).
There has been extensive clinical research, using both
observational and interventional study designs, that allows
some quantification of the effects of maternal anthropometric indices, dietary intake in pregnancy, and nutritional
supplements with respect to measures of fetal size and
maturity at birth. Overall, these studies find a strong positive association between maternal pre-pregnancy nutrition
status and the ability of a mother to nourish her growing
fetus. Recent evidence also suggests that periconceptional
undernutrition, as well as pregnancy undernutrition, are
important determinants of the length of gestation. Gestational weight gain and nutritional interventions during
pregnancy appear able to modify this association by
altering the rate of fetal growth, although the extent of the
modification appears to be dependent on maternal baseline
nutrition status, and is modest.23 Current estimates of nutrition needsare provided in Table 10-1.
Macronutrients
In terms of maternal macronutrient status, there is some
evidence that balanced protein/energy supplementation
may be beneficial for decreasing rates of low birth weight
(LBW) and small for gestational age (SGA) deliveries,
especially in populations where women have chronically
marginal nutrition status prior to pregnancy.15 However,
overall analysis of the available evidence suggests that
maternal supplementation with balanced or high-protein
diets had no beneficial effects on fetal growth. There is
limited evidence that protein supplementation adversely
affected fetal growth rate (as measured by mean birth
weight) and therefore potentially increased LBW deliveries.
The effect of energy/protein restriction has been also evaluated in women who were classified as obese pre-pregnancy
or had rapid early gestational weight gain. In women who
were obese before pregnancy, there have been no benefits to
fetal growth of restricting energy and protein during gestation, although evidence from controlled trials is limited. 23
It has also been reported that high intakes of protein and
fat during pregnancy may impair development of the
fetal pancreatic beta cells and lead to insulin deficiency in
theoffspring.16
108
On the other hand, very recent studies have demonstrated that a low-protein diet in utero had a deleterious
effect on bone development in the offspring that persisted
into adulthood.24 The offspring displayed significant differences in bone structure and density at various sites. These
differences are indicative of significantly altered bone
turnover.25
Table 10-1 Recommended Daily Nutrient Intakes During Pregnancy
Water
Energy
Carbohydrate
Total fiber
Linoleic acid
Linolenic acid
Protein
Vitamin A
Vitamin C
Vitamin D
Vitamin E
Vitamin K
Thiamin
Riboflavin
Niacin
Vitamin B6
Folate
Vitamin B12
Pantothenic acid
Biotin
Choline
Calcium
Chromium
Copper
Fluoride
Iodine
Iron
Magnesium
Manganese
Molybdenum
Phosphorus
Selenium
Zinc
Potassium
Sodium
Chloride
3L
Varies by age, pregnancy stage, BMI, activity
175 g
28 g
13 g
1.4 g
71 g
750770 mcg*
8085 mg/d*
5 mcg
15 mg
7590 mcg*
1.4 mg
1.4 mg
18 mg
1.9 mg
600 mcg
2.6 mcg
6 mg
30 mcg
450 mg
10001300 mg*
2930 mcg*
1000 mcg
3 mg
220 mcg
27 mg
350400 mg*
2 mg
50 mcg
7001250 mg*
60 mcg
1112 mg*
4.7 g
1.5 g
2.3 g
* Varies by age group.

Adapted from U.S. Dietary Reference Intakes (www.nap.edu).
Calcium
In terms of specific micronutrients, maternal calcium
supplementation may have a beneficial effect on fetal
growth, particularly in women with low calcium status at
the outset of pregnancy or who were classified as being at
risk of gestational hypertension. Calcium supplementation during pregnancy can be linked directly to increased
bone density and bone length of neonates.26 The effects on
fetal growth appeared to come partly from a reduction in
preeclampsia and resultant lengthened gestation.23
Iron
Some studies have reported that iron deficiency anemia
early in pregnancy was associated with greater than a
twofold increase in the risks of LBW and preterm delivery.21
In addition, reduced iron availability for brain iron accretion is associated with persisting developmental and
behavioral changes. A number of conditions associated with
fetal growth retardation or macrosomia such as diabetes,
placental insufficiency, and smoking restrict iron availability
during gestation and predispose to later iron deficiency. 27
Folic Acid and Vitamin B12
In well-nourished populations, folic acid needs are usually

met by dietary intake. However, in some countries (eg, the
United States), it is recommended that pregnant women
consume 600 mcg of folic acid per day to reduce the risk
of neural tube defects (Table 10-1). A dietary deficiency of
folate interferes with the growth of the fetus. Low maternal
folate intake (< 240 mcg/d) has been associated with a
greater than threefold increase in the risk of LBW and
preterm delivery. A metabolic effect of folate deficiency is
elevation of homocysteine, and women with high homocysteine levels are more likely to have a reproductive history
of preeclampsia, preterm delivery, LBW, or fetal growth
restriction.21 A recent study carried out in India has highlighted that dietary methyl donors including B12 and folate
seem to play a major role in fetal programming. Maternal
low B12 status along with normal to high folate status
predicted later adiposity and insulin resistance in children.
Thus, 1-C (methyl) metabolism seems to play a key role in
fetal programming.28
Vitamin E
The plasma concentration of -tocopherol, the most
common isomer of vitamin E, was positively related to fetal
growth (birth weight for gestation), reduced small-forgestation births, and increased risk of large-for-gestation
births. Concentrations of -tocopherol were positively
related to the use of prenatal multivitamins before and

during pregnancy and to vitamin E in the maternal diet.
Emerging evidence suggests that the effect of vitamin E on
fetal growth may be via increased blood flow and nutrient
supply to the fetus.21
Multiple Micronutrients
There have been few studies published to examine whether
multiple micronutrient supplements might be more
beneficial than single micronutrients. There is evidence of
interactions of several micronutrients at the metabolic level.
Little is yet known about the significance of these interactions for pregnancy outcomes, especially in developing
countries where nutrient deficiencies rarely occur in isolation and multiple micronutrient deficiencies are common. 29
A meta-analysis of global multinutrient supplementation
studies found a small effect on birth weight between ironfolate supplementation or placebo. 30
Impact of Nutrition and Other Stresses

on Fetal Metabolism, Organ Growth,
andDevelopment
Deprivation of nutrients and/or oxygen in utero alters fetal

metabolism in a manner that changes body growth and
the development of individual fetal tissues. 31 The effects of
varying nutrient availability on fetal metabolism depend
on the specific nature of the nutrition variation and on
the duration, severity, and gestational age at onset of the
insult. Deprivation of oxidative substrates such as glucose
produces a different metabolic response in the fetus from
that seen from oxygen deprivation alone or when there is
combined oxygen and substrate deficiency. These different
nutrition challenges also have different effects on the uteroplacental tissues and on the fetal hormonal environment,
both of which influence the availability and metabolic fate
of specific nutrients in the fetus. 32
Many of the nutritionally induced alterations in
fetal metabolism and growth are likely to be mediated
by hormonal changes in either the mother or the fetus.
Dietary restriction is known to alter maternal concentrations of growth hormone (GH), insulin-like growth factors
(IGFs), insulin, glucocorticoids, leptin, thyroid hormones,
and placental lactogen. 31 These hormones alter maternal
metabolite concentrations that in turn influence fetal
substrate availability, particularly for those metabolites
crossing the placenta against a concentration gradient. In
general, reducing fetal delivery of oxygen and nutrients
lowers anabolic hormones (eg, insulin, IGFs, and thyroid
hormones) and increases catabolic hormone concentrations
109
(eg, cortisol, catecholamines, glucagons, and GH). The

anabolic hormones tend to increase the uptake and utilization of glucose and reduce the oxidation of amino acids.
They also enhance protein accretion by stimulating protein
synthesis, by reducing proteolysis, or both. The catabolic
hormones tend to increase fetal glucose production by activating hepatic gluconeogenesis. They also reduce protein
accretion and fetal uptake of amino acids.
The fetal HPA axis is particularly vulnerable to changes
in the intrauterine environment. In humans, most brain and
HPA development occurs in utero. However, in species often
used as models of in utero manipulation that give birth to
immature offspring (eg, rodents), most brain development
occurs in the early postnatal days. 33,34
Prenatal stress has a profound effect on neuroendocrine
development and function. Exposure of the fetus to elevated
glucocorticoids appears to be the central link between
prenatal stress and modification of HPA axis development and function. There is evidence that antenatal stress/
anxiety has a programming effect on the fetus that lasts
at least until mid-childhood and results in higher rates of
behavioral and emotional problems. 35 Cognitive and behavioral modifications have also been linked to alterations in
HPA axis activity and prenatal glucocorticoid exposure.
Prenatal stress has been associated with changes in memory
and behavior, and with depression, anxiety, chronic fatigue
syndrome, and schizophrenia. 33 These alterations in HPA
axis function, behavior, and cognition as a result of prenatal
stress have been related to changes in brain corticosteroid
receptor populations and alterations in hippocampal and
hypothalamic neuronal development. 36
Numerous studies in animals and humans have demonstrated that synthetic glucocorticoid administration can
also promote HPA hyperactivity. Synthetic glucocorticoids
are poorly catabolized by placental 11-hydroxysteroid
dehydrogenase type 2 (11HSD2), and readily pass to the
fetus. 37 Fetal glucocorticoid exposure alters the expression
of glucocorticoid receptors, and impacts every level of the
HPA axis. Synthetic glucocorticoids are often administered
to women threatened with preterm delivery to enhance
fetal lung maturation to reduce morbidity and mortality
at a time in gestation when endogenous fetal cortisol levels
would normally be quite low. Due to recent clinical observations and animal studies of this practice, concerns have
been voiced by international expert groups. In spite of
these concerns, administration of repeated doses of antenatal corticosteroids to pregnant patients continues to be
common clinical practice. 33
Programming of the fetal HPA axis appears to play a
110
central role in the link between fetal growth and long-term

disease in adulthood (Figure 10-1). Stress-induced prenatal
programming of HPA axis function can increase the risk
of developing cardiovascular and metabolic diseases. On
another front, evidence is also accumulating rapidly that
chronic stimulation of the HPA axis and resulting excess
glucocorticoid exposure may play a role in the development of visceral obesity. Because regulation of energy and
food intake under stress is important for survival, it is not
surprising that the HPA axis is not only the conductor of
appropriate stress responses, but also tightly intertwined
with the regulation of appetite. 38
History and Epidemiology of the

FetalOriginsof Disease
Hypothesis
Early nutrition programming is the concept that nutrition experiences in early life can program an individuals
metabolism and development and influence later health
outcomes. In 1962, McCance39 observed that the size of a
weanling rat varied inversely with the number of littermates
suckled by the dam. Further experimental work in both rats
and pigs illustrated that the earlier in life the animal was
exposed to food restriction, the more permanent the effects

on adult size, despite attempts to obtain catch-up growth.40
Competition among fetuses for intrauterine food supply or
littermates for milk can lead to periods of undernutrition
during critical periods of development. The fetus or neonate
adapts by slowing the rate of cell division in certain organs
in such a way as to permanently change or program metabolism and growth potential.
Barker and colleagues proposed the developmental
or fetal origins of adult disease in humans in 1986. The
hypothesis was based on observations that the highest rates
of CHD in a geographical region of England were associated with increased infant mortality in the same population
decades earlier.41 Further epidemiological evidence was
provided from 2 large studies of males from Hertfordshire
and Sheffield, England, that demonstrated a strong correlation between LBW, low weight for length at 1 year, and
small head circumference with death from CHD.42,43 It
is of interest to note that the relationship between LBW
and CHD was related to slow fetal/infant growth rather
than prematurity. The association between reduced size at
birth and risk factors for CHD including obesity, hypertension, hyperlipidemia, and non-insulin-dependent diabetes
mellitus (NIDDM) has been confirmed from cohort
Figure 10-1 Scheme of the role that programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis during development plays in the link between
fetal growth and long-term disease in adulthood. Gc: Glucocorticoids; Dex: Dexamethasone.
studies in various countries.4449 A systematic review of 80

studies found that there was a 2-mmHg decrease in systolic
blood pressure per kilogram increase in birth weight.48
A review of 48 papers examining the relationship of birth
weight and later glucose and insulin metabolism demonstrated that LBW was correlated with adverse glucose and
insulin metabolism, possibly related to insulin resistance.49
Fetal overnutrition in infants of diabetic mothers may also
cause an increased risk of glucose intolerance and NIDDM
in later life. 50 A study in Pima Indians demonstrated a
U-shaped relationship between birth weight and prevalence
of NIDDM with high birth weight explained by the presence of gestational diabetes. 51
Expansion to Postnatal Growth Period

Although nutrition effects during fetal life have been shown
to be important determinants of susceptibility to later health
effects, postnatal events modify the influence of prenatal
growth. In evaluating the fetal origins of disease hypothesis
it has been recognized that it is important to adjust for early
weight gain and current body size. Numerous epidemiological studies show that the highest risk for cardiovascular
disease (CVD) and associated disorders is in adults who
were small at birth and became overweight or obese during
childhood or adulthood.44,5255 The thrifty phenotype
hypothesis proposed by Hales and Barker postulates that
the fetus selectively distributes nutrients to certain organs
during periods of undernutrition, leading to permanent
metabolic changes that enhance its chance of survival
during periods of limited postnatal nutrition. 56 If adequate
food becomes available postnatally, the prenatal metabolic adaptations to undernutrition are detrimental in that
obesity and related metabolic disorders may develop. 57
Lucas and colleagues proposed the term programming to explain the mechanism whereby an early stimulus
or insult occurring at a critical or sensitive period results in
a permanent or long-term change. 58 Current research seeks
to identify critical periods during prenatal and postnatal life
when nutrition deficiencies or excesses may influence the
risk of chronic adult disease.
Recent evidence suggests that rapid weight gain during
infancy may be associated with an increased incidence of
childhood or adult obesity and cardiovascular risk factors.
The majority of the studies show consistent associations
between LBW and rapid weight gain in infancy with
increased risk of CHD. In addition, an observational study
from Helsinki demonstrated that slow weight gain during
infancy followed by a rapid weight gain after 1 year of age
increased the risk of coronary disease, irrespective of birth
111
size. 54 A systematic review of 15 studies examining the role

of rapid growth in infancy and childhood on later obesity
found 13 publications that demonstrated a significant association of early rapid growth with obesity prevalence in later
life. 59 Another systematic review that evaluated both size at
birth and rate of growth in infancy concluded that infants
who are at the highest end of the distribution for weight,
or who grew rapidly during infancy, are at increased risk
of subsequent obesity.60 Although controversy exists as to
the specific periods of infancy and childhood that predict
later adiposity, several observational studies have indicated that weight gain in the first half of infancy may be a
critical period.6163 In formula-fed infants in whom repeated
measures of infant weight gain were available, Stettler and
colleagues showed that rapid weight gain in the first week of
life was associated with risk of overweight in adulthood.64
Several reviews have demonstrated that breastfeeding
may reduce the risk of later obesity. It has been suggested
that the benefits of breastfeeding may be due to slower
growth in the breastfed compared to the formula-fed infant.
The differences in growth rate between breastfed and
formula-fed infants are greatest in the first few weeks of life,
a critical period for programming of obesity.64
Observational studies support the hypothesis that early
postnatal nutrition plays an important role in the development of obesity and related cardiovascular risk factors,
but limited clinical evidence exists on the effects of early
nutrition programming in term infants. In a recent study,
SGA term infants randomly assigned to a nutrient-enriched
formula at birth had higher diastolic blood pressure at 6 to
8 years.65 In a secondary analysis, the diastolic blood pressure was greater in children who had more rapid weight
gain from birth to 9 months.65 Support for the growth
acceleration hypothesis in term infants was demonstrated
in a study that utilized multiple measurements of growth
from birth to 5 years in relation to blood pressure.66 Rapid
increases in weight in the first 6 months of life predicted
elevated diastolic blood pressure in adults, independent of
fetal growth.66 LBW and rapid postnatal growth are associated with later elevated blood pressure indicating the
importance of both prenatal and postnatal factors in the
programming of later health effects. Improved maternal
nutrition and prevention of rapid percentile-crossing weight
gain in infants could have a substantial impact on the development of adult chronic diseases.
112
Integration of Pre- and Postnatal

Programming Effects
Gluckman and colleagues use the term developmental

plasticity (defined as the ability of an organism to develop
in various ways, depending on the particular environment
or setting) to provide a framework for the observations on
the impact of early growth on later health.20
The first models to explain the developmental origins of
health and disease (DOHaD) idea were the thrifty phenotype and the fetal salvage hypothesis in which a fetus
adapts to survive a deprived intrauterine environment. 56,67
These theories were later expanded to include the postnatal
environment and termed a predictive adaptive response.68
The risk of disease is increased when the postnatal environment does not match what is predicted prenatally. Animal
studiesin which nutritional, endocrinologic, or surgical
manipulation from conception to weaning have been used
to induce permanent changes in the offspringprovide
biological support for the concept of developmental plasticity and its role as a key determinant in the risk of later
chronic disease.
Early Programming in the Premature Infant

Prospective interventional studies performed by Singhal,
Lucas et al in preterm infants have demonstrated the importance of early nutrition for long-term health outcomes.69
More than 900 preterm infants were randomly assigned in
2 parallel trials to receive (a) banked breast milk or preterm
formula or (b) standard term formula or preterm formula.
The preterm infants fed breast milk for a period of 4 weeks
had improved lipid profiles,70 lower blood pressure,71 lower
leptin concentrations, and decreased insulin resistance72,73
at 13 to 16 years compared to the infants fed preterm
(nutrient-enriched) formula. The lipoprotein profile,
C-reactive protein (a marker for the low-grade inflammatory response associated with the atherosclerotic process),
and blood pressure did not differ significantly between
infants randomized to standard infant formula and those
fed preterm formula.70,71 The ratio of leptin to fat mass (a
marker of obesity) was significantly higher in children fed
the preterm formula compared to the children who received
breast milk or standard term formula.72 Fasting 32-33
proinsulin concentration (a marker of insulin resistance)
was significantly higher in children who received preterm
formula, and further analysis demonstrated that differences
in weight gain (or loss) in the first 2 weeks of life was the
only factor related to later proinsulin concentrations, irrespective of size at birth.73 These landmark studies provide
the first experimental clinical evidence that faster postnatal
growth and a nutrient-dense diet may be a risk factor for

later CVD.
Although slower growth in preterm infants may
have benefits for later health outcomes,69 the risks of
adverse consequences on cognition must be considered.
Numerous studies have demonstrated that growth restriction in preterm infants is associated with long-term short
stature and cognitive deficits. Preterm infants fed standard
formula compared to nutrient-enriched formula demonstrated a significant reduction in intelligence quotient (IQ )
and neurocognitive impairment at 7 to 8 years of age.74
Higher bone mineralization and improved linear growth
in childhood has been reported in preterm infants fed a
preterm formula versus unfortified breast milk or standard
formula.75,76 There are clear benefits for the use of specialized formulas in preterm infants relative to term formulas to
support brain development that outweigh the later risks of
cardiovascular disorders. Short-term advantages of dietary
supplementation of at-risk infants have also been demonstrated in developing countries where more rapid weight gain
up to 2 years of age was associated with decreased hospital
admissions and reduced mortality.77 Further research is
needed to determine optimal growth to achieve cognitive
benefits (in preterm infants) and short-term health benefits
in at-risk populations while minimizing the longer-term
risk of chronic disease.
Animal Models
Animal models of early growth restriction have been used to

better understand its relationship with adult human disease
and to provide insight into underlying molecular mechanisms. Nutritional, hormonal, and surgical insults during
pregnancy have been shown to result in growth restriction
in various species.78
Animal Models of Dietary Manipulation

Dietary manipulation by global caloric restriction, reduction of dietary protein content, iron restriction, or dietary
fat supplementation have all been studied in rodents and
ovine models. The most common model is the pregnant
rat subjected to malnutrition. However, a limitation of
the rodent model is that the rat is an altricial animal, born
with a poorly developed central nervous system and autocrine system, with significant maturation during weaning.
The guinea-pig may be a more relevant model as these
animals are precocial and born with well-developed central
nervous, endocrine, and cardiovascular systems. Because
of the polytocous nature of rats and guinea-pigs, there may
be considerable variability in fetal and neonatal nutrient
supply to individual offspring within a litter. In contrast,

sheep pregnancies are usually singleton or twin.79
In the maternal low-protein animal models there are
striking parallels with the development of type 2 diabetes
and/or the metabolic syndrome. In this model, rats are
fed a low-protein (5%-8%) diet during pregnancy that
restricts the growth of the offspring. If such offspring are
cross-fostered to mothers fed a control diet (20% protein)
during lactation, they gain weight rapidly and, by weaning
(21 days of age), have similar body weights to controls.
However, this catch-up growth has a detrimental effect on
longevity. Permanent growth restriction results if maternal
protein restriction is continued during lactation, even after
the offspring are weaned to a control diet. Maternal protein
restriction has been shown to have long-term effects on
the structure and function of individual organs. Beta-cell
proliferation and islet size were significantly reduced in
the pancreas. However, a functional defect in glucosestimulated insulin secretion from islets of adult low-protein
offspring is only observed when an additional dietary insult
such as high fat or sucrose feeding is introduced post
natally.80 Maternal protein restriction has also been shown
to have long-term effects on insulin-sensitive tissues. There
are structural and functional changes in the liver. Skeletal
muscle is more sensitive to insulin in terms of its ability to
stimulate glucose uptake. Adipocytes have an elevated basal
and insulin-stimulated glucose uptake and increased levels
of insulin receptors.78
Nutrition restriction is also one of the most common
experimental methods of fetal insult used for investigation
into the mechanisms of programmed hypertension. This was
one of the first methods to demonstrate that the timing of
the insult is critical to the programming response. A reduction of nephron number was observed when the nutrition
insult coincided with the nephrogenic period. Slow fetal
growth also leads to alterations in the normal regulatory
systems involved in the long-term control of blood pressure
regulation. The pathogenesis of hypertension programmed
by in utero insult is multi-factorial and appears to involve
intrinsic intrarenal defects and alterations in extrarenal
regulatory systems critical to renal sodium excretion. A role
for sex steroids was also demonstrated.81
Severe food restriction (to only 30% of ad libitum
intake) during pregnancy has also been shown to induce
severe intrauterine growth restriction in rats. In addition
to expressing hypertension in adulthood, these offspring
have increased fasting plasma insulin compared to control
offspring. They also have increased food intake, consistent
with findings in humans suggesting early growth restriction
113
is associated with adult central adiposity.82 Less severe

food restriction (to 50% of ad libitum intake) from day 15
of pregnancy to weaning has been shown to result in insulinopenia and an age-dependent loss of glucose tolerance in
12-month-old male offspring.83
Iron
Feeding rats and sheep iron-deficient diets during pregnancy leads to anemia and growth restriction of the fetus.
The offspring have decreased iron concentrations in brain
tissue that cannot be normalized by iron treatment after
weaning. In addition, behavioral differences and alterations
in cardiovascular development have been noted.78 Gestational conditions that compromise fetal iron status include
maternal iron deficiency, diabetes mellitus, and hypertension. Animal models have demonstrated that early iron
deficiency affects neuronal and glial energy metabolism,
monoamine metabolism, and myelination.19 It also induces
genomic changes coding for signal transduction, dendritic
structure, and energy metabolism that last well into adulthood, in spite of later iron repletion. Early iron sufficiency
may be critical for long-term neurologic health.19
Animal models are also used to study early life influences on appetite and feeding behavior. Studies of rodent
models indicate that fetal undernutrition determines adult
adiposity. It is unclear whether the increase in central
adiposity is related to increased food intake or reduced
energy expenditure, although evidence exists to suggest
that both may be involved. Rats subjected to intrauterine
protein restriction exhibited increased preference for highfat foods. Feeding of energy-dense foods to rats that were
undernourished in utero promoted a greater degree of
obesity than noted in animals with adequate nutrition in
fetal life. Programming of appetite may stem from remodeling of hypothalamic structures that control feeding
and programming of the expression of genes involved in
responses to orexigenic hormones. Recent work has defined
circuitry in the hypothalamus that appears to mediate many
of the effects of the adipocyte-derived hormone leptin on
feeding and glucose homeostasis. Evidence accumulated
primarily in mice indicates that these circuits develop as
projections from the arcuate nucleus of the hypothalamus.
Leptin appears to play a crucial neurotrophic role governing
development of these pathways that regulate food intake
and adiposity.84 Early programming of appetite and obesity
is a complex phenomenon and the understanding of how
maternal nutrition determines later energy balance is at a
very early stage.85
114
Animal Models Induced by Glucocorticoid Exposure
Animal Models Induced by Surgical Manipulation
Several animal studies have shown that prenatal glucocorticoid excess, either from endogenous overproduction from
maternal stress or through exogenous administration to the
mother or fetus, reduces birth weight and causes hypertension, hyperglycemia, and behavioral abnormality in the
offspring. These effects are transmitted across generations
without further exposure to glucocorticoids, an observation that supports an epigenetic mechanism.86
Rat offspring that have been exposed to excess prenatal
glucocorticoids undergo catch-up growth postnatally
and normalize body weight by weaning. Outcomes from
such offspring when they are adults are consistent with
the hypothesis that rapid postnatal catch-up growth is
deleterious to health.78 There are also accumulating data in
rodents to suggest that prenatal glucocorticoid overexposure programs an adverse adult cardiovascular, metabolic,
neuroendocrine, and behavioral phenotype. The phenotypic outcome is similar to that of the low-protein model.
Fetal glucocorticoid overexposure may be a common
mechanism for mediating fetal growth retardation and
metabolic programming. This suggestion is based on the
observation that dietary protein restriction during rat
pregnancy reduces 11-HSD2 activity. This enzyme, as
mentioned earlier, serves as a placental barrier to maternal
glucocorticoids by rapidly metabolizing maternal glucocorticoids to inert 11-keto forms to minimize fetal exposure to
glucocorticoids.78
HPA regulation can be programmed by nutrient restriction. In fetal rats nutrient restriction results in blunted
diurnal patterns of adrenocorticotropic hormone (ACTH)
at 4 weeks postnatal age, alterations in basal plasma corticosterone in adulthood, and altered basal HPA axis activity. 33
Normally, the presence of 11-HSD2 in the placental syncytiotrophoblasts protects the fetus from maternally derived
glucocorticoids. Maternal glucocorticoid levels are much
higher than fetal levels for most of pregnancy, so a relative
deficiency in placental 11-HSD2 would put the fetus at
great risk of increased glucocorticoid exposure. 87 In some
studies, a strong positive correlation has been reported
between placental 11-HSD2 activity and fetal weight at
term and birth weight in preterm infants. Maternal protein
restriction in rodents reduces the activity of 11-HSD2 in
the placenta. 11-HSD2 activity is influenced by multiple
maternal environmental factors and its modulation may
be a mechanism through which a variety of environmental
insults exert their programming effects. 86
Reduction in placental blood flow and consequent restriction of oxygen, nutrient transport, and fetal growth can
be produced in the rat by uterine artery ligation in late
gestation, uterine and umbilical artery embolism, or
carunclectomy.78,79 At 2 weeks of age, growth-retarded
offspring in this model have reduced nephron number. This
nephron deficit was associated with impaired renal function at 2 weeks of age despite compensatory hypertrophy
of remaining nephrons. Also, molecular analysis of skeletal
muscle from fetuses and 21-day-old offspring following
uterine artery ligation revealed that this mode of growth
restriction is associated with changes in both mitochondrial gene expression and function. In female offspring,
after uterine artery ligation, growth restriction was associated with increased fasting blood glucose levels and with
impaired glucose tolerance and lower insulin secretion
during a glucose tolerance test.78
Third and Future Generation Effects
Adverse events during pregnancy can affect not only the

offspring of the pregnancy but also the next generation. In a
UK study examining the relationship of adult blood pressure
to the mothers fetal growth and size at birth, it was demonstrated that reduced fetal growth was associated with raised
blood pressure in the next generation. 88 The researchers
concluded that if the growth of a female fetus is restricted,
there are changes in her physiology and metabolism that
lead to elevated blood pressure in the next generation.
Adults who were born during the Dutch famine and
whose mothers had inadequate nutrition during the first 2
trimesters of pregnancy were more likely to be obese and
have abnormal lipid profiles than adults whose mothers had
poor nutrition during the third trimester. 89 Infants born to
mothers who were malnourished during the third trimester
were leaner but had impaired glucose tolerance. Infants who
were of normal birth weight born to severely malnourished
mothers went on to deliver smaller babies in the next generation. One explanation for the intergenerational effects on
birth weight is that the hormonal environment of the uterus
of the undernourished mother may affect the reproductive tract of the fetus. A possibly similar transgenerational
transmission of longevity propensity has been identified for
males in epidemiologic studies of food supply during early
spermatogenesis.90 Although the mechanisms behind these
relationships are poorly understood, epigenetic dysregulation of the insulin-like growth factor 2 (IGF-2) gene has
been proposed. IGF-2 is a key factor in human development and growth and is maternally imprinted. Individuals
who were prenatally exposed to malnutrition during the

Dutch famine had less DNA methylation of the IGF-2
gene compared with their unexposed same-sex siblings 6
decades later.91 These data support the hypothesis that early
life environmental conditions cause epigenetic changes in
humans that persist throughout life.
Implications for Future Health
Dietary inadequacy, imbalance, or excess can all impact fetal

development. Some of these changes persist throughout
life or leave the individual vulnerable to later environmental and dietary conditions that can adversely impact
health and longevity. Underlying fetal morphological and
functional changes related to pregnancy, postnatal diet,
and various stressors and their adult consequences have
been delineated. Now we are beginning to understand the
molecular determinants of these changes and the dietary
and environmental factors controlling them. Both over- and
undernutrition in utero and in early life can increase risks
for adverse metabolic outcomes including type 2 diabetes,
CVD, and obesity. The seriousness of these events is amplified by evidence that certain potentially adverse epigenetic
effects induced in the female fetus may persist through at
least an additional generation.
Current agricultural production and food distribution
and changes in diet and activity patterns are associated with
a historically high prevalence of obesity, diabetes, and their
complications. As many as a third of todays children in
some states are destined to become diabetic, given obesity
rates and genetic predisposition. In developed countries,
many of these may now be in the second or third generation of families expressing this phenotype. Many come
from environments with a history of food and micronutrient scarcity. In many parts of the world, these contrasting
nutrition states coexist contemporaneously. In the course
of a lifetime, individuals can be expected to pass from
one dietary camp to the other, magnifying the potential
adverse developmental impacts inherent to both. In India
we now have the phenomenon of the thin, fat Indian that
has given India the distinction of the worlds highest rate
of diabetes, despite a lower ranking for obesity. Based on
what is emerging from the DOHaD literature and the investigation of epigenetics, we can expect the consequences of
dietary scarcity and surfeit and their coexistence to exert
their adverse effects in future generations in the absence of
fresh insights on how to intervene to break this cycle. An
inability to meet potential major population increases in
health care costs related to morbidity patterns associated
with DOHaD-associated conditions could itself become
115
a driver of morbidity and mortality, as well as a potential

source of economic and political instability. Already, it is
estimated that todays children in the United States will,
for the first time in generations, not live longer than their
parents.
The most frequent of the DOHaD-associated conditions include hypertension, diabetes, coronary artery
disease, and the complications of obesity. For each of these
conditions, primary prevention is far preferable to, and far
less expensive than, treatment and secondary or tertiary
preventive measures. However, medical treatments have
developed far faster than the behavioral, cultural, and social
changes required to alter the trajectory of the development
of these conditions. In light of this, medical solutions should
be sought along with the broader public health initiatives
that will be required to improve the quality of life for the
developing fetus and neonate.
Implications for Current Practice
What implications can be drawn from current knowledge

in this area for nutrition advice in the practice of obstetrics, pediatrics, neonatology, and public health? Given that
preconceptual nutrition status is at least as important as
nutrition status during pregnancy, planned pregnancies in
mature women with good nutrition status is a highly desirable starting point. This requires approaches to maximizing
nutrition status of fertile women of childbearing age beyond
an exclusive focus on pregnancy and lactation, especially
where pregnancies are unlikely to be planned. During
pregnancy, adequate energy, protein, and micronutrients,
including methyl donors, can be expected to have a salutary
effect on developmental outcomes related to fetal nutrition
status. There is some evidence to indicate excesses of fat and
protein during pregnancy are to be avoided, and long-chain
n-3 fatty acids, especially docosahexaneoic acid, may have
beneficial impact on mental, visual, and behavioral development. Monitoring fetal growth, maternal weight gain, and
maternal blood sugar can detect deviations from expected
developmental patterns.
For term infants, it appears to be desirable to continue
on a relative growth trajectory (percentile) similar to
that experienced in utero. Traditionally, normalizing
the growth of in utero growth-retarded infants has been
accepted as the de facto goal of good nutrition. Based on
more recent findings, these children may be metabolically
more suited to a slower rate of growth. Percentile crossing in
infancy, and later, appears to increase risk of the DOHaDassociated conditions. In the first 2 weeks of life and after
about 4 months of age, breastfeeding may lead to less weight
116
gain than formula feeding and can be viewed as particularly beneficial in this population. An important medical
concern in such infants is to support brain development,
but most of the data on the importance of early nutrition for
brain development come from studies of premature infants.
It remains largely unknown if nutritional supplementation
and growth acceleration are beneficial in this regard for term
growth-retarded infants. For infants in underdeveloped
countries who develop extrauterine growth retardation
later in infancy and early childhood, short-term nutritional
supplementation has been found to reduce acute morbidity
and mortality (as well as progression of their malnutrition).
Premature infants, especially extremely low birth
weight (ELBW) infants, are at high risk of extrauterine
growth retardation. Their nutrition requirements exceed
those of term infants, given their immature development
and body composition. In these infants, developmental
achievement and reduced neurological complications are
associated with higher growth rates. Premature infants,
both in-hospital and following hospital discharge, are very
responsive to nutritional supplementation. Data from Lucas
and Singhal have been taken by some to demonstrate that
rapid growth should not be encouraged for this population,
based on higher blood pressure, leptin, blood lipids, and
split proinsulin values in premature infants when fed premature formula compared to term formula or human milk.
However, in their studies, these markers of cardiovascular
risk were not elevated above those for typical term infants.
These same investigators demonstrated developmental
disadvantages in these infants at least through childhood
from receiving standard term formulas versus more nutrientrich premature formula. Interestingly, while premature
infants fed premature formula grew faster than breastfed
infants, their neuro-developmental status was not better
than that of breastfed infants. Bone mineralization is
improved in premature infants given mineral-rich premature and post-discharge formulas compared to standard
term formulas. However, this may not persist into
adulthood.92
Human milk with human milk fortifier is the current
recommended approach for small premature infants as it can
preserve the beneficial nutrition and immunologic effects
of human milk while providing additional energy, protein,
minerals, and other micronutrients. For formula-fed premature infants, premature, not term, formula is recommended.
However, there is no evidence postdischarge formulas have
improved developmental outcomes versus infants fed standard term formulas after hospital discharge. However, in the
smallest infants, they have been observed to enhance head
growth. The recent U.S. data from Ehrenkranz on the positive developmental outcome of encouraging early growth in
premature infants dictates against any go-slow approach for
these infants to possibly reduce markers of future cardiovascular risk (to below values observed in healthy term
infants).93
Future Research Needs
This is a rich area for potential investigation at all levels

of biological research. At the molecular level, we need
specific descriptions of the molecular changes underlying
the DOHaD phenomenon in various organs and the mechanisms controlling these molecular changes, including
nutrition influences. In physiology, there remain opportunities to explore the developmental impact of organ-specific
effects of general and nutrient-specific under- and overnutrition at various stages of fetal and infant development.94
Beardsall et al lists opportunities for studies of glucose
control in the fetus relative to body composition, pancreatic development, and in utero programming of glucose
control.94 The epidemiologists, who did much to initiate
this field of research, can tell us more about the similarities and differences of effects of different stressors (eg,
gestational malnutrition versus diabetes) on the expression of the DOHaD-related morbidity. More remains
to be done to elucidate the relation of intrauterine and
postnatal effects (and their interaction). Clinical investigators can prospectively study the developmental impact
of growth acceleration in various populations and age
groups of infants and young children looking at infection
and immune outcomes, cardiovascular and metabolic risk
factors, bone health, and neurodevelopment. There may be
better versus worse times or target populations for catchup growth. There appears to be great potential in exploring
very early or later drug or hormonal interventions to reverse
the underlying molecular basis of some DOHaD-associated conditions. For example, administration of leptin (a
pleomorphic hormone during gestation) in late gestation
or shortly after birth may reverse the development of the
expected postnatal phenotype of the growth-retarded
fetus or alter the development of appetite regulation.95,96
There is also the potential to alter the epigenetic phenotype through controlled exposure to methyl donors or
other agents directly affecting epigenetic mechanisms.97,98
1. The dominant fuel source for the healthy fetus is:

A. Fatty acids because they are the richest source of
energy
B. Amino acids because they promote rapid growth
C. Galactose, because the fetus cannot utilize glucose
D. Glucose transported from the maternal circulation
2. Nutrition programming is a process that:
A. Is specific to the fetus
B. Occurs only in animals
C. Occurs early in life and may extend beyond a single
generation
D. Is a transient response to nutrient availability
3. Upward growth percentile-crossing in infancy and
early childhood:
A. Reduces short-term infectious mortality and leads
to lower adult blood pressure
B. Has been associated with increased risk for development of features of the metabolic syndrome
C. Helps prevent subsequent rebound obesity
D. Improves glucose control later in life
References
1. Pardi G, Cetin I. Human fetal growth and organ development: 50 years of discoveries. Am J Obstet Gynecol.
2006;194(4):10881099.
2. Hay WW Jr. Placental-fetal glucose exchange and fetal
glucose metabolism. Trans Am Clin Climatol Assoc.
2006;117:321340.
3. Hay WW Jr. Recent observations on the regulation of fetal
metabolism by glucose. J Physiol. 2006;572(pt 1):1724.
4. Battaglia FC. Clinical studies linking fetal velocimetry, blood
flow and placental transport in pregnancies complicated
by intrauterine growth retardation (IUGR). Trans Am Clin
Climatol Assoc. 2003;114:305313.
5. Battaglia FC. In vivo characteristics of placental amino acid
transport and metabolism in ovine pregnancy--a review.
Placenta. 2002;23(Suppl A):S3S8.
6. Battaglia FC, Wilkening R, Meschia G. Unique organ specific
characteristics of amino acid metabolism in early development. Trans Am Clin Climatol Assoc. 1995;106:141149.
7. Barry JS, Anthony RV. The pregnant sheep as a model for
human pregnancy. Theriogenology 2008;69(1):5567.
8. Regnault TR, Friedman JE, Wilkening RB, Anthony RV, Hay
WW Jr. Fetoplacental transport and utilization of amino acids
in IUGR--a review. Placenta. 2005;26(Suppl A):S52S62.
9. Sparks JW, Hay WW Jr, Bonds D, Meschia G, Battaglia
FC. Simultaneous measurements of lactate turnover rate
and umbilical lactate uptake in the fetal lamb. J Clin Invest.
1982;70(1):179192.
117
10. Grillo MA, Lanza A, Colombatto S. Transport of amino

acids through the placenta and their role. Amino Acids.
2008;34(4):517523.
11. Myers RE, Hill DE, Holt AB, Scott RE, Mellits ED, Cheek DB.
Fetal growth retardation produced by experimental placental
insufficiency in the rhesus monkey. I. Body weight, organ size.
Biol Neonate. 1971;18(5):379394.
12. Howarth C, Gazis A, James D. Associations of Type 1 diabetes
mellitus, maternal vascular disease and complications of pregnancy. Diabet Med. 2007;24(11):12291234.
13. Kanaka-Gantenbein C, Mastorakos G, Chrousos GP. Endocrine-related causes and consequences of intrauterine growth
retardation. Ann N Y Acad Sci. 2003;997:150157.
14. Ward JW, Wooding FB, Fowden AL. Ovine feto-placental
metabolism. J Physiol. 2004; 554(Pt 2):529541.
15. de Onis M, Villar J, Gulmezoglu M. Nutritional interventions
to prevent intrauterine growth retardation: evidence from
randomized controlled trials. Eur J Clin Nutr. 1998;52(Suppl
1):S83S93.
16. Shiell AW, Campbell DM, Hall MH, Barker DJ. Diet in late
pregnancy and glucose-insulin metabolism of the offspring 40
years later. BJOG 2000;107(7):890895.
17. McMillen IC, MacLaughlin SM, Muhlhausler BS, Gentili
S, Duffield JL, Morrison JL. Developmental origins of adult
health and disease: the role of periconceptional and foetal
nutrition. Basic Clin Pharmacol Toxicol. 2008;102(2):8289.
18. Wu G, Bazer FW, Cudd TA, Meininger CJ, Spencer
TE. Maternal nutrition and fetal development. J Nutr.
2004;134(9):21692172.
19. Georgieff MK. The role of iron in neurodevelopment: fetal
iron deficiency and the developing hippocampus. Biochem Soc
Trans. 2008;36(pt 6):12671271.
20. Gluckman PD, Hanson MA, Cooper C, Thornburg KL.
Effect of in utero and early-life conditions on adult health and
disease. N Engl J Med. 2008;359(1):6173.
21. Scholl TO. Maternal nutrition before and during pregnancy.
Nestle Nutr Workshop Ser Pediatr Program. 2008;61:7989.
22. Martin-Gronert MS, Ozanne SE. Maternal nutrition during
pregnancy and health of the offspring. Biochem Soc Trans.
2006;34(pt 5):779782.
23. Morton SMB. Maternal nutrition and fetal growth and development. In: Gluckman P, Hanson M, eds. Developmental
Origins of Health and Disease. UK: Cambridge University Press; 2006:98129.
24. Lanham SA, Roberts C, Cooper C, Oreffo RO. Intrauterine

programming of bone. Part 1: alteration of the osteogenic
environment. Osteoporos Int. 2008;19(2):147156.
25. Lanham SA, Roberts C, Perry MJ, Cooper C, Oreffo RO.
Intrauterine programming of bone. Part 2: alteration of skeletal structure. Osteoporos Int. 2008; 19(2):157167.
26. Thomas M, Weisman SM. Calcium supplementation during
pregnancy and lactation: effects on the mother and the fetus.
Am J Obstet Gynecol. 2006;194(4):937945.
27. Rao R, Georgieff MK. Iron in fetal and neonatal nutrition.
Semin Fetal Neonatal Med. 2007;12(1):5463.
28. Yajnik CS, Deshmukh US. Maternal nutrition, intrauterine
programming and consequential risks in the offspring. Rev
Endocr Metab Disord. 2008;9(3):203211.
118
29. Ramakrishan U, Manjrekar R, Rivera J, Gonzales-Cossio

T. Micronutrients and pregnancy outcome : A review of the
literature. Nutr Res. 1999;19:103159.
30. Shah PS, Ohlsson A. Effects of prenatal multimicronutrient
supplementation on pregnancy outcomes: a meta-analysis.
CMAJ. 2009;180(12):E99108.
31. Fowden AL, Ward JW, Forhead A. Control of fetal metabolism: relevance to developmental origins of health and disease.
In: Gluckman P, Hanson M, eds. Developmental Origins
of Health and Disease. UK: Cambridge University Press;
2006:143158.
32. Fowden AL, Forhead A. The role of hormones in intrauterine
development. In: Barker DJP, ed. Fetal Origins of Cardiovascular and Lung Disease. New York, NY: Marcel Dekker Inc;
2000:199228.
33. Sloboda D, Newnham J, Moss T, Challis J. The fetal hypothalamic-pituitary-adrenal axis: relevance to developmental
origins of health and disease. In: Gluckman P, Hanson M, eds.
Developmental Origins of Health and Disease. UK: Cambridge
University Press; 2006:191-205.
34. Dobbing J, Sands J. Comparative aspects of the brain growth
spurt. Early Hum Dev. 1979;3(1):7983.
35. OConner TG, Heron J, Golding J, Glover V. Maternal
antenatal anxiety and behavioural/emotional problems in
children: A test of a programming hypothesis. J Child Psychol
Psychiatry. 2003;44:10251036.
36. Welberg L, Seckl J. Prenatal stress, glucocorticoids
and the programming of the brain. J Neuroendocrinol.
2001;13(2):113128.
37. Seckl JR, Holmes MC. Mechanisms of disease: glucocorticoids, their placental metabolism and fetal programming
of adult pathophysiology. Nat Clin Pract Endocrinol Metab.
2007;3(6):479488.
38. Adam TC, Epel ES. Stress, eating and the reward system.
Physiol Behav. 2007;91(4):449458.
39. McCance RA. Food, growth, and time. Lancet.
1962;2(7258):671676.
40. Widdowson EM, McCance RA. A review: new thoughts on
growth. Pediatr Res. 1975;9(3):154156.
41. Barker DJ, Osmond C. Infant mortality, childhood nutrition,
and ischaemic heart disease in England and Wales. Lancet.
1986;1(8489):10771081.
42. Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ.
Weight in infancy and death from ischaemic heart disease.
Lancet. 1989;2(8663):577580.
43. Barker DJP, Osmond C, Simmonds SJ, Wield GA. The relation of small head circumference and thinness at birth to
death from cardiovascular disease in adult life. Br Med J.
1993;306:422426.
44. Frankel S, Elwood P, Sweetnam P, Yarnell J, Smith GD. Birthweight, body-mass index in middle age, and incident coronary
heart disease. Lancet. 1996; 348(9040):14781480.
45. Stein CE, Fall CH, Kumaran K, Osmond C, Cox V, Barker
DJ. Fetal growth and coronary heart disease in south India.
Lancet. 1996;348(9037):12691273.
46. Leon DA, Lithell HO, Vagero D, et al. Reduced fetal growth
rate and increased risk of death from ischaemic heart disease:
cohort study of 15,000 Swedish men and women born 191529. BMJ. 1998;317(7153):241245.
47. Forsen T, Osmond C, Eriksson JG, Barker DJ. Growth

of girls who later develop coronary heart disease. Heart.
2004;90(1):2024.
48. Huxley RR, Shiell AW, Law CM. The role of size at birth and
postnatal catch-up growth in determining systolic blood
pressure: a systematic review of the literature. J Hypertens.
2000;18(7):815831.
49. Newsome CA, Shiell AW, Fall CH, et al. Is birth weight related
to later glucose and insulin metabolism?A systematic
review. Diabet Med. 2003;20(5):339348.
50. Dabelea D, Pettitt DJ. Intrauterine diabetic environment
confers risks for type 2 diabetes mellitus and obesity in the
offspring, in addition to genetic susceptibility. J Pediatr Endocrinol Metab. 2001;14(8):10851091.
51. McCance DR, Pettitt DJ, Hanson RL, et al. Birth weight
and non-insulin dependent diabetes: thrifty genotype,
thrifty phenotype, or surviving small baby genotype? BMJ.
1994;308(6934):942945.
52. Fall CH, Osmond C, Barker DJ, et al. Fetal and infant
growth and cardiovascular risk factors in women. BMJ.
1995;310(6977):428432.
53. Eriksson JG, Forsen T, Tuomilehto J, Winter PD, Osmond
C, Barker DJ. Catch-up growth in childhood and death
from coronary heart disease: longitudinal study. BMJ.
1999;318(7181):427431.
54. Eriksson JG, Forsen T, Tuomilehto J, Osmond C, Barker DJ.
Early growth and coronary heart disease in later life: longitudinal study. BMJ. 2001;322(7292):949953.
55. Rich-Edwards JW, Kleinman K, Michels KB, et al. Longitudinal study of birth weight and adult body mass index in
predicting risk of coronary heart disease and stroke in women.
BMJ. 2005;330(7500):1115.
56. Hales CN, Barker DJ. Type 2 (non-insulin-dependent)
diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992;35(7):595601.
57. Ozanne SE, Hales CN. Early programming of glucose-insulin
metabolism. Trends Endocrinol Metab. 2002;13(9):368373.
58. Lucas A. Programming by early nutrition in man. Ciba Found
Symp. 1991;156:3850.
59. Monteiro PO, Victora CG.
Rapid growth in infancy and childhood and obesity in later lifea systematic review. Obes Rev.
2005;6(2):143154.
60. Baird J, Fisher D, Lucas P, et al. Being big or growing fast:
systematic review of size and growth in infancy and later
obesity. BMJ. 2005;331(7522):929.
61. Stettler N, Zemel BS, Kumanyika S, Stallings VA. Infant
weight gain and childhood overweight status in a multicenter,
cohort study. Pediatrics. 2002;109(2):194199.
62. Stettler N, Kumanyika SK, Katz SH, Zemel BS, Stallings
VA. Rapid weight gain during infancy and obesity in young
adulthood in a cohort of African Americans. Am J Clin Nutr.
2003;77(6):13741378.
63. Dennison BA, Edmunds LS, Stratton HH, Pruzek RM. Rapid
infant weight gain predicts childhood overweight. Obesity.
2006;14(3):491499.
64. Stettler N, Stallings VA, Troxel AB, et al. Weight gain in the
first week of life and overweight in adulthood: a cohort study
of European American subjects fed infant formula. Circulation. 2005;111(15):18971903.
65. Singhal A, Cole TJ, Fewtrell M, et al. Promotion of faster

weight gain in infants born small for gestational age: is
there an adverse effect on later blood pressure? Circulation.
2007;115(2):213220.
66. Ben Shlomo Y, McCarthy A, Hughes R, Tilling K, Davies D,
Smith GD. Immediate postnatal growth is associated with
blood pressure in young adulthood: the Barry Caerphilly
Growth Study. Hypertension. 2008;52(4):638644.
67. Cianfarani S, Germani D, Branca F. Low birthweight and adult
insulin resistance: the catch-up growth hypothesis. Arch Dis
Child. Fetal Neonatal Ed. 1999;81(1):F71F73.
68. Gluckman PD, Hanson MA. The consequences of being born
smallan adaptive perspective. Horm Res. 2006;65(Suppl
3):514.
69. Singhal A, Lucas A. Early origins of cardiovascular disease: is there a unifying hypothesis? Lancet.
2004;363(9421):16421645.
70. Singhal A, Cole TJ, Fewtrell M, Lucas A. Breastmilk
feeding and lipoprotein profile in adolescents born preterm:
follow-up of a prospective randomised study. Lancet.
2004;363(9421):15711578.
71. Singhal A, Cole TJ, Lucas A. Early nutrition in preterm infants
and later blood pressure: two cohorts after randomised trials.
Lancet. 2001;357(9254):413419.
72. Singhal A, Farooqi IS, ORahilly S, Cole TJ, Fewtrell M, Lucas
A. Early nutrition and leptin concentrations in later life. Am J
Clin Nutr. 2002;75(6):993999.
73. Singhal A, Fewtrell M, Cole TJ, Lucas A. Low nutrient intake
and early growth for later insulin resistance in adolescents
born preterm. Lancet. 2003;361(9363):10891097.
74. Lucas A, Fewtrell MS, Morley R, et al. Randomized trial of
nutrient-enriched formula versus standard formula for postdischarge preterm infants. Pediatrics. 2001;108(3):703711.
75. Chan GM. Growth and bone mineral status of discharged
very low birth weight infants fed different formulas or human
milk. J Pediatr. 1993;123(3):439443.
76. Fewtrell MS, Prentice A, Jones SC, et al. Bone mineralization
and turnover in preterm infants at 8-12 years of age: the effect
of early diet. J Bone Miner Res. 1999;14(5):810820.
77. Victora CG, Barros FC, Horta BL, Martorell R. Short-term
benefits of catch-up growth for small-for-gestational-age
infants. Int J Epidemiol. 2001;30(6):13251330.
78. Ozanne SE. Metabolic programming in animals. Br Med Bull.
2001;60:143152.
79. Armitage JA, Khan IY, Taylor PD, Nathanielsz PW, Poston L.
Developmental programming of the metabolic syndrome by
maternal nutritional imbalance: how strong is the evidence
from experimental models in mammals? J Physiol. 2004;561(Pt
2):355377.
80. Desai M, Crowther NJ, Lucas A, Hales CN. Organ-selective
growth in the offspring of protein-restricted mothers. Br J
Nutr. 1996;76(4):591603.
81. Ojeda NB, Grigore D, Alexander BT. Developmental
programming of hypertension: insight from animal models of
nutritional manipulation. Hypertension. 2008; 52(1):4450.
119
82. Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman
PD. Fetal origins of hyperphagia, obesity, and hypertension
and postnatal amplification by hypercaloric nutrition. Am J
Physiol Endocrinol Metab. 2000;279(1):E83E87.
83. Woodall SM, Johnston BM, Breier BH, Gluckman PD.
Chronic maternal undernutrition in the rat leads to delayed
postnatal growth and elevated blood pressure of offspring.
Pediatr Res. 1996;40(3):438443.
84. Bouret SG, Simerly RB. Developmental programming of
hypothalamic feeding circuits. Clin Genet. 2006;70(4):295301.
85. Langley-Evans SC, Bellinger L, McMullen S. Animal models
of programming: early life influences on appetite and feeding
behaviour. Matern Child Nutr. 2005;1(3):142148.
86. Drake AJ, Tang JI, Nyirenda MJ. Mechanisms underlying the
role of glucocorticoids in the early life programming of adult
disease. Clin Sci. (Lond) 2007;113(5):219232.
87. Fowden AL, Forhead AJ. Endocrine mechanisms of intrauterine programming. Reproduction. 2004;127(5):515526.
88. Barker DJ, Shiell AW, Barker ME, Law CM. Growth in utero
and blood pressure levels in the next generation. J Hypertens.
2000;18(7):843846.
89. Stein AD, Lumey LH. The relationship between maternal
and offspring birth weights after maternal prenatal famine
exposure: the Dutch Famine Birth Cohort Study. Hum Biol.
2000;72(4):641654.
90. Pembrey ME, Bygren LO, Kaati G, et al. Sex-specific, maleline transgenerational responses in humans. Eur J Hum Genet.
2006;14(2):159166.
91. Heijmans BT, Tobi EW, Stein AD, et al. Persistent epigenetic differences associated with prenatal
exposure to famine in humans. Proc Natl Acad Sci. USA
2008;105(44):1704617049.
92. Fewtrell MS, Williams JE, Singhal A, Murgatroyd PR, Fuller
N, Lucas A. Early diet and peak bone mass: 20 year follow-up
of a randomized trial of early diet in infants born preterm.
Bone. 2009;45(1):142149.
93. Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA,
Poole WK. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely
low birth weight infants. Pediatrics. 2006;117(4):12531261.
94. Beardsall K, Diderholm BM, Dunger DB. Insulin and carbohydrate metabolism. Best Pract Res Clin Endocrinol Metab.
2008; 22(1):4155.
95. Alexe DM, Syridou G, Petridou ET. Determinants of early life
leptin levels and later life degenerative outcomes. Clin Med
Res. 2006;4(4):326335.
96. Palou A, Pico C. Leptin intake during lactation prevents
obesity and affects food intake and food preferences in later
life. Appetite. 2009;52(1):249252.
97. Stocker CJ, Cawthorne MA. The influence of leptin on
early life programming of obesity. Trends Biotechnol.
2008;26(10):545551.
98. Zeisel SH. Nutrigenomics and metabolomics will change
clinical nutrition and public health practice: insights from
studies on dietary requirements for choline. Am J Clin Nutr.
2007;86(3):542548.
11
Human Milk
Learning Objectives
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Breastfeeding. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Preterm Breast Milk. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Fortification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Banked Human Milk. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Vitamin D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Growth of Breastfed Infants. . . . . . . . . . . . . . . . . . . . . . .
Breast Milk Safety and Administration . . . . . . . . . . . . . .
Breast Milk and Maternal Medications . . . . . . . . . . . . . .
120
120
121
122
122
123
123
123
124
125
1. List 3 benefits of the use of human milk for the infant.

2. Describe the 10 steps to successful breastfeeding.
3. State the American Academy of Pediatrics recommendation for the use of vitamin D with an exclusively
human milk fed infant.
Introduction
Breastfeeding is advocated throughout the world. The

American Academy of Pediatrics (AAP), the Canadian
Pediatric Society, the International Pediatric Association, the World Health Organization (WHO), and others
all have policies that recommend breastfeeding as the
preferred method of feeding for infants.14 The Healthy
People 2010 goals proposed by the United States Surgeon
General include breastfeeding initiation rates of 75% and
continued breastfeeding rates of 50% at 6 months and 25%
at 12 months5 which are close to being achieved nationally
although significant state-to-state variability remains.6
The advantages of breastfeeding are numerous and
include nutritional, immunologic, bonding, and societal
benefits (Table 11-1). Some of this may be attributed to the
establishment of beneficial bacteria in the gastrointestinal
tract of the infant through the use of breast milk which
contains probiotics, especially Bifidobacterium bifidum and
Lactobacillus. Breastmilk also contains growth factors,
including oligosaccharides, that promote the growth of these
bacteria and are generally called probiotics.7 The bifidus flora
of the breastfed infant is thought to activate the immune
system and defend against pathogens.8 The colonization of
breastfed infants gastrointestinal tracts has been different
than that of formula-fed infants. This may be changing as
prebiotics and probiotics have now been added to some infant
formulas in an effort to duplicate this benefit.9
HUMAN MILK
Table 11-1 Benefits of Breastfeeding

Improved mother-infant bonding
More rapid uterine involution
Mother
Every facility providing maternity services and care for

newborn infants should:
1. Have a written breastfeeding policy that is routinely communicated

to all health care staff.
Decreased incidence of premenopausal breast cancer
2. Train all health care staff in skills necessary to implement this policy.
Decreased incidence of ovarian cancer
3. Inform all pregnant women about the benefits and management

ofbreastfeeding.
Antibacterial factors: Secretory IgA, IgM, IgG, IgD,

Bifidobacterium growth factor, lactoferrin, complement
C1-9, factor binding proteins, lysozyme, lactoperoxidase,
macrophages, neutrophils, B and T lymphocytes, lipid,
growth factors, nucleotides, vitamins A, E, C1,10,11
Society
Table 11-2 Ten Steps to Successful Breastfeeding3
Postpartum weight loss
May protect against development of osteoporosis
Infant
121
4. Help mothers initiate breastfeeding within 30 minutes after birth.

5. Show mothers how to breastfeed and how to maintain lactation
even if they should be separated from their infants.
6. Give newborn infants no food or drink other than breast milk,
unlessmedically indicated.
Decreased incidence of gastrointestinal illness, respiratory

illness, otitis media, urinary tract infections, sudden infant
death syndrome1217
7. Practice rooming inallow mothers and infants to remain

together24 hours a day.
Lower incidence of allergies, even with a family history

of atopy1822
9. Give no artificial teats or pacifiers (also called dummies or

soothers) to breastfeeding infants.
May have lower incidence of later chronic diseases such

as Crohns disease, lymphoma, specific genotypes of
diabetes mellitus type 12326
10. Foster the establishment of breastfeeding support groups and

refer mothers to them on discharge from the hospital or clinic.
Reduced time off work for mothers of breastfed infants

for infants illness
Reduced health care costs1
For the premature infant the use of breast milk may

offera particular advantage in decreasing the incidence of
necrotizing enterocolitis (NEC).2729 Research by MeinzenDerr suggested a dose-related association of breast milk
feeding with a reduction in risk of NEC or death in extremely
low birthweight infants.28 However, in a randomized trial of
extremely premature infants, there was no difference in the
incidence of NEC between the group of infants fed donor
human milk and those fed preterm formula. 30 Kleinman,
Walker, and Schanler have suggested a protective effect
against infection in premature infants who are fed their
own mothers milk. 31,32
Breastfeeding
In 1991 the WHO and United Nations International

Childrens Fund (UNICEF) established an international
program to promote breastfeeding, the Baby Friendly
Hospital Initiative (BFHI).3 This incorporated a 10-step
program to promote and support breastfeeding (Table 11-2).
8. Encourage breastfeeding on demand.
Reprinted with permission from Baby-Friendly USA Web site,

http://www.babyfriendlyusa.org. Accessed December 31, 2009.
The management of the breastfeeding dyad requires

skill and knowledge to achieve a successful outcome for
both the mother and infant. Unfortunately, there are still
reports of hypernatremic dehydration among exclusively
breastfed neonates due to inadequate intake with potentially devastating consequences. The recommendation from
analyses of these reports is for close and regular follow-up of
breastfed infants by a health care provider. 3335
Evidence-based guidelines from the Academy of
Breastfeeding Medicine are available that provide recommendations for best practice in the management of term,
near-term (3537 week), and premature infants. 3638 Late
preterm (near-term) infants with gestational ages between
3436 6/7 weeks are at particular risk for lactation problems
as these infants may appear to be competent early in breastfeeding when they are not and may fool even experienced
mothers. These infants may have difficulty extracting milk
and stimulating the mother to produce an adequate milk
supply. 39 Late preterm infants are more likely to require
rehospitalization in the first 2 weeks after birth and have
poor lactation outcomes such as early cessation of breastfeeding, jaundice, dehydration, and poor growth.40 Their
mothers are also at risk for delayed lactogenesis.40 Meier et
al. and Wight describe strategies to work with the motherinfant dyad in establishing and maintaining maternal milk
supply and adequate intake for the infant. 39,40
122
The mothers of premature or sick term infants have the

challenge of pumping breast milk. Strategies to facilitate
pumping are available.41 A discussion of these is beyond the
scope of this chapter and interested readers are referred to
the book by Wight et al and to several works by Paula Meier
PhD RN. She has written extensively on the promotion
of lactation in an inner-city newborn intensive care unit
(NICU) setting,42 evaluation of the efficiency of different
breast pumps,43 and the role of nipple shields in facilitating
milk transfer for preterm infants.44
Preterm Breast Milk
Breast milk from mothers of preterm infants often may

have increased amounts of protein, sodium, chloride, and
iron for 3 weeks45 to approximately 1 month after delivery.46
For optimal growth preterm infants need augmentation of
breast milk due to their increased needs for protein, phosphorus, calcium, and zinc.4749 Previously it was thought
that, at least in terms of bone mineralization, as infants born
prematurely grew into childhood their bone density would
normalize. A new study by Chan et al demonstrated that
premature infants, < 1.5 kg at birth, continue to show lower
bone mineral content and density and tend to be significantly smaller for age than their term counterparts when
studied at 5 to 9 years of age. 50 Fortification is an acceptable method of augmenting breast milk for a premature
infant.27,47,48
There are different methods of fortification that can be
utilized including powdered human milk fortifier or mixing
higher calorie (30 calorie) premature formula in a 1:1
mixture or other ratios with breast milk. The final nutrient
content can vary significantly depending on the fortifier
selected (Table 11-3). Many prefer human milk fortifier in
order to use the maximal amount of human milk. There is an
increase in osmolality when the fortifier is added to breast
milk, 51 but there appears to be no difference in the incidence of side effects,48 NEC, 52 or altered gastric emptying. 53
A liquid fortifier, Prolact+4 H 2MF, is made from human
milk and comes as +6, +8, and +10 with increasing amounts
of calories and protein. 54 This product is much more expensive than traditional human milk fortifiers.
Table 11-3 Nutrient Composition of Human Milk and Fortified Human Milk
Based on Intake of 150 mL/kg5459
Preterm Milk
Term Milk
Preterm milk with
Enfamil Human
Milk Fortifier with
iron
Preterm milk with
Similac Human
Milk Fortifier
Preterm/term
milk 1:1 with
Similac Special
Care 30 cal/oz
Prolact+4
H2MF
Recommended
Intake for
preterm infants
Calories
Protein
Calcium
Phosphorus
101 cal/kg
102 cal/kg
2.1 g/kg
1.5 g/kg
37.5 mg/kg 19.5 mg/kg

42 mg/kg
21 mg/kg
mixed to
120 cal/kg
3.75 g/kg
172.5 mg/
kg
94.5 mg/kg
120 cal/kg
3.6 g/kg
207 mg/kg
117 mg/kg
4.35 g/kg
preterm milk
125 cal/kg
174 mg/kg 95.6 mg/kg
3.75 g/kg
term milk
Fortifies up
Added
Added
120 cal/kg
minerals
to 3.45 g/kg minerals
120 cal/kg
Fortification
3-4 g/kg/d
120-230
mg/kg
60-140 mg/
kg
Sometimes due to a disease process a term infant

cannot tolerate full volume feedings. In this case higher
calorie human milk can be made, but not using the same
products that are used for the preterm infant as the levels
of calcium and phosphorus may be too high. An individualized approach is necessary based on the prescribed volume
and the calorie, protein, and mineral needs for that infant.
Term infant formula may be used to augment breast milk to
keep a good protein, carbohydrate, and lipid ratio.
A concept sometimes called lacto engineering may also
be used to increase calories, using the higher calorie hind
milk to augment the caloric content of the milk. This will not
alter the need for fortification for a preterm infant, but it can
help supply additional calories. A creamatocrit is a measurement for estimating the fat content and therefore the caloric
content of a human milk sample. A microhematocrit tube is
filled with milk and spun in a centrifuge. The layer of fat is
measured as with a blood hematocrit.60,61 Regression equations are as follows:
Fresh breast milk: Energy(kcal/dL) = 5.99 creamatocrit (%) + 32.5 and
Frozen breast milk: Energy (kcal/dL) = 6.20 creamatocrit (%) + 35.1.62
Research is being conducted on the content of hind
milk. There appear to be no significant differences in creamatocrit values of the milk of mothers of preterm, small for
gestational age, and term infants.63 The creamatocrit values
appear to increase until 16 weeks postpartum and then
HUMAN MILK
decline.63 The circadian variation of fat content in human

milk has been evaluated, and although spot values may be
misleading, consistent sampling does show a trend in 2
studies for samples expressed at night to have greater fat
content.64,65 The vitamin A and E levels also appear to be 1.6
times higher in hind than foremilk, something to consider
when planning fortification.66 Medela has a commercial,
easy-to-use creamtocrit instrument that also computes
the calories per ounce and fat grams.67 Validation studies
and tests using creamatocrit measurements performed by
mothers have also been done.6870
There has been controversy concerning the effect of
iron as one of the ingredients in human milk fortifiers on
the antimicrobial properties of human milk. A reduced
antimicrobial effect of human milk with an iron-containing
fortifier has been demonstrated against Escherichia coli (E.
coli), Staphylococcus, Enterobacter sakazakaii (E. sakazakaii),
and Group B streptococcus in one study,71 and against E.
coli, Staphylococcus aureus, Pseudomonas aeruginosa, and
Candida albicans in a second study 72 when these organisms
were added to human milk. A proposed explanation is the
effect of iron on the antibacterial effects of lactoferrin, which
is diminished when lactoferrin is saturated with iron.71 In
another study, no effect was seen in the counts of resident
flora and E. sakazakaii using fortifiers added to fresh milk in
a time span of 6 hours.73 The human milk-derived fortifier
when added to breast milk did not affect the antimicrobial
properties of the milk.74
123
Banked donor pasteurized human milk is used in many

nurseries, either as a bridge to feed early if the mothers own
milk is not yet in, or as a substitute for the mother who cannot
supply sufficient milk or who has chosen not to pump. Some
nurseries use donor milk in the first few weeks after delivery
as that is the peak time for contracting NEC. Donor milk may
be collected from preterm or term mothers; obviously there
is a much greater pool available from mothers of term infants.
The pasteurization in particular alters some of the properties of human milk.46 If donor-banked term milk is used for a
preterm infant, there will be increased needs for supplemental
protein, calcium, and phosphorus as the levels of these nutrients are lower in donor term milk than in preterm milk.75
beginning in the first 2 months after birth.77 Rickets, an

example of extreme vitamin D deficiency, continues to
be reported in the United States and other Western countries, predominantly in the breastfed population and in
infants with darker skin pigmentation.78,79 Historically we
relied upon the effect of sunlight on our skin to stimulate
synthesis of vitamin D from cholesterol as our main source.
There is normally very little vitamin D in breast milk. In
a lactating mother supplemented with 400 International
Units of vitamin D, the vitamin content of her own milk
ranges from < 25 to 78 International Units/L.80 There is
some research on providing women with very large doses of
vitamin D, thereby increasing the content of their milk. At
this time there is a need for research concerning the safety
and efficacy of this method prior to recommendation to a
larger population.80 There is also now concern about the
age at which direct sunlight exposure is initiated, with the
current recommendation that infants under 6 months be
kept out of direct sunlight.81 In following these guidelines,
vitamin D supplementation is necessary. More vitamin
D-only products are now made and are included in the new
paper on vitamin D.76
The iron content in human milk is very low, although
more bioavailable compared to iron in iron-fortified
infant formula.82 Iron needs in the first 6 months of life
for a breastfed infant rely on the infants stores at birth. 82
In healthy breastfed term infants iron deficiency before
6 months of age is observed but uncommon. Typically at
4 to 6 months, iron-rich complementary foods are added,
although the newer guidelines are for exclusive breastfeeding for 6 months.83
Premature infants do not have the same iron stores as
term infants, and infants who are hospitalized may have
blood sampled for testing, further depleting their iron stores.
Premature infants typically receive iron supplementation
due to their low stores at birth and beneficial effect has been
documented in the literature.84 Iron deficiency in infants
is concerning as it appears to lead to developmental delay,
which is irreversible.84 Infants who are breastfed exclusively
for 6 months may be at increased risk of iron deficiency. 82
Ziegler et al studied the effect of early (at 1 month) iron
administration on breastfed term infants. 85 Early supplementation was feasible and well tolerated by most infants. 86
Vitamin D
Growth of Breastfed Infants
Banked Human Milk
The latest statement regarding vitamin D from the

AAP is to supplement with 400 International Units per
day beginning soon after birth.76 This replaces the 2003
statement that recommended 200 International Units
Growth of breastfed infants differs from formula-fed

infants. The WHO has published a growth curve87 based
on infant growth data from one site in the United States as
well as sites in Brazil, Ghana, India, Norway, and Oman.
124
The intention was to choose sites where breastfeeding

was commonly practiced and provide lactation support to
mothers to help them comply with the feeding standards
required to construct this growth curve. The factors were:
exclusive or predominate breastfeeding for the first 4
months, introduction of complementary food between 4 and
6 months, and partial breastfeeding to be continued until at
least 12 months.88 Comparing the 2000 Centers for Disease
Control and Prevention (CDC) growth curve to the WHO
curve, there are notable differences in the growth trajectory of breastfed infants, with breastfed infants growing
more rapidly in the first 2 months and less rapidly from 3
to 12 months in relation to the CDC curve. Linear growth
is higher until 4 months. The growth trajectories show that
infants in the CDC curve are heavier and shorter than the
WHO reference population.89
Breast Milk Safety and Administration
In 2001, a powdered infant formula, Portagen (which

was not a standard formula for preterm infants), was used
and prepared in a NICU for preterm infants. A 33-week
infant became ill and died; the cerebral spinal culture grew
E. sakazakaii. Because this is a rare cause of neonatal meningitis, the state health board and the CDC became involved.
In the investigation it was shown that not only opened cans
of the formula contained the bacteria but also the unopened
cans as well. This launched an investigation into the bacterial
counts of powdered formula, for unlike liquid concentrate
or ready to feed, it is not sterile.90,91 In the guidelines issued
by the CDC in 2002, it stated that formula products should
be based on nutrition needs with alternatives to powder
forms used whenever possible; and hang times limited to 4
hours.90 The Food and Drug Administration issued a letter
to professionals with similar recommendations.92 This has
implications for the use of powdered human milk fortifiers
as well as the use of expressed breast milk. Safety remains a
paramount concern in the provision of any nutrition to the
preterm or term infant. Detailed guidelines published by
the American Dietetic Association (ADA) have been established for the collection, labeling, transporting, storage,
and administration of expressed breast milk.93 The Human
Milk Banking Association of North America also published
guidelines for the handling of breast milk in hospitals,
daycare settings, and the home.94 The following are some of
the ADA key points:
Mothers are encouraged to express milk ideally as soon as
possible after birth (or breastfeed if the infant is able).93
Mothers are encouraged to pump every 2 to 3 hours
or at least 8 times in 24 hours using a hospital grade
pump, using a double kit to not only save time but also
increase hormone levels, leading to increased milk

production.9395
Breast milk should be stored in sterile or aseptic food
grade plastic or glass containers that are built to withstand long-term freezing. They need to have close-fitting
caps that provide an airtight closure; a nipple is not an
acceptable cap.93
Labels should include the name of the contents:
expressed breast milk, infants name, medical record or
identification number, date and time of milk expressed,
medications or supplements taken by the mother,
whether the milk is fresh or frozen, date and time of milk
thawed, and expiration. The expiration will depend on
whether the milk is fresh or frozen. Labels should be
made of a material that the writing on the label can still
be read after freezing and moisture.93
Frozen milk should not be transported in ice as ice is
warmer than frozen milk and could thaw the milk. Blue
ice containers freeze at a colder temperature and are
acceptable for use.93
Length of time milk may be stored at different storage
temperatures93:
Storage Method
Temperature
Room temperature
Cooler with ice packs
Refrigerator,
thawedmilk
Refrigerator,
fortified milk
Refrigerator,
fresh milk
Freezer, home unit
Freezer
Freezer
25C, 75F
15C, 59F
4C, 39F
Length of Time
Recommended
<4h
24 h
24 h feeding when
possible
4C, 39F
24 hours
4C, 39F
48 h
20C, 4F
70C, 94F
3 mo
612 mo
> 12 mo
As breast milk is not homogenized, separation of fat

may occur when breast milk is used in tube feedings.
Research has shown a 17% fat loss in intermittent
feeding but a 34% loss in a continuous tube feeding.95
While some nurseries never use human milk in a
continuous feeding setup due to the losses, others
believe that although it is not ideal it is the best therapy
for the infant and they will accept, and try to minimize,
the losses via the tube. These techniques include using
a shortened tubing length and tilting the feeding pump
syringe upward,96 as well as transitioning to bolus feedings when possible.93
The hang time for breast milk should be 4 hours and the
syringe and tubing should be changed every 4 hours
aswell.93
HUMAN MILK
Only the milk to be given per feed should be warmed.

Excessive heat could harm the infant and destroy
factors such as IgA and enzymes. Any milk left in a
bottle should be discarded.93
Hospitals should have policies to cover the
misadministration of breast milk. Unfortunately this
continues to be a problem in nurseries, and strategies
have been employed to decrease the incidence of
misadministration.9799 A thorough schematic is
presented in the ADA manual.93
In addition to concerns about bacterial contamination,
cytomegalovirus (CMV) in breast milk has been addressed.
Freezing at 20C has been discussed as a method of
decreasing the viral load of CMV in breast milk. Freezing
at this temperature does not appear to decrease secretory
IgA, lysozyme, lactoferrin, C3 complement, or the function
of cells in breast milk.100 While freezing at 20C for various
time periods does appear in studies to decrease viability of
CMV, it is not certain what freezing time period is safe for
high viral loads and what would be necessary to achieve 100%
inactivity. A full discussion of this issue is beyond the scope of
this article, and a review of the topic is available.101
Breast Milk and Maternal Medications
Health professionals are often asked questions about the

use of medications in mothers who are lactating. Riordan
and Auerbach state that there are 3 knowns about medications and breast milk: (1) most drugs pass into breast milk;
(2) almost all medication appears in only small amounts,
usually less than 1% of the maternal dosage; and (3) very few
drugs are contraindicated for breastfeeding women.102,103
That does not mean, however, that caution should not be
taken when prescribing medications to lactating women.
Hales Medications and Mothers Milk is a useful reference
that is updated regularly and compiles the known data
about medications, assigning a risk code.104 The evaluation
of the safety of medications for premature infants depends
on 3 factors according to Hale: the amount of medication
in the milk, the oral bioavailability of the medication, and
the ability of the infant to clear the medication.105 Some of
the drugs of concern in general are the chemotherapeutic
agents, radioactive isotopes, drugs of abuse, lithium, ergotamine, and drugs that suppress lactation. Antihistamines
may reduce milk supply.105
125
1. Why is the late preterm infant at particular risk for

lactation problems?
A. The infant may be mislabeled as a term infant and
treated as such.
B. The infant may have difficulty extracting milk
sufficiently.
C. The infant appears competent at breastfeeding
when he or she is not.
D. The mothers of these infants are at risk for delayed
lactogenesis.
E. All of the above.
2. Can the use of higher calorie hind milk from the use
of lactoengineering replace fortification in a preterm
infant?
A. Yes
B. No
3. Could there be nutrition problems affecting growth
with the use of donor banked human milk for preterm
infants?
A. Yes
B. No
References
1. American Academy of Pediatrics, Committee on Nutrition. Kleinman RE, ed. Pediatric Nutrition Handbook. 6th
2009:55.
2. Canadian Paediatric Society Nutrition Committee, American
Association of Pediatrics Committee on Nutrition. Breastfeeding; a commentary in celebration of the international year
of the child.1979. Pediatrics. 1978;65:591601.
3. International Pediatric Association: Recommendations for
action programmes to encourage breastfeeding. Acta Paediatr
Scand. 1976;65:275277.
4. WHO/UNICEF. Protecting, promoting, and supporting
breastfeeding; the special role of maternity services, a joint
WHO/UNICEF statement. Geneva Switzerland 1989, World
Health Organization.
5. US Department of Health and Human Services. Healthy
People 2010: Understanding and Improving Health and Objectives for Improving Health. Vols. 1, 2. 2nd ed. Washington, DC:
US Dept of Health and Human Services; 2000.
6. Centers for Disease Control and Prevention. Breastfeeding
Report Card, United States: Outcome Indicators. http://www.
cdc.gov/breastfeeding/data/report_card2.htm.Accessed
November 12, 2009.
7. Lawrence RA, Lawrence RM. Breastfeeding: A Guide for the
Medical Profession. 6th ed. St. Louis, MO: Mosby; 2005:187.
126
8. Fanaro S, Vigi V. Infant formulas supplemented with prebiotics: intestinal microbiota and immune responses. Minerva
Pediatr. 2008;60:327335.
9. Hatakka K, Savilahti E, Ponka A, et al. Effect of long-term
consumption of probiotic milk on infections in children
attending day care centres: double blind, randomized trial.
BMJ. 2001;322:1327.
10. May JT. Microbial contaminants and antimicrobial properties
of human milk. Microbiol Sci. 1988;5:4246.
11. Goldman AS, Garza C, Nichols BJ, et al. Immunologic factors
in human milk during the first year of lactation. J Pediatr.
1982;100:563.
12. Howie PW, Forsyth JS, Ogston SA, et al. Protective effect of
breastfeeding against infection. BMJ. 1990;336:92.
13. Duncan B, Ey J, Holberg CJ, Wright AJ, et al. Exclusive breastfeeding for at least 4 months protects against otitis media.
Pediatrics. 1993;91:867872.
14. Aniansson G, Alni B, Andersson A, et al. A prospective cohort
study on breastfeeding and otitis media in Swedish infants.
Pediatr Infectious Dis J. 1994;12:183188.
15. Paradise JL, Elster BA, Tan L. Evidence in infants with cleft
palate that breast milk protects against otitis media. Pediatrics.
1994;94:853860.
16. Pisacane A, Grazione L, Mazzarella G, et al. Breastfeeding and
urinary tract infections. J Pediatr. 1992;120:8789.
17. Vennemann MM, Bajanowski T, Brinkman B, et al. Does
breastfeeding reduce the risk of sudden infant death
syndrome? Pediatrics. 2009;123:e406e410.
18. Saarinen IJM, Kajosaari M, Backnman A, et al. Prolonged
breastfeeding as prophylaxis for atopic disease. Lancet.
1979;2:163166.
19. Kramer MS. Does breastfeeding help protect against atopic
disease? Biology, methodology and a golden jubilee of controversy. J Pediatr. 1988;112:181190.
20. Thygarejan A, Burks AW. American Academy of Pediatrics
recommendations on the effect of early nutritional interventions on the development of atopic disease. Curr Opin Pediatr.
2008;20:698702.
21. Greer FR, Sicherer SH, Burks W, et al. Effects of nutritional
interventions on the development of atopic disease in infants
and children; the role of maternal diet restriction, timing
of introduction of complementary foods, and hydrolyzed
formulas. Pediatrics. 2008;121:183190.
22. Hanson LA, Adlerberth I, Carlsson B, et al. Host defense of
the neonate and the intestinal flora. Acta Peadiatric Scand.
1989; 351(suppl):122125.
23. Koletzko S, Sherman P, Corey M, et al. Role of infant feeding
practices in development of Crohns disease in childhood.
BMJ. 1989;298:16171618.
24. Gerstein HC. Cows milk exposure and type I diabetes
mellitus. Diabetes Care. 1994;17:1319.
25. Savilahti E, Saarinen KM. Early infant feeding and type I
diabetes. Eur J Nutr. 2009;48(4):243249.
26. Davis MK, Savitz DA, Graubard BI. Infant feeding and childhood cancer. Lancet. 1988;2:365368.
27. Schanler RJ. The use of human milk for premature infants.
Pediatr Clin N Am. 2001;48:207219.
28. Meinzen-Derr J, Poindexter B, Wrage L, et al. Role of human

milk in extremely low birth weight infants risk of necrotizing
enterocolitis or death. J Perinatol. 2009;29:5762.
29. Sisk PM, Lovelady CA, Dillard RG, et al. Early human
milk feeding is associated with a lower risk of necrotizing
enterocolitis in very low birth weight infants. J Perinatol.
2007;27428433.
30. Schanler RJ, Lau C, Hurst NM, et al. Randomized trial of
donor human milk versus preterm formula as substitutes for
mothers own milk in the feeding of extremely low birthweight
infants. Pediatrics. 2005;116:400406.
31. Schanler RJ. Mothers own milk, donor human milk, and
preterm formulas in the feeding of extremely premature
infants. J Pediatr Gastroenterol Nutr. 2007;48:S175S177.
32. Kleinman RE, Walker WA. The enteromammary immune
system. Dig Dis Sci. 1979;24:876882.
33. Wang AC, Chen SJ, Yuh YS. Breastfeeding associated
neonatal hypernatremic dehydration in a medical center: a
clinical investigation. Acta Paediat Taiwan. 2007;48:186190.
34. Unal S, Arhan E, Kara N, et al. Breastfeeding associated
hypernatremia: retrospective analysis of 169 term newborns.
Pediatr Int. 2008;50:2934.
35. Yaseen H, Salem M, Darwich M. Clinical presentation of
hypernatremic dehydration in exclusively breastfed neonates.
Indian J Pediatrics. 2004;71:10591062.
36. Academy of Breastfeeding Medicine. Guidelines for
hospital discharge of the breastfeeding term newborn and
mother. Going home protocol. 2007, Sep 2 (3)158165.
http://www.guideline.gov/summary/summary.aspx?doc_
id=11556&nbr=5987&ss=15. Accessed November 12, 2009.
37. Academy of Breastfeeding Medicine. Breastfeeding the near
term infant (35 to 37 weeks gestation). 2004 Aug 22. http://
www.guideline.gov/summary/summary.aspx?ss=15&doc_
id=11227&nbr=5874. Accessed November 12, 2009.
38. Academy of Breastfeeding Medicine. Transitioning the breastfeeding/breastmilk-fed premature infant from the neonatal
intensive care unit to home. 2004 Sep 17. http://www.guideline.gov/summary/summary.aspx?doc_id=11229. Accessed
November 12, 2009.
39. Wight N. Breastfeeding the borderline near term infant. Pediatric Ann. 2003;32:329336.
40. Meier PP, Furman LM, Deenhardt M. Increased lactation risk
for late preterm infants and mother: evidence and management strategies to protect breastfeeding. J Midwifery Womens
Health. 2007;52:579587.
41. Wight NE, Morton JA, Kim JH. Best Medicine Human Milk in
the NICU. Amarillo, TX: Hale Publishing, LP; 2008.
42. Meier PP, Engstrom JL, Mingolelli SS, et al. The Rush
Mothers Milk Club: Breastfeeding interventions for mothers
with very-low-birthweight infants. J Obstet Gynecol Neonatal
Nurs. 2004;33:164172.
43. Meier PP, Engstrom JL, Hurst NM, et al. A comparison of the
efficiency, comfort and convenience of two hospital-grade
electric breast pumps for mothers of very low birth weight
infants. Breastfeed Med. 2008;3:141120.
44. Meier PP, Brown LP, Hurst NN, et al. Nipple shields for
preterm infants: effect on milk transfer and duration of breastfeeding. J Hum Lact. 2000;16:106114.
HUMAN MILK
45. Chazpak N, Ruiz JG, KMC Team. Breast milk composition in

a cohort of preterm infants mothers followed in a ambulatory
program in Colombia. Acta Paediatr. 2007;96:17351739.
47. Morales Y, Schanler RJ. Human milk and clinical outcomes
in VLBW infants: how compelling is the evidence of benefit?
Semin Perinatol. 2007;31:8388.
48. Mukhopadhyay K, Narang A, Mahajan R. Effect of human
milk fortification in appropriate for gestation and small for
gestation preterm babies: a randomized trial. Indian Pediatrics.
2007;44:286290.
49. Carey DE, Rowe JS, Goetz CA, et al. Growth and phosphorus
metabolism in premature infants fed human milk, fortified
human milk, or special premature formula. Am J Dis Child.
1987;141:511.
50. Chan GM, Armstrong C, Moyer-Mileur L, et al. Growth and
bone mineralization in children born prematurely. J Perinatol.
2008; 28:619623.
51. Janjindami W, Chotsampancharoen T. Effect of fortification
on the osmolality of human milk. J Med Assoc Thai. 2006;
99:14001403.
52. Bhat BA, Gupta B. Effects of human milk fortification on
mortality factors in very low birthweight infants. Ann Saudi
Med. 2003;23:2831.
53. Yigit S, Akgoz A, Memisoglu A, et al. Breast milk fortification: effect on gastric emptying. J Matern Fetal Neonatal Med.
2008;21;843846.
54. Prolacta Web site. http://www.Prolacta.com. Accessed
January 2009.
55. Sapsford A. Composition of human milk and selected enteral
products. In: Groh Wargo S, Thompson M, Cox J, eds. Nutritional Care for High Risk Newborns. 3rd ed. Chicago, IL:
Precept Press; 2000:664
56. Abbott Nutrition Web site. http://www.abbottnutrition.com/
products. Accessed January 2009.
57. MeadJohnson Nutrition Web site. http://www.mjn.com.
Accessed January 2009.
58. Groh Wargo S. Recommended enteral nutrient intakes. In:
Groh Wargo S, Thompson M, Cox J, eds. Nutritional Care
for High Risk Newborns. 3rd ed. Chicago, IL: Precept Press;
2000:234.
59. Ziegler EE. Protein requirements of very low birth weight
infants. J Pediatric Gastroenterol Nutr. 2007;45:S170S174.
61. Lucas A, Gibbs JAH, Lyster RLI, et al. Creamatocrit: simple
clinical technique for estimating fat concentration and energy
value of human milk. Br Med J. 1978;1:1018.
62. Wang CD, CHU PS, Mellen BG, et al. Creamatocrit and
the nutrient composition of human milk. J Perinatol.
1999;19:343346.
63. Chatterjee R, Chatterjee S, Datta T, et al. Longitudinal study
of human milk creamatocrit and weight gain in exclusively
breastfed infants. Indian Pediatrics. 1997; 34:901904.
64. Lubetsky R, Mimouni FB, Dollberg S, et al. Consistent
circadian variations in creamatocrit over the first 7 weeks of
lactation: a longitudinal study. Breastfeed Med. 2007;2:1518.
127
65. Weber A, Loui A, Jochum F, et al. Breast milk from mothers

of very low birthweight infants: variability in fat and protein
content. Acta Paediatr. 2001;90:772775.
66. Bishara R, Dunn MS, Merko SE, et al. Nutrient composition
of hindmilk is produced by mothers of very low birth weight
infants born at less than 28 weeks gestation. J Hum Lact.
2008;24:159167.
67. Medala Web site. http://www.medelabreastfeedingus.com/
for-professionals/lc-information. Accessed February 2009.
68. Meier PP, Engstrom JL, Zuleger JL, et al. Accuracy of a userfriendly centrifuge for measuring creamatocrit on mothers
milk in a clinical setting. Breastfeed Med. 2006;1:7987.
69. Griffith TL, Meier PP, Bradford LP, et al. Mothers performing
creamatocrit measures in the NICU: accuracy, reactions, and
cost. J Obstet Gynecol Neonatal Nurs. 2000;29:249257.
70. Meier PP, Engstrom JL, Murtaugh MA, et al. Mothers milk
feedings in the neonatal intensive care nursery: accuracy of
the creamatocrit technique. J Perinatol. 2002; 22:646649.
71. Chan GM. Effect of powdered human milk fortifier
on the antibacterial actions of human milk. J Perinatol.
2003;23:620623.
72. Ovali F, Ciftci I, Cetinkaya Z, et al. Effects of human milk
fortifier on the antimicrobial properties of human milk. J Perinatol. 2006;26:761763.
73. Telang S, Berseth CL, Ferguson PW, et al. Fortifying fresh
human milk with commercial human milk fortifiers does not
affect the bacterial growth during 6 hours at room temperature. J Am Diet Assoc. 2005;105:567572.
74. Chan GM, Lee MI, Rechman DJ. Effects of a human milkderived human milk fortifier on the antibacterial actions of
human milk. Breastfeed Med. 2007;2:205208.
75. Wojcik KY, Rechtman DJ, Lee, ML, et al. Macronutrient
analysis of a nationwide sample of breast milk. J Am Diet Assoc.
2009; 109:137140.
76. Wagner CL, Greer FR; American Academy of Pediatrics
Section on Breastfeeding; American Academy of Pediatrics
Committee on Nutrition. Prevention of rickets and vitamin
D deficiency in infants, children, and adolescents. Pediatrics.
2008:122:11421152.
77. Gartner LM, Greer FR; American Academy of Pediatrics
Section on Breastfeeding; American Academy of Pediatrics
D deficiency: new guidelines for vitamin D intake. Pediatrics.
2003;111:908910.
78. Kreiter SR, Schwartz RP, Kirkman HN, et al. Nutritional
rickets in African American breastfed infants. J Pediatr.
2000;137:153157.
79. Ward LM. Vitamin D deficiency in the 21st century: a persistent problem among Canadian infants and mothers. CMAJ.
2005;172:769770.
80. Wagner CL, Hulsey TC, Fanning D, et al. High dose vitamin
D supplementation in a cohort of breastfeeding mothers and
their infants; a six month follow-up pilot study. Breastfeed
Med. 2006;1:5970.
81. American Academy of Pediatrics, Committee on Environmental Health. Ultraviolet light: a hazard to children.
Pediatrics. 1999;104:328333.
128
82. American Academy of Pediatrics, Section on Breastfeeding.

Breastfeeding and the use of human milk. Pediatrics.
2005;115:496506.
83. Chantry CJ, Howard CR, Auinger P. Full breastfeeding duration and risk for iron deficiency in U.S. infants. Breastfeeding
Med. 2007;2:6373.
84. Steinmacher J, Pohlandt F, Bode H, et al. Randomized trial
of early versus late enteral iron supplementation in infants
with a birth weight of less than 1301 grams: neurocognitive development at 5.3 years corrected age. Pediatrics.
2007;120:538546.
85. Ziegler EE, Nelson SE, Jeter JM. Iron supplementation
of breastfed infants from an early age. Am J Clin Nutr.
2009;89(2):525532.
86. Lozoff B, Jimenez E, Hagen J, et al. Poorer behavioral and
developmental outcome more than 10 years after treatment
for iron deficiency. Pediatrics. 2000;105:E51.
87. World Health Organization. The WHO Child Growth Standards. www.who.int/childgrowth/standards/en. Accessed
January 30, 2009.
88. WHO Multicentre Growth Reference Study Group. Breastfeeding in the WHO Multicentre Growth Reference Study.
Acta Paediaticia. 2006;(Suppl)450:1626.
89. de Onis M, Onyango AW. The Centers for Disease Control and
Prevention 2000 growth charts and the growth of breastfed
infants. Acta Paediatrica. 2003;92:413419.
90. Enterobacter sakazakaii infections associated with the use of
powdered infant formulaTennessee 2001. MMWR Weekly.
April 12, 2002;298300.
91. Bowen AB, Braden CR. Invasive Enterobacter sakazakaii
disease in infants. Emerging Infectious Diseases. August 2006.
http://www.cdc.gov/ncidod/EID/vol12no08/05-1509.htm.
Accessed November 12, 2009.
92. Food and Drug Administration. Health professionals letter
on Enterobacter sakazakii infections associated with use of
powdered (dry) infant formulas in neonatal intensive care
units. April 11, 2002, revised October 10, 2002.
93. Sapsford A, Lessen R. Expressed human milk. In: Robbins

ST, Beker LT, eds. Infant Feedings: Guidelines for Preparation of
Formula and Breastmilk in Health Care Facilities. Chicago, IL:
American Dietetic Association; 2004.
94. Human Milk Banking Association of North America. 2006
Best Practice for Expressing, Storing and Handling of Mothers
Own Milk in Hospital and at Home. Raleigh, NC: Human Milk
Banking Association of North America; 2006.
95. Martinez FE, Desai ID, Davidson AGF, et al. Ultrasonic
homogenization of expressed human milk to prevent fat loss
during tube feeding. J Pediatr Gastroenterol Nutr. 1987;6:593.
96. Narayan I, Singh B, Harvey D. Fat loss during feeding of
human milk. Arch Dis Child. 1984; 59:475477.
97. Zeilhofer UB, Frey B, Zandee J, Bernet V. The role of critical
incident monitoring in detection and prevention of breast
milk confusions. Eur J Pediatr. 2009;168(10):12771279.
98. Dougherty D, Giles V. From breast to bottle: quality assurance for breast milk management. Neonatal Network. 2000;
19:2125.
99. Drenckpohl D, Bowers L, Cooper B. Use of the six signs methodology to reduce incidence of breast milk administration
errors in the NICU. Neonatal Network. 2007; 26:161166.
100. Lawrence RA. Storage of human milk and the influence of
procedures on immunological components of human milk.
Acta Paediatr Suppl. 1999;88:1418.
101. Lawrence RM. Cytomegalus in human breast milk: risk to the
premature infant. Breastfeeding Med. 2006;1:99107.
102. Riordan J. Drugs and breastfeeding. In: Riordan J, Auerbach
K, eds. Breastfeeding and Human Lactation. 2nd ed. Sudbury,
MA: Jones and Bartlett; 1998,163219.
Grove Village, IL: American Academy of Pediatrics; 2009:71.
104. Hale T. Medications and Mothers Milk. 13th ed. Amarillo, TX:
Hale Publishing, LP; 2008.
105. Hale T. Medication in breastfeeding mothers of preterm
infants. Pediatric Ann. 2003;337347.
Infant Formulas and

ComplementaryFeeding
12
Kelly Green-Corkins, MS, RD, CNSD and Timothy Sentongo, MD
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
Types of Infant Formulas. . . . . . . . . . . . . . . . . . . . . . . . . . 130
Standard Milk-Based Term Infant Formulas
Term Formulas Designed for Symptoms of Intolerance
Premature or Low Birth Weight Formulas
Premature Discharge Formulas
Specialized Infant Formulas
Functional Ingredients in Infant Formulas. . . . . . . . . . . . 135

DHA/ARA
Forms of Infant Formula and Mixing Guidelines . . . . . . . 137

Introducing Complementary Foods
to the Infants Diet. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Toddler Formulas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Learning Objectives
1. Explain the basis for and regulation of infant formulas.

2. Discuss reasons for functional ingredients in infant
formulas.
3. Differentiate infant formulas and target populations.
4. Describe how increased caloric concentrations may
influence tolerance.
5. Summarize reasoning behind current guidelines for
introducing complementary foods to an infants diet.
Introduction
The World Health Organization recommends human milk

as the sole source of nutrition for healthy full-term infants
birth to 6 months of age.1 Breastfeeding provides benefits
to the infant that infant formula can not. Breastfeeding
promotes gastrointestinal development and function,
immune support, and neurodevelopment. 2 It is not always
possible for a mother to breastfeed, or a mother may
choose not to breastfeed due to cultural, social, or health
reasons. Iron-fortified infant formulas are appropriate
substitutes for human milk. No matter what the choice or
reason for not breastfeeding, a mother should be supported
in her decision. 3
Because human milk is the optimal source of nutrition
for an infant, infant formulas are designed to be similar to
human milk and/or to promote a similar response as seen
in the breastfed infant.4 Even with the latest functional
ingredients added (docosahexaenoic acid [DHA] and
arachidonic acid [ARA], nucleotides, probiotics, prebiotics),
infant formulas are still not able to provide the hormones,
immunoglobulins, enzymes, and live cells that are in human
milk. 3 Infant formulas are designed using cows milk or
soy as a base. Although infant formula manufacturers will
129
130
never be able to completely replicate human milk, research

continues and there are modifications to improve the quality
of infantformulas. 3
Regulation
An infant formula is defined by the Federal Food, Drug,

and Cosmetic Act (FDCA) as a food which purports to be
or is represented for special dietary use solely as a food for
infants by reason of its simulation of human milk or its suitability as a complete or partial substitute for human milk.5
Infant formulas designed to meet a specific medical need
(ie, premature infant formulas) are considered exempt
because the nutrition requirements of infants with certain
medical conditions differ from those of healthy infants.
Exempt formulas are not exempt from monitoring or regulation and need to meet certain criteria. All infant formula
manufacturers must begin with safe ingredients that are
approved for use in infant formulas, or are generally recognized as safe (GRAS). 5
The Infant Formula Act of 1980 (revised 1986), an
amendment to the FDCA, was developed due to an incident
involving inadequate chloride in a soy-based formula that
resulted in metabolic acidosis in several infants.6 The Food
and Drug Administration (FDA) is responsible for monitoring the manufacturers that make infant formulas. There
are federal regulations on quality control, labeling, nutrient
levels, formula recall, new product notification, and exempt
products. There are established levels for 29 nutrients and
maximum levels for 9 nutrients. Manufacturers are required
to declare on the label the levels of each nutrient provided,
and the manufacturer must analyze each batch of formula
to ensure the declared levels of all essential nutrients are
being provided. The FDA reviews the analysis records and
will perform tests on the formula to monitor the manufacturers. 5 The concentration of nutrients in infant formula
is higher than in human milk because of the decreased
bioavailability in infant formula. 3,7
Types of Infant Formulas
Information included in this section and the accompanying

tables is up-to-date as of the time of publication. For the
most current information, please visit the manufacturers
Web sites (Table12-1).
Table 12-1 Infant Formula Manufacturer Web Sites

Manufacturer
Product Line
Web Site
Abbott
Nutritionals
Mead Johnson
Nestle Gerber
Nutricia
Similac
www.abbottnutrition.com
Enfamil
GOOD START
Neocate and
other products
Bright Beginnings
Parents Choice
some modulars
www.meadjohnson.com
www.gerber.com
www.nutricia-na.com
PBM Nutritionals
Vitaflo
www.pbmproducts.com
www.vitaflousa.com
Standard Milk-Based Term Infant Formulas

Standard milk-based infant formulas (Table 12-2) are
designed to meet the needs of healthy infants birth to 1 year
of age. The protein source is cows milk, which is iron-fortified. Most formula-fed infants will consume one of these
products.
A subgroup of the standard infant formulas is organic.
In order to be labeled organic, the formula ingredients must
be certified organic and meet U.S. Department of Agriculture regulations. Ingredients must be produced without
pesticides, added growth hormones, or antibiotics.
Term Formulas Designed for Symptoms of Intolerance

Formulas designed for symptoms of intolerance (Table
12-3)are milk-based and are appropriate for the full-term
infant. Modifications include partial hydrolysis of the
protein, reduced lactose or lactose-free, and added rice
starch.
Partially Hydrolyzed Protein
Formulas containing partially hydrolyzed protein are not
considered hypoallergenic and are not intended to be used
for treatment of any allergic condition or disease. Partially
hydrolyzed formulas contain reduced or no lactose and
each product is different in the type of protein hydrolyzed
and degree of hydrolysis. Therefore, assumptions can not
be made that all partially hydrolyzed protein formulas offer
identical benefits.8
The benefits of partially hydrolyzed 100% whey protein
have been studied and research demonstrates that it may
decrease the risk of atopic dermatitis in infants with a
family history of allergic disease. 8 The product containing
the partially hydrolyzed 100% whey protein is considered a
routine milk-based infant formula.
Another product on the market contains partially
hydrolyzed whey and casein. This product is marketed
for intolerances but does not have research to suggest the
INFANT FORMULAS AND COMPLEMENTARYFEEDING
131
Table 12-2 Standard Milk Based Infant Formulas (per 100 calories) The standard dilution for these products is 0.67 kcal/mL (20 kcal/oz).
Product
(Manufacturer)
Protein g (% kcal)
Source
Bright Beginnings
Milk-based
(PBM Nutritionals)
2.2 (9%)
10.9 (43.6%)
nonfat milk, whey lactose
protein concentrate
Bright Beginnings
Organic
(PBM Nutritionals)
2.2 (9%)
organic reduced
minerals whey,
nonfat milk
10.6 (42%)
lactose
Enfamil LIPIL w/iron

(Mead Johnson)
2.1 (8.5%)
(liquid): reduced
minerals whey,
nonfat milk
(powder): whey
protein concentrate,
nonfat milk
2.1 (8.5%)
whey, nonfat milk
10.9 (43.5%)
lactose
2.2 (9%)
whey protein
concentrate
(enzymatically
hydrolyzed, reduced
in minerals)
2.2 (9%)
whey protein
concentrate
(enzymatically
hydrolyzed, reduced
in minerals)
2.2 (9%)
whey protein
concentrate
(enzymatically
hydrolyzed, reduced
in minerals)
2.1 (8.4%)
nonfat milk, whey
protein concentrate
Enfamil PREMIUM
(Mead Johnson)
GOOD START Gentle

PLUS
(Nestle/Gerber)
GOOD START Nourish

PLUS
(Nestle/Gerber)
GOOD START Protect

PLUS
(Nestle/Gerber)
Parents Choice Milk

Formula DHA & ARA
(PBM Nutritionals)
CHO g (% kcal)
Source
Fat g (% kcal)
Source
Na
mg
K
mg
Ca Phos Fe
mg mg mg
Osmolal- Comments
ity mOsm
5.3 (47.7%)
27 108 82
palm olein, soy oil,
coconut oil, high
oleic safflower or
sunflower oil
5.3 (48%)
23 84 63
organic palm or
palm olien, high
oleic safflower
or sunflower oil,
coconut oil, soy oil
5.3 (48%)
27 108 78
coconut oil, high
oleic sunflower oils
43 1.8
added nucleotides
42 1.8
added nucleotides, DHA

17 mg, ARA 34 mg
43 1.8
300
DHA 17 mg, ARA 34 mg

PRSL 18.9/100 cals
11 (43.5%)
5.3 (48%)
27 108 78
lactose, galacto- palm olein, soy oil,
oligosaccharides coconut oil, high
oleic sunflower oils
43 1.8
300
11.2 (45%)
lactose, corn
maltodextrin
5.1 (46%)
coconut oil, high
oleic safflower or
sunflower oil
27 108 67
38 1.5
250
added nucleotides
28 mg/L, DHA 17 mg,
ARA 34 mg
PRSL 19.1/100 cals
added prebioticgalactooligosaccharide (GOS)
46 mg added
nucleotides, DHA 0.32%,
ARA 0.64% PRSL
19.5/100 cals
11.2 (45%)
lactose, corn
maltodextrin
5.1 (46%)
coconut oil, high
oleic safflower or
sunflower oil
27 108 67
38 1.5
250
5 mg added nucleotides
PRSL 19.5/100 cals
No DHA and ARA
11.2 (45%)
lactose, corn
maltodextrin
5.1 (46%)
coconut oil, high
oleic safflower or
sunflower oil
27 108 67
38 1.5
250
46 mg added
nucleotides, DHA 0.32%,
ARA 0.64%
PRSL 19.5/100 cals
10.9 (43.6%)
lactose
5.3 (47.7%)
27 108
coconut oil, high
oleic safflower or
sunflower oil
Parents Choice Organic 2.2 (9%)
10.6 (42%)
5.3 (48%)
23 84
(PBM Nutritionals)
organic reduced
organic lactose organic vegetable
mineral whey
oils (palm or
palm olein, high
oleic safflower or
sunflower, coconut,
soy)
Similac Advance
2.07 (8%)
11.2 (43%)
5.4 (49%)
24 105
EarlyShield
nonfat milk, whey lactose,
high oleic safflower
(Abbott Nutritionals)
protein concentrate galactose oligo- oil, soy oil, coconut
saccharides
oil
(GOS)
Similac Organic
2.07 (8%)
10.56 (42%)
5.49 (49%)
24 105
organic nonfat dry organic corn
organic high oleic
milk
maltodextrin,
sunflower oil,
organic lactose, organic soy oil,
organic sugar
organic coconut oil
78
43 1.8
DHA, ARA
63
42 1.8
DHA, ARA
78
42 1.8
310
added nucleotides,
DHA 0.15%, ARA 0.40%
PRSL 18.7/100 cals
added prebiotics, GOS
78
42 1.8
225
DHA 0.15%, ARA 0.40%

PRSL 18.8/100 cals
unmodified whey:casein
18:82
132
Table 12-3 Infant Formulas for Symptoms of Intolerance (per 100 calories) Standard dilution is 0.67 kcal/mL (20 kcal/oz).
Product
(Manufacturer)
Protein g (% kcal)
Source
Bright Beginnings
Gentle
(PBM Nutritionals)
CHO g (% kcal)
Source
Fat g (% kcal)
Source
Na
mg
2.3 (9%)
10.8 (43%)
nonfat milk, whey corn syrup solids,
protein hydrolysate lactose
5.3 (48%)
palm olein, coconut
oil, soy oil, high
oleic safflower or
sunflower oil
Enfamil AR LIPIL
(Mead Johnson)
2.5 (10%)
nonfat milk
11 (44%)
lactose,
rice starch,
maltodextrin
Enfamil
Gentlease LIPIL
(Mead)
2.3 (9%)
partially
hydrolyzed
nonfat milk and
whey protein
concentrate
Phos
mg
Fe
mg
32 108 82
46
1.8
added nucleotides,
DHA, ARA
5.1 (46%)
cocnut oil, high oleic
sunflower oil
40 108 78
53
1.8 240 RTU

230
Powder
DHA 17 mg,
ARA 34 mg
PRSL 22/100 cals
10.8 (43%)
corn syrup solid,
lactose
5.3 (48%)
coconut oil, high
oleic sunflower oil
32 108 82
46
1.8 220
DHA 17 mg,
ARA 34 mg
PRSL 20/100 cals
Parents Choice
Gentle
(PBM Nutritionals)
2.3 (9%)
10.8 (43%)
nonfat milk, whey corn syrup solids
protein hydrolysate
5.3 (48%)
palm olein, cocnut
oil, soy oil, high
oleic safflower or
sunflower oil
32 108 82
46
1.8
DHA, ARA
Parents Choice
Lactose Free
with Lipids
(PBM Nutritionals)
2.3 (9%)
whey protein
concentrate, milk
protein isolate
10.8 (43%)
corn syrup solids
5.3 (48%)
palm olein, coconut
oil, soy oil, high
oleic safflower or
sunflower oil
32 108 82
46
1.8
DHA, ARA
Parents Choice
Sensitivity
(PBM Nutritionals)
2.6 (10%)
milk protein
isolate
10.5 (42%)
corn syrup solids,
sucrose
5.3 (48%)
palm olein, coconut
oil, soy oil, high
oleic safflower or
sunflower oil
36 130 195 130
DHA, ARA
Similac Isomil DF 2.66 (11%)

10.1 (40%)
(Abbott Nutritionals) soy protein isolate, corn syrup solids,
L-methionine
sucrose
5.46 (49%)
soy oil, cocnut oil
44 108 105 75
1.8 240
no DHA or ARA,
soy protein
Similac Sensitive
2.14 (9%)
(Abbott Nutritionals) milk protein
isolate
10.7 (43%)
corn maltodextrin,
sugar
5.4 (49%)
oil, soy oil, coconut
oil
30 107 84
56
1.8 200
DHA 0.15%,
ARA 0.40%
PRSL 19.9/100 cals
Similac
2.14 (9%)
Sensitive RS
milk protein
(Abbott Nutritionals) isolate
10.7 (43%)
corn syrup, rice
starch, sugar
5.4 (49%)
oil, soy oil, coconut
oil
30 107 84
56
1.8 180
DHA 0.15%,
ARA 0.40%
PRSL 19.9/100 cals
same potential benefits as the partially hydrolyzed 100%

wheyprotein.
Lactose-free
Lactose is only present in mammalian milk. Lactosefree formulas have similar calorie, protein, fat, and
micronutrient content as standard milk-based formulas.
Lactose-free formulas, including soy formulas, may be indicated in infants with suspected transient lactase deficiency
secondary to gastroenteritis or protracted diarrhea. Parents
with lactose intolerance may assume their infants are also
K
mg
Ca
mg
Osmolal- Comments
ity mOsm
lactose intolerant. However, most babies make adequate

amounts of lactase and congenital lactase deficiency is
extremely rare. Milk-based lactose-free formulas are not
indicated in galactosemia.
Added Rice Starch
Added rice starch formulas are standard milk-based infant
formulas designed to thicken in the acidic environment of
the stomach to decrease spitting-up episodes.9 Rice starch
is added as part of the carbohydrate content; therefore,
the macronutrient distribution remains consistent with
133
Table 12-4 Soy-Based Infant Formulas (per 100 calories) Standard dilution for soy-based formulas is 0.67 kcal/mL (20 kcal/oz).
Product
(Manufacturer)
Protein g (% kcal)
Source
CHO g (% kcal)
Source
Enfamil ProSobee 2.5 (10%)

10.6 (42%)
LIPIL
soy protein isolate, corn syrup solid
L-methionine
(Mead Johnson)
GOOD START
Soy PLUS
(Nestle/Gerber)
2.5 (10%)
enzymatically
hydrolyzed soy
protein isolate,
L-methionine
Similac Isomil
2.45 (10%)
Advance
soy protein isolate,
(Abbott Nutritionals) L-methionine
Bright Beginnings 2.5 (10%)
Soy
soy protein isolate,
L-methionine
(PBM Nutritionals)
Parents Choice
Soy DHA and ARA
(PBM Nutritionals)
2.5 (10%)
soy protein isolate
11 (44%)
corn maltodextrin,
sucrose
10.3 (41%)
corn syrup solids,
sugar
10.6 (42%)
corn syrup solids
10.6 (42%)
corn syrup solids
Fat g (% kcal)
Source
Na
mg
5.3 (48%)
coconut oil, high oleic
sunflower oil
5.1 (46%)
coconut oil, high
oleic safflower or
sunfloweroil
5.46 (49%)
oil, soy oil, cocnut oil
5.3 (48%)
palm olein, coconut
oil, soy oil, high oleic
safflower or sunflower
oil
5.3 (48%)
palm olein, coconut
oil, soy oil, high
oleic safflower or
sunfloweroil
standard milk-based infant formulas. Rice cereal may be

added to standard infant formula to achieve a similar effect;
however, it increases the caloric density and may result in
clogged nipples. Added rice starch formulas are not substitutes for thickened formula indicated for risk of aspiration.
Currently there are 2 added rice starch products on the
market; one of the products is lactose-free while the other
has reduced lactose. Each product has studies to support
that the added rice starch decreases episodes of spitting
up.9,10
Soy-Based Formulas
Soy-based formulas (Table 12-4) are designed to meet the
needs of healthy infants birth to 1 year of age. The protein
source is soy, supplemented with methionine to make it a
complete protein source. These formulas are fortified with
iron and are lactose-free. It is estimated that about 25%
of infants consuming formula will consume a soy-based
formula. Soy-based infant formulas have higher calcium
and phosphorus than standard cows milk-based formulas
because of reduced bioavailability secondary to phytates.11
Soy-based formulas offer no advantage over cows milkbased formulas except for a few indications. Indications for
soy-based formula are infants with galactosemia or hereditary lactase deficiency (rare), or if a vegetarian human milk
substitute is requested.12
Soy-based formulas are not recommended for premature infants as they are not designed to meet the premature
K
mg
Ca
mg
Phos
mg
Fe
mg
Osmolal- Comments
ity mOsm
36
120 105 69
1.8 liquid 200 DHA 34 mg,

powder
ARA 17 mg
170
PRSL 23/100 cals
40
116 105 63
1.8 180
DHA, ARA
PRSL 22.9/100 cals
44
108 105 75
1.8 200
36
120 105 83
1.8
DHA 0.15%,
ARA 0.40%
PRSL 22.8/100 cals
DHA 17 mg,
ARA 34 mg PRSL
36
120 105 69
1.8
DHA, ARA
PRSL 22.9/100 cals
infants specific needs.12 Soy milk protein is no less allergenic than cows milk protein. 3 Infants with documented
cows milk allergy should not be given a soy formula
because 10% to 14% of these babies will also have a sensitivity to soy protein.13,14 Infants with acute gastroenteritis
who were previously well can be managed with rehydration
and continued use of human milk or their usual cows milkbased formula at the standard dilution.12
Premature or Low Birth Weight Formulas

Premature or low birth weight (LBW) formulas (Table
12-5) come in ready-to-feed nurser bottles that are available for hospital use only. These formulas are milk-based
and designed to meet the special nutrition needs of preterm
infants (born less than 37 weeks gestation) and/or infants
born less than 1500 g (which is considered very low birth
weight [VLBW]) while in the hospital, if human milk is
not available. The unique characteristics of this group of
formulas include increased protein, carbohydrate blends
of lactose and glucose polymers, fat blends containing
a portion of fat as medium-chain triglycerides (MCTs)
to promote fat absorption, and increased calcium and
phosphate to promote net mineral retention and bone
mineralization.15,16 Premature infant formulas are available
with low iron or iron-fortified. One of the 3 formulas available has partially hydrolyzed 100% whey protein. The other
2 formulas contain intact whey and casein proteins.
134
Premature Discharge Formulas

Premature discharge formulas (Table 12-6) are designed to
meet the nutrition needs of the infant born prematurely or
the LBW infant who is transitioning home. These formulas
are milk-based with higher levels of calcium and phosphorus than standard term infant formulas. They provide a
nutrient intake that is between a preterm and term formula.
The American Academy of Pediatrics (AAP) supports the
use of preterm discharge formulas to postnatal age of 9 to12
months corrected age or until weight for length is maintained above the 25th percentile. 3
Specialized Infant Formulas

Extensively Hydrolyzed Protein
Formulas containing extensively hydrolyzed protein (Table
12-7) are considered hypoallergenic according to AAP and
FDA standards, meaning that most children with cows
milk protein sensitivity will not have an allergic reaction to
these formulas. The protein in these formulas is extensively
hydrolyzed by heat or enzymes, resulting in free amino
acids and small peptides. The fat content is made up of longchain triglycerides (LCTs), varying amounts of MCTs, and
polyunsaturated vegetable oils to supply essential fatty acids
(EFAs). These formulas are lactose-free and because of the
hydrolyzed protein have a higher osmolarity. Protein hydrolysates are recommended in infants intolerant of cows milk
and soy proteins, and those with significant malabsorption
due to gastrointestinal or hepatobiliary disease (eg, cystic
fibrosis, short gut syndrome, biliary atresia, cholestasis,
protracted diarrhea). 3,17
Amino Acid Based
Amino acid-based infant formulas (Table 12-8) are indicated
in extreme protein hypersensitivity or when intolerance
symptoms persist on an extensively hydrolyzed formula.18
Approximately 2% to 10% of infants with cows milk protein
allergy develop persistent symptoms despite therapy with
partially hydrolyzed formula and thus require an amino
acid-based formula.19 There is no additional benefit to using
an amino acid-based formula if an extensively hydrolyzed
casein formula is effective. Other indications for the amino
Table 12-5 Premature Infant Formulas (per 100 calories) Standard dilution varies and can be 0.67 kcal/mL (20 kcal/oz) or 0.8 kcal/mL (24 kcal/oz).
Product
(Manufacturer)
Protein g (% kcal)
Source
Enfamil Premature
LIPIL
20 cal/oz (low iron or
iron fortified)
(Mead Johnson)
Enfamil Premature
LIPIL
24 cal/oz
(low iron or iron
fortified)
(Mead Johnson)
GOOD START
Premature
24 cal/oz
(Nestle/Gerber)
3 (12%)
11 (44%)
non-fat milk, whey corn syrup solids,
protein concentrate lactose
5.1 (44%)
MCT oil, soy oil, high
oleic vegetable oil
58
98
165 83
0.5 240
1.8
3 (12%)
11 (44%)
non-fat milk, whey corn syrup solids,
5.1 (44%)
oleic vegetable oil
58
98
165 83
0.5 300
1.8
3 (12%)
enzymatically
hydrolyzed whey
protein isolate
(from cows milk)
3 (12%)
nonfat milk, whey
protein concentrate
10.5 (42%)
corn maltodextrin,
lactose
5.2 (46%)
oleic safflower or
sunflower oil
55
120 164 85
1.8 275
Ca:Phos
ratio 1.9:1
10.3 (41%)
corn syrup solids,
lactose
5.43 (47%)
MCT, soy oil,
coconutoil
43
129 180 100
0.37 235
1.8
DHA 0.25%,
ARA0.40%, PRSL
27.8/100 cals
10.3 (41%)
3 (12%)
5.43 (47%)
MCT, soy oil,
coconutoil
43
129 180 100
0.37 280
1.8
DHA 0.25%,
ARA0.40%, PRSL
27.8/100 cals
3 (12%)
7.73 (31%)
6.61 (57%)
MCT, soy oil,
coconutoil
43
129 180 100
1.8 325
DHA 0.25%,
ARA0.40%, PRSL
27.8/100 cals
Similac Special
Care
20 cal/oz (low iron
oriron fortified)
Similac Special
Care
24 cal/oz (low iron
oriron fortified)
Similac Special
Care
30 cal/oz
CHO g (% kcal)
Source
Fat g (% kcal)
Source
Na
mg
K
mg
Ca
mg
Phos
mg
Fe
mg
Osmolal- Comments
ity mOsm
DHA 17 mg, ARA

34mg, PRSL 27/100
cals, nucleotides
28mg/L, Ca:Phos
ratio 2:1
DHA 17 mg, ARA
34mg, PRSL 27/100
cals, nucleotides
34mg/L, Ca:Phos
ratio 2:1
135
Table 12-6 Premature Discharge Infant Formulas (per 100 calories) Standard dilution for these formulas is 0.73 kcal/mL (22 kcal/oz).
Product
(Manufacturer)
Protein g (% kcal)
Source
Enfamil
EnfaCare LIPIL
(Mead Johnson)
2.8 (11%)
whey protein
concentrate,
nonfatmilk
CHO g (% kcal)
Source
10.4 (42%)
powder: lactose,
corn syrup solids
RTU: maltodextrin,
lactose
10.1 (40%)
Similac NeoSure 2.8 (11%)
(Abbott Nutritionals) nonfat milk, whey corn syrup solids,
Fat g (% kcal)
Source
Na
mg
K
mg
Ca
mg
Phos
mg
Fe
mg
Osmolal- Comments
ity mOsm
5.3 (47%)
high oleic sunflower
or safflower oil, soy
oil, MCT, coconut oil
35
105 120 66
42 mg added
1.8 powder
nucleotides, DHA
260
liquid 250 17mg, ARA 34 mg,
PRSL 24/100 cals
5.5 (49%)
soy oil, coconut oil,
MCT
33
142 105 62
1.8 250
acid-based formulas include eosinophilic gastrointestinal

disorders and transitioning from parenteral to enteral feedings and short bowel syndrome (SBS).19
Carbohydrate Free
These formulas (Table 12-9) are designed for the
management of carbohydrate metabolism disorders and
carbohydrate malabsorption issues (eg, glucose-galactose
malabsorption).20 The physician or healthcare professional
prescribes a carbohydrate to be added to the formula and it
is usually titrated up to make the formula 20 kcal/oz.21
Reduced Fat/Modified Fat
These reduced or modified fat formulas (Table 12-10) can
be used in conditions of decreased bile salts, fat malabsorption, defective lymphatic transport of fat, chylothorax, or
long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency.
Due to the risk of essential fatty acid deficiency (EFAD),
these formulas should only be used under the supervision
DHA 0.15%,
ARA0.40%, PRSL
25.2/100 cals
of a physician. Evaluation of triene:tetraene ratio may be

needed to detect EFAD, and addition of EFAs at a volume of
3% to 5% of total kilocalories may be indicated with some of
the formulas with lower levels of the long-chain fatty acids.
Reduced Mineral
The mineral content of this formula (Table 12-11) is close
to the mineral content of human milk and is designed to
treat calcium disorders.21 The formula may also be used for
infants with impaired renal function. An additional source
of iron may need to be considered. Infants consuming this
formula should be monitored by a medical professional.
Functional Ingredients in Infant Formulas

DHA/ARA
Long-chain polyunsaturated fatty acids (LCPUFAs) in
infant feeding refer to docosahexaenoic acid (DHA) and
arachidonic acid (ARA). DHA and ARA are synthesized
Table 12-7 Extensively Hydrolyzed Protein Infant Formulas (per 100 calories)
Product
(Manufacturer)
Protein g (% kcal)
Source
CHO g (% kcal)
Source
Fat g (% kcal)
Source
Nutramigen LIPIL
(Mead Johnson)
2.8 (11%)
extensively
hydrolyzed casein,
L-cystine, L-tyrosine,
L-tryptophan
2.8 (11%)
extensively
hydrolyzed casein,
L-cystine, L-tyrosine,
L-tryptophan
2.8 (11%)
casein hydrolysate,
amino acids
10.3 (41%)
corn syrup solids,
modified corn
starch
5.2 (48%)
47
sunflower oil
10.3 (41%)
corn syrup solids,
modified corn
starch
5.3 (48%)
47
sunflower oil
10.2 (41%)
corn syrup solids,
dextrose, modified
corn starch
RTU-no dextrose
Similac Alimentum 2.75 (11%)
10.2 (41%)
Advance
casein hydrolysate, sugar, modified
(Abbott Nutritionals) L-cystine, L-tyrosine, tapioca starch
L-tryptophan
47
5.6 (48%)
MCT, soy oil, corn oil,
high oleic safflower or
sunflower oil
RTU-no corn oil
5.54 (48%)
44
oil, MCT, soy oil
Nutramigen with
Enflora LGG
(Mead Johnson)
Pregestimil LIPIL
(Mead Johnson)
Na
mg
K
mg
Ca
mg
Phos
mg
Fe
mg
Osmolal- Comments
ity mOsm
1.8 liquid 320 DHA 17 mg,

ARA34mg,
powder
PRSL 25/100 cals,
300
lactose and sucrose
free
110 94 52
1.8 300
DHA 17 mg,
ARA 34 mg,
PRSL 16.8/100 cals,
*added probiotic
Lactobacillus GG
110 pwdr pwdr 1.8 RTU 280 DHA 17 mg,
94 52
ARA 34 mg pwdr,
RTU RTU
PRSL 25/100 cals,
115 75
RTU - PRSL
26/100cals
110 94
52
118 105 75
1.8 370
DHA 0.15%,
ARA0.40%,
PRSL 25.3/100 cals
136
Table 12-8 Free Amino Acid Infant Formulas (per 100 calories)
Product
(Manufacturer)
Protein g (% kcal)
Source
CHO g (% kcal)
Source
Fat g (% kcal)
Source
Similac EleCare
(Abbott Nutritional)
3.1 (15%)
free L-aa
10.7 (43%)
corn syrup solids
Neocate Infant
DHA & ARA
(Nutricia)
3.1 (12%)
free aa
11.7 (47%)
corn syrup solids
4.8 (42%)
45 150 116 84.2 1.5 350
oil, MCT oil, soy oil
4.5 (41%)
37.3 155.1 124 93.1 1.85 375
refined vegetable oil
(soy oil, coconut oil,
high oleic sunflower
oil)
5.3 (48%)
47 110 94 52
1.8 350
sunflower oil
Nutramigen AA LIPIL 2.8 (11%)

(Mead Johnson)
free amino acids
10.3 (41%)
corn syrup solids,
modified tapioca
starch
Na
mg
K
mg
Ca
mg
Phos
mg
Fe
mg
Osmolal- Comments
ity mOsm
DHA, ARA
PRSL 28/100 cals
available without
DHA & ARA also
DHA 17 mg,
ARA 34 mg,
PRSL 16.8/100 cals
Table 12-9 Carbohydrate-Free Formulas (per 100 calories)

Product
(Manufacturer)
Protein g (% kcal)
Source
CHO g (% kcal)
Source
Fat g (% kcal)
Source
Na
mg
RCF*
3.0 (12%)
10.1 (40%)
5.3 (48%)
44
(Abbott Nutritionals) soy protein isolate, selected by
L-methionine
physician or health oil, coconut oil, soy oil
care professional
3232A
2.8 (11%)
13.5 (54%)
4.2 (35%)
43
(Mead Johnson)
extensively
choice by physician, MCT, corn oil
hydrolyzed casein, modified tapioca
L-cystine, L-tyrosine, starch as stabilizer
L-tryptophan
*based on 100 calories when 52 gm of CHO are added to 13 oz of concentrate
from the dietary EFAs alpha-linolenic acid (-3) and linoleic

acid (-6), respectively. Endogenous synthesis of LCPUFAs
begins in the first days of life.22
DHA and ARA are present in human milk. Breastfed
infants have higher plasma and erythrocyte lipid concentrations of DHA and ARA compared to infants fed formula
without DHA and ARA.23 Furthermore, DHA and ARA are
the major fatty acids in neural tissues and DHA is a major
component of photoreceptor cells.24 The major supply of
LCPUFAs to the fetus during development is from maternal
plasma.25 Therefore, the clinical significance of this seems
to be more prominent for the preterm infant as compared to
the term infant.22
Nucleotides
Nucleotides are compounds formed of phosphoric acid,
a sugar, and a purine or pyrimidine base that are synthesized, degraded, and salvaged in the body. This continuous
process takes place to a larger degree in the gut and immune
system than the rest of the body because cells are more
rapidly turning over.26 Dietary nucleotides are thought to
have effects on intestinal growth and development, healing
K
mg
Ca
mg
Phos
mg
Fe
mg
Osmolal- Comments
ity mOsm
108 105 75
1.8 168
no DHA/ARA
PRSL 25.8/100cals
109 94
1.88 type of
CHO will
influence
59 gm CHO added
to 1 quart prepared
product, PRSL
25/100 cals
63
the intestinal mucosa, and may contribute to the pool of

nucleotides available to the proliferation of lymphocytes.27
A source of dietary nucleotides may be important for infants
whose tissue turnover rates may be higher (eg, the preterm
infant or infants with chronic diarrhea).26 There is still a
question as to what the appropriate level of dietary nucleotides should be and which ones should be used. The levels
and types of nucleotides that are currently being provided
in infant formulas have not shown any deleterious effects.28
Prebiotics and Probiotics
Prebiotics are complex dietary carbohydrates present
in breast milk and several foods that are not digestible or
absorbable by the human gastrointestinal tract.29,30 They
include fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS). Prebiotics become the fuel for beneficial
bacteria in the gut and stimulate their growth. This gives the
beneficial bacteria a competitive advantage over the other
bacteria in the gut. 31
Probiotics are defined as non-pathogenic organisms
in the food supply that provide a benefit to the host. 32
Bifidobacteria is the most prevalent species that colonizes
the intestines of breastfed infants. 33,34 It is thought that

the higher percentage of bifidobacteria may be associated
with some health benefits. 35 Bifidobacteria lactis added to
infant formula has been shown to be safe and increases the
percentage of bifidobacteria in the microflora. 35
Lactobacillus GG (rhamnose) is another species of
bacteria prevalent in the intestines of healthy infants.
Studies suggest that an extensively hydrolyzed protein
formula with supplemented LGG may be more effective in
the treatment of cows milk protein allergy than the same
formula without supplementation. 36
Forms of Infant Formula

and Mixing Guidelines
Infant formula is available in 3 forms: ready-to-feed, liquid

concentrate, and powder. All forms are nutritionally
complete and are regulated. There are small differences
between the 3 forms for technical reasons.7 Liquid concentrate and powder forms require the addition of potable water
to reconstitute and can be mixed to various caloric dilutions
according to the special need of the infant.
Ready-to-feed is the most commonly used form in
hospitals as it is considered commercially sterile. It is
convenient and limits opportunity for contamination. The
137
manufacturers provide many different formulas in standard caloric dilution and some formulas at higher caloric
concentrations in convenient ready-to-feed nurser bottles.
Consumers can purchase ready-to-feed formula at standard dilution in quart-sized bottles or single-serving nurser
bottles. Ready-to-feed formula is the most expensive form
as the consumer is paying for the convenience.
Liquid concentrate is also considered commercially
sterile, but because it needs to be mixed with water to make
a standard dilution, it offers more opportunity for potential
contamination than ready-to-feed. Liquid concentrate is the
second choice in hospitals and can be used to make highercaloric concentrations. It is easy to mix for consumers and
offers some financial savings over ready-to-feed.
Powder is not sterile and must be mixed with water.
Because it is not sterile, it may contain pathogenic bacteria. 37
Powder formula has been associated with Enterobacter sakazakii contamination in immunocompromised neonates in
healthcare facilities.38 Because of the population that they
serve, hospitals only use powder when there is no other option
available.39 Reconstituted powder formulas have been safely
consumed by millions of infants worldwide over the past half
century, so parents of healthy newborns should continue
to feel comfortable using powder infant formulas. The
Table 12-10 Modified Fat Formulas (per 100 calories)

Product
(Manufacturer)
Protein g (% kcal)
Source
Enfamil Enfaport
LIPIL
(Mead Johnson)
3.5 (14%)
10.2 (41%)
calcium caseinate, corn syrup solids
sodium caseinate
5.4 (45%)
MCT (84%), soy oil
Monogen
(Nutricia)
2.7 (11%)
whey protein
concentrate,
L-amino acids
3 (12%)
2.8 (25%)
48
MCT (as fractionated
coconut oil), walnut
oil
4.6 (41%)
55
Lipistart
(vitaflo)
CHO g (% kcal)
Source
16 (64%)
corn syrup solids
12 (47%)
Fat g (% kcal)
Source
Na
mg
30
K
mg
Ca
mg
Phos
mg
Fe
mg
Osmolal- Comments
ity mOsm
115 94
52
1.8 280 (30

cal/oz)
86
48
108 105 77
62
250-22
cal/oz
370-30
cal/oz
180-22
cal/oz
205-24
cal/oz
272-30
cal/oz
DHA, ARA
PRSL 29/100 cals
*comes in RTU, 30
cal/oz. Water can be
added to dilute to
lower concentrations
essential fatty acid
ratio n6:n3 of 4.6:1
*for > 1 y old
*for > 1 y old
Table 12-11 Reduced Mineral Infant Formula (per 100 calories)

Product
(Manufacturer)
Protein g (% kcal)
Source
Similac PM 60/40
2.2 (9%)
(Abbott Nutritionals) whey protein
concentrate,
sodium caseinate
CHO g (% kcal)
Source
Fat g (% kcal)
Source
Na
mg
10.2 (41%)
lactose
5.6 (50%)
24
oil, soy oil, coconut oil
K
mg
80
Ca
mg
56
Phos
mg
28
Fe
mg
Osmolal- Comments
ity mOsm
0.7 280
no DHA & ARA

PRSL 18.3/100 cals
138
ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology, and Nutrition) Committee on Nutrition
recommends that in the home powder infant formulas should
be freshly prepared for each feeding and any remaining milk
discarded to minimize potential risk of contamination.40
Consumers choose it because it is the least expensive form
and can be quickly mixed at any location when needed.
Water
Tap water or boiled and cooled water is adequate to use when
preparing formula for healthy infants with a normal immune
system and who are fed orally.41 Municipal tap water is more
regulated than bottled water. Municipal tap water is fluoridated whereas most bottled water is not. Bottled water or
infant fluoridated bottled water may be a good choice when
tap water is from a well because well water may contain high
levels of certain minerals. In hospitals only chilled, sterile
water is recommended in formula preparation.42
Infants consuming either human milk or infant formula
exclusively do not have a need for additional water in their diets.
Human milk or infant formula provides adequate free water for
hydration in hot or dry climates and if the infant is febrile.3
Standard Dilution
When mixing formulas, healthcare professions should
suggest that parents read the manufacturer instructions
on the can as instructions may vary by manufacturer and
by product. In powdered formulas, only use the scoop that
comes with that particular formula because scoop sizes are
different for each formula. Standard dilution for term infant
formulas is 20 kcal/oz, or 0.67 kcal/mL, and can be made
by mixing 1 scoop of powder for each 2 oz of water, or by
mixing a 13-oz can of concentrate with 13 oz of water.
Increasing Caloric Concentration
For special feeding situations, both powdered infant
formula or infant formula concentrate can be reconstituted
(Table 12-12) to provide formula with more concentrated
calories than standard dilution. 21 Concentrated liquids
from all manufacturers contain 40 kcal/oz, so the same
instructions for preparation and caloric concentration can
be used forall.
Table 12-12 Increasing Caloric Concentration of Term Infant Formulas

with Standard Dilution of 20 kcal/oz or 0.67 kcal/mL
Concentration
Amount of Powder/Liquid
Water
(oz)
20 kcal/oz
(0.67 kcal/mL)
4 scoops powdered formula*

8
13 oz liquid concentrate
13
5 scoops powdered formula*
8
24 kcal/oz
(0.8 kcal/mL)
9
5.5 scoops powdered
8
27 kcal/oz
(0.9 kcal/mL)
formula*
6
*Use only the scoop provided with the specific formula. Scoop sizes vary
from product to product.
Modular Macronutrients
Modular macronutrients can be used to increase caloric
concentration. Modulars are available as protein, carbohydrate, fat, and combinations of macronutrients. The fat
and/or carbohydrate modulars may not add as significantly
to the potential renal solute load (PRSL) and osmolality as
concentrating the formula with less water, and fat and/or
carbohydrate modulars should be considered when concentrating calories higher than 24 calories per ounce. Modular
macronutrients will not increase the concentration of
micronutrients like concentrating just the formula powder
or concentrate. This may be desirable in some situations
(renal insufficiency) and not desirable in other situations
(increased calcium and phosphorus needs in prematurity).
Modulars can be added to the formula when mixing
or they can be mixed with water and delivered as a bolus
through the tube separate from formula. To boost caloric
intake of formula, some common food products or ingredients may also be used (eg, table sugar, vegetable oil, or corn
starch). These ingredients may not be ideal, but they are
much less expensive than the manufactured modulars.
Increasing Concentration of Breast Milk
Infants born prematurely often have caloric and nutrient
deficits, even at discharge, and although breast milk is the
best choice for feeding these infants, it may not meet all of
the caloric and nutrient needs of the infant with significant comorbidities.43 Expert opinion and studies show
that preterm infants discharged from the hospital at suboptimal weight being fed breast milk should continue to be
supplemented to assure adequate nutrient intake.44,45 Some
healthcare professionals suggest adding premature infant
formula or infant formula powder to expressed breast milk to
increase the caloric and nutrient density. There is no evidence
for or against this practice, and there is a great potential for
error. Close medical monitoring is suggested.46
Introducing Complementary Foods

to the Infants Diet
The AAP recommends exclusive breastfeeding for a

minimum of 4 months, but preferably 6 months. There is
no nutrition indication to start complementary foods any
earlier than 4 to 6 months of age, and starting solids as early
as 4 months of age has not shown any adverse effects on
growth.3
Each infant develops at his or her individual rate. An
infant is usually ready for solid foods when birth weight has
doubled, there is truncal stability to sit with support, and
neuromuscular maturation has been achieved.2 Other signs
may include frequently putting things in the mouth, leaning
forward and opening the mouth to indicate a desire for
food, and consuming more than 32 ounces of human milk
or formula each day.2
There is no evidence to support the introduction
of foods in any certain order. The general rule is to add 1
single-ingredient food at a time and wait about 3 to 5
days before introducing a new food, watching for possible
intolerances or allergic reactions. 3 Some parents want to
make their own baby foods. Parents should cook the food
until soft and put it in a baby food grinder or blender until
the desired consistency is reached. For infants just starting
on solid foods, the consistency should be a smooth puree.
Older infants can tolerate small consistent-sized bits in their
food. Parents should avoid adding salt or sugar. 3
A good time to advance textures is when the infant
starts teething. Parents should be aware that rub on
teething medications can interfere with chewing and swallowing because muscles in the throat can become numb.
Careful observation is advised.
139
amounts of protein, sodium, potassium, and chloride. Milk

is also limited in EFAs, zinc, and vitamin E. 3
Foods to Avoid the First Year
Foods that are difficult to chew or can easily choke a child
or be aspirated should be avoided up to about 4 years of
age. Foods to avoid include, but are not limited to, hotdogs,
nuts, grapes, raisins, raw carrots, popcorn, and rounded
candies. 3
Honey is another food to avoid during the first year of
life. Honey contains a bacteria that results in botulism. The
infants developing immune system is not able to adequately
protect against the bacteria. Botulism is potentially very
serious and can result in death if not diagnosed and treated
properly in the infected infant. 3
Toddler Formulas
Toddlers consuming adequate amounts of nutrients, especially iron, from solid foods do not need formula. Whole
cows milk is appropriate after 1 year of age. Toddler formulas
(Table 12-13) contain higher amounts of iron, vitamin C,
and vitamin E than cows milk and contain nutrients such
as zinc that cows milk does not contain. The calcium and
phosphorus levels of the toddler formulas are higher than
infant formulas to match the needs of the growing toddler.
Toddler formulas contain DHA and ARA.
Juice
After 6 months of age fruit juice can be introduced in a cup
and should be limited to 4 to 6 oz/d. 3 Only 100% fruit juice
should be offered. Fruit juice displaces the more nutrientdense human milk or infant formula and therefore should
be used in limited amounts. Infants should not be offered
juice in a bottle or in a cup that can be carried around and
should not consume juice just before bed because of the
increased risk for dental caries. Overconsumption of juice
can lead to osmotic diarrhea due to the high fructose and
sorbitol content. 3
Milk
Milk (whole, 2%, 1%, skim, goat), other than infant formula,
should be avoided during the first year of life. Milk is lower
in iron and has a higher renal solute load due to the higher
140
Table 12-13 Toddler Formulas (per 100 calories) Standard dilution for these products is 0.67 kcal/mL (20 kcal/oz).
Product
(Manufacturer)
Protein g (% kcal)
Source
CHO g (% kcal)
Source
Fat g (% kcal)
Source
Na
mg
K
mg
Ca
mg
Phos
mg
Fe
mg
Osmolal- Comments
ity mOsm
GOOD START
Gentle PLUS 2
(Nestle/Gerber)
2.2 (9%)
11.2 (45%)
whey protein
lactose, corn
concentrate
maltodextrin
(from cows milk,
enzymatically
hydrolyzed, reduced
in minerals)
5.1 (46%)
27
oil
108 190 106
265
DHA 0.32%,
ARA 0.64%,
PRSL 146/L
GOOD START
Protect PLUS 2
(Nestle/Gerber)
2.2 (9%)
11.2 (45%)
whey protein
lactose, corn
concentrate
maltodextrin
(from cows milk,
enzymatically
hydrolyzed, reduced
in minerals)
5.1 (46%)
27
oil
108 190 106
265
DHA 0.32%,
ARA 0.64%,
PRSL 146/litre
*added probiotics,
Bifidobacteria
lactis
Enfagrow
Premium
NextStep
(Mead Johnson)
2.6 (10%)
non-fat milk
10.5 (42%)
5.3 (48%)
36
lactose, corn syrup palm olein, soy oil,
solids
sunflower oils
130 195 130
270
DHA 17 mg,
ARA 34 mg,
PRSL 26/100cals
300
DHA 0.15%,
ARA 0.40%,
PRSL 20/100 cals
Similac Go & Grow

2.07 (8%)
10.56 (43%)
Milk-based
non-fat milk, whey lactose
(Abbott Nutritionals) protein concentrate
5.49 (49%)
oil, soy and coconut
oils
24
105 150 81
Bright Beginnings 2 2.6 (10%)

non-fat milk
(PBM Nutritionals)
10.5 (42%)
corn syrup solids,
lactose
5.3 (48%)
vegetable oils
36
130 195 130
DHA 17 mg,
ARA 34 mg,
PRSL 26/100cals
Bright Beginnings 2 2.6 (10%)

with prebiotics
non-fat milk
(PBM Nutritionals)
10.5 (42%)
corn syrup solids,
lactose
5.3 (48%)
vegetable oils
36
130 195 130
DHA 17 mg,
ARA 34 mg,
PRSL 26/100cals
* with added
prebiotic, FOS
Parents Choice
Stage 2 Formula
(PBM Nutritionals)
2.6 (10%)
non-fat milk
10.5 (42%)
corn syrup solids,
lactose
5.3 (48%)
36
safflower oil
130 195 130
DHA, ARA
GOOD START Soy

Plus 2
(Nestle/Gerber)
2.8 (11%)
enzymatically
hydrolyzed soy
protein isolate
10.9 (44%)
corn maltodextrin,
sucrose
5.0 (45%)
40
oil
116 190 106
180
DHA 0.32%,
ARA 0.64%,
PRSL 175/liter
Similac Go & Grow

2.45 (10%)
10.3 (41%)
Soy-based
soy protein isolate, corn syrup solids,
(Abbott Nutritionals) L-methionine
sugar
5.46 (49%)
49
oil, soy oil, coconut oil
108 150 100
200
DHA 0.15%,
ARA 0.40%,
PRSL 23.7/100 cals
Enfagrow Soy
Next Step
(Mead Johnson)
4.4 (40%)
36
sunflower oils
120 195 130
230
DHA 17 mg,
ARA 34 mg,
PRSL 30/100 cals
3.3 (13%)
11.8 (47%)
soy protein isolate, corn syrup solids
L-methionine
1. Which formula(s) is indicated for transient lactose

intolerance?
A. Enfamil AR LIPIL
B. Parents Choice Gentle
C. Similac Sensitive
D. B and C
2. What is the standard dilution of term infant formulas?

A. 15 kcal/oz
B. 20 kcal/oz
C. 25 kcal/oz
D. 30 kcal/oz
3. According to the Federal Food, Drug, and Cosmetic

Act, infant formulas that meet a specific medical need
.
are considered
A. Exempt
B. GRAS (generally recognized as safe)
C. Specialized
D. Medical foods
4. Prebiotics are:
A. Oligosaccharides
B. Complex dietary carbohydrates that are not digestible by humans
C. The fuel for beneficial bacteria in the gut
D. All of the above
References
1. World Health Organization. The World Health Organizations

infant feeding recommendation. http://www.who.int/nutrition/topics/infantfeeding_recommendation/en/. Accessed
December 15, 2008.
2. American Academy of Pediatrics, Section on Breastfeeding.
Breastfeeding and the use of human milk. Pediatrics.
1997;100:10351039.
Grove Village, IL: American Academy of Pediatrics; 2009.
4. Aggett PJ, Agostini C, Goulet O, et al. The nutritional and
safetyassessment of breast milk substitutes and other dietary
products for infants: a commentary by the ESPGHAN
Committee on Nutrition. J Pediatr Gastroenterol Nutr.
2001;32:256258.
5. Federal Food, Drug, and Cosmetic Act, 412, Title 21 Code
of Federal Regulations 106, 107.
6. Infant metabolic acidosis and soy-based formula United
States. MMWR. November 15, 1996:45(45);985988. http://
www.cdc.gov/mmwr/preview/mmwrhtml/00044475.htm.
Accessed December 1, 2008.
7. Klish, WJ. Special infant formulas. Pediatrics in Review.
1990;12:5562.
8. VonBerg A, Koletzko S, Filipiak B, et. al. Certain hydrolyzed formulas reduce the incidence of atopic dermatitis
but not that of asthma; three year results of the German
Infant Nutrition Intervention Study. J Allergy Clin Immunol.
2007;119(3):71187125.
9. Vanderhoof JA, Moran JR, Harris CL, et.al. Efficacy of a
prethickened infant formula: a multicenter double blind,
randomized, placebo controlled parallel group trial in 104
infants with symptomatic gastroesophageal reflux. Clin
Pediatr. 2003;41:483495.
10. Among healthy 2-month-old infants compared to a standard
formula. Data on file, AJ68, May 2007. Ross Products Division, Abbott Laboratories, Columbus, Ohio.
141
11. Mimouni F, Campaigne B, Naylan M, Tsang RC. Bone

mineralization in the first year of life in infants fed human
milk, cow-milk formula or soy-based formula. J Pediatr.
1993;122(3):348354.
12. Bhatia J, Greer F and the Committee on Nutrition.
Use of soy-based formulas in infant feeding. Pediatrics.
2008;121;10621068.
13. Zeigler RS, Sampson HA, Bock SA, et al. Soy allergy in infant
and children with IgE-associated cows milk allergy. J Pediatr.
1999;134(5):614622.
14. Klemola T, Vanto T, Juntunen-Blackman K, Kalimo K,
Korpela R, Verjonen E. Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cows milk
allergy: a prospective, randomized study with a follow-up to
the age of 2 years. J Pediatr. 2002;140(2):219224.
15. Picaud JC, Decullier E, Plan O, et al. Growth and bone mineralization in preterm infants fed preterm formula or standard
term formula after discharge. J Pediatr. 2008;153:616621.
16. Klein CJ. Nutrient requirements for preterm infant formulas.
J Nutr. 2002;132(Suppl 16-I):1395S1577S.
17. American Academy of Pediatrics Committee on Nutrition. Hypoallergenic infant formulas. Pediatrics.
2000;106:346349.
18. Sicherer SH, et al. Hypoallergenicity and efficacy of an amino
acid-based formula in children with cows milk and multiple
food hypersensitivities. J Pediatr. 2001;138:688693.
19. Hill DJ, Murch SH, Rafferty K, et al. The efficacy of amino acidbased formulas in relieving symptoms of cows milk allergy: A
systematic review. Clin Exp Allergy. 2007;37:808822.
20. Wright EM. Glucose galactose malabsorption. Am J Physiol.
1998;275(5):G87982.
21. Joeckel RJ, Phillips SK. Overview of infant and pediatric
formulas. Nutr Clin Prac. 2009;24:356362.
22. Agostoni C, Riva E. Role and function of long-chain polyunsaturated fatty acids in infant nutrition. In: Raiha NC,
Rubaltelli FF, eds. Infant Formula: Closer to the Reference.
Nestle Nutrition Workshop Series. Pediatric Program. Vol
47 Suppl. Philadelphia, PA: Lippincott Williams & Wilkins;
2002.
23. Makrides M, Neumann MA, Simmer K, Gibson RA. Erythrocyte fatty acids of term infants fed either breastmilk, standard
formula, or formula supplemented with long-chain polyunsaturates. Lipids. 1995;30(10):941948.
24. Martinez M. Tissue levels of polyunsaturated fatty
acids during early human development. J Pediatr.
1992;120:S129S138.
25. Berghaus TM, Demmelmair H, Koletzko B. Fatty acid composition of lipid classes in maternal and cord plasma at birth. Eur
J Pediatr. 1998;157:763768.
26. Boza JJ, Martinez-Augustin O. Role and function of nucleotides in infant nutrition. In: Raiha NC, Rubaltelli FF, eds.
Infant Formula: Closer to the Reference. Nestle Nutrition Workshop Series. Pediatric Program. Vol 47 (Suppl) Philadelphia,
PA: Lippincott Williams & Wilkins; 2002.
27. Carver JD. Advances in nutritional modifications of infant
formulas. Am J Clin Nutr. 2003;77:1550S1554S.
142
28. Koletzko B, Baker S, Cleghorn G, et al. Global standard for

the composition of infant formula: recommendations of an
ESPGHAN coordinated international expert group. J Pediatr
29. Arslanoglu S, Moro GE, Boehm G. Early supplementation
of prebiotic oligosaccharides protects formula-fed infants
against infections during the first 6 months of life. J Nutr.
2007;137:24202424.
30. Roberfroid M. Prebiotics: the concept revisited. J Nutr.
2007;137(Suppl 2):830S837S.
31. Kullen MJ, Bettler J. The delivery of probiotics and prebiotics
to infants. Current Pharmaceutical Design. 2005;11:5574.
32. Saavedra JM. Clinical applications of probiotic agents. Am J
Clin Nutr. 2001;73:1147S1151S.
33. Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, et al. Analysis
of intestinal flora development in breast-fed and formulafed infants by using molecular identification and detection
methods. J Pediatr Gastroenterol Nutr. 2000;30:6167.
34. Yoshioka H, Iseki K, Fujita K. Development and differences of
intestinal flora in the neonatal period in breast-fed and bottlefed infants. Pediatrics. 1983;72:317321.
35. Saavedra JM. Use of probiotics in pediatrics: rationale,
mechanisms of action, and practical aspects. Nutr Clin Pract.
2007;22:351365.
36. Baldassarre M, Laforgia N, Grosso R, et al. Lactobacillus
GG improves recovery from cow milk protein allergy colitis
compared to extensively hydrolyzed formula alone. Dig Liv
Dis. 2008;40:A82.
37. Drudy D, Mullane NR, Quinn T, Wall PG, Fanning F. Enterobacter sakazakii: an emerging pathogen in powdered infant
formula. Clin Infect Dis. 2006;42:9961002.
38. Enterobacter sakazakii infections associated with the use of a

powdered infant formulaTennessee 2001. MMWR Weekly.
April 12, 2002:51(14);298300. http://www.cdc.gov/mmwr/
preview/mmwrhtml/mm5114a1.htm. Accessed March 20,
2009.
39. Whaley T, Robbins S. Strategies for Implementing the Guidelines for Handling of Infant Feeding. Building Block for Life.
2004:27(3).
40. ESPGHAN Committee on Nutrition. Preparation and
handling of powdered infant formula: a commentary by the
ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol
Nutr. 2004;39(4):320322.
41. Mueller C, Nestle M. Regulation of medical foods: toward a
rational policy. NCP. 1995;10:815.
42. Robbins ST, Beker LT. Infant feedings; Guidelines for preparation of formula and breastmilk in health care facilities.
Chicago, IL: American Dietetic Association; 2004.
43. Groh-Wargo S, Sapsford A. Enteral nutrition support of
the preterm infant in the neonatal intensive care unit. NCP.
2009;24(3):363376.
44. Aggett PJ, Agostoni C, Axelsson I, et al. Feeding preterm
infants after hospital discharge: a commentary by the
ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol
Nutr. 2006;42(5):596603.
45. OConnor DL, Khan S, Weishuhn K, et al. Growth and
nutrient intakes of human milk fed preterm infants provided
with extra energy and nutrients after hospital discharge. Pediatrics. 2008;121:766776.
46. Academy of Breastfeeding Medicine. Clinical Protocol #12,
Transitioning the breastfeeding/breastmilk-fed premature infant from the neonatal intensive care unit to home.
September 17, 2004. www.bfmed.org. Accessed October 8,
2009.
Growth Assessment and Monitoring
13
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Growth Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
Weight
Height (Length/Stature)
Head Circumference
Weight-for-Length
Failure to Thrive
Body Mass Index (BMI)
Ideal Body Weight (IBW)
Interpretation of Growth Charts and Percentiles . . . . . . 146

Assessing Linear Growth Potential
Limitations of Growth Charts as a Diagnostic Tool. . . . . 147
Learning Objectives
1. Understand the importance of growth assessment in

pediatrics.
2. Learn appropriate techniques and parameters for
assessing growth.
3. Employ growth charts in the assessment of growth
disorders.
4. Understand limitations of growth charts.
Introduction
Normal growth and development from infancy through

adolescence to adulthood is the ultimate goal of pediatric
care. Growth is most rapid during infancy, decelerates
during childhood, and has a final increase in velocity during
puberty. The relative protein and energy requirements of
infants, children, and adolescents mirror the growth phase.
Effective nutrition support requires assessment of nutrition
status; protein, energy, fluid, and electrolyte requirements;
and monitoring response to intervention. These objectives are accomplished through careful and repeated
measurements of growth, nutrition status, and biochemical
parameters over time.
The growth parameters most easily obtained are weight
(kg), length/height (cm), head circumference (cm), and
body mass index (BMI) (kg/m 2). Other equally informative
but less frequently obtained parameters include skinfold
measurements, extremity circumferences, and limb lengths.
The Centers for Disease Control and Prevention (CDC) has
published reference charts (www.cdc.gov/growthcharts) for
monitoring growth in North American children aged from
birth to 20 years. In 2006 the World Health Organization
(WHO) published international weight, length/height, and
BMI-for-age growth standards for children aged from birth
143
144
to 5 years. The data used to derive WHO growth standards

were based on healthy breastfed infants and young children
representing all continents. Free download of these charts
is available at www.who.int/childgrowth/standard/cht.
Later in 2007 the WHO also published height- and BMIfor-age growth charts for children aged 5 to 19 years, and
weight-for-age growth standards for children aged 5 to 10
years (http://www.who.int/childgrowth/en/).
After age 2 years the linear growth in most healthy
children stabilizes along a percentile channel that projects
to a final height within 2 standard deviations (SDs)
(8.5cm) of the calculated mid-parental height.1 Likewise
BMI after age 2 years can now be linked to adolescent and
adult BMI, thus providing a window of opportunity for
early intervention to prevent obesity. Thus growth charts
are important road maps for assessing growth status,
response to nutrition intervention, and detection of growth
disorders. Every pediatric clinician should become familiar
with use and interpretation of childhood growth charts.
Growth Assessment
Proper instruments, accurate measurement techniques,

and appropriate reference data are essential for meaningful
assessment and interpretation of growth status.
Appropriate time intervals between measurements
should be used when monitoring short- and long-term
growth. Weight measurements, which are easy to obtain
and associated with the least measurement error, should be
made frequently. Length/height increments occur more
slowly. Length/height is more reliably assessed over longer
intervals because even with good technique, measurements
may be associated with an inter-observer measurement error
of 0.5 cm.2 Middle upper arm circumference and triceps
skinfold thickness are more difficult to measure reliably and
reproducibly; however, they correlate well with nutrition
status.3 See Table 13-1 for suggested time intervals.
Pubertal status based on the Tanner system for growth
of pubic hair in both sexes, breast development in girls, and
genital development in boys should also be assessed for the
purposes of interpreting growth velocity during later childhood and adolescence. 5
Weight
Infants should be undressed to the diaper and older children
measured in light clothing using an age-appropriate scale.
Measurements should be in metric units (kg) and rounded
off to 1 decimal point.
Table 13-1. Recommended Time Intervals for Monitoring Short- and

Long-Term Growth in Children3,4,11
Measurement
Age Group
Pre-term
infants
Birth
to 6 mo
Weight (kg)
636 mo
220 y
Pre-term
infants
Length (cm)
Birth to 6 mo
636 mo
Height (cm)
220 y
Birth to 6 mo
Head circumference
(cm)
636 mo
BMI (kg/m2)
220 y
Soft tissue measurements
Mid-arm circumference (mm)
Triceps skinfold (mm)
Short-Term
Long Term
Follow-Up
Daily
Weekly
12 wk
14 wk
28 wk
2 mo
6 mo
12 mo
4 wk
4 wk
2 mo
6 mo
612 mo
2 mo
6 mo
12 mo
36 mo
4 wk
4 wk
4 wk
312 mo
112 mo
The updated 2000 CDC age- and gender-based weightfor-age growth reference charts for children aged birth to
36months and 2 to 20 years should be used (see Chapter
33). Individualized weight-for-age percentiles and SD scores
(z scores) may be computed using the free access CDC Epi
Info nutrition calculator and statistics program. 6 Diseasespecific growth charts are available for Down syndrome,7
achrondroplasia, 8 and other genetic disorders. 3
Height (Length/Stature)
Linear growth status (cm) is influenced by hereditary
factors, nutrition, chronic disease, and genetic disorders.
Correct equipment and measuring technique are important
for obtaining reliable assessments. Accuracy is improved by
repeating the measurements and obtaining an average. Serially obtained growth measurements should be plotted on
age- and gender-appropriate CDC growth reference charts.
Length (supine) is measured to the nearest 0.1 cm in
children younger than 3 years or older children who cannot
stand. Length should be assessed using a length board
(stadiometer) or firm surface. It requires 2 measurers: one
to position the head and the other to stretch and straighten
the legs so that the knees are flat and feet at a 90-degree
angle with the footboard. 3
Standing height is measured to the nearest 0.1 cm. It is
obtained after age 2 years in children able to support their
weight evenly on both feet. Subjects should stand barefooted
with heels, buttocks, shoulders, and back of head against the
measuring device and eyes looking straight ahead. 3
The updated 2000 CDC age- and gender-based
GROWTH ASSESSMENT AND MONITORING
combined growth reference charts for children aged birth

to 36 months and 2 to 20 years, respectively, should be used.
Individualized length/height for age percentiles and SD
scores (z scores) can be computed using the free access CDC
Epi Info nutrition calculator and statistics program.6
Disease-specific growth charts are available for Down
syndrome, achondroplasia, and other genetic disorders. 3,7,8
Tanner-Whitehouse height velocity charts may be used
to monitor rate of height gain in girls aged 1 to 16 years
and boys aged 1 to 19 years.9 Height below the 5th percentile indicates short stature. Height velocity below the 5th
percentile suggests severely stunted growth that warrants
assessment of pubertal status, screening for familial short
stature, constitutional growth delay, and evaluation for
chronic illness (eg, chronic inflammatory diseases, endocrinopathy, and skeletal and genetic disorders).
Children with musculoskeletal deformities (eg,
cerebral palsy, spinal kypho-scoliosis, and extremity
contractures) that prevent accurate measurement of stature
may be assessed using upper-arm and lower-limb lengths.
Obtaining these measurements requires training in anthropometry and special instruments (anthropometers). Growth
reference charts are available for upper-arm and lower-limb
extremity lengths for girls aged 3 to 16 years and boys aged
3 to 18 years.10
Head Circumference
Brain growth occurs most rapidly from birth to age 36
months and thereafter slows down. Head circumference
(cm) must be routinely measured using a non-stretchable
measuring tape. Anteriorly the tape is placed just superior to the eyebrows and posteriorly it is placed so that the
maximum circumference is measured. 3
Impaired brain growth and size is a rare complication
of chronic malnutrition and is not characteristic of primary
skeletal disorders. Therefore, children with disproportionately sized heads should be evaluated for other disorders
impacting brain or skull size.
Weight-for-Length
Weight-for-length percentiles provide a means of assessing
a childs weight while taking into account his or her length.
They are used to screen overweight and underweight in
children aged < 36 months. See 2000 CDC weight-forlength growth reference charts for children aged birth to
36months.
Increased weight-for-length percentile > 90% indicates overweight.11 When associated with significantly
decreased length percentile (< 5%), increased weight-for-
145
length percentile suggests there is a non-nutrition etiology

for impaired linear growth (eg, growth hormone deficiency
and other endocrine, genetic, and skeletal disorders).
Decreased weight-for-length (< 5th percentile) is consistent with nutrition failure to thrive (FTT). Impaired growth
in children with nutrition FTT is characterized by weight
more severely impaired than length and head circumference. FTT may be secondary to organic factors (ie, illness
impairing food intake, digestion, absorption, or utilization).
Non-organic FTT refers to factors external to the child (eg,
food deprivation). Mixed organic and non-organic FTT may
occur following infections, gastroenteritis, or any illnesses
associated with prolonged inadequate calorie intake
secondary to inappropriate food restrictions or behavioral
feeding problems.
Failure to Thrive
The term FTT is not a diagnosis or specific disease entity
but denotes weight gain or linear growth that is less than
expected for age. FTT may be referred to as wasting when
weight is disproportionately affected vs. stunting when
length/height is significantly impaired.
Wasting may occur following an acute illness. The
growth changes are: weight-for-length percentile or BMI
percentile < 5th percentile (~2 SD) or involuntary lack of
weight gain or loss resulting in dropping below any 2 major
percentile channels (95th, 90th, 75th, 50th, 25th, 10th,
and5th).
Stunting occurs following chronic inadequate caloric
intake, disease, or endocrinopathy. The diagnostic growth
findings are: length or height < 5th percentile (~2 SD) or
consecutive height measurements dropping below any
2major percentile channels.
Marasmus is moderate-to-severe FTT without edema.
Kwashiorkor is moderate-to-severe FTT in association with
hypoalbuminemia and edema.
The WHO classifies FTT as moderate or severe using
criteria of weight-for-length/height and length/height-for-age
SD scores and presence or absence of edema (Table 13-2).
Table 13-2 World Health Organization Classification of Malnutrition12
Classification
Edema
Moderate
Severe
No
Yes (Edematous
malnutrition)
Weight-for-length
3 to 2
< 3 (wasting)
z score*
Height-for-age z score*
3 to 2
< 3 (stunting)
*Growth channels of WHO international growth charts are along z scores
3; 2; 1; 0; 1; 2 and 3.
146
Body Mass Index (BMI)

BMI is a composite index used to relate appropriateness
of body weight for height. It is computed by dividing body
weight in kilograms by height in meters squared (weight
(kg)/height (m)2). It is very useful for screening and classifying overweight and obesity. However, BMI does not
distinguish between overweight from excess body fat,
increased muscle mass, or even increased weight attributed to large bones in tall people. Therefore, additionally
estimating body fat stores by physical exam or measuring
triceps skinfold thickness is essential for interpreting BMI.
The normal range of BMI substantially changes with age
in children. BMI is initially low at birth and then rapidly
increases during infancy to peak at age ~1 year. BMI values
then gradually decline, reaching a nadir between ages 2 to 4
years. It then rebounds at age ~7 years as children begin to
accrue gender unique body fat patterns (adiposity rebound)
and steadily increases throughout puberty and adolescence.
Early occurrence of BMI rebound (before age 5.5 years) is
associated with a longer period of accumulating body fat
and thus greater risk for persistent overweight throughout
childhood, adolescence, and into adulthood.13
The importance of BMI is its strong correlation with risk
for cardiovascular disease and morbidity. Growth charts
correlating BMI values of children and adolescents with
adulthood BMI have been available since 2000. Therefore,
BMI is very useful for screening and monitoring overweight
and obesity in children and adolescents. The definition of
overweight is BMI for age 85th and < 95th percentile.
The terminology obesity denotes excess body fat and the
associated health risks. The cutoff for obesity in youth is
defined as BMI for age 95th percentile or calculated BMI
30 kg/m2 , whichever is lower.11
BMI for age < 10th percentile may be used to assess
underweight or risk for underweight. However, BMIs
correlation with risk for morbidity is less sensitive for underweight patients.
CDC age- and gender-based BMI growth reference
charts for 2000 are available for children and adolescents aged
2 to 20 years.6 Computing BMI z score is also available online
using the free access CDC Epi Info nutrition calculator.6
Ideal Body Weight (IBW)

This is a method to compare the patients actual weight with
the median weight for stature. It is calculated as follows:
[Patients measured weight (kg)/50th percentile weight (kg)
for patients height] 100. A variation of 10% is considered
within normal. A value > 120% corresponds to significant
overweight. The Waterlow criteria classify 80% to 90% mild
wasting; 70% to 80% moderate wasting; 60% to 70% severe

wasting, and < 60% as severe wasting14 approaching incompatibility with survival.15
IBW changes more rapidly than BMI. Therefore it may
be used to monitor short-term response to nutrition support
or weight reduction therapy.
Computing IBW requires a growth chart and several
steps unlike BMI, which is a simple calculation with known
cutoff values that correlate with morbidity.
Interpretation of Growth Charts

and Percentiles
A percentile value represents the proportion of children at

a given age with growth parameters similar to or less than
the measured value. The most effective way to use growth
charts diagnostically is through serial measurements. The
major percentile channels are labeled lines extending on
the growth chart. They correspond with the 5th, 10th, 25th,
50th, 75th, 90th, and 95th percentiles.
The 50th percentile corresponds to the median/mean
measurement for the growth parameter at a specific age. The
5th and 95th percentiles correspond to ~2 SDs away from
mean value. Growth measurements further than 2 SDs
from the mean are significantly deviated from normal and
thus require evaluation for disease.
Serially obtained growth measurements that rise or
drop below 2 major percentile channels represent accelerated or decelerated growth, respectively. This calls for
verifying accuracy of the growth plot and in-depth evaluation if confirmed.
Growth measurements falling below the 5th percentile or exceeding the 95th percentile (~2 SDs) cannot be
assigned a percentile value. This is because distribution of
measurements above or below the 5th and 95th percentiles
is skewed. Therefore comparison of growth measurements
that fall outside the 2-SD range is best assessed by using z
scores (SD scores) (Table 13-3). SD scores for any growth
measurement can be computed using Web-based Epi-Info
Nutrition anthropometric software (CDC Epi Info nutrition calculator).6
Table 13-3 Comparison of Percentiles and SD Scores (z scores)
Percentile
Corresponding z score
0.1
3rd
16th
50th
84th
97th
99.9th
3
2
1
0
1
2
3
GROWTH ASSESSMENT AND MONITORING
Assessing Linear Growth Potential

The childs height percentile before pubertal growth should
fall within 2 SDs (8.5 cm) of the mid-parental height
determined as follows1:
Boys ([Fathers height (cm) + mothers height (cm) +
13 cm]/2) 8.5
Girls: ([Fathers height (cm) + mothers height (cm)
13 cm]/2) 8.5
Pubertal stage should always be assessed because of its significant impact on interpretation of weight and height gain in
females > 8 to 9 years and males > 12 to 13 years. Validated
self-assessment figures for pubertal status are available.
Limitations of Growth Charts

as a Diagnostic Tool

The reliability of growth charts as an assessment tool

depends on accuracy of growth measurements. Therefore the nutrition specialist should be trained in proper
nutrition assessment technique.
The specificity of growth charts in detecting growth
disorders is higher with serially obtained measurements
(longitudinal data). Interpretation of growth disorders
should not be based on a single growth measurement.
Growth charts are important for detecting extreme deviations from normal. Thus milder deviations (< 2 SDs)
may be overlooked.
Growth charts are a screening tool and not diagnostic.
Growth charts do not replace careful history, physical
examination, and diagnostic tests.
BMI is a ratio of weight corrected for height. It correlates very well with body fat and risk for cardiovascular
disease. However, weight is composed of body fat and
fat-free mass (organs, muscle, and bones). Tall and/or
muscular people tend to have high BMI values unrelated
to body fat (ie, increased weight attributed to large bones
and muscle mass). Obesity specifically refers to excess
body fat and the associated medical risks. Therefore BMI
alone is inadequate for diagnosing obesity. Diagnosis of
obesity additionally requires estimation of excess body
fat by either physical exam or skinfold anthropometry.11
1. BMI at age 18 months is correlated with BMI in

adolescence.
A. True
B. False
2. Diagnosis of obesity is based on BMI for age > 85th
percentile.
A. True
B. False
147
3. The CDC recommends terminology of obesity in children with BMI > 95th percentile.
A. True
B. False
4. Diagnosis of FTT or wasting is based on each of the
following except:
A. Length < 3rd percentile
B. Weight-for-length or BMI < 3rd percentile
C. Change in weight percentile from 90th to 50th
D. Change in weight percentile from 50th to 25th
5. The 50th percentile weight, height, or BMI for age
corresponds with the following z score:
A. 2
B. 1
C. 0
D. 1
E. 2
6. Which of the following is incompatible with survival?
A. BMI < 3rd percentile
B. Change in weight percentile from 75th to 5th
percentile
C. Height z score 5
D. 60% of ideal body weight
7. Length measurements in an 18-month-old toddler are
obtained with the child standing upright.
A. True
B. False
References
1. Tanner JM, Goldstein H, Whitehouse RH. Standards for childrens height at ages 2-9 years allowing for heights of parents.
Arch Dis Child. 1970;45(244):755762.
2. Ulijaszek SJ. Measurement error. In: Ulijaszek SJ, Johnston
FE, Preece MA, eds. The Cambridge Encyclopedia of Human
Growth and Development. Cambridge, UK: Cambridge
University Press; 1998:28.
3. Zemel BS, Riley EM, Stallings VA. Evaluation of methodology for nutritional assessment in children: anthropometry,
body composition, and energy expenditure. Annu Rev Nutr.
1997;17:211235.
4. Owen GM. The assessment and recording of measurements
of growth of children: report of a small conference. Pediatrics.
1973;51(3):461466.
5. Tanner JM. Normal growth and techniques of growth assessment. Clin Endocrinol Metab. 1986;15(3):411451.
6. Centers for Disease Control and Prevention. Epi Info Downloads. http://www.cdc.gov/epiinfo/downloads.htm. Accessed
November 12, 2009.
7. Myrelid A, Gustafsson J, Ollars B, Anneren G. Growth charts
for Downs syndrome from birth to 18 years of age. Arch Dis
Child. 2002;87(2):97103.
148
8. Hoover-Fong JE, McGready J, Schulze KJ, Barnes H, Scott

CI. Weight for age charts for children with achondroplasia.
Am J Med Genet A. 2007;143A(19):22272235.
9. Tanner JM, Davies PS. Clinical longitudinal standards for
height and height velocity for North American children. J
Pediatr. 1985;107(3):317329.
10. Spender QW, Cronk CE, Charney EB, Stallings VA. Assessment of linear growth of children with cerebral palsy: use
of alternative measures to height or length. Dev Med Child
Neurol. 1989;31(2):206214.
11. Barlow SE; Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment
of child and adolescent overweight and obesity: summary
report. Pediatrics. 2007;120(Suppl 4):S164S192.
12. World Health Organization G. The management of severe

malnutrition: A manual for physicians and other senior health
workers. 1999:47. http://whqlibdoc.who.int/hq/1999/
a57361.pdf. Accessed November 12, 2009.
13. Whitaker RC, Pepe MS, Wright JA, Seidel KD, Dietz WH.
Early adiposity rebound and the risk of adult obesity. Pediatrics. 1998;101(3):E5
14. Waterlow JC. Classification and definition of protein-calorie
malnutrition. Br Med J. 1972;3(5826):566569.
15. Cahill GF Jr. Starvation in man. N Engl J Med.
1970;282(12):668675.
Obesity and Metabolic Disorders
14
Michelle Battista, BS, PhD Candidate and Robert Murray, MD
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
What Is the Metabolic Syndrome in Adults? . . . . . . . . . . 150
Metabolic Syndrome Controversies AmongAdults . . . . . 150
Cut-points
Etiology
Synergistic Risk and Treatment
What Is the Metabolic Syndrome in Children? . . . . . . . . 151

Select Metabolic Syndrome Controversies in Children
Applying the Metabolic Syndrome Cluster

toaPediatric Population . . . . . . . . . . . . . . . . . . . . . . . . . 153
A Clinical Approach to the Identification
of the Metabolic Syndrome and Its Attendant
Cardiovascular Disease Risks. . . . . . . . . . . . . . . . . . . . . . 153
Establishing a Risk Factor Profile: Expert Committee
Recommendations
Role of Socioeconomic Status and Ethnicity
Nutrition and Physical Activity Behaviors
Acanthosis Nigricans
Expert Committee Recommendations . . . . . . . . . . . . . . . 155

BMI Percentile
The Family Health History
Behaviors
A Focused Review of Systems and TargetedPhysicalExamination
Laboratory Analysis
The Element of Time. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156

The Role of Weight Reduction, Proper
Nutrition, and Physical Activity. . . . . . . . . . . . . . . . . . . . . 157
Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
Learning Objectives
1. Identify the components that comprise the metabolic

syndrome diagnosis in the adult population.
2. Describe the most common reasons why the metabolic syndrome, as a diagnosable entity, has not been
accepted in the pediatric population.
3. Learn about the Expert Committee Recommendations
in pediatric practice.
Introduction
Since the early 1900s evidence has suggested the coexistence of chronic disorders associated with diabetes mellitus
and coronary heart disease (CHD).1 It wasnt until the
years between 1980 and 1990 that scientists developed an
understanding of the mechanisms underlying the connection between obesity, hypertension, hyperlipidemia, and
type 2 diabetes mellitus and its relationship to increased
cardiovascular disease (CVD) risk. Metabolic syndrome
was a term first used to describe how environmental and
genetic factors work together to produce this constellation
of chronic metabolic disorders.1 However, it was the earlier
work of Gerald Reaven2 that set the precedent for how the
metabolic syndrome is applied within the clinical world
today. In 1988, Reavens Banting Lecture described the relationship between hyperinsulinemia, glucose intolerance,
hypertension, and free-fatty acid metabolism and their
association with CVD. Reaven hypothesized that the state
of insulin resistance was the driver for metabolic change and
represented the common pathophysiological link between
these otherwise unrelated metabolic events.2
Through the 1990s, distinct perspectives on the etiology
of metabolic syndrome began to emerge, coupled with
the inclusion of additional biomarkers such as measures
149
150
of insulin resistance and markers of pro-inflammation to

augment the original components. This newfound knowledge resulted in several monikers being applied: syndrome
X, the deadly quartet, and the insulin resistance
syndrome. However, in 1999 the term metabolic syndrome
reappeared, now evolved from a hypothesis to a clinical
entity. It is an emerging diagnosis applied to the adult population and, to a lesser extent, pediatrics. The diagnosis of
metabolic syndrome has been subject to criticism, as much
remains unknown about the cumulative risk of its components and the utility of making this diagnosis. 3,4 Despite
these criticisms, identification of metabolic syndrome and
its component disorders among adults or children offers
useful information about the patients metabolic risk, particularly that associated with future cardiovascular morbidity
and mortality. 5
diagnosable entity. The controversy begins with the criteria

used. Currently, there are 3 sets of diagnostic criteria widely
accepted for the metabolic syndrome. These include definitions from the National Cholesterol Education Program,
Adult Treatment Panel III (NCEP-ATP III),6 the World
Health Organization,7 and the International Diabetes
Federation (IDF).8 Each of their components, etiological
perspectives, and intervention strategies can be summarized (Table 14-1).
Fundamentally, the components that comprise each
of the metabolic syndrome definitions are similar. They
feature a measure of body fatness, hypertension, triglycerides, high-density lipoprotein (HDL) cholesterol, and some
measure of glucose intolerance. Yet, it is important to note
the distinctive arrangement of diagnostic criteria and the
management focus of the 3 definitions.
What Is the Metabolic Syndrome in Adults?
Metabolic Syndrome Controversies

AmongAdults
The early work of Hanefield and Reaven described the metabolic syndrome as a constellation of metabolic risk factors
including obesity, hypertension, dyslipidemia, and glucose
intolerance, all of which are associated with increased cardiovascular mortality. However, today the metabolic syndrome
is no longer viewed as a novel concept, but has surfaced as a
Lack of a single set of criteria for the metabolic syndrome

in adults has created confusion among practitioners. Such
inconsistencies hamper determinations of the specificity
and sensitivity of the metabolic syndrome diagnosis, as
well as its prevalence.9 Experts offer several reasons why a
Table 14-1 Etiology and Diagnostic Criteria of the Metabolic Syndrome in Adults
National Cholesterol
Education Program, Adult
Treatment Panel III (NCEPATP III)6
World Health Organization
(WHO)7
International Diabetes
Federation (IDF)8
Diagnostic Criteria
Etiological Underpinnings
Recommendations
Three or more of the following:

1) Abdominal Obesity
2) Elevated Triglycerides
3) Low HDL-Cholesterol
4) Hypertension
5) Raised Fasting Plasma Glucose
A measure of glucose intolerance
characterized by:
1) Impaired Glucose Tolerance
2) Impaired Fasting Glucose
3) Diabetes
4) Insulin Resistance
Plus 2 or more of the following:
6) Low HDL- Cholesterol
7) Hypertension
8) Microalbuminuria
A measure of body fatness
characterized by:
The etiological perspective focuses on

risk for cardiovascular disease which
is attributed to environmental and
genetic causes.
To control risk, NCEP-ATP III

recommends weight control and
physical activity as target therapeutic
interventions.
The etiological perspective focuses on

ameliorating risk for type 2 diabetes
mellitus which is attributed to the
state of insulin resistance.
To control risk, WHO recommends

weight control, physical activity, and
the use of insulin sensitizing agents
as target therapeutic interventions.
The etiological perspective focuses

on the need to establish a universally
accepted definition for metabolic
syndrome in research and clinical
practice.
Similar to the NCEP-ATP III, IDF

recommends lifestyle changes
including reducing calorie intake,
increasing physical activity, and
altering dietary habits to mitigate risk.
Plus 2 or more of the following:

3) Low HDL-Cholesterol
4) Hypertension
5) Raised Fasting Plasma Glucose
OBESITY AND METABOLIC DISORDERS
consensus definition for the metabolic syndrome has not

been reached.
Cut-points
Evidence has failed to identify appropriate cut-point values
for any given metabolic component. Worldwide adoption
of Westernized eating and physical activity behaviors has
resulted in an increased prevalence of obesity, diabetes,
stroke, and heart disease in what were once healthy populations. Researchers have learned that the degree of metabolic
risk associated with developing CVD is distinct among
people with diverse ethnic backgrounds. One good example
is the differences of dyslipidemias among various ethnic
groups. In the African American population, the standard cutoff values for triglycerides and HDL-cholesterol
predicted insulin resistance is only 17%.10 Furthermore
insulin resistance and triglycerides were found to be
inverselycorrelated (ie, as insulin levels rose with insulin
resistance, triglycerides fell). In this way markers for dyslipidemia within the range of normal may prove insensitive
and fail to identify individuals, particularly African Americans, who are insulin resistant and at risk for cardiovascular
damage.11 Furthermore, ethnic differences in metabolic risk
have been reported for measures of waist circumference
and hypertension among African Americans, Hispanics,
Caucasians, Iranians, and Asians.9,1215 These findings
justify the need to assess the obese patient with a tailored
approach to capture global metabolic risks.
Etiology
Controversy around the metabolic syndrome has
surrounded the criteria utilized to make the diagnosis.
Because the etiological underpinnings of the metabolic
syndrome are substantially altered by ethnic variability
it is difficult to build a single, all-inclusive definition.1,4,9
Since Reaven, the basic connecting point uniting the
various components has been insulin resistance. Yet even
in this there is controversy. Some believe that the primary
pathway leading to the metabolic syndrome is the result of
glucose intolerance and diabetes9 whereas others suggest
that glucose has no direct role in the metabolic syndrome
or insulin resistance.16,17 These individuals promote the
surprising hypothesis that it is disordered fat metabolism,
not glucose metabolism, which is the etiologic prime mover
for development of insulin resistance and, as a result, the
metabolic syndrome. Although the current research has not
yet detailed the sequence of events leading to the insulinresistant state that precedes the metabolic syndrome,
mounting evidence supports the role of abnormal fat
metabolism.16,17
151
Synergistic Risk and Treatment

Is the risk of metabolic syndrome greater than the sum of its
parts? In other words, is it truly a syndrome? Even Gerald
Reaven challenged the idea that the diagnosis of the metabolic syndrome was itself a clinical entity of greater value
than its individual components. From a clinical standpoint,
the influence of the metabolic syndrome suggests to the practitioner the presence of CVD risk and therefore should be
fully evaluated and aggressively treated.4 Evidence implies
that after adjusting for each of its individual components, the
metabolic syndrome is no longer associated with early CVD
mortality.18 In an analysis of diabetics and non-diabetics
with the presence or absence of the metabolic syndrome,
those with diabetes and the metabolic syndrome had the
highest prevalence (19.2%) of CHD mortality, followed by
individuals with metabolic syndrome only (13.9%). Despite
this significant association of the metabolic syndrome and
CVD mortality, multivariate analysis confirmed the presence of elevated blood pressure, diabetes, and low HDL
cholesterol, not the metabolic syndrome, were significant
predictors for CHD.19 Similarly, the evaluation of metabolic
syndrome and the 11-year risk of incident CVD confirmed
that when all 5 metabolic syndrome parameters are considered, metabolic syndrome as a whole does not incur greater
CVD risk when compared with the sum of the individual
components.20
Even though data suggest that the entity of the metabolic syndrome does not incur risk greater than the sum
of its parts, it has been shown that individuals diagnosed
with the cluster of disorders that comprise the metabolic
syndrome suffer greater cardiovascular morbidity and
mortality when compared with individuals without the
syndrome. According to the NCEP-ATP III Framingham
Risk Score, approximately one-third of individuals with
the metabolic syndrome are classified as high risk. 21
As demonstrated in the Framingham Offspring and
San Antonio Heart Study, the predicted risk of CHD in
individuals with the metabolic syndrome was significant
(11.8% and 9.8%, respectively) when compared with individuals without the metabolic syndrome (7% and 6.8%,
respectively). Studies looking at incident CVD mortality
indicate a twofold increase among individuals having
the metabolic syndrome compared to those without the
syndrome.19,20,22
What Is the Metabolic Syndrome in Children?
Similar to the adult classification of the metabolic syndrome,

no consensus definition in the pediatric population exists,
despite begin widely studied among adolescents. This has
created further controversy in the utility of the metabolic
152
syndrome in children. A recent review23 published in 2008

reported 40 unique definitions characterizing pediatric
metabolic syndrome, most emanating from the NCEP
definition for adults. 23 Depending on the criteria used to
classify the syndrome, prevalence among obese children
and adolescents ranges from 26% to 49.7%. 2426 However,
there are a few fundamental problems with the metabolic
syndrome in children and adolescents. 27 Lack of consensus
on etiology, age, and developmentally appropriate cut-point
measures for components of the metabolic syndrome in
children, the effects of growth stage, puberty, and ethnicity
as well as emerging evidence on the role of non-traditional
risk factors, all need to be considered. This discussion will
focus briefly on issues such as cut-points, puberty, and nontraditional risk factors including the pro-inflammatory
state and anatomical changes to the vasculature. Brambilla
et al 27 offers a more complete review of the major and minor
concerns with the metabolic syndrome in children and
adolescents. Furthermore, a scientific statement from the
American Heart Association (AHA) was released in 2009.
In this update to the 2003 report, the AHA provides a more
comprehensive synopsis of the current advancements, challenges, and limitations to applying the metabolic syndrome
to the child and adolescent populations. 28
Select Metabolic Syndrome Controversies in Children

Cut-point
Pediatric-specific cut-points that are sensitive to age, gender,
and ethnicity have not been adapted for the majority of the
metabolic syndrome components,27,29,30 thus making it difficult to classify the syndrome as a diagnosable entity in the
pediatric population. Wide variations in pediatric-specific
cut-points have been found across studies23 with many
assigning arbitrary threshold values with no proven basis to
predict future health risk. 31 One example that is subject to
much debate is the value of waist circumference to substantiate metabolic syndrome risk in children. Some argue
that measurements of visceral fat, when compared with
other measures of body fatness, are the single most predictive anthropometric value of the metabolic syndrome. 32
However, in children, percentile values for waist
circumference are poorly established across age groups.
Furthermore, the currently established cut-point references
for waist circumference in children are not suitable for all
ethnic populations, as most guidelines result from studies
conducted in white, European descendents. 33 Even if the
appropriate, age-specific cut-points were established for
children, the value of waist circumference is arbitrary, as no
standardized protocol has been accepted for obtaining its

measurement in clinical practice. 34
Puberty
Perhaps the greatest confounding factor for the application of metabolic syndrome in pediatrics is the change of
the bodys metabolic milieu that occurs during the years of
puberty. The combined metabolic effects of growth hormone
and insulin-like growth factor 1 (IGF-1) are associated with
a normal state of mild insulin resistance, which follows the
onset of puberty. 35 Furthermore, this phenomenon appears
to be independent of body fat. 36 Thus, from the standpoint
of the metabolic syndrome, puberty-induced insulin resistance complicates the task of attributing insulin resistance
to the normal pubertal changes versus the metabolic consequences of overweight and obesity.
Non-Traditional Cardiovascular Risk Factors
Insults to the cardiovascular system are associated with
obesity and insulin resistance in childhood and adolescence.
Formation of plaques and fatty streaks, deposited in the
blood vessel walls, are associated with abnormal lipids and
high blood pressure. All of these abnormalities have been
found among obese children and adolescents. For example,
excess body weight drives metabolic change resulting in
insulin resistance and even vascular dysfunction. Over time
anatomical changes to the arterial wall begin to develop and
by some are thought to be the earliest indicators of risk for
CVD. 37,38 Further damage to the blood vessel wall compromises arterial distensibility. At this point the ability for the
blood vessel to contract and relax is compromised. Vascular
resistance rises and high blood pressure ensues. 37 Disruption
of the anatomical and physiological integrity of the vascular
system appears to develop silently during childhood, even as
young as age 5. The persistence of these anatomical vascular
changes signifies a new wave of non-traditional cardiovascular risk factors that, like hypertension and dyslipidemia,
need to be evaluated and treated aggressively. Happily the
evidence demonstrates that through physical activity and
proper nutrition these changes can be reversed. 37
Since Reavens lecture in 1988, another major finding
has occurred that has expanded our perspective on the metabolic syndrome. Chronic inflammation has been found not
only to be closely associated with obesity in adults, children,
and adolescents but also connected with each element of the
metabolic syndrome. 3942 This interconnectedness shapes
the development of CVD. Among a number of actions,
chronic inflammation, as identified by the biomarker highsensitivity C-reactive protein (hs-CRP), promotes platelet
adhesion, a critical step in the expansion of atherosclerotic

plaques. Further, in CVD the atherosclerotic lesion is
expanded and made unstable by the influx of inflammatory cells, resulting in heart disease and stroke.43 This link
between the immune-inflammatory system and the bodys
metabolism is a consequence of cytokines secreted from
excess adipose tissue.
Far from being a passive storage site for triglycerides,
the adipocyte produces a vast array of chemokines with
paracrine and endocrine functions.44,45 Among them are
several pro-inflammatory cytokines. Not all adipocytes
are the same. Visceral fat is far more inflammatory than
peripheral fat, explaining why waist circumference, as a
proxy for visceral fat, is such a key sign when assessing
risk in obese patients.46,47 Such adipokines released from
metabolically active adipose tissue include tumor necrosis
factor-alpha (TNF-), C-reactive protein, and interleukin-6
(IL-6), all of which have been implicated in accelerating the
atherosclerotic process.44,45 Obesity and the subsequent
pro-inflammatory state are suspected as the underlying
mechanisms responsible for the progression of insulin
resistance. Consequently, the triad of obesity, inflammation, and insulin resistance is associated with the metabolic
syndrome in children. Children and adolescents who are
morbidly obese are more insulin resistant and present with
higher levels of inflammatory biomarkers including IL-6,
intracellular adhesion molecule-1 (ICAM), and E-selectin,
compared to lean counterparts.42,46 In obese children and
adolescents, the presence of traditional metabolic syndrome
components is associated with non-traditional risk factors
such as CRP and IL-6.4750 Furthermore, early functional
and morphological changes to cardiovascular function,
measured by intima-media thickness and flow-mediated
dilation, are present with markers of inflammation and the
metabolic syndrome. 39,43,51
Non-alcoholic fatty liver disease (NAFLD) has also
been implicated as an adverse consequence of carrying
excess weight in childhood. In general it is estimated
that 38% of obese children have NAFLD. 52 Diagnosis
is confirmed by liver biopsy. The relationship between
NAFLD and the presence or development of the metabolic
syndrome is less understood, particularly in the pediatric
population. However, evidence shows a positive correlation between increased levels of aminotransferases and
the number of metabolic syndrome risk factors present
among children diagnosed with NAFLD. 53 Schwimmer et
al54 demonstrated that children with NAFLD have significantly more CVD risk factors associated with the metabolic
syndrome than children without NAFLD. 54 Although
153
more studies are needed to determine the pathophysiology,

natural history, and treatment of NAFLD, 55 an expert
committee recognizes that the biomarkers for liver function,
alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are reasonable markers for NAFLD and are
an important part of the laboratory assessment of the obese
child. 56 The Expert Committee recommendations appear
later in this chapter (Table 14-2).
Applying the Metabolic Syndrome Cluster

toaPediatric Population
Irrespective of the ability to make a formal diagnosis of the

metabolic syndrome in the pediatric population, evidence
of the clustering of the metabolic syndrome components in
children and adolescents suggests (1) that the bodys metabolic milieu is adapting to the presence of excess body fat,
(2) that the clustering of metabolic risk factors infer greater
risk for CVD mortality compared with peers who do not
present with the metabolic syndrome phenotype, and (3)
that the collective and individual metabolic risks represent
a high-risk finding among children and adolescents. Developing metabolic risk at a young age implies that the health
burden of cardiovascular damage will be greatly amplified
by time the child ages into adulthood. The imperative raised
in the original concept of the metabolic syndrome remains,
which was to identify insulin-resistant individuals at greatest
risk for CVD and in most urgent need for lifestyle intervention.4
The overweight pediatric patient represents the leading
edge of cardiovascular risk. A comprehensive approach to
the assessment of metabolic syndrome and its components
allows the pediatrician to observe the development of metabolic risk at its earliest stages and intervene to arrest the
prospect of lifelong CVD risk.
A Clinical Approach to the Identification of

the Metabolic Syndrome and Its Attendant
Cardiovascular Disease Risks
Establishing a Risk Factor Profile: Expert Committee
Recommendations56
Essentially, risk is defined as someone or something in a
state of high susceptibility. Factors indicating future risk
for disease are evident at a young age. The clinical utility
of the metabolic syndrome to establish a childs risk profile
may be greatly enhanced when combined with other clinical practice tools that help identify disease risk. Family
history, race, socioeconomic status, and eating and physical
activity behaviors all contribute to the future health risk
of the child. For example, children having a first-degree
154
relative with type 2 diabetes mellitus double their risk for

developing the disease. 57 Furthermore, the components of
the metabolic syndrome are documented to track across
generations. In the Northern Manhattan Family Study, 58
the heritability of metabolic syndrome components was
strikingly significant. 58 Among overweight and obese
Hispanic youth, genetic determinants appear to predict the
components of metabolic syndrome, as 68% and 60% of
children, respectively, reported a family history of diabetes
and cardiovascular disease. 59
Role of Socioeconomic Status and Ethnicity

Low socioeconomic status is highly associated with the
development of overweight and obesity among American
children.6062 Lower cumulative family income is significantly associated with the onset of health conditions that
limit childhood activities and require treatment by a pediatrician.61 However, in other countries lower socioeconomic
class does not necessarily indicate higher prevalence of
health risk. In fact, Chinese and Russian children from
upper-level income groups are reported to have a higher
incidence of overweight and obesity compared with middle
and lower socioeconomic groups, an indication of access to
a more Western lifestyle.62 Furthermore, when socioeconomic status is a factor along with race/ethnicity, the risk for
obesity is even greater. For example, Hispanic and black children from lower socioeconomic groups are significantly at
greater risk for obesity than their Caucasian counterparts.63
Nutrition and Physical Activity Behaviors

A recent review by the members of the American Dietetic
Association examined the relationship between eating and
sedentary behaviors on the development of overweight and
obesity in childhood.64 Consuming large amounts of sugarsweetened beverages and fruit juices was found to increase
caloric intake and displace more nutritious foods from the
diet. Although at this time evidence is lacking to support
the relationship between sugar-sweetened beverages, fruit
juices, and increased adiposity, epidemiological evidence
has suggested that fruit and vegetable consumption may be
protective against the development of childhood obesity.64
Sedentary lifestyle behaviors have also been implicated
as a potential cause of pediatric overweight and obesity. A
recent study showed that 35% of boys and 25% of girls watch
4 or more hours of television (TV) each day.65 Irrespective
of socioeconomic status and race, children who watch more
TV are less physically active and are more overweight.63
Furthermore, TV watching also influences appetite, particularly if the child is already overweight or obese. In one
study looking at Saturday morning TV broadcasts, more

than 50% of the commercials featured promoted food items
and over 90% of these food-oriented commercials featured
high-sugar/salt and high-fat foods.66 As Halford67,68 et al
found, overweight and obese children respond to such
advertisements by consuming more calories and choosing
more snack foods after viewing such broadcasts.65,66
In light of the sedentary behaviors that children and
adolescents are displaying today, recent national recommendations emphasize that children participate in at least
1 hour of moderate to vigorous physical activity each day. 56
These recommendations are based on evidence from a
systematic review that highlights the effects of physical
activity on health and behavioral outcomes.69 Children
who participate in higher levels of physical activity are
leaner. For those children who are overweight and obese,
physical activity has been shown to reduce total body fat
provided these children are physically active for 30 to 60
minutes 3to7 days per week. When examining variables of
cardiovascular health, a consistent level of physical activity
improves high-density lipoprotein (HDL) cholesterol and
triglycerides in high-risk children. Changes to the cardiovascular risk profile have been found to occur irrespective
of any significant changes in weight reduction.69
Acanthosis Nigricans
Insulin resistance and subsequent hyperinsulinemia initiate
a series of cascading metabolic events signaling total body
changes in metabolism. Ultimately the clustering of metabolic parameters, as seen in the metabolic syndrome, brings
attention to the serious health risks that are associated with
insulin resistance and obesity. Furthermore, such metabolic
changes identify individuals in most urgent need for lifestyle
intervention. Essentially, identifying certain physical signs
may alert clinicians early in the clinical course.
Risk associated with family history, socioeconomic
status, and nutrition and physical activity behaviors may be
effective screening tools for prevention activities. However,
as evidence suggests, a substantial number of children
and teens already have acquired the first signs of metabolic changes, which will with time place a serious health
burden on their cardiovascular system. Unlike family
history, ethnicity, lifestyle, behavior, and body mass index
(BMI) that predict future health burdens, the skin sign of
acanthosis nigricans represents a physical manifestation of
existing metabolic change.
Several studies indicate that acanthosis nigricans
is relatively common among children and adolescents,
particularly those who are obese. In a broad population
155
the prevalence of acanthosis nigricans among African

American, Hispanic, and Caucasian youth is 19.4%, 23.1%,
and 4.9%, respectively.70 However, when overweight and
obese sub-populations are examined specifically, rates of
acanthosis nigricans are much higher. Among an ethnically
diverse sample of obese children, acanthosis nigricans was
seen in 46%. With rates of obesity beyond the 99th percentile, children present with acanthosis nigricans 70% of the
time.70
National directives have recognized acanthosis nigricans screening as a non-invasive tool to identify burgeoning
changes in metabolism that are associated with numerous
risk factors for CVD, including abnormal lipid and glucose
metabolism.7174 Pediatricians are urged to obtain laboratory tests on overweight and obese children who present
with acanthosis nigricans including a complete fasting lipid
profile, fasting glucose, and markers of liver function. 56
The Family Health History
Expert Committee Recommendations56
The focused review of systems and targeted physical examination of the child should be comprehensive in nature and
include, but not be limited to, the presence of anxiety, polyuria/dipsia, headaches, sleep problems, abdominal pain (a
focused review of systems); acanthosis nigricans, the presence of dysmorphic features, hirsutism and extreme acne,
tonsillar hypertrophy, abdominal tenderness, unexpected
rates of linear growth, and undescended testicles. A crucial
part of the childs physical exam should be the blood pressure, but it must be obtained using the correct cuff size at
rest. The results are then assessed using tables comparing
systolic and diastolic readings against normals for the
childs height percentile to ascertain at risk values over the
90th percentile and hypertensive values above the 95th
percentile.76
Due to the lack of a standard definition to diagnose the metabolic syndrome in the adult and pediatric populations, the
best course of treatment for individuals with the syndrome
remains to be determined. Experts disagree on whether the
metabolic syndrome should be treated differently from the
treatment prescribed for the individual components of the
syndrome. Some counsel a more comprehensive approach
to treatment for patients with the metabolic syndrome. Yet
what we do know is the chronic disease components that
derive the metabolic syndrome are a direct result of excess
adiposity and subsequent insulin resistance. Therefore,
national directives established by an expert committee
may be used as a guideline to assess overweight and obese
children and adolescents for health risks and mediate with
the appropriate lifestyle and treatment interventions. These
evidence-supported guidelines were published as a supplement to Pediatrics in December 2007, titled the Expert
Committee Recommendations Regarding the Prevention,
Assessment, and Treatment of Child and Adolescent Overweight and Obesity.56 There are 6 steps to consider when
assessing a childs health risk in a practice-based setting:
BMI Percentile
At least annually, but ideally at each well child visit, the
childs height and weight should be measured and the BMI
percentile value should be calculated and plotted on the
growth chart. The pediatrician should be looking for BMI
percentile trends that show an increasing weight-for-height
trajectory and classify the child as underweight, normal
weight, overweight, or obese. 56,75
Family health history is a strong indicator of future health

risk for a child, particularly if the risk is identified in a firstdegree relative. However, unlike the other health risks,
family health history is not modifiable. It does, however,
represent an important context for a discussion about a
childs risk for chronic diseases that are fueled by excess
body weight.
Behaviors
A targeted history should capture information about nutrition and physical activity habits of the overweight or obese
child and the family. This information should serve as the
baseline and basis for prevention and intervention counseling directed both at the child and the family.
A Focused Review of Systems and

TargetedPhysicalExamination
Laboratory Analysis
More invasive testing is required for overweight and obese
children to identify health risks that may be otherwise
hidden. It is important to note that Expert Committee56
guidelines on further laboratory testing mirror most of
the components that comprise the metabolic syndrome.
Table 14-2 lists what labs should be drawn at what degree of
obesity and at what age. The physician also should explore
concerns raised during the history and physical exam,
investigated fully along with the testing recommended for
all overweight children.
The above have been described by the Expert
Committee56 more explicitly and provide the pediatrician
with practice-ready guidelines to assess the global health
risk of the overweight or obese child. Furthermore, these
156
Table 14-2 Laboratory Testing Guidelines Based on Age, BMI Percentile, and Risk Factors Present
Laboratory Testing
Parameters
Fasting Lipid Profile (Cholesterol,

HDL,LDL, and Triglycerides)
Age 29 years
BMI %
85th95th (with no additional risk factors*)
BMI %
> 85th95th (with additional risk factors*)
BMI %
> 95th99th (with or without additional risk factors*)
BMI %
> 99th (with or without additional risk factors*)
Age 1018 years
BMI %
85th95th (with no additional risk factors*)
BMI %
> 85th95th (with additional risk factors*)
BMI %
> 95th99th (with or without additional risk factors*)
BMI %
> 99th (with or without additional risk factors*)
Fasting Glucose
(Every 2 years)
Hepatic Function (ALT and

AST; Every 2years)
X
X
X
X
X
X
*Risk factors refer to those risks found during the assessment of family history and physical examination. The laboratory guidelines recommended by the
Expert Committee are merely baseline recommendations. Any concerns found during the assessment of the family history and/or physical examination
should be evaluated and monitored.
recommendations emphasize the need for risk identification to occur sooner in the childs life, rather than later,
as identification of these health risks ultimately leads to
the establishment of an intervention program targeted at
reducing obesity-related comorbidities and controlling
body weight.
The Element of Time
CVD morbidity and mortality is the ultimate outcome of

individuals who carry metabolic risk. The younger the child
is when metabolic risk is acquired, the higher the likelihood of tracking these components into adulthood.7779 For
example, if overweight status continues past their first decade
of life, excess body weight tracks into adulthood for 80% of
them.77,80 On examining the metabolic syndrome, metabolic
predictors also track quite well across childhood, through
young adulthood and into adulthood.78,79 The diagnosis of
the metabolic syndrome in childhood increases the odds
of developing the metabolic syndrome and type 2 diabetes
mellitus in adulthood 9-fold and 11-fold, respectively.79
Examining metabolic changes associated with the
metabolic syndrome among elementary age children reveals
a startling trend. When adult definitions are adjusted to
reflect the pediatric-specific cut-points, the prevalence of
metabolic syndrome among pre-pubescent overweight
and obese children ranges from 39% to 59%.81 Even more
sobering is the number of children who exhibit at least
1 metabolic abnormality secondary to obesity. In urban

Mexico, among obese school-aged children screened for
metabolic syndrome risk, 90% had insulin resistance based
on the homeostasis model assessment (HOMA). In addition, 14% of all children screened were at risk for or already
frankly hypertensive.82 In eastern Kansas, 18% and 37% of
elementary school children had elevated blood pressure or
triglycerides, respectively.83 The most common metabolic
abnormalities among overweight school-aged children from
urban Chicago screening were impaired fasting glucose
(21%), raised triacylglycerols (11%), and elevated blood
pressure (11%).84
Fortunately in pediatrics, the elements of time and
growth are on our side. Yet, time is a double-edged sword for
overweight children. Left untreated, the morbidity associated with the array of comorbidities is magnified over time.
So, children identified with risk factors in their first decade
will face health challenges even in their young adulthood
and middle age. Yet, data indicate that the cardiovascular
consequences of metabolic dysfunction are reversible if
detected early and corrected with appropriate management,
including a highly nutritious diet and improved fitness. 37
Therefore, the call to healthcare providers is to focus on mitigating risks in very young children, especially because the
metabolic syndrome is unreliable in the pubescent population. Recent national recommendations on lipid screening85
recognized the long-term consequences of obesity on
children in their first decade of life. The committee recommends screening children with risk factors beginning at the
age of 2 years with close follow-up, particularly where there
is a strong family history.85
The Role of Weight Reduction,

ProperNutrition, and Physical Activity
The underlying driver of metabolic dysfunction is excess

adipose tissue. Therefore, fundamentally, the initial treatment is optimal nutrition, increased physical activity/
physical fitness, and weight maintenance. Evidence shows
that for the obese patient a modest reduction in excess
body weight of as little as 5% to 7% induces significant
health benefits, including a decrease in triglycerides, LDL,
and VLDL cholesterols; raised HDL cholesterol; lowered
blood pressure; and improvements in insulin action with
improved glucose status.86,87 Optimal nutrition, particularly a diet rich in fruits, vegetables, and low-fat dairy (as
described in the DASH diet) has been shown to prevent
increases in blood pressure during early childhood. 88 The
DASH diet significantly improved measures of systolic
and diastolic blood pressure among adolescents with documented hypertension.89
Physical activity alone is documented to alter CVD
risk. In the prevention of coronary artery disease, individuals who are more physically active cut their risk in
half, compared with sedentary individuals. In adults,
comprehensive lifestyle interventions that include physical
activity result in modest reductions in body fat, 5% to 7%,
and demonstrate significant health benefits, starting with
a lowered insulin resistance. 86,87 Irrespective of weight
loss, exercise alone still demonstrates improvement of
CVD outcomes. Among individuals with established
CVD, exercise-only interventions significantly reduce
cardiac mortality and total mortality by 31% and 27%,
respectively.90
The physiological and functional changes to the
vasculature develop silently during childhood and are
fueled by obesity. As mentioned, the damage is amenable
if detected early and intervention is administered. For
obese children and adolescents already presenting with
early CVD risk the use of exercise training has been
supported as one management strategy. Irrespective
of significant reductions in weight, exercise training
demonstrates marked improvementin endothelial dysfunction. Worsening endothelial dysfunction, measured by
flow-mediated dilation, is a predictor of future adverse
cardiovascular events and correlates with measures of
body fatness. Children who perform exercise training,
157
particularly high-intensity exercise training, show marked

improvement in vascularfunction.9193
Mounting evidence in support of optimal nutrition,
physical activity, and weight maintenance to ameliorate
obesity and therefore lessen CVD risk, has prompted
the Expert Committee56 to establish 9 core messages for
pediatricians to reinforce as preventive and treatment strategies, applicable both for low-risk and high-risk children.
Evidence-informed prevention and treatment goals should
focus on:
1) Limiting sugar-sweetened beverages
2) Encouraging a healthful diet with at least 9 servings of
fruits and vegetables
3) Limiting television and screen time to 2 hours a day or
less
4) Eating breakfast daily
5) Limiting eating out away from home
6) Encouraging family meals
7) Limiting portion sizes
8) Engaging in 1 hour or more of moderate to vigorous
physical activity each day
9) Breastfeeding exclusively until 6 months of age
For some high-risk children, optimal nutrition,
physical activity, and weight maintenance efforts are ineffective at controlling weight and reducing the burden of
comorbidities. A more aggressive intervention is required.
Lipid-lowering drug therapies, particularly statins, have
been approved for use in children, as young as 8 years of
age at the highest risk.85 It is important to emphasize that
pharmacological treatments have demonstrated safety and
effectiveness among high-risk children and adolescents only94
and are not recommended for children presenting with
moderate lab values or risk. Similarly, bariatric weight-loss
surgery has been used in the United States as a treatment
option for morbidly obese adolescents. Bariatric weight loss
in this population is proven to be successful at mitigating the
comorbidities of excess body weight.95 However, an expert
panel of pediatricians and surgeons has recommended that
candidates demonstrate certain physical and psychological
readiness before receiving bariatric surgery.95 Therefore,
whether the treatment for the obese child includes pharmacological or surgical intervention, it is crucial for the
practitioner to assess the risk status of the child. Utilizing
practice-ready tools and guidelines provided by the Expert
Committee on the Assessment, Prevention and Treatment
of Child and Adolescent Overweight and Obesity56 can
assist the practitioner in evaluating risk and making decisions on the appropriate treatment course for the obese
child or adolescent.
158
Summary
In the decade following Reavens Banting Lecture in 1988, 2

the metabolic syndrome evolved from a concept to a diagnosis. Despite providing useful information on metabolic
risk and the susceptibility for developing CVD, the clinical
utility of the metabolic syndrome diagnosis remains controversial among researchers in adult and pediatric medicine.
Among children and adolescents, the lack of consensus on
the definition of the metabolic syndrome is compounded
by (1) the inability to define metabolic thresholds using
pediatric-specific cut-points, (2) the role of natural metabolic changes during puberty, and (3) the application of
emerging, non-traditional CVD risk factors in the metabolic
syndrome definition. But the very presence of the metabolic
syndrome in the pediatric population suggests that a shift
in metabolism fueled by excess body weight is underway.
Further, the presence of risk factors in early childhood
means that damage to the cardiovascular system has begun.
When metabolic risk factors present in a cluster, the clinical
course and health outcomes for that child are compromised, unless interventions are undertaken. The Expert
Committee on the Assessment, Prevention and Treatment of Child and Adolescent Overweight and Obesity56
underscored the role of the clinician to identify metabolic
risk factors at the earliest stage possible, institute treatment, and follow up closely. Identification of metabolic risk
in a child may prove beneficial for several reasons: (1) the
threat of evolving cardiovascular damage throughout the
lifespan can be reversed, if identified early and coupled with
aggressive lifestyle changes, and (2) weight management is
easier due to growth, along with the potential to influence
home and school environments. Practice-ready guidelines
emphasize a 6-step approach to assessing health risk in practice. For children at any risk level, the Expert Committee56
recommends evidence-based counseling supported by the
9 core messages for prevention and treatment. For children
presenting with substantial health risks associated with
the metabolic syndrome, pediatricians should focus on a
comprehensive intervention strategy, including optimal
nutrition, physical activity, weight maintenance, and, when
appropriate, pharmacological and/or surgical intervention.
1. Which factors are most restrictive in the diagnosis of

the metabolic syndrome in pediatrics?
A. Puberty
B. Ethnicity
C. Gender
D. Established cut-points
E. Lack of consensus on the clinical component disorders of the metabolic syndrome
2. Which of the following was not an original intention of
the metabolic syndrome as a conceptual entity?
A. To identify the most at-risk individuals for cardiovascular disease
B. To establish the clinical cluster as a diagnosable
entity
C. To explain the connection between otherwise unrelated metabolic events
D. To identify an individual in most urgent need of
lifestyle intervention
3. After identifying a 5-year-old child with a body mass
index > the 95th percentile, what would be the most
inappropriate next steps in the childs care?
A. Obtain a detailed family history
B. Discuss lifestyle behaviors
C. Perform a targeted physical exam and review of
systems
D. Obtain a laboratory analysis
E. Refer to sub-specialty care
F. Simply monitor the childs weight over the next 12
months
References
1. Leslie BR. Metabolic syndrome: historical perspectives. Am J

Med Sci. 2005;330:264268.
2. Reaven GM. Role of insulin resistance in human disease.
Diabetes. 1988;37:15951606.
3. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic
syndrome: time for a critical appraisal. Diabetologia.
2005;48:16841699.
4. Reaven GM. The metabolic syndrome: is this diagnosis necessary? Am J Clin Nutr. 2006;83:12371247.
5. Blaha MJ, Bansal S, Rouf R, Golden SH, Blumenthal RS,
DePilippis AP. A practical ABCDE approach to the metabolic syndrome. Mayo Clin Proc. 2008;83:932943.
6. Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults. Executive Summary of the
Third Report of the National Cholesterol Education Program
(NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment
Panel III). JAMA. 2001;285:24862497.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis
and classification of diabetes mellitus provisional report of a
WHO consultation. Diabet Med. 1998;15:539553.
International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. 2006. www.idf.
org/webdata/docs/IDF_Meta_def_final.pdf.
Kahn JM, Beevers DG. Management of hypertension in ethnic
minorities. Heart. 2005;91:11051109.
Sumner AE, Finley KB, Genovese DJ, Criqui MH, Boston
RC. Fasting triglyceride and triglyceride-HDL cholesterol
ratio are not markers of insulin resistance in African Americans. Arch Intern Med. 2005:165:13951400.
Sumner AE, Cowie CC. Ethnic differences in the ability of
triglyceride levels to identify insulin resistance. Atherosclerosis. 2008;196:696703.
Zhu S, Heymsfield SB, Toyoshima H, Wang Z, Piertrobelli A,
Heshka S. Race-ethnicity-specific waist circumference cutoffs
for identifying cardiovascular disease risk factors. Am J Clin
Nutr. 2005;81:409415.
Esteghamati A, Ashraf H, Rashidi A, Meysamie A. Waist
circumference cut-off points for the diagnosis of metabolic syndrome in Iranian adults. Diabetes Res Clin Prac.
2008;82:104107.
Oka R, Kobayashi J, Yagi K, et al. Reassessment of the cutoff
values of waist circumference and visceral fat area for identifying Japanese subjects at risk for the metabolic syndrome.
Diabetes Res Clin Pract. 2008;79:474481.
Ferdinand KC, Saunders E. Hypertension related morbidity
and mortality in African Americanswhy we need to do
better. J Clin Hypertens. 2006;8: 2131.
Unger J. Reinventing Type 2 diabetes: pathogenesis, treatment, and prevention. JAMA. 2008;299:11851187.
Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat
storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev. 2002;23:201229.
Iribarren C, Go AS, Husson G, et al. Metabolic syndrome and
early-onset coronary artery disease: is the whole greater than
its parts? J Am Coll Cardiol. 2006;48:18001807.
Alexander CM, Landsman PB, Teutsch SM, Haffner SM.
NCEP-defined metabolic syndrome, diabetes, and prevalence
of coronary heart disease among NHANES III participants
age 50 years and older. Diabetes. 2003;52:12101214.
McNeill AM, Rosamond WD, Girman CJ, et al. The metabolic syndrome and 11 year risk of incident cardiovascular
disease in the atherosclerosis risk in communities. Diabetes
Care. 2005;28: 385390.
Hoang KC, Ghanderhari H, Lopez VA, Barboza MG, Wong
ND. Global coronary heart disease assessment of individuals with the metabolic syndrome in the U.S. Diabetes Care.
2008;31:14051409.
Tong W, Lai H, Yang C, Ren S, Dai S, Lai S. Age, gender, and
metabolic syndrome related coronary heart disease in U.S.
adults. Int J Cardiol. 2005;104:288291.
Ford ES, Li C. Defining the metabolic syndrome in children
and adolescents: will the real definition please stand up? J
Pediatr. 2008;152:160164.
159
24. Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med.
2004;89:108113.
25. Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH.
Prevalence of metabolic syndrome phenotypes in adolescents: findings from the third national health and nutrition
examination survey, 1998-1994. Pediatr Adolesc Med.
2003;157:821827.
26. de Ferranti SD, Gauvreau K, Ludwig DS, Neufeld EJ,
Newburger JW, Rifai N. Prevalence of the metabolic
syndrome in American adolescents: findings from the third
national health and nutrition examination survey. Circulation.
2004;110:24942497.
27. Brambilla P, Lissau I, Flodmark CE, et al. Metabolic risk factor
clustering estimation in children: to draw a line across pediatric metabolic syndrome. Int J Obes. 2007;31:591600.
28. Steinberger J, Daniels SR, Eckel RH, et al. Progress and
Challenges in Metabolic Syndrome in Children and Adolescents: A Scientific Statement From the American Heart
Association Atherosclerosis, Hypertension, and Obesity in
the Young Committee of the Council on Cardiovascular
Disease in the Young; Council on Nursing; and Council on
Nutrition, Physical Activity, and Metabolism. Circulation.
2009;119:628647.
29. Huang TT. Finding thresholds of risk for components of the
pediatric metabolic syndrome. J Pediatr. 2008;152:158159.
30. Zimmet P, Alberti KG, Kaufman F, et al; IDF Consensus
Group. The metabolic syndrome in children and adolescents:
an IDF consensus report. Pediatr Diabetes. 2007; 8:299306.
31. Joliffe CJ, Janssen I. Development of age specific adolescent
metabolic syndrome criteria that are linked to the Adult Treatment Panel III and International Diabetes Federation criteria.
J Am Coll Cardiol. 2007;27:891898.
32. Moreno LA, Pineda I, Rodriquez G, Fleta J, Sarria A, Bueno M.
Waist circumference for the screening of metabolic syndrome
in children. Acta Pediatr. 2002;91:13071312.
33. Seidell JC, Perusse L, Despres JP, Bouchard C. Waist and
hip circumference have independent and opposite effects on
cardiovascular disease risk factors: the Quebec family study.
Am J Clin Nutr. 2001;74:315321.
34. Moreno LA, Joyanes M, Mesana MI, et al; AVENA Study
Group. Harmonization of anthropometric measurements for
a multicenter nutrition survey in Spanish adolescents. Nutrition. 2003;19:481486.
35. Moran A, Jacobs DR Jr, Steinberger J, et al. Association
between the insulin resistance of puberty and the insulin-like
growth factor/growth hormone axis. J Clin Endocrinol Metab.
2002;87:48174820.
36. Hannon TS, Janosky J, Arslanian SA. Longitudinal study
of physiological insulin resistance and metabolic changes of
puberty. Pediatr Res. 2006;60:759763.
37. Groner JA, Joshi M, Bauer JA. Pediatric precursors of adult
cardiovascular disease: noninvasive assessment of early
vascular changes in children and adolescents. Pediatrics.
2006;118(4):16831691.
38. Woo KS, Chook P, Yu CW, et al. Overweight in children is associated with arterial endothelial dysfunction and intima-media
thickness. Int J Obes Relat Metab Disord. 2004;28:852857.
160
39. Ferri C, Croce G, Confini V, et al. C-reactive protein: interaction with the vascular endothelium and possible role in human
atherosclerosis. Curr Pharm Des. 2007;13:16311645.
40. Valle M, Maros R, Gascon F, Canete R, Zafra MA, Morales R.
Low-grade systemic inflammation, hypoadiponectinemia and
a high concentration of leptin are present in very young obese
children, and correlate with metabolic syndrome. Diabetes
Metab. 2005; 3:5562.
41. Soriano-Guillen L, Hernandez-Garcia B, Pita J,
Dominguez-Garrido N, Del Rio-Camacho G, Rovira A.
High-sensitivity C-reactive protein is a good marker of
cardiovascular risk in obese children and adolescents. Eur J
Endocrinol. 2008;159:R1R4.
42. Poirier P, Giles TD, Bray GA, et al. Obesity and cardiovascular
disease: pathophysiology, evaluation and effect of weight loss.
Arterioscler Thromb Vasc Biol. 2006;26:968976.
43. Pai JK, Pischon T, Ma J, et al. Inflammatory markers and the
risk of coronary heart disease in men and women. N Engl J
Med. 2004;351:25992610.
44. Wozniak SE, Gee LL, Wachtel MS, Frezza EE. Adipose tissue:
the new endocrine organ? A review article. Dig Dis Sci. 2009
Sep;54(9):1847-56. Epub 2008 Dec 4.
45. Antuna-Puente B, Feve B, Fellahi S, Bastard JP. Adipokines:
the missing link between insulin resistance and obesity.
Diabetes Metab. 2008;34:211.
46. Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral
and subcutaneous adipose tissue compartments: association
with metabolic risk factors in the Framingham Heart Study.
Circulation. 2007;116:3948.
47. Pou KM, Massaro JM, Hoffmann U, et al. Visceral and
subcutaneous adipose tissue volumes are cross-sectionally
related to markers of inflammation and oxidative stress: the
Framingham Heart Study. Circulation. 2007;116:12341241.
48. Lee S, Bacha F, Gungor N, Arslanian S. Comparison of
different definitions of pediatric metabolic syndrome: relation to abdominal adiposity, insulin resistance, adiponectin,
and inflammatory biomarkers. J Pediatr. 2008;152:177184.
49. Retnakaran R, Zinman B, Connelly PW, Harris SB, Hanley
AJG. Nontraditional risk factors in pediatric metabolic
syndrome. J Pediatr. 2006;148:176182.
50. Langenberg C, Bergstrom J, Scheidt-Nave C, Pfeilschifter J,
Barrett-Connor E. Cardiovascular death and the metabolic
syndrome: role of adiposity signaling hormones and inflammatory markers. Diabetes Care. 2006;29:13631369.
51. Kapiotis S, Holzer G, Schaller G, et al. A pro-inflammatory
state is detectable in obese children and is accompanied by
functional and morphological vascular changes. Arterioscler
Thromb Vasc Biol. 2006;26:25412546.
52. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C,
Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118:13881393.
53. Manco M, Marcellini M, Devito R, Comparcola D, Sartorelli
MR, Nobili V. Metabolic syndrome and liver histology
in paediatric non-alcoholic steatohepatitis. Int J Obes.
2008;32:381387.
54. Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook
S. Cardiovascular risk factors and the metabolic syndrome
in pediatric non-alcoholic fatty liver disease. Circulation.
2008;15:277283.
55. Barshop NJ, Sirlin CB, Schwimmer JB, Lavine JE. Review
article: epidemiology, pathogenesis and potential treatment of
paediatric non-alcoholic fatty liver disease. Aliment Pharmacol
Ther. 2008;28:1324.
56. Barlow SE; Expert Committee. Expert committee recommendations regarding the prevention, assessment, and treatment
of child and adolescent overweight and obesity: summary
report. Pediatrics. 2007;120:S164S192.
57. Dallo FJ, Weller SC. Effectiveness of diabetes mellitus
screening recommendations. Proc Natl Acad Sci.
2003;100:1057410579.
58. Lin HF, Boden-Albala B, Juo SH, Park N, Rundek T, Sacco
RL. Heritabilities of the metabolic syndrome and its components in the Northern Manhattan study. Diabetologia.
2005;48:2006-2012.
59. Butte NF, Comuzzie AG, Cole SA, et al. Quantitative genetic
analysis of the metabolic syndrome in Hispanic children.
Pediatr Res. 2005;58:12431248.
60. Goodman E. The role of socioeconomic status gradients in
explaining differences in US adolescents health. Am J Public
Health. 1999;89:15221528.
61. Chen E, Martin AD, Matthews KA. Trajectories of socioeconomic status across childrens lifetime predict health.
Pediatrics. 2007;120:e297e303. doi:10.1542/peds.20063098.
62. Wang Y. Cross national comparison of childhood obesity: The
epidemic and the relationship between obesity and socioeconomic status. Int J Epidemiol. 2001;30:11291136.
63. Singh SG, Kogan MD, Van Dyck PC, Siahpush M. Racial/
ethnic, socioeconomic, and behavioral determinants of
childhood and adolescent obesity in the United States:
analyzing independent and joint associations. Ann Epidemiol.
2008;18:682695.
64. American Dietetic Association. Factors associated with childhood overweight. http://www.adaevidencelibrary.com/topic.
cfm?cat=2792. Accessed December 3, 2008.
65. Marshall SJ, Gorely T, Biddle SJH. A descriptive epidemiology
of screen-based media use in youth: a review and critique. J
Adolesc. 2006;29:333349.
66. Kotz K, Story M. Food advertisements during childrens
Saturday morning television programming: are they consistent with dietary recommendations? J Am Diet Assoc.
1994;29:12961300.
67. Halford JC, Gillespie J, Brown V, Pontin EE, Dovey TM. Effect
of television advertisements of foods on food consumption in
children. Appetite. 2004;42:221225.
68. Halford JC, Boyland EJ, Hughes GM, Stacey L, McKean S,
Dovey TM. Beyond brand-effect of television food advertisements on food choice in children: the effects of weight status.
Public Health Nutr. 2008;11:897904.
69. Strong WB et al. Evidence based physical activity for schoolage youth. J Pediatr. 2005;146:732737.
70. Nguyen TT, Keil MF, Russell DL, et al. Relation of acanthosis
nigricans to hyperinsulinemia and insulin sensitivity in
overweight African American and white children. J Pediatr.
2001;138(4)474480.
71. Mukhtar Q , Cleverley G, Voorhees RE, McGrath JW.
Prevalence of acanthosis nigricans and its association with
hyperinsulinemia in New Mexico adolescents. J Adoles Health.
2001;28:372376.
72. Sinha S, Schwartz RA. Juvenile acanthosis nigricans. J Am
Acad of Dermatol. 2007;57:502508.
73. Ice CL, Murphy E, Minor VE, Neal WA. Metabolic syndrome
in fifth grade children with acanthosis nigricans: results from
the CARDIAC project. World J Pediatr. 2009;5:2330.
74. Guran T, Turan S, Akcay T, Bereket A. Significance of acanthosis nigricans in childhood obesity. J Paediatr and Child
Health. 2008;44:338341.
75. Murray R, Battista M. Managing the risk of childhood overweight and obesity in primary care practice. Curr Probl Pediatr
Adoles Health Care. 2009;39:145166.
76. National High Blood Pressure Education Program Working
Group on High Blood Pressure in Children and Adolescents.
The fourth report on the diagnosis, evaluation, and treatment
of high blood pressure in children and adolescents. Pediatrics.
2004;114(suppl):555576.
77. Freedman DS, Khan LK, Serdula MK, Dietz WH, Srinivasan
SR, Berenson GS. Racial differences in the tracking of childhood BMI to adulthood. Obes Res. 2005;13:928935.
78. Katzmarzyk PT, Prusse L, Malina RM, Bergeron J, Desprs
JP, Bouchard C. Stability indicators of the metabolic syndrome
from childhood and adolescence to young adulthood: the
Quebec family study. J Clin Epidemiol. 2001;54:190195.
79. Morrison JA, Fredman LA, Wang P, Glueck CJ. Metabolic
syndrome in childhood predicts adult metabolic syndrome
and type 2 diabetes mellitus 25-30 years later. J Pediatr.
2008;152:201206.
80. Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH.
Predicting obesity in young adulthood from childhood and
parental obesity. N Engl J Med. 1997;337:869873.
81. Golley RK, Magarey AM, Steinveck KS, Baur LA, Daniels
LA. Comparison of metabolic syndrome prevalence using
six different definitions in overweight pre-pubertal children enrolled in a weight management study. Int J Obes.
2006;30:853860.
82. Perichart-Perera O, Balas-Nakash M, Schiffman-Selechnik
E, Barbato-Dosal A, Vadillo-Ortega F. Obesity increases
metabolic syndrome risk factors in school-aged children
from an urban school in Mexico City. J Am Diet Assoc.
2007;107:8191.
83. Dubois, K et al. Prevalence of the metabolic syndrome
in elementary school children. Acta Paediatrica.
2006;95:10051011.
84. Braunschweig CL, Gomez S, Liang H, et al. Obesity and risk
factors for the metabolic syndrome among low-income, urban,
African American schoolchildren: the rule rather than the
exception? Am J Clin Nutr. 2005;81:970975.
161
85. Daniels SR, Greer FR, and the Committee on Nutrition. Lipid
screening and cardiovascular health in childhood. Pediatrics.
2008;122:198208.
86. McBride PE, Einerson JA, Grant H, et al. Putting the diabetes
prevention program into practice: a program for weight
loss and cardiovascular disease reduction with metabolic
syndrome or type 2 diabetes mellitus. J Nutr Health Aging.
2008;12:745s749s.
87. Racette SB, Weiss EP, Hickner RC, Holloszy JO. Modest
weight loss improves insulin action in African Americans.
Metabolism. 2005;54:960965.
88. Moore LL, Singer MR, Bradlee ML, et al. Intake of fruits,
vegetables and dairy products in early childhood and subsequent blood pressure changes. Epidemiol. 2005;16:411.
89. Couch SC, Saelens BE, Levin L, Dart K, Falciglia G, Daniels
S. The efficacy of a clinic based behavioral nutrition intervention emphasizing a DASH-type diet for adolescents with
elevated blood pressure. J Pediatr. 2008;152:494502.
90. Thompson PD, Buchner D, Pina IL, et al. American Heart
Association Council on Clinical Cardiology Subcommittee
on Exercise, Rehabilitation, and Prevention; American
Heart Association Council on Nutrition, Physical Activity,
and Metabolism Subcommittee on Physical Activity. Exercise and Physical Activity in the Prevention and Treatment
of Atherosclerotic Cardiovascular Disease: A Statement
from the Council of Clinical Cardiology and the Counsel
on Nutrition, Physical Activity and Metabolism. Circulation.
2003;24:31093116.
91. Hopkins ND, Stratton G, Tinken TM, et al. Relationships
between measures of physical fitness, physical activity, body
composition, and vascular function in children. Atherosclerosis. 2009; 204:244249.
92. Meyer AA, Kundt G, Lenschow U, Schuff-Werner P, Kienast
W. Improvement of early vascular changes and cardiovascular risk factors in obese children after a six-month exercise
program. J Am Coll Cardiol. 2006;7:18651870.
93. Watts K, Beye P, Siafarikas A, et al. Exercise training normalizes vascular dysfunction and improves central adiposity in
obese adolescents. J Am Coll Cardiol. 2004;19:18231827.
94. McCrindle BW, Urbina EM, Dennison BA, et al. American
Heart Association Atherosclerosis, Hypertension, and
Obesity in Youth Committee; American Heart Association
Council of Cardiovascular Disease in the Young; American
Heart Association Council on Cardiovascular Nursing.
Drug therapy of high-risk lipid abnormalities in children and
adolescents: a scientific statement from the American Heart
Association Atherosclerosis, Hypertension, and Obesity in
Youth Committee, Council of Cardiovascular Disease in the
Young, with the Council on Cardiovascular Nursing. Circulation. 2007;115:19481967.
95. Spear BA, Barlow SE, Ervin C, et al. Recommendations for
treatment in children and adolescents with overweight or
obesity. Pediatrics. 2007;120:S254S288.
15
Lipid Disorders
Shirley Huang, MD, and Melanie Katrinak, RD, CSP, LDN
CONTENTS
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Types of Lipid Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Genetic
Polygenic
Other
Screening and Lab Interpretation. . . . . . . . . . . . . . . . . . . 163

Dietary Cholesterol
Dietary Fats
Simple Carbohydrates
Fiber
Plant Sterols/Stanols
Omega-3 Fatty Acids
Soy Protein
Garlic
Antioxidants
Physical Activity
Pharmacologic Intervention . . . . . . . . . . . . . . . . . . . . . . . 167
162
Learning Objectives
1. Understand cardiovascular disease risk and the etiologies of lipid disorders.

2. Describe how to screen for lipid disorders and interpret
lab results.
3. Discuss the role of dietary factors and physical activity
in treating lipid disorders.
Background
Cardiovascular disease (CVD) remains the leading cause

of death and morbidity in the United States.1 Risk factors
for CVD include family history of early heart disease,
abnormal serum cholesterol levels, high blood pressure,
insulin resistance, diabetes mellitus, physical inactivity,
obesity, cigarette smoking, and certain medications. The
specific abnormal serum cholesterol levels include a high
concentration of low-density lipoprotein (LDL) cholesterol, a low concentration of high-density lipoprotein
(HDL) cholesterol, and high triglycerides. While CVD is
considered an adult disease, research has shown that the
process of arthrosclerotic CVD begins early in life and is
progressive throughout the lifespan.24 High cholesterol in
childhood accelerates the atherosclerotic process and places
the child at risk for CVD as an adult. Children with high
LDL cholesterol are also likely to have high levels as adults. 5
With increasing rates of obesity in children over the past 3
decades, the rates of obesity-related lipid disorders have also
risen.6,7 Nutrition intervention during childhood plays a
critical role in CVD prevention and dyslipidemia treatment
to reduce the risk of CVD.
LIPID DISORDERS
Types of Lipid Disorders

Genetic
Two of the most common genetic lipid disorders will be
described. These disorders are unique and require an individualized diet and treatment plan with a lipid specialist
and registered dietitian or other skilled clinician.
Familial Hypercholesterolemia
There are 2 types of familial hypercholesterolemia (FH):
homozygous FH and heterozygous FH. Homozygous
FH is rare, with an occurrence of approximately 1 in 1
million, with total cholesterol levels ranging from 600 to
1000 mg/dL. Skin xanthomas (cholesterol plaques) may
also be found in these patients at birth or before 6 years of
age. Angina pectoris and myocardial infarction can occur
before 6years of age. Heterozygous FH has an occurrence
from 1 in 200 to 1 in 500, with total cholesterol levels
exceeding 230 mg/dL and LDL cholesterol exceeding
160 mg/dL. No other clinical symptoms are present in
the first decade of life, but by the second decade, tendon
xanthomas of the hands may be found in 10% to 15% of the
children.8 Nearly all patients with FH require medications
in addition to lifestyle behavior interventions to normalize,
or at least improve, their LDLlevels.1
Lipoprotein Lipase Deficiency
Lipoprotein lipase (LPL) deficiency results in high levels
of triglycerides, which presents in infancy with abdominal
pain and hypertriglyceridemia.8 Because LPL deficiency
involves a specific metabolic abnormality or defect, dietary
intervention requires only restriction in fat and not simple
carbohydrates (compared to polygenic hypertriglyceridemia
which responds to a restriction of simple carbohydrates).
Treatment requires long-term weight control and a diet
of 20 g of fat daily. The diet can be supplemented with
medium-chain triglycerides (MCTs), which will not
increase triglyceride levels, to provide another source of fat
and calories.
Polygenic
Of all types of lipid disorders, polygenic hypercholesterolemia (nonfamilial) is the most common. Lifestyle factors
such as diet, weight, and physical inactivity combined
with a genetic susceptibility are the cause of this form of
dyslipidemia. High triglycerides and low HDL levels are
often seen with obesity and/or a diet with food and drinks
high in simple carbohydrates. In the metabolic syndrome
(Chapter 14), a constellation of findings including high
163
triglyceride levels, low HDL levels, abdominal obesity, high

blood pressure, insulin resistance, and fatty liver increases
the risk of CVD and diabetes mellitus.6,9,10 In children who
are obese with a body mass index 95th percentile for age
and gender, 52% have high triglycerides, and 50% have low
HDL levels.6 Children with polygenic hypercholesterolemia
often respond well to nutrition and lifestyle behavioral
interventions.
Other
Other causes of lipid disorders include medications and
certain disease states. Medications such as progestins,
anabolic steroids, glucocorticoids, psychotherapeutic
drugs, and retinoic acid acne treatment can cause abnormal
lipid levels. In addition, diseases such as untreated hypothyroidism, renal disease, polycystic ovarian syndrome
(PCOS), or liver disease may also cause dyslipidemias.11
Screening and Lab Interpretation
Tables 15-1 and 15-2 indicate who should be screened for

lipid disorders and the screening procedure. Interpretation of the resultant fasting lipid profile is delineated in
Table 15-3.
Table 15-11
Who to screen?
Any patient > 2 years of age with any of the following CVD risk factors:
A parent, grandparent, aunt, or uncle with cardiovascular disease
< 55 years (male) or < 65 years (female). Cardiovascular disease
includes: myocardial infarction, sudden cardiac death, coronary
bypass surgery, balloon angioplasty, angina pectoris, coronary
atherosclerosis, peripheral vascular disease, or stroke or
A parent with a total cholesterol > 240 mg/dL or
A family history that is not available (adopted child) or
Other cardiovascular risk factors: obesity (BMI > 95th percentile),
sedentary lifestyle, smoking, hypertension, diabetes, congenital
heart disease, renal disease or
Treatment with retinoid acid, anticonvulsants, or oral contraceptives
Table 15-21
How to screen?
After a 9-12 hour fast, obtain a fasting lipid profile that includes:
Total cholesterol (TC)
High-density lipoprotein cholesterol (HDL)
Triglycerides (TG)
Low-density lipoprotein cholesterol (LDL), calculated*
If TG > 400 mg/dL, a Direct LDL needs to be ordered
* Calculated LDL = TC(HDL-TG/5) (if TG < 400 mg/dL)
164
Figure 15-1
*A more conservative HDL cut-point is chosen here. HDL > 40 mg/dL is a cut-point used in pediatric and adult
metabolic syndrome.1,6 The American Heart Assocation recommends HDL > 35 mg/dL in pediatrics.20
Adapted from The Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults (Adult Treatment Panel III).1
Nutrition Management
The emphasis on a healthy diet and lifestyle is key in the
prevention of CVD and treatment of abnormal lipid levels.12
To prevent CVD in all children 2 years old, recommendations include a daily diet with total fat < 30% total calories,
saturated fat < 10% of total calories, trans fat < 1% of total
calories, and dietary cholesterol < 300 mg.1 Furthermore,
CVD prevention also includes increasing consumption of
fruits, vegetables, fish, whole grains, and reduced-fat dairy
products while reducing the intake of fruit juice, sugarsweetened beverages and foods, and salt.13 For children 2
years old at risk for CVD, the daily diet should be further
restricted to saturated fat < 7% of total calories and dietary
cholesterol to < 200 mg.1 For children between 12 months
and 2 years of age who are overweight, obese, or have a
family history of obesity, dyslipidemia, or CVD, reduced
fat milk is now considered safe and appropriate.1 Additional
dietary management for high-risk patients should always be
tailored based on individual lipid profile and involve counseling with a lipid specialist and registered dietitian or other
skilled clinician to ensure effective nutrition intervention
while maintaining appropriate growth and development.
Dietary Cholesterol
Dietary cholesterol is found in animal-based foods and
can be reduced by limiting foods such as butter, egg yolk,
high-fat meat, beef, poultry with skin, and whole milk dairy
products. Although limiting dietary cholesterol has less of a
serum lipid lowering effect and has a more variable response
among individuals than limiting saturated and trans fats, it
is still important because cholesterol and saturated fat are
found together in most foods.9,14 In general, LDL may be
decreased by 3% to 5% if dietary cholesterol is restricted
to < 200 mg daily. In addition, an increase of 100 mg/d of
dietary cholesterol increases total serum cholesterol by 2 to
3 mg/dL.
Dietary Fats
Saturated Fats
Limiting saturated fats can help to lower LDL levels.14 Saturated fat is found more in animal- than plant-based foods.
A major source of saturated fat is red meat, but dairy products are also commonly overlooked as a source of saturated
fat in childrens diets. Plant-based sources of saturated fat
LIPID DISORDERS
165
are mainly found in tropical oils (coconut, palm, and palm

kernel), which are often used in commercially baked goods.
To reduce saturated fat intake, whole milk dairy products
may be replaced with low-fat or non-fat (skim) dairy products, and leaner cuts of meat may be recommended. Low-fat,
reduced fat, and baked cookies, crackers, and other baked
goods should be consumed instead of full-fat versions. Using
additional saturated fat in the cooking process should be
limited. Low-fat cooking methods such as broiling, grilling,
steaming, microwaving, poaching, or baking are preferable
to frying. Saturated fats should be limited to < 7% total calories in children with high cholesterol.
hypertriglyceridemia, other than LPL deficiency, primarily

need to limit their intake of simple carbohydrates. Simple
sugars and carbohydrates, found in foods such as sweetened
beverages, desserts, snacks, and white breads and other
refined starches, raise triglycerides more than saturated and
trans fats. For children who are overweight or obese with
high triglycerides, limiting dietary fat, especially saturated
and trans fats, and increasing physical activity should also be
recommended in addition to limiting simple carbohydrates
because obesity will have a direct effect on triglyceride
levels.13
Trans Fats
Trans fats, or hydrogenated fats, are produced when fat is
hydrogenated to make it solid at room temperature. In
the process of hydrogenation, bonds in the cis position are
switched to the trans position, which has been shown to
increase LDL and decrease HDL cholesterol. Trans fats
are found mostly in stick margarine, high-fat baked goods,
shortening, commercial frying oils, and fried snack foods.
Examples of these foods are doughnuts, pastries, crackers,
cookies, potato and tortilla chips, french fries, and other
bakery and snack foods. Trans fats should be limited to
< 1% of total calories for all children 2 years old.1 Nutrition labels are allowed to list zero grams of fat per serving if
the product contains less than 0.5 g of trans fat per serving.
Therefore, to ensure a food is completely free of trans fat, it
is important to check the ingredients for hydrogenated and/
or partially hydrogenated oils.
Fiber combined with a low-fat diet may help to improve

cholesterol levels further. Soluble fiber such as oat bran,
psyllium, pectin, and guar gum decreases LDL cholesterol primarily, and has some effect on increasing HDL
cholesterol.17 An increase in soluble fiber of 5 to 10 g/d may
reduce LDL by 3% to 5%.9 One study found that children
who consumed 6.4 g of soluble fiber as psyllium decreased
their LDL by 7%.18 Fiber binds to bile acids and decreases
cholesterol absorption. Specific guidelines for the suggested
amount of fiber intake for children with dyslipidemia
currently do not exist, and remain controversial. However,
general guidelines for estimating adequate fiber intake in
children are found in the dietary reference intake (DRI)
and are generally much higher than most children and
adolescents consume.19 Another commonly used method
is adding 5 to the childs age to obtain the recommended
daily intake of fiber in grams, up to 20 g/d (for example,
a 6-year-old child should consume approximately 11 g of
fiber), although there is limited supporting evidence for this
calculation.17,20
Monounsaturated and Polyunsaturated Fats

Children with dyslipidemia are encouraged to replace saturated and trans fats with the healthier monounsaturated and
polyunsaturated fats, which decrease LDL cholesterol.1,15
Monounsaturated fats are found in avocados, many nuts
and seeds, and vegetable oils such as olive, canola, peanut,
and sesame oil.13 Polyunsaturated fats are found in most
nuts and seeds, fatty fish (salmon, tuna, mackerel, herring,
and trout) and vegetable oils like soybean, corn, safflower,
and sunflower oils.16 It is important to note that while these
fats are healthy, they are still calorically dense and should
be limited as recommended by the Dietary Guidelines for
Americans,13 especially for weight maintenance or loss.
Simple Carbohydrates
For the general population, current recommendations
encourage choosing mostly complex carbohydrates with
a limited intake of simple carbohydrates.13 Patients with
Fiber
Plant Sterols/Stanols
Plant sterols and stanols are essential components of cell
membranes in plants that are structurally similar to cholesterol. Plant stanols are saturated sterols and have no double
bonds. Their action is to inhibit absorption of dietary
cholesterol and to decrease re-absorption of cholesterol
from bile. Plant sterols or stanol esters have been incorporated into margarine/butter spreads, granola bars, yogurt
drinks, oatmeal, cereal, and some other foods and are also
available in caplets. A randomized control study in children
using 2 g of plant sterol in margarine per day decreased LDL
by 8%.21 Plant sterols are considered safe for children at
recommended doses of 2 g/d to lower LDL levels. However,
they may theoretically have the potential to decrease levels
of fat-soluble vitamins such as vitamin A (beta carotene)
166
or vitamin E (alpha tocopherol), which can typically be

prevented by increasing intake of food sources of both. A
multivitamin may be considered if additional risk factors for
vitamin deficiency are present. 21
benefits of soy remain controversial, soy can provide polyunsaturated fatty acids, fiber, vitamins, and minerals beneficial
for cardiovascular and overall health.17
Omega-3 Fatty Acids
Garlic may have beneficial cardiovascular effects such

as lowering LDL cholesterol, lowering blood pressure,
reducing platelet aggregation, and acting as an antioxidant
and anti-inflammatory agent.24 However, the mechanism
of garlics actions are unclear. Other studies have shown no
cardiovascular effect in children.20 At this time, there are no
recommendations regarding the use of garlic for lowering
cholesterol in children.
The omega-3 fatty acids, docosahexaenoic acid (DHA)

and eicosapentaenoic acid (EPA), are found in fish oils and
ocean fish (herring, mackerel, salmon, and sardines), and
lower triglycerides by inhibiting very low-density lipoprotein (VLDL) and apolipoprotein B (apoB) synthesis. 22
While fish intake has been shown to be cardioprotective,
it has no effect on total cholesterol, LDL, or HDL and has
only been shown to lower triglycerides. Still, the American
Heart Association (AHA) and American Academy of
Pediatrics (AAP) recommend increasing fish consumption for CVD prevention; no specific guidelines exist for
pediatrics, but the recommendation for adults is 2 servings
per week.23 DHA and EPA may be synthesized from alphalinolenic acid, which is found in flaxseed oil, canola oil, soy
oil, and walnuts. A total of 2 to 4 g of DHA/EPA may be
recommended for triglycerides > 500 mg/dL.24,25 This level
of intake, in general, cannot be achieved by seafood intake
alone and requires supplementation or medication. It should
be noted that over-the-counter fish oil supplements are
often dosed with the total grams of fish oil, but one should
pay attention to total grams of combined DHA and EPA,
and not total grams of fish oil, in dosing supplements for the
treatment of high triglycerides.
Soy Protein
The effect of soy on lowering cholesterol remains controversial. While some studies show soy isoflavones can decrease
LDL and triglycerides and increase HDL, others show little
or no effect. Although a daily intake of 25 g of soy in adults
may decrease total and LDL cholesterol from 1.5% to 4.5%,
this may be related more to the use of soy as a substitute for
foods high in saturated fat.22,24,26 No recommendations have
been made for children. While the cholesterol-lowering
Garlic
Antioxidants
Antioxidants have been raised as a possible treatment for
high cholesterol because oxidized LDL is implicated in
plaque development. Although daily supplementation of
vitamins C and E may improve endothelial function, largescale clinical trials have not shown any benefit related to the
primary or secondary prevention of CVD. 24,27 Studies in children are limited, and antioxidant vitamin supplementation
is not currently recommended to manage dyslipidemia.27
Physical Activity
Physical activity is beneficial for children and adolescents
with dyslipidemia, due to its effects on raising HDL and
decreasing triglyceride levels. Improvement of LDL levels
and insulin resistance have also been documented.28,29 In
addition, physical activity plays a critical role in maintaining
an appropriate weight, which also affects cholesterol levels.
Physical activity should be encouraged in all patients with
dyslipidemia unless another medical condition contraindicates this. New physical activity guidelines recommend that
children have at least 60 minutes of moderate to vigorous
physical activity daily, including vigorous physical activity
at least 3 days per week. 30
Nutrition and physical activity recommendations for
specific lipid abnormalities are summarized in Table 15-3.
TABLE 15-3 Summary of Nutrition and Physical Activity Recommendations for Specific Lipid Abnormalities
Lipid Abnormality
Fiber
Simple
Carbohydrates
Dietary
Cholesterol
Trans Fat
Saturated Fat
Omega-3 Fats
Physical
Activity
High LDL
Increase
DGA
< 200 mg
< 1% total kcal
< 7% total kcal
DGA
Increase
High TG
DGA
Decrease
< 200 mg
< 1% total kcal
< 7% total kcal
Increase
Increase
Low HDL
DGA
DGA
< 200 mg
< 1% total kcal
< 7% total kcal
DGA
Increase
DGA = Dietary Guidelines for Americans 2005.

LIPID DISORDERS
Pharmacologic Intervention
Medications may be considered in conjunction with nutrition and physical activity interventions for patients 8 years
and older with an LDL 190 mg/dL (or 160 mg/dL with
a family history of early heart disease or 2 additional risk
factors present, or 130 mg/dL or > 100 mg/dL depending
if Type 1 diabetes mellitus or other high-risk conditions
exist).1,31 HMG CoA-reductase inhibitors, or statins, are the
recommended class of medications to lower LDL levels in
pediatrics. Statins have been shown to be safe and effective
in lowering cholesterol in a number of clinical trials, though
they have generally been short-term. 3236 Patients, however,
need to be monitored closely for liver and muscle side
effects. Niacin and bile acid-binding resins are other classes
of cholesterol-lowering medications but are not routinely
recommended in pediatrics due to limited effectiveness and
poor compliance. Cholesterol-absorption inhibitors are the
newest class that are often combined with other medications
such as statins, but have not yet been extensively studied in
children.
1. Which of the following values is least important in

assessing a fasting lipid profile?
A. Triglycerides
B. Total cholesterol
C. LDL
D. HDL
2. What percentage of trans fats is recommended by the
American Heart Association?
A. < 5% total calories/day
B. < 10% total calories/day
C. < 30% total calories/day
D. < 1% total calories/day
3. In which lipid profile would omega-3 fats be beneficial
for a pediatric patient?
A. LDL 200 mg/dL, triglycerides 80 mg/dL, HDL 50
mg/dL
B. LDL 110 mg/dL, triglycerides 550 mg/dL, HDL 25
mg/dL
C. LDL 120 mg/dL, triglycerides 150 mg/dL, HDL 25
mg/dL
D. LDL 180 mg/dL, triglycerides 100 mg/dL, HDL 30
mg/dL
167
References
1. Daniels SR, Greer FR; Committee on Nutrition. Lipid

screening and cardiovascular health in childhood. Pediatrics.
2008;122:198208.
2. Newman WP III, Freedman DS, Voors AW, et al. Relation of
serum lipoprotein levels and systolic blood pressure to early
atherosclerosis: the Bogalusa Heart Study. N Engl J Med.
1986;314(3):138144.
3. Berenson GS, Srinivasan SR, Bao W, Newman WP III,
Tracy RE, Wattigney WA. Association between multiple
cardiovascular risk factors and the early development of
atherosclerosis. The Bogalusa Heart Study. N Engl J Med.
1998;338(23):16501656.
4. McGill HC Jr, McMahan CA, Malcom GT, Oalmann MC,
Strong JP; for the PDAY Research Group. Effects of serum
lipoproteins and smoking on atherosclerosis in young men
and women. Aterioscler Thromb Vasc Biol. 1997:17(1):95106.
5. Webber LS, Osganian V, Luepker RV, et al. Cardiovascular
risk factors among third grade children in four regions of
the United States. The CATCH Study: Child and Adolescent Trial for Cardiovascular Health. Am J Epidemiol.
1995;141(5):428439.
6. Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH.
Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition
Examination Survey, 1988-1994. Arch Pediatr Adolesc Med.
2003;157:821827.
7. Ogden CL, Carroll MD, Flegal KM. High body mass index for
age among US children and adolescents, 2003-2004. JAMA.
2008;299(20):24012405.
8. Kwiterovich PO. Diagnosis and management of familial
dyslipidemia in children and adolescents. Pediatr Clin North
Am. 1990;37:14891523.
9. Expert Panel on Detection, Evaluation, and Treatment of
High Blood Cholesterol in Adults. Executive Summary of the
Third Report of the National Cholesterol Education Program
(NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment
Panel III). JAMA. 2001;285:24862497.
10. Schwimmer JB, et al. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease.
Circulation. 2008;118:277283.
11. Kwiterovich PO. Recognition and management of dyslipidemia in children and adolescents. J Clin Endocrinol Metab.
2008;93(11):4200-4209.
12. Rose G. Sick individuals and sick populations. Int J Epidemiol.
1985;14(1):3238.
13. US Department of Health and Human Services. 2005 dietary
guidelines for Americans. http://www.healthierus.gov/
dietaryguidelines. Accessed November 12, 2009.
14. Howell WH, McNamara DJ, Tosca MA, Smith BT, Gaines
JA. Plasma lipid and lipoprotein responses to dietary
fat and cholesterol: a meta-analysis. Am J Clin Nutr.
1997;65:17471764.
15. American Academy of Pediatrics Policy Statement. Cholesterol in Childhood. (RE9805) Pediatrics. 1998;101:141147.
168
16. American Heart Association. Face the Fats. http://www.

americanheart.org/presenter.jhtml?identifier=3046074
17. Dalidowitz C. Nutrition management of dyslipoproteinemia.
In: Nevin-Folino NL, ed. Pediatric Manual of Clinical
Dietetics. 2nd ed. Chicago, IL: American Dietetic Association;
2003:319340.
18. Davidson MH, Dugan LD, Burns JH, Sugimoto D, Story K,
Drennan K. A psyllium enriched cereal for the treatment of
hypercholesterolemia in children: a controlled, double-blind,
cross-over study. Amer J Clin Nutr. 1996;63:96102.
Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty
Acids, Cholesterol, Protein, and Amino Acids (Macronutrients).
Washington DC: National Academy Press; 2005.
20. Kavey RE, Daniels SR, Lauer RM, et al. American
Heart Association guidelines for primary prevention of atherosclerotic

cardiovascular disease beginning in childhood. Circulation. 2003;107(11):15621566; copublished in J Pediatr.
2003;142(4):368372.
21. Tammi A, Ronnemaa T, Miettinen TA, et al. Effects of gender,
apolipoprotena E phenotype and cholesterol-lowering by
plant stanol esters in children: the STRIP study. Special Turku
Coronary Risk Factor Intervention Project. Acta Paediatr.
2002;91(11):11551162.
22. Krummel D. Nutrition in cardiovascular disease. In: Mahan
LK, Escott-Stump S, eds. Krauses Food, Nutrition, and
Diet Therapy. 10th ed. Philadelphia, PA: WB Saunders Co;
2000:571.
23. Nutrition Committee of the American Heart Association.
AHA Dietary Guidelines. Circulation. 2000:2296.
24. Fletcher B, Berra K, Ades P, et al. Managing abnormal
blood lipids: a collaborative approach. Circulation.
2005;112:31843209.
25. Kris-Etherton PM, Harris WS, Appel LJ; American Heart
Association Nutrition Committee. Fish consumption, fish oil,
omega-3 fatty acids, and cardiovascular disease. Circulation.
2002;106:27472757.
26. Erdman JW Jr. AHA Science Advisory. Soy protein and
cardiovascular disease: a statement for healthcare professionals from the Nutrition Committee of the AHA.
Circulation. 2000;102:25552559.
27. Engler MM, Engler MB, Malloy MJ, et al. Antioxidants vitamins C and E improve endothelial function in children with
hyperlipidemia: Endothelial Assessment of Risk From Lipids
in Youth (EARLY) Trial. Circulation. 2003;108:10591063.
28. Maron BJ, Chaitman BR, Ackerman MJ, et al. Recommendations for physical activity and recreational sports participation
for young patients with genetic cardiovascular diseases. Circulation. 2004;109(22):28072816.
29. Strong WB, Malina RM, Blimkie CJ, et al. Evidencebased physical activity for school-age youth. J Pediatr.
2005;146(6):732737.
30. US Department of Health and Human Services. 2008 physical
activity guidelines for Americans. http://www.health.gov/
paguidelines. Accessed November 12, 2009.
31. Kavey R, Aladda V, et al. Cardiovascular Risk Reduction
in High-Risk Patients: A Scientific Statement From the
American Heart Association Expert Panel on Population
and Prevention Science; the Councils on Cardiovascular
Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure
Research, Cardiovascular Nursing, and the Kidney in Heart
Disease; and the Interdisciplinary Working Group on Quality
of Care and Outcomes Research: Endorsed by the American
Academy of Pediatrics. Circulation. 2006;114:27102738.
32. de Jongh S, Ose L, Szamosi T, et al. Efficacy and safety of
statin therapy in children with familial hypercholesterolemia:
a randomized double-blind, placebo-controlled trial with
simvastatin. Circulation. 2002;106(17):22312237.
33. Lambert M, Lupien PJ, Gagne C, et al. Treatment of familial
hypercholesterolemia in children and adults: effect of
lovastatin. Canadian Lovastatin in Children Study Group.
Pediatrics. 1996;97(5):619628.
34. McCrindle BW, Ose L, Marais AD. Efficacy and safety
of atorvastatin in children and adolescents with familial
hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. J Pediatr.
2003;143(1):7480.
35. de Jongh S, Lilien MR, opt Roodt J, et al. Early statin therapy
restores endothelial function in children with familial hyper
cholesterolemia. J Am Coll Cardiol. 2002;40(12):21172121.
36. Wiegman A, Hutten BA, de Groot E, et al. Efficacy and safety of
statin therapy in children with familial hypercholesterolemia:
a randomized controlled trial. JAMA. 2004;292(3):331337.
Use of Popular and Fad Diets
16
Catherine Christie, PhD, RD, Julia A. Watkins, PhD, MPH, and Judith C. Rodriguez, PhD, RD
Learning Objectives
CONTENTS
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical Approach to the Overweight/Obese Child or
Adolescent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Use of Fad and Popular Diets . . . . . . . . . . . . . . . . . . . . . .
Lifelong Weight Management. . . . . . . . . . . . . . . . . . . . . .
Types of Fad and Popular Diets. . . . . . . . . . . . . . . . . . . . .
169
170
170
171
171
Behavioral Weight-Loss Plans

Food-Focused Weight Loss Plans
Reduced Macronutrient Content Plans
Food Group Guides/Exchange Systems
Food Timing/Meals and Snacks Combinations
Commercial Meal/Snack Replacements
Other Plans
Diets Designed for Use with Children. . . . . . . . . . . . . . . . 174

Balanced Macronutrient Low-Kilocalorie Diets
Traffic Light Diet
Food Guide Pyramid
Multidisciplinary Behavior Change Programs
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
1. Describe the importance of weight maintenance versus

weight loss recommendations when working with
children and adolescents.
2. Critique one of the discussed popular/fad diets for use
with children.
3. Critique another popular/fad diet discussed for use with
adolescents.
4. Assess the efficacy of a balanced macronutrient
low-kilocalorie diet for use with children.
Background
The incidence and prevalence of childhood overweight and

obesity is increasing worldwide.1 This increase is associated
with multiple health risks and adverse effects in childhood as
well as later in life such as sleep problems, endocrine disorders,
respiratory problems, gastrointestinal problems, skin conditions, orthopedic disorders, and cardiovascular risk factors.2
Dietary intake data are also of concern. Less than 40%
of U.S. youth meet the U.S. Dietary Guidelines for saturated
fat, which is related to risk for heart disease and diabetes.3
According to the Youth Risk Behavior Surveillance (YRBS)
survey, 80% of adolescents do not eat fruits and vegetables 5
or more times per day, which impacts on the findings that only
39% of youth 2 to 17 years meet the U.S. Department of Agricultures recommendations for fiber.4,5
There is a need for successful, scientifically sound weightloss measures with dietary, physical activity, and social support
components to assist youth. According to the YRBS survey, a
large number of adolescents use unhealthy methods to lose or
maintain weight, evidenced by the finding that during the 30
days preceding the survey, 12.3% of students went without
eating for 24 hours or more, 4.5% had vomited or taken
169
170
laxatives; and 6.3% had taken diet pills, powders, or liquids

without a doctors advice.4
Systematic reviews of childhood obesity and expert
committee recommendations have emerged over the last
several years69 and all agree that child and adolescent
obesity treatment should:
be directed at motivated families in which the child
and/or parents perceive obesity to be a problem and
appear willing to make lifestyle changes
be directed at the entire family rather than just the
overweight/obese child
aim for weight maintenance unless body mass index
(BMI) is > 99th percentile
be more intensive than has been the norm
combine changes in diet plus changes in physical
activity and/or reduction in sedentary behavior
The current definitions state that if BMI is greater than
or equal to the 95th percentile, the child is obese, and if
BMI is between the 85th and 94th percentiles, the child is
overweight (Table 16-1).
Table 16-1 Weight Recommendations According to Age and BMI Percentile9
Age
25 years
BMI of 85th to
94th percentile
BMI of 95th
percentile
611 years
BMI of 85th to
94th percentile
BMI of 95th to
98th percentile
BMI of 99th
percentile
Target
Weight maintenance until BMI of < 85th percentile

or slowing of weight gain, as indicated by
downward deflection of BMI curve.
Weight maintenance until BMI of < 85th
percentile; however, if weight loss occurs with
healthy, adequate energy diet, then it should
not exceed 1 lb/mo. If greater loss is noted,
then patient should be monitored for causes of
excessive weight loss.
or gradual weight loss of ~1 lb/mo. If greater loss
is noted, then patient should be monitored for
causes of excessive weight loss.
Weight loss not to exceed average of 2 lb/wk.
If greater loss is noted, then patient should be
monitored for causes of excessive weight loss.
1218 years
BMI of 85th to
94th percentile

BMI of 95th to
Weight loss until BMI of < 85th percentile, no
98th percentile
more than average of 2 lb/wk. If greater loss
is noted, then patient should be monitored for
causes of excessive weight loss.
BMI of 99th
Weight loss not to exceed average of 2 lb/wk.
percentile
If greater loss is noted, then patient should be
monitored for causes of excessive weight loss.
Reproduced with permission from Pediatrics, Vol. 120, page 254, copyright
2007 by the American Academy of Pediatrics.
Clinical Approach to the Overweight/Obese

Child or Adolescent
The American Dietetic Association evidence-based analysis

of pediatric overweight literature on intervention programs
reported positive effects from 2 specific kinds of interventions: (1) multi-component, family-based programs
for children between the ages of 5 and 12 and (2) multicomponent school-based programs for adolescents. The
components included were behavioral counseling, promotion of physical activity, parent training/modeling, dietary
counseling, and nutrition education.10
Interventions should be based on the familys readiness
to change and include the following recommendations9:
consumption of 5 servings of fruits and vegetables per
day
minimization or elimination of sugar-sweetened
beverages
limits of 2 hours of screen time per day, no television
in the room where the child sleeps, and no television if
the child is < 2 years of age
1 hour of physical activity per day
In addition, parents and family members should be counseled to facilitate the following eating behaviors:
eating breakfast daily
limiting meals outside the home, including at fast-food
venues and other restaurants
eating family meals at least 5 or 6 times per week
allowing the child to self-regulate his or her meals and
avoiding overly restrictive behaviors
Use of Fad and Popular Diets
Parents of overweight or obese children may be overweight

themselves and often look to popular diets as a means of
losing weight. Because these diets are often adopted by the
family and modified for children or adolescents, a discussion
of the use of popular diets for pediatric patients is warranted.
Family-friendly popular diets include elements of
healthy eating that are applicable or can be easily modified
to safely include children. Popular diets can be categorized
into 7 major types: behavioral, food-focused, reduced
macronutrient content, food group guides or exchange
systems, food timing or specific combinations of meals and
snacks, commercial meal or snack replacements, and an
other category for plans that do fit in any previous category.11 Within each category of weight-loss diets, many are
effective in reducing weight because regardless of the plan
or claim, they principally lower caloric intake by prescribing
limits on food intake. However, the scientific evidence
consistently concludes that successful weight loss should be
USE OF POPULAR AND FAD DIETS
coupled with a plan that enables the dieter to manage weight

over a lifetime.11 The more extreme the plan, the more difficult it is to follow over the long term. The key for lifelong
weight management is following a plan individualized to
each persons needs. Kilocalorie- and portion-controlled
diets seem to be more conducive to long-term compliance
than fat- and carbohydrate-restricted diets.12
According to the Weight Control Registry,13 adults who
are successful at losing weight and keeping it off individualize their changes in lifestyle to include eating and exercise
behaviors that they can sustain for a lifetime. Therefore,
when considering any diet plan individuals should consider
nutrition, food variety, moderate intake, food portions, rate
of including these into their lifestyle, ways to continue them
for an extended time, and how to add physical activity. For
many, the term diet evokes thoughts of something temporary. The resultant on-off mindset produces short-term
change only and does not address the underlying behaviors
that created the need to diet in the first place.
Successful weight-reduction programs reduce body
weight and body fat gradually by decreasing caloric intake
and increasing caloric expenditure. An increase in physical
activity builds or maintains muscle mass and, together
with aerobic activity, determines the utilization of body
fat reserves and thus the metabolic rate or the rate of kilocalories being burned. Diets that promise immediate or fast
weight loss are not recommended as they defy the scientific
basis for metabolism, particularly in children as normal
growth may be inhibited. Such claims are at best misleading
and at worst, potentially harmful. The calculation of
energy balance reveals that fat loss occurs at the rate of 1
to 2 pounds per week, even when a person severely restricts
caloric intake. To lose 1 pound of body fat per week, a negative caloric deficit of 3500 kilocalories or 500 kilocalories
for 7 days must occur. Weight loss greater than the recommended 1 to 2 pounds per week can only occur by losing
muscle and water in addition to fat.14
It is important for families to set a reasonable and
reachable goal for weight loss with their physician and a
registered dietitian before undertaking a diet. When planning a change in diet for the family, the plan should first be
evaluated to see if it is compatible with their lifestyle and
health needs. It should be a plan that the family can foresee
continuing indefinitely. A lifestyle change is required to
prevent periods of on and off dieting and regression to the
previous habits which initially caused weight gain. On and
off dieting results in weight regain, which could negatively
impact health and affect disease progression.
171
Lifelong Weight Management
The following 5 steps to lifelong weight management are

helpful for families who are considering a change in their
diet for weight loss of any family member11:
1. Eat food in appropriate portion sizes.
A. Meat, poultry, and fish servings should be the size of
a deck of cards or a bar of soap.
B. Pasta, rice, and other grains should not be larger
than the size of a tennis ball.
C. Legumes should be about half the size of a tennis
ball.
D. A piece of cheese should be about the size of four dice.
2. Focus on slow, gradual weight loss or weight maintenance in children through regular eating and physical
activity. Skipping meals has not been shown to help
weight loss. Breakfast is particularly important for children and adolescents.
3. Eat a variety of foods with an emphasis on whole grains,
fruits, vegetables, low-fat dairy products, lean meats,
poultry, fish, legumes, nuts, and seeds.
4. Drink water and avoid sweetened caloric beverages.
5. Limit fats, added sugars, and refined foods.
Types of Fad and Popular Diets
Although there are a myriad of fad and popular diets, most

share some common claims or principles that enable them
to be grouped into a few categories.
Behavioral Weight-Loss Plans

A recent example of a behavioral weight-loss plan is the
French Women Dont Get Fat15 diet. This diet makes the
following basic recommendations:
Avoid the extremes of either going hungry or
feelingstuffed.
Avoid obsessing about eating and dieting.
Do not skip meals or induce feelings of deprivation.
Eat nuts as snacks or sprinkled over foods.
Eat the real thing in moderation instead of using
substitutes.
Eat 3 daily meals that include carbohydrates, proteins,
and fats.
Do not replace regular meals with beverages such as
shakes or smoothies.
Eat yogurt with active cultures.
Eat without stuffing yourself or feeling guilty.
Enjoy high-quality bread and chocolate in moderate
amounts.
Enjoy fresh foods and flavorful fruits and vegetables in
season.
172
Enjoy different seasonings by using either fresh or dried

herbs and spices.
Focus on small portions of high-quality foods.
If you relapse, simply get back on track.
Make physical activity an integral part of your day.
Plan what to eat in advance.
Savor meals, slow down, relax, and stop what you are
doing to eat.
Take pleasure in eating and focus on the good not
bad things to eat.
While not exclusive to this diet, behavioral approaches to
weight loss that include portion control, regular physical
activity, self-efficacy and self-regulation, and the monitoring
of eating and weight have been shown to be effective for
successful long-term weight management in adults.12 These
principles are also recommended for children and adolescents.9 Behavioral strategies to help overweight children and
their families include establishing a regular meal and snack
pattern; eating smaller portions at meals and snacks; limiting
second helpings to fresh fruit and non-starchy vegetables;
selecting lower-fat dairy products; eating more foods that are
baked, broiled, grilled, or boiled instead of fried; selecting
healthful snacks that include low-fat protein along with fresh
fruit, vegetables, or whole grain bread and cereals; and when
eating out, selecting more healthful options or splitting larger
servings to share with other family members or peers.8
Food-Focused Weight Loss Plans

One of the oldest and most well-known examples of a foodfocused weight-loss plan is the grapefruit diet. Although
grapefruit is credited with containing a special fat-burning
enzyme, no scientific evidence exists to substantiate that
claim. Weight loss is achieved through limited food selection, reduced caloric intake, and loss of fluid. Complex
carbohydrates and snacks between meals are forbidden,
while most vegetables and all meat and fish are allowed.
Meals comprise eggs, meat or fish, salads, vegetables, skim
milk, tomato juice, and unlimited amounts of black coffee
or tea. Each meal is accompanied by half a grapefruit or half
a cup of unsweetened grapefruit juice. If no behavioral or
lifestyle changes are instituted, it is likely that weight lost
will be regained over time.11 This type of plan would not
be recommended for children or adolescents due to the
potential for nutrient deficiencies, severely restricted caloric
intake, and excessive weight loss.
Reduced Macronutrient Content Plans

The best known of the low-carbohydrate plans may be
the Atkins Diet16 followed by the South Beach Diet.17 The
most recent Atkins diet promotes 5 nutrition rules: a high

consumption of protein and fiber, substantial vitamin and
mineral intake, low amounts of sugar, and the elimination
of trans fats. Although physical activity is encouraged with
the diet plan, the main focus is on high-protein, low-carbohydrate eating. Short-term research studies tracking the
progress of adults on the diet have reported high levels of
satiety, a temporary improvement in blood lipids and glucose
levels, some loss of body fat, and the sparing of muscle
protein.18,19 In a recent 2-year trial, researchers concluded
Mediterranean-style diets that are not necessarily lower
fat but focus on healthier fats and low-carbohydrate diets
may be effective alternatives to low-fat diets. The more positive effects on lipids with the low-carbohydrate diet and on
glycemic control with the Mediterranean-style diet indicate
that diets should be tailored to individual preferences and
health risks.20 Whereas reducing intake of simple sugars
may be appropriate for children and adolescents, lowcarbohydrate plans should not be recommended due to the
potential low intake of fiber, nutrients, and kilocalories to
support growth and development.
The South Beach Diet17 is a variation on the carbohydrate-restricted diet divided into 3 phases. Phase I allows
lean meats, chicken, egg or egg substitutes, fish, olive oil,
vegetables, salads, nuts, and some low-fat milk. Phase II
introduces lower glycemic-index carbohydrates in limited
amounts. Fruits are recommended for lunch or dinner,
but not breakfast. Whole grain bread, sweet potatoes, and
brown or wild rice in modest portions replace white bread,
white potatoes, and white rice. Mashed, steamed cauliflower
replaces mashed potatoes. Sandwiches are replaced by fillings in lettuce wraps. This phase lasts for 2 weeks or until
the desired weight is lost. If overindulgence occurs during
this phase, the recommendation is to return to Phase I for
1 week. Phase III is the lifelong maintenance phase where
the emphasis is on the good carbohydrates and fats with
restriction of the bad carbohydrates and fats. This lowkilocalorie, high-protein, lower-carbohydrate plan allows
healthy fats, high-fiber foods, and selected carbohydrates
in moderate amounts. The evidence suggests that moderate
intake of carbohydrates, proteins, and healthy fats facilitates weight management in adults.10 This plan is adaptable
for use with children particularly in Phase III. However,
the entire family should be committed to focusing on > 5
fruits and vegetables per day, minimizing sweetened beverages, increasing physical activity, and reducing sedentary
behaviors as well as eating breakfast daily, limiting meals
outside the home including at fast-food venues and other
restaurants, eating family meals at least 5 or 6 times per
week, allowing the child to self-regulate his or her meals,

and avoiding overly restrictive behaviors.9
The Pritikin Diet21 and the Dean Ornish Diet22 are the
most well-known of the low-fat diets. Both diets were originally developed for the prevention and treatment of heart
disease and also became popular as weight-loss diets. The
Pritikin plan comprises a total caloric breakdown of 10%
fat, 10% to 15% protein, and 75% to 80% carbohydrates with
35 g of fiber, less than 100 mg of cholesterol, and 600 mg of
sodium. Exercise and stress management are integral to the
plan. Encouraged as a life-long commitment, this restrictive, very low-fat, high-fiber plan requires extensive menu
planning and may be difficult to implement as it entails
careful label reading and product comparison.11 In addition,
there are no studies that have evaluated the use of this diet
in children or adolescents.
Like the Pritikin plan, the Dean Ornish Diet22 allows
only 10% of kilocalories from fat. It also limits sugar and
honey. The restriction on fat and simple sugars prevents
individuals from consuming excess kilocalories and the
high-fiber content contributes to a feeling of fullness. In
addition, the diet promotes whole foods and a high intake
of phytochemicals from vegetarian-based foods and forbids
meat, nuts, seeds, avocados, white flour, white rice, and fried
foods. The diet also advocates a comprehensive lifestyle
change including stress management training, smoking
cessation, meditation, and moderate exercise. There is
strong scientific evidence to support the plans claim to
reverse the risk of heart disease in adults, and the resulting
weight loss is due to the caloric restriction.22 However, there
are no studies that have evaluated the use of this diet in children or adolescents.
Food Group Guides/Exchange Systems

One example of a food group or exchange plan is the Volumetrics Weight-Control Plan.23 Food choices are based on
kilocalorie density. Fat, fiber, protein, and water content
of foods all affect energy or kilocalorie density. By eating
predominantly filling, low-kilocalorie, dense foods, smaller
portions of a few high-kilocalorie, dense foods can be
included and the person will still lose weight due to the
overall kilocalorie restriction. Low-energy, dense foods
include fruits and vegetables, skim milk, broth-based soups,
fat-free salad dressings, pasta, cooked high-fiber grains,
potatoes, legumes, low-fat meats, salads, low-fat soups,
low-fat cheeses, cottage cheese, frozen yogurt, and nonkilocalorie beverages. This diet is complemented by regular
exercise and behavior management, which includes keeping
a food and exercise log, not skipping meals, identifying
173
and managing cues to overeating, stress management, and

making a plan to handle setbacks. There are no forbidden
foods and treats are allowed as long as the predominant
eating style is low-kilocalorie density. There is strong scientific evidence that reducing caloric intake combined with
exercise and behavior management produces weight loss in
adults.12 There are no studies that have evaluated the use of
this diet in children or adolescents however it does contain
many of the elements recommended (eg, focusing on > 5
fruits and vegetables per day, minimizing sweetened beverages, increasing physical activity and reducing sedentary
behaviors as well as eating breakfast daily, limiting meals
outside the home including at fast-food venues and other
restaurants, and allowing the child to self-regulate his or her
meals and avoiding overly restrictive behaviors).9
Food Timing/Meals and Snacks Combinations

A recent example of this category is the Suzanne Somers
Diet.24 According to this diet, eating fat does not cause
weight gain, sugar is more fattening than fat, and carbohydrates are not essential in the diet. According to Ms. Somers,
weight gain is caused by hormonal imbalances and successful
weight loss depends on keeping insulin stable following
digestion. This is achieved by eating certain foods in specific
combinations, cutting carbohydrate intake, and eliminating
sugars and refined carbohydrates, starchy foods, white flour,
caffeine, and funky foods. Meals should not be skipped and
after eating fruit, the dieter should wait 20 minutes before
consuming other foods. There are 2 levels to this diet. Level
1 is the most restrictive and is designed to initiate weight
loss. Level 2 is the maintenance phase and introduces some
protein, fat, and carbohydrate combinations. The rationale
for the diets effectiveness is not substantiated by scientific
data; however weight loss may be achieved due to the many
food restrictions and the total caloric intake of the structured
meals.11 This type of plan would not be recommended for
children or adolescents due to the lack of scientific validity
in the premise, the potential for nutrient deficiencies, and
severely restricted caloric intake.
Commercial Meal/Snack Replacements

One of the largest commercial weight-loss programs is
WeightWatchers.25 WeightWatchers, International, Inc.
has more than 1.5 million members attending one of its
50,000 weekly meetings around the world. WeightWatchers
was one of the first to incorporate a walking program and
emphasize physical activity as a necessary part of dieting.
The POINTS Weight-Loss System assigns a point value to
activities and food which is determined by the number of
174
kilocalories, total fat, and dietary fiber in a defined serving.

Each person is given a daily POINTS target that will lead to
a caloric deficit that translates into 1 to 2 pounds per week
weight loss. A second plan called the Core Plan focuses
on choosing foods with low energy density. By routinely
monitoring hunger cues and with an allowance for periodic
indulgences, the Core Plan has been shown to produce
weight losses equal to the POINTS system. There is strong
evidence to support a lifestyle plan that includes regular
monitoring and support systems using commonly available foods. The emphasis on portion control and low energy
density foods can be translated to many food settings,
and the recipes help teach dieters to prepare dishes lower
in kilocalories. Members do pay a fee for the weight-loss
services including those on the Internet and for WeightWatchers-branded food items.11 WeightWatchers does not
recommend its plan for children and instead discusses childrens needs in terms of 2 goals: ensuring the child grows
and develops normally and helping the child reach a healthy
weight. Weight maintenance strategies are recommended
for children as young as 3 years of age26 and weight gain in
overweight young children should be limited to 2 pounds
for every inch of growth.25 Over age 4, it is recommended
that the child maintain weight until the BMI drops down
into the normal range, below the 85th percentile. 27
Other Plans
Eat Right for Your Type28 was on the New York Times bestseller list and remains a popular diet plan today. The book
provides 4 diets based on the Blood Types O, A, B, and AB.
People with Type O blood are described as hunters, who
need a diet with high protein, lean, chemical-free meat,
poultry, and fish with limited grains, beans, and legumes.
Those with type A blood, the cultivators, need to eat predominantly vegetarian with fish and an emphasis on vegetables,
tofu, grains, beans, legumes, and fruit. Type B, the nomads,
should eat meat (no chicken), dairy, grains, beans, legumes,
vegetables, and fruit. Type AB, the enigma, can eat a mixed
diet in moderation including meat, seafood, dairy, tofu,
beans, legumes, grains, vegetables, and fruit. Each blood
type has a long list of forbidden foods including specific
meats and poultry, seafood, dairy, eggs, oils and fats, nuts
and seeds, beans, legumes, cereals, breads, muffins, grains,
pasta, vegetables, fruit, juices, fluids, spices, condiments,
herbal teas, and other beverages.
Each of the blood-type diets consists of whole, unprocessed foods and all recommend the consumption of
vegetables, which provide fiber, health-promoting nutrients,
and phytochemicals. Physical activity, stress management,
and reducing health risks in the environment are integrated

into each plan. However, there is no scientific validity to the
idea that diet should be defined by blood type. By limiting
specific foods and sometimes food groups, those who follow
the diet can lose weight, but the elimination of specific foods
and groups is based on a premise without adequate scientific
evidence.11 This diet plan is not recommended for children
or adolescents.
Diets Designed for Use with Children

Balanced Macronutrient Low-Kilocalorie Diets
Evidence does suggest that short- and long-term reduced
energy (less than 1200 kcal) may be an effective part of a
multi-component weight-management program in children
6 to 12 years of age.29 In the adolescent population, the use
of reduced energy (not less than 1200 kcal) is generally
effective for short-term weight loss but without continuing
dietary intervention, weight is regained. 29
Traffic Light Diet

The Traffic Light Diet was designed to promote weight
loss, provide adequate kilocalories and nutrients for growth
and development, and be easy to follow. 30 The diet divides
foods into 11 categories, with the foods in each category
then separated into 3 color groups: green, yellow, and red.
These colors correspond to the colors of a traffic light and
signify GO (green), eat as much as you like; approach with
CAUTION (yellow), eat in moderate amounts; and STOP
(red), do not eat. Green foods are those foods that contain
less than 20 kcal per average serving and are found only in
the vegetable and free foods categories. Yellow foods are
foods that are within 20 kcal per average serving of the
caloric value of the average food within that food group.
Yellow foods are items from the 4 basic food groups, which
a child should eat in recommended amounts in order to
obtain adequate nutrition. Red foods are foods that exceed
the caloric value of a yellow food, thereby lowering the
nutrient density of the food. In addition, red foods include
any food that is made to resemble red food, as low-kilocalorie lasagna, which might not be a red food in terms of
kilocalories, but is labeled a red food because a person will
not break the habit of eating lasagna if often substituting
low- for high-kilocalorie lasagna. Participants are limited to
4 red foods per week.
Results showed a clear superiority of the parent and
child intervention including diet and self-monitoring by
both parent and child (Group I) over diet and self-monitoring by the child alone (Group II) and the control group
with no diet or self-monitoring (Group III). After 8months

and 21 months of treatment, the results for children in
the 3 treatment groups were similar. Childrens weight
decreased by 16.6%, 18.6%, and 16.1% in Groups I, II, and
III, respectively. However, after 5 years, the children in
Group I maintained their relative weight change (-13.6%),
while children in Group II were at baseline (+3.3%) and the
children in Group III were heavier (+7%). 31
Food Guide Pyramid

The Food Guide Pyramid was designed as a general guide for
diet and exercise in adults; however it was used as a dietary
component in childhood weight management in one study
of adolescents. The results found that the adolescents using
the Food Guide Pyramid actually gained weight over the
course of the study compared with adolescents who ate a
balanced macronutrient low-kilocalorie diet. 32
Multidisciplinary Behavior Change Programs

Two examples of multidisciplinary behavior change
programs for overweight children and their families are
SHAPEDOWN and Kidshape. Both were developed in
academic medical centers and are offered in community
settings such as hospitals or clinics with interdisciplinary
teams of health professionals. They often include the disciplines of nutrition, exercise physiology, endocrinology,
psychology, family therapy, adolescent medicine, family
medicine, and/or behavioral and developmental pediatrics.
SHAPEDOWN incorporates behavioral techniques
to address underlying issues of the childs or adolescents
weight. Included are problem solving, communication, and
parenting skills (eg, limit setting and nurturing). In addition, cognitive therapy, stress management techniques,
and body image therapies are used. 33 SHAPEDOWN
was shown to produce significant long-term outcomes in a
controlled study of 66 adolescents followed for 15 months
who were randomly assigned to experimental or control
groups. There were no significant differences between
groups in any of the variables studied at the beginning of
the study. The SHAPEDOWN group at the end of the
treatment (3 months) and at 1 year follow-up (15 months)
significantly decreased relative weight and significantly
improved weight-related behavior, self-esteem, depression,
and knowledge. The control group made no significant
improvement in any of these variables except self-esteem. 34
KidShape is a 9-week comprehensive family-based
pediatric weight management program for overweight children and their families. Classes are divided into 3 major
parts including a registered dietitian teaching adults and
175
kids together about healthy eating for weight loss, separate meetings for adults and children with a mental health
professional to learn to change habits and behaviors and
receive group support, and meetings for adults to discuss
their specific questions while kids participate in 30 minutes
of aerobic exercise; during 2 weeks adults and kids exercise together. 35 Program effectiveness was evaluated in
a study of 1,022 families from 24 community-based and
hospital-based sites in Pennsylvania and California from
2004 through 2006. Food records, activity logs, program
questionnaires, and participant BMIs were obtained at the
beginning and the end of the program. Statistically significant improvements in BMI, eating, physical activity, and
self-esteem were reported. 36 A follow-up study looked at a
convenience sample of 86 children at 3 months, 88 children
at 6 months, 30 children at 12 months, and 15 children at 18
to 24 months after completion of the KidShape program.
Graduates of the program maintained a significant change
in BMI up to 24 months after the program and reported
continued improvement in eating and physical activity. 37
Conclusion
There are many diets that will result in weight loss or weight
maintenance in adults and children because they control
and lower caloric intake. The scientific evidence is strong
that a successful weight-loss or weight-maintenance plan
for children and adolescents should include reduced kilocalorie intake though consumption of 5 servings of fruits
and vegetables per day and minimization or elimination
of sugar-sweetened beverages (which are both present in
a balanced macronutrient reduced kilocalorie diet and the
Traffic Light Diet) as well as the behavioral components
(eg, eating breakfast daily, limiting meals outside the home
including at fast-food venues and other restaurants, eating
family meals at least 5 or 6 times per week, allowing the child
to self-regulate his or her meals and avoiding overly restrictive behaviors). Long-term weight management happens
when a plan is individualized to a familys needs and preferences. Kilocalorie- and portion-controlled diets such as the
balanced macronutrient low-calorie diets and the Traffic
Light Diet have been studied over time and may be more
conducive to long-term compliance in families than fat- and
carbohydrate-restricted diets.
Reviewing the various categories of popular and fad diets
indicates that all have strengths and weaknesses and have the
potential to result in weight loss in adults. However, for children and adolescents, these diets have not been studied due
to potential risks for growing children and adolescents from
elimination of key food groups, greater-than-recommended
176
caloric restriction, adverse behavioral patterns of eating, and/

or lack of scientific evidence for the basis of the diets recommendations. The key requirement for dietary treatment of
overweight children and adolescents is to initiate and maintain lifelong healthy eating habits that focus on unhealthy
weight in the short term and foster improved health outcomes
in the long term. Family involvement, and particularly
parental involvement in weight control, weight maintenance,
and weight-loss interventions, is associated with weight loss
in children, and the use of behavior change techniques as an
integral part of the program improves weight outcomes for
both children and parents.38
1. According to the American Dietetic Association

Evidence Analysis Library, which of the following clinical
approaches had positive effects when working with overweight/obese children ages 5 to 12?
A. Multi-component, school-based
B. Behavioral, family-based
C. Multi-component, family-based
D. Diet, family-based
2. The parents of an 8-year-old child have decided to implement changes that will promote healthier lifestyle habits
among all the family members. Which of the following
changes is in line with changes recommended when there
is readiness to change?
A. Adding a salad or vegetable to lunch and dinner meals
B. Substituting the dinner soda with a caffeine free
beverage
C. Limiting family television viewing time to 3 hours
a day
D. Taking the family for a 30-minute walk after dinner
3. Diets that have been studied for use with children or
adolescents include:
A. The Food Guide Pyramid and The (Childrens) Atkins
Plan
B. The Traffic Light Diet and the Food Guide Pyramid
C. The Traffic Light Diet and the Pritikin Plan
D. The Volumetrics and the Exchange Plans
4. Many of the popular/fad diets commonly used by adults
are generally not recommended for children for all of the
following reasons except:
A. Their potential negative risks to a growing child
related to the elimination or decrease of a key food
group
B. Greater than recommended caloric restriction

C. Promotion of an adverse eating pattern
D. Adequate scientific data for use in children for the
diet/plan
References
1. World Health Organization. Diet, Nutrition and the Prevention

of Chronic Diseases. WHO TRS 916. Geneva: WHO/FAO;
2003.
2. Weiss R, Dziurra J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med.
2004;350:23622374.
3. US Department of Agriculture. Continuing Survey of Food
Intakes by Individuals 199496. US Dept. of Agriculture, Agricultural Research Service; 1998.
4. Centers for Disease Control and Prevention. Youth Risk
Behavior SurveillanceUnited States, 2005. Morbidity &
Mortality Weekly Rep. 2006;55(SS-5):1108.
5. Lin BH, Guthrie J, Frazao E. American childrens diets not
making the grade. Food Rev. 2001;24(2):817.
6. Washington, R. Overview of the expert recommendations for
the assessment, prevention, and treatment of child and adolescent overweight and obesity. Obes Manage. 2008;2:20-23.
7. Barlow SE and the Expert Committee. Expert committee
recommendations on the assessment, prevention, and
treatment of child and adolescent overweight and obesity.
Pediatrics. 2007;120 (suppl4):S163S288.
8. Kirk S, Scott BJ, Daniels SR. Pediatric obesity epidemic: treatment options. J Am Diet Assoc. 2005;105:S44S51.
9. Spear BA, Barlow SE, Ervin C, et al. Recommendations for
treatment of child and adolescent overweight and obesity.
Pediatrics. 2007;120;S254S288.
10. Position of the American Dietetic Association: individual-,
family-, school-, and community-based interventions for pediatric overweight. J Am Diet Assoc. 2006;106:925945.
11. Rodriguez J. The Diet Selector. Philadelphia, PA: Running
Press; 2007.
12. American Dietetic Association. Adult Weight Management
Evidence Based Nutrition Practice Guideline. ADA Evidence
Library. 2008. http://www.adaevidencelibrary.com/topic.
cfm?cat=2798. Accessed July 28, 2008.
13. National Weight Control Registry. http://www.nwcr.ws/
Research/default.htm. Accessed May 27, 2008.
14. Evans SA, Parsons AD, Overton JM. Homeostatic responses
to caloric restriction: influence of background metabolic rate.
J Appl Physiol. 2005;99(4):13361342.
15. Guiliano M. French Women Dont Get Fat. New York, NY:
Random House; 2005.
16. Atkins RC. Atkins New Diet Revolution. New York, NY: M.
Evans & Co; 2002.
17. Agatson A. The South Beach Diet. New York, NY: Random
House; 2003.
18. Sharman MJ, Gomez AL, Kraemer WJ, Volek JS. Very
low-carbohydrate and low-fat diets affect fasting lipids and
postprandial lipemia differently in overweight men. J. Nutr.
2004;134:880885.
19. Brehm BJ, Seeley RJ, Daniels SR, et al. A randomized trial comparing a very low carbohydrate diet and a
kilocalorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol
Metab. 2003;88(4):16171623.
20. Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a
low-carbohydrate, Mediterranean, or low-fat diet. N Engl J
Med. 2008;359:229241.
21. Pritikin R. The New Pritikin Program. New York, NY: Simon
& Schuster; 2000.
22. Ornish D. Eat More Weight Less. New York, NY: Harper
Collins; 1993.
23. Rolls B, Barnett RA. The Volumetrics Eating Plan. New York,
NY: Harper Collins; 2005.
24. Somers S. Eat Great, Lose Weight. New York, NY: Random
House; 1999.
25. WeightWatchers. www.weightwatchers.com. Accessed
December 10, 2008.
26. Barlow S, Dietz W. Obesity evaluation and treatment: expert
committee recommendations. Pediatrics. 1998;102(3).
27. Daniels SR, Arnett DK, Eckel RH, et al. Overweight in
children and adolescents: pathophysiology, consequences,
prevention and treatment. Circulation. 2005;111:19992012.
28. DAdamo P, Whitney C. Eat Right for Your Type. New York,
NY: GP Putnam & Sons; 1996.
29. American Dietetic Association. Pediatric Weight Management Evidence Based Nutrition Practice Guidelines. ADA
Evidence Library. www.adaevidenceanalysislibrary.com.
177
30. Epstein LH, Valoski A, Wing RR, McCurley J. Ten-year

follow-up of behavioral, family based treatment for obese children. JAMA. 1990;264:25192523.
31. Epstein LH, Valoski A, Wing RR, McCurley J. Ten-year
outcomes of behavioral family-based treatment for childhood
obesity. Health Psychol. 1994;13:373383.
32. Saelens BE, Sallis WF, Wilfley DE, Patrick K, Cella JA, Buchta,
R. Behavioral weight control for overweight adolescents initiated in primary care. Obes Res. 2002;10:22-32.
33. SHAPEDOWN information and description. http://www.
shapedown.com/SD_About.html. Accessed August 4, 2009.
34. Mellin LM, Slinkard LA, Irwin CE Jr. Adolescent obesity
intervention: validation of the SHAPEDOWN program. J Am
Diet Assoc. 1987;87:333338.
35. KidShape information and description. http://www.
kidshape.com/. Accessed August 7, 2009.
36. Rivard CW, Neufeld N. A comprehensive outcome analysis of
a multi-site, multi state family-based pediatric weight management program. J Am Diet Assoc. 2007;107(8):A-11.
37. Rivard CW, Neufeld N. A long-term comprehensive evaluation of a family based pediatric weight management program
implemented in multiple community based and hospital based
sites. J Am Diet Assoc. 2008;109(9):A-94.
38. McLean N, Griffin L, Toney K, Hardeman W. Family involvement in weight control, weight maintenance and weight-loss
interventions: a systematic review of randomized trials. Int J
Obesity. 2003;27:9871005.
17
Sports Nutrition
Jackie Buell, PhD, RD, LD, ATC, LAT and Diane L. Habash, PhD, RD, LD
Learning Objectives
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Carbohydrates
Protein
Fat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Hydration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Vitamins and Minerals. . . . . . . . . . . . . . . . . . . . . . . . . . . .
Timing to Sport. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Recovery Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Bedtime Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nutrition Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Nutrition Resources. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
181
181
182
182
183
183
183
183
1. Outline the distribution and quantity of macronutrients

in the diet of the child/adolescent athlete, and with
attention to timing around sport.
2. Discuss differences in adult and youth heat dissipation,
and suggest fluid intake to help protect the young
athlete from heat injury and poor performance due to
dehydration.
3. Describe to young athletes how to think about fueling
(food) relative to the timing of sport to maximize muscle
glycogen (pre-event) and encourage muscle growth/
strength (post-event).
4. Provide young athletes and their supporters with educational Web sites and professional organizations to locate
current information and resources.
Introduction
The drive to improve and perfect performance is not new to

athletes of any age. As a result of the desire to excel, athletes
train harder and longer, and may look for dietary supplements or other nutrition advantages. Depending on the
sport, athletes perceive that they can gain a further edge over
competitors by changing their body weight or composition.
Young athletes who are highly motivated in their sport and
performance may not be well educated about the potential
impact of proper nutrition or dietary supplements. Research
suggests they obtain most of their information from teachers
and parents, followed by trainers, friends, and Web sites.1
These athletes are ripe for information in this teaching opportunity for the healthcare professional, and the following
conversation points2 may make the greatest impact:
tips focused on sports performance with some attention
to body image and weight issues since these are likely
significant motivators for the athlete;
178
SPORTS NUTRITION
a positive approach and reinforcement counseling with

goal setting;
inclusion of the family when appropriate;
suggestions for recipes, shopping, and cooking tips
when family is included;
encouragement for the athlete to take responsibility for
food choices, eating behaviors, and some preparation
and packing of foods; and
involvement of the athlete in diet evaluation and subsequent goal determinations and goal evaluations.
The spectrum of young athletes, from child through young
adult, undoubtedly differs from other groupsincluding
those of different ages, less active peers, and adultsin
terms of nutrition needs. Research on this young cohort
spectrum is sparse. Working to evaluate or improve the diet
of a young athlete likely involves using the (non-athletic)
life-stage dietary reference intake (DRI) peer standards
with extrapolation on how exercise, motion inefficiency,
or growth/development might influence the standards.
In addition to the life-stage DRI energy (kilocalories)
and protein recommendations to support growth, young
athletes need to consume enough additional calories to
cover the needs of sport if the desire is to remain in energy
balance and fuel the muscle for growth and performance.
Because more research exists for adult populations, it is
tempting to apply adult recommendations to identify sports
nutrition goals for young individuals. It is wise to remember
that children and youth are different, such as their degree
of motion inefficiency, 3 and this may invalidate the adultto-child extrapolation. Nonetheless, due to a lack of data on
broad groups of child or adolescent athletes, this chapter will
extrapolate from peer and adult cohort recommendations.
Achieving the desired caloric balance is the starting
nutrition consideration and calculation for athletes of all
ages. Athletes with significant caloric imbalances may
demonstrate undesired weight gain or weight loss, and this
is the usual reason for nutrition intervention with a young
athlete. The best starting number is to use the life-stage
energy needs as outlined in the current DRIs according to
activity level.4 Be aware that many child/adolescent athletes
may exceed the very active physical activity category within
the DRI, and consider increasing the estimated calories
accordingly to achieve the desired weight maintenance or
gain goals. This is particularly true with adolescents during
the growth spurt engaged in high-intensity sports (eg,
basketball, soccer, lacrosse, etc.) who usually desire to gain
lean mass. Such athletes may need upwards of 6000 calories
daily to tip the energy balance to favor muscle mass accretion, and these same athletes would lose weight consuming
179
4500 calories daily. Estimating energy needs and monitoring for desirable changes is necessary to confirm the
accuracy of the energy prescription.
Carbohydrates
The most obvious dietary need within the calories allotted
for the young athlete should be carbohydrate to fuel the
muscle. It has long been accepted that carbohydrate is
the primary fuel for human muscle as intensity of activity
increases, and this is well confirmed in adult athletes. It is
suggested that children may be able to use even more carbohydrate as substrate than adults5; thus, fueling the muscle
to at least the adult mass-dependent recommendation is
prudent. In adults, carbohydrate has been demonstrated
to be supportive before, during, and after endurance exercise when enough calories are consumed overall. 6 Ensuring
5 g of carbohydrate per kilogram body weight is the basic
starting point for all athletes.7,8 The need for carbohydrate
increases as the time and intensity of activity increases. The
more serious athlete who practices daily for 1 to 2 hours
might increase this fueling to 7 g/kg up through 11 to 12
g/kg for 3 to 4 hours of intense exercise per day.7,8 It is not
as simple as asking the frequency and length of practices;
to apply these guidelines it is important to gauge the actual
time spent in high-intensity activity. Most sport practice
sessions include periods of inactivity and rest. Including the
downtime of sessions would overestimate fueling needs.
Consuming too much simple carbohydrate may increase
dental cariesespecially when the choices include sticky
and fermentable sourcesand there is a high degree of
variability in how humans tolerate high carbohydrate. It is
prudent to consider the athletes preferences, tolerance, and
performance enhancement when fine-tuning the carbohydrate in the diet.
Awareness of the underlying health benefits of the
source of carbohydrate should also be emphasized in this
cohort as a strategy to encourage lifelong healthy habits.
Carbohydrate in the diet comes mostly from the grains,
fruit, and milk food groups with smaller contributions
from the vegetable group. Overall encouragement to use
whole grains over refined products will improve the fiber
content and nutrient density of the diet and may confer
long-term health benefits. The value of fruit in the diet is
uncontested, and the child or adolescent athlete needs 4
servings of milk/dairy daily for skeletal health. Even though
vegetables provide a minimal contribution, promoting
them for carbohydrate advantages may encourage better
consumption in this young population. Another potential
advantage of encouraging healthier carbohydrate sources
180
in this population is the carryover it might extend to the

athletes family unit. The use of high-carbohydrate recommendations for individuals who do not tolerate carbohydrate
well due to allergies or metabolic issues (such as diabetes)
should be approached with caution and attention to tolerance. In general, there is very little nutrition value in the use
of sugar-sweetened beverages, and the evaluating clinician
should be vigilant for overuse of these products and the
amount of sugar and empty calories they contribute to the
overall diet. The current DRI would accept up to 25% of the
diet in simple sugars.4 An exception where consumption
of sugar-sweetened drinks may actually be desirable and
helpful is the appropriate use of commercial sports drinks
designed to help the athlete maintain hydration and blood
glucose levels with timing around and during practice
orevents.9
Table 17-1 Translation of Gram Recommendations to Foods

Primary Foods
Carbohydrates Grains
(4 kcal/g)
Fruits
Milk
Vegetables
Protein
Meat
(4 kcal/g)
Milk
Beans
Peanut Butter
Fats
(9 kcal/g)
saturated
polyunsaturated
Practical application: Athletes weight 2.2 = kg body weight,
multiply by 5 g/kg to recommend minimal daily carbohydrate intake.

Consuming 0.5 to 1 g/kg within the hour prior to exercise, with a
predilection for liquid sources for those unable to eat right before
practice or events, may better prepare the muscle for high-intensity
work. For events lasting longer than 90 minutes, consumption of a
formulated glucose-electrolyte solution may help maintain blood
glucose and glycogen stores to delay fatigue. Recovery nutrition
would also include 1 g/kg taken immediately after exercise if the next
meal is not immediately available. Note the fraction of the total daily
carbohydrate that is suggested to surround the competition to keep
the muscle fueled. This nutrient timing is novel to many athletes and
is simply a snack-planning issue for desired results. See Table 17-1 to
help translate the grams to actual foods.
Protein
Protein is not typically viewed as energy for sport, but is
critical for growth and development. The amount of protein
needed in the athletes diet remains controversial in all
populations.10,11 The DRI for protein, without consideration
of athletic activity, ranges from the adult recommended
dietary allowance (RDA) of 0.8 g/kg/d to the child adolescent recommendation of 1.05 g/kg/d,4 and this current
protein DRI excludes additional protein possibly available
for muscle fueling or metabolism. It is well-documented
that adult athletes are able to utilize more than these DRIrecommended amounts to support the muscle protein
turnover and energy demands of varying activities.12 In
general, nutrition recommendations for adult athletes
encompass a range of about 1 to 1.7 g/kg/d.13 Bulk-seeking
strength athletes top the recommendation chart at 1.7 g/
kg/d as the extrapolated upper threshold that nitrogen
balance studies have demonstrated can physiologically be
used for lean mass accretion.14 It is intuitive that the upper
threshold for the child or adolescent athlete may be slightly
higher than these adult values due to compounded growth and
monounsaturated
Portion
1 oz equivalent, cup

starchy beans
1 medium fruit
8 oz milk, 6 oz yogurt
1/2 cup cooked, 1 cup raw
1 oz equivalent
8 oz milk, 6 oz yogurt,
1oz cheese
1/2 cup starchy
1 TBSP counts as 1 fat
and 1 protein
1 tsp equivalent of animal
fat (butter, bacon, cream,
shortening, sourcream)
1 tsp plant oil (corn,
safflower, soy)
1 TBSP regular salad
dressing
(2 TBSP reduced fat)
1 tsp mayonnaise
(1TBSP reduced fat)
1 TBSP sunflower seeds
1 tsp oil (canola, olive,
peanut)
2 TBSP or 1/6 medium
avocado, 8 large black
olives or 10 green
6 nuts of most nuts
1 TBSP sesame seeds
Grams
Per
Portion
15
15
12
5
7
8
7
7
5
5
development needs in addition to the usual lean mass goals. It

has become an easy-to-remember recommendation for adult
athletes to consume 1 g/lb (2.2 g/kg) of body weight, and this
would likely be an appropriate recommendation for youth as
well when it is desirable to assure that the athlete has more than
adequate protein for lean mass accretion and muscle metabolism. Phillips article is helpful in understanding the argument
over adequate (required) versus advantageous protein, and
addresses the potential fat loss associated with high-protein
diets as well as the metabolic inefficiency of using protein for
energy.11 It should be emphasized that consuming more than
about 2 g/kg/d is not necessary for muscle growth and may
actually suppress muscle protein synthesis.15 Protein conversations often include debates around the safety of high-protein
diets, but examination of the literature finds little evidence of
liver or kidney function issues in healthy adult athletes.16 There
is no research on high-protein diets in child, preadolescent, or
adolescent athletes, but error on the side of safety where the
ceiling is defined as 2.2 g/kg would be prudent. High-protein
diets will displace carbohydrate from the diet and that is not in
the best interest of performance.
SPORTS NUTRITION
The quality of protein in the athletes diet should also be

assessed. The protein in animal products should contain all the
essential amino acids, and the essential amino acids have been
demonstrated most important to the muscle during and after
exercise.17 Athletes who rely on plant proteins need to ensure
a wide variety and adequate amount of plant protein sources
to provide sufficient essential amino acids consumed over the
course of a day.18 The use of processed protein supplements,
especially among males, is quite popular in the form of wheybased protein powders, shakes, and energy bars. Reminding
the athlete that there is no formal (ie, Food and Drug Administration) oversight for these food products to ensure label
accuracy, purity, and lack of adulteration should be part of the
educational conversation. The protein literature demonstrates
that strength19 and endurance20 athletes can easily consume
this higher level of protein within the habitual diet without
using supplements. It is critical to remember that high-protein
diets will unduly tax the unhealthy liver and kidneys, but is not
proven to be an issue for healthy livers or kidneys in adults.16
Practical application: Athletes body weight in pounds is equal
to grams of total protein for maximal muscle support such as heavy

endurance exercise or muscle-building training phases. Athletes not
engaged in endurance exercise or muscle-building phases of training
would likely fare well with 1.1 to 1.4 g/kg. The growth phase of the
athlete must always be taken into consideration for protein needs
where periods of increased growth place the athlete at a higher protein
need. For best muscle recovery, athletes should strive to consume
about 15 g of good-quality protein (along with adequate carbohydrate)
immediately after exercise to support a positive growth environment.
See Table 17-1 to help translate the grams to actual foods.
Fat
The ideal amount and type of fat in the diet remains as controversial for athletes as it is in general. The current acceptable
macronutrient distribution range from the DRIs calls for 20%
to 35% of the calories be taken as fat. Prudent heart health
recommendations encourage incorporation of mono- and
polyunsaturated fats to displace many of the typical saturated fats in the Western diet.21 When athletes are struggling
to maintain body mass during the competitive season, it is
imperative to encourage calorie-dense foods which typically
include a higher fat proportion. The hormonal milieu in the
body is undoubtedly supported by an adequate fat intake and
calorie balance. Recent literature has addressed fat loading
as a method of supporting fueling for sub-maximal endurance
exercise, but the studies thus far demonstrate a loss of high
gear or reduced ability to reach or sustain high intensity,22 and
there is no research on how these diets may influence body
composition or cardiovascular health (in child athletes).
181
Practical application: Fat should provide 20% to 35% of daily
energy. The total energy recommendation multiplied by 0.2 and 0.35

will yield a range of calories of fat, and dividing the calories by 9
calories per gram will calculate the grams of fat desired. It is standard
to derive the needed protein and carbohydrate first, then ensure the
suggested fat is within this caloric range for the athlete.
Hydration
Ensuring adequate hydration is a safety concern as well as a

performance advantage.2325 Dehydration may contribute to a
decrement in aerobic performance at as little as 2% per body
weight in adults, and may be life-threatening to adults at levels
of 7% to 8% per body weight depending on the athlete.25 Children do not adapt as well as adults to heat extremes or thirst
mechanism, and differ from adults in production of metabolic
heat and sweat capacity26 demonstrating the likely difference
in heat balance at any given intensity or environment. Research
in young male populations by the Bar-Or group demonstrates
reduced aerobic capacity and increased core temperature at 1%
dehydration.26 Additionally, the American Academy of Pediatrics outlines the physiological differences in sweating and
heat dissipation in children and adolescents.23 The research on
youth hydration and physiology convince the sports nutrition
practitioner to ensure hydration awareness in young athletes.
Young athletes have been demonstrated to be less aware of
fluid needs (thirst) and need strong encouragement and guidance from the parent, coach, and/or athletic trainer to consume
fluids as often as the weather and activity dictate.9 Professional
organization guidance statements (Table 17-2) call for ensured
pre-hydration, evaluation of the practice environment (heat,
humidity, available shade, clothing modifications), adequate
fluid breaks every 15 to 20 minutes during activity, and intentional rehydration after activity.
Table 17-2 Professional Organization Guidance Statements on Hydration
American Academy of
Pediatrics (2000)23
Athlete should begin well-hydrated.

During activity, periodic drinking should
be enforced with 5 oz of water or salted
beverage for 88-lb child or 9 oz for
132-lb adolescent (with inferred volume
adjustment for body size differences).
National Athletic Trainers

Association (2000)24
Pre-hydrate 34 hr before with

1720 oz, then 710 oz 1020 minutes
immediately before; consume 710 oz
during activity; post-exercise hydration
aims to provide 125%150% losses.
American College of Sports

Medicine (2007)25
Slowly consume 57 mL/kg at least 4 hr

prior; if urine is concentrated consume
35 mL/kg 2 hours before; event
hydration focuses on individual sweat
rate and tolerance.
182
The recommendation for consumption of plain water

versus commercially prepared sports drinks containing
carbohydrate, sodium, and/or potassium likely depends
on voluntary fluid consumption, the length of the athletic
session, pre-event carbohydrate status, and the sodium loss
of the individual. Athletes who sweat profusely and lose a
lot of sodium are best to also be aware of their sodium needs
alongside fluid needs. Bar-Or has demonstrated the flavor
and sodium content of a drink to be important to voluntary consumption by young athletes. 27,28 Foods helpful
in replacing sodium include soup, pretzels, or liberal salt
shaker use. The use of sugar-flavored milk products has
become common in recovery nutrition,29 and it is notable
that an 8 oz glass of milk typically contains 120 to 170 mg of
sodium (depending on brand and type), which would also
contribute to fluid balance.2931 Shirreffs and Maughan have
nicely demonstrated the value of sodium in the rehydration
plan. 32 When discussing additional sodium intake, advice
should be tailored to the likely salt loss of the athlete.
Heavy sodium loss indicators: Eyes burn when sweat gets in them,
workout shirts appear to have rings of salt around sweat areas, granular
feeling to skin after workout at the side of face where sideburns would be.
If the practitioner is able to estimate energy expenditure, it is

relatively simple to suggest a daily drinking plan to provide
1 mL/kcal of fluid as a starting point. It is common practice
to screen for dehydration risks by weighing athletes before
and after practice, and to encourage consumption of 150%
of the fluids (weight) lost (approximately 3 cups or 24 oz per
pound lost). Evaluation of urine osmolality, refractometry,
and bioelectrical impedance are among the current trends
for evaluation of hydration status, 33 but likely the most practical to teach is evaluation of urine color. For athletes with
significant sweat losses and muscle-cramping issues, it is
helpful to calculate a personalized sweat rate to formulate
the strongest hydration plan.
Practical application: Hydration should be a continuous process
throughout the athletes day, but routine hydration with respect to

exercise should also be habit. Athletes should ensure pre-hydration
with 5 to 7 mL/kg of fluids at least 4 hours before events; this leaves
enough time for the body and kidneys to produce urine for evaluation
of hydration status. If urine is still concentrated (color and smell),
consume an additional 3 to 5 mL/kg 2 hours prior. Fluid breaks every
15 to 20 minutes during activity should provide about 5 oz for the
smaller child (88 lb) and 9 oz for the adolescent (132 lb). Rehydration
is best achieved with consuming fluid equal to 150% of the weight lost
during activity. This means drinking about 24 oz of fluid per pound lost.
Co-ingestion of sodium will help replenish lost sodium, which is critical
to maintaining hydration.
Overdrinking can lead to hyponatremia, but this is usually

limited to smaller athletes who drink large amounts of
water (hypotonic) over a period of hours while engaged
in endurance exercise. Use of a sports drink for activities
lasting longer than 60 to 90 minutes may help avoid this
life-threatening condition. Teaching children and adolescents to drink an appropriate amount is an important task
for safe participation and good health.
Vitamins and Minerals
Athletes or their parents often ask if a vitamin-mineral

supplement is necessary or protective. Athletes consuming
at least 1800 calories per day within a diet that includes a
wide variety of foods from all food groups do not likely need
to supplement the vitamins and minerals. Athletes who
restrict food choices like red meat (iron), milk (calcium),
and carbohydrates (B vitamins) from the diet may benefit
from supplementation. The inclusion of a generalized multivitamin where the label reflects 100% to 200% Daily Value
for most contained nutrients is likely harmless when the
supplement is a known and reputable brand. There is no
evidence that consuming supplements containing large
amounts of antioxidants protects the body. In fact, there
is evidence in adults that this sort of therapy may actually
oppose the goals of the supplement. 34 In general, a one-aday style vitamin-mineral supplement should not be seen
as a substitution for a balanced and variety-filled diet, but
may be a low-risk answer for parents or athletes worried
about dietary adequacy.
Timing to Sport
A common pattern seen in some young athletes is to eat

sparse calories early in the day with the bulk of energy
consumption later in the day. It is a positive health habit
to distribute energy consumption throughout the day, and
this habit has the added benefit for athletes of providing the
muscle with more consistent access to storage fuels as well.
Athletes who wait to eat most of their calories late in the
day are usually so hungry that it is hard to make positive
decisions about which foods to eat and how much should be
consumed. It may be better for hunger levels, metabolism,
body composition, and muscle fueling to eat multiple small
meals throughout the day (every 2 to 4 hours) to achieve
energy balance instead of imploding the body with too
many calories late in the day.
An athlete cannot underestimate the importance of
breakfast on a daily basis. On non-competition days, a
mixed breakfast supplying ample carbohydrate and about
25% of the daily calories will refuel the muscle and liver
SPORTS NUTRITION
from the overnight fast and should be consumed before

practices. On competition days when breakfast is the
pre-event meal, the athlete should consider that the carbohydrate will pre-fuel the muscle while the protein and fat
of the meal will determine the satiety during competition. Finding the timing of consumption and mixture of
foods to promote high-intensity competition along with a
comfortable gastrointestinal system is the task to practice
and master during non-competition sessions. Most athletes
do well with a fairly high carbohydrate meal (at least 1 g/
kg body weight (BW)) and about 3 oz of lean protein with
1 or 2 fat portions (Table 17-3) 2 to 3 hours (no more than
about 4 hours) before competition. Some athletes perform
well when they further top off the muscle carbohydrate by
consuming 40 to 60 g of carbohydrate within 1 hour of
competition. An athlete needs to experiment with various
foods to know what works best; some athletes will prefer
fluid sources of carbohydrate for gut comfort this close to
intense exercise. Consumption of high-fiber, high-fat, or
high-sugar foods can cause abdominal distress in some
individuals resulting in abdominal cramping, gas, and/or
diarrhea. Table 17-4 provides examples of fueling ideas for
the day of the competition.
Recovery Nutrition
Recovery nutrition has become one of the hottest recommendation topics in recent years of sports nutrition.17,35
Consuming an appropriate recovery snack immediately
after exercise should become habit for athletes who do not
have at least 24 hours to recover the muscle nutritionally.
A recovery snack should be a priority for multiple-event
athletes or when the daily routine demands multiple practices close together. An appropriate recovery snack for
adult athletes suggests 40 to 60 g of carbohydrate and 15 to
20g of good-quality protein to provide the essential amino
acids. The carbohydrate for recovery has demonstrated a
more rapid period of glycogen restoration, and the additional calories in protein stimulate the muscle to set up an
anabolic environment.15,36 The current research supports
essential amino acids as the stimulus for this anabolic
change and leucine (a branched-chain essential amino acid)
is likely important to the response. 37
183
fat any differently than other eating throughout the day

assuming the calorie consumption matches calories needed.
It is the overall calorie balance that is important. As long
as the nighttime snack is within the daily calorie needs of
the individual, the timing is not important. It is common
to suggest the use of dairy products (eg, low-fat milk or
yogurt) late in the evening for the possible positive influence on fat metabolism38 and continued anabolic support to
the muscle.
Nutrition Challenges
Common nutrition-related issues that young athletes may

experience are listed in Table 17-5. Young athletes are often
serious about their bodies and sports, and a healthcare
practitioners respect and guidance can help them through
nutrition-related challenges.
Nutrition Resources
Many resources are available that can provide greater depth

across the field of sports nutrition. In a field that is subject to
popular opinion and media-sensitized measures of performance, the information given to athletes, caregivers, and
coaches should be grounded in and supported by evidencebased science. See Table 17-6 for resources suggested by the
authors. (All Web sites accessed January 20, 2009.)
Bedtime Nutrition
Bedtime nutrition is another recommendation that serious

athletes should consider. Concerns about eating after a
certain time of the evening and if a protein supplement
should be taken are commonplace in adult populations.
Bedtime snacking does not necessarily convert to body
184
Table 17-3 Examples of Meals and Snacks Used With Timing Around Sport
Description
Pre-game
Target is high carbohydrate within mixed diet
(34 hr prior)
2 cups whole wheat pasta with 1 cup sauce and 3 oz lean meat, 1
Pasta meal
cup of salad, 1 piece garlic bread, and 1 cup 2% milk
Fast food
Wendys grilled chicken with baked potato with broccoli cheesesauce
Larger athletes might add a small Frosty to above to bring total to
Pre-event
Target is well-tolerated carbohydrates
(2060 min prior)
12 oz sweet tea with 1 oz animal crackers
20 oz sports drink
2 oz pretzels with water
During event
Sports drink only warranted if longer than 90 minutes of intense
(48 oz every
activity (otherwise water is great)
1520 min)
Per 8 oz
Gatorade G
Gatorade G2 series
Powerade
Powerade Zero
Accelerade (incl 4 g protein)
Recovery
(within 45 min)
Target is intentional mix of carbohydrate and good-quality protein
kcal
g CHO
g pro
g fat
797
120
54
18
780
1080
117
143
44
59
16
31
kcal
g CHO
g pro
g fat
231
160
200
48
40
47
2
0
6
4
0
0
kcal
g CHO
Na (mg)
K (mg)
50
25
60
0
80
kcal
Target
200300
14
7
17
0
15
g CHO
Target
4060
110
110
55
55
120
g pro
Target
1015
30
30
30
33
15
g fat
1 cup ready-to-eat cereal (eg, multi-grain Cheerios) with 1 cup

250
50
skim milk and 1 medium banana
Peanut butter (1 TBSP) and jelly (1 TBSP) sandwich on 2 slices
368
52
whole wheat bread with 1 cup milk
Turkey sandwich with 2 slices bread and about 2 oz turkey with 12
300
50
oz sports drink
1 cup lowfat chocolate milk with 1 oz pretzels
259
50
1 mozzarella string cheese stick, 1 cup green grapes, 1 medium
215
44
orange with water
PowerBar and water
247
48
kcal = calories, g CHO = grams of carbohydrate, g pro = grams of protein, g fat = grams fat, Na = sodium, K = potassium
Target low
11
1.5
20
10
18
11
2.5
10
10
Table 17-4 Fueling Ideas for the Day of Competition

Timing
Nutrition Goals
Example (always relative to athlete size and energy needs)
Breakfast at least 34 hr from event
Balanced meal heavy on

carbohydrate
High carbohydrate
Liquid carbohydrate 3060 g/hr
Whole grain or fruit pancakes with syrup, 8 oz milk, side of fresh fruit,
2oz lean meat, 16 oz water after meal will begin hydration on right path
12 oz sports drink, piece of fruit or pretzels; if urine is strong, morewater
48 oz of sports drink every 1520 minutes
Carbohydrate and good-quality

protein (3:1 or 4:1 ratio of
carbohydrate to protein)
Carbohydrate with little protein
and little fat
8 oz chocolate milk with peanut butter (limit to 1 TBSP)

and jelly sandwich on whole grain bread
Pre-event snack 12 hr before

During event if high intensity lasts
longer than 90 minutes
After event within 45 minutes if
multiple events (Recovery snack)
Snacks between meals not as close
to event
Meals not close to time of event
Balanced with carbohydrate,

adequate protein, and fat
Trail mix with 2 TBSP dried cranberries or raisins, 1 tsp peanuts,

and 1 oz mozzarella cheese stick
-ORTurkey or ham sandwich with 2 oz meat, 2 slices whole grain bread,
tomato/lettuce as tolerated, with glass of water
Plate surface divided as 1/4 meat, 1/4 whole grain, 1/2 brightly colored
fruits and vegetables with glass of milk
SPORTS NUTRITION
185
Table 17-5 Common Issues for Athlete Nutrition

Issue
Possible Indicators and Concerns
Solutions
Limited nutrition
knowledge
related to sports
performance
Cannot describe desirable pre-game meals or

recovery eating
Has
no hydration plan
Provide reputable Web sites

Suggest easy-to-read books
Stress planning and organization for having foods and beverages available
Practice having all the foods and beverages needed for sport
Note timing of events and fuel/hydrate accordingly
Note travel impact on eating and hydrating opportunities and on performance
Identify community partners (eg, a Certified Specialist in Sports Dietetics(CSSD))
Picky eater
Low variety in habitual diet

Does

not like entire food groups
Educate on advantages of diet with varied food groups to include performance

advantages of carbohydrate foods
Encourage athlete to bring foods that she or he likes so the athlete is at
leastfueling
Encourage practice for fuel/hydration
Eating on a budget Eating 1 or 2 meals per day

or low income
Eating little meat and lots of bread and pasta
Discuss planning strategies for foods typically afforded

Buy in bulk and separate/store in pantry/freezer
Help athlete understand correct amount of protein to prevent
undernutritionoroverspending
Cook in bulk and freeze for later access
Buy generic for most foods
Buy fruits and vegetables in season
Ensure family is not eligible for federal food assistance program
Male athlete
with high growth
expectations
Questions about how much protein needed or what

supplements will work
overt in desire to be bigger
Usually

Stress that normal physical activity and adequate nutrition optimize growth
Educate that growth has genetic and environmental components
Consider that intense exercise may be associated with delayed growth
Check and reinforce appropriate athlete vs parent expectations of lean
massaccretion; use growth charts
Weight control
expectations
(typically females)
Secondary sex characteristics not desirable to

somefemale athletes
Underfueling to avoid gaining weight; poor
performanceand health detriments may result
Poor

self-esteem and/or self-image
Overt comments about not liking body parts
(eg,bellyor thighs)
Unhealthy control methods (eg, diet pills,
smoking,vomiting, laxatives, or starvation)
Explain puberty progression and risks of stifling puberty

When in doubt, suggest evaluation by psychological professional and dietitian
Early intervention may avoid Female Athlete Triad outcome (see below)
Vegetarianism
Often occurs in young females who want to lose

weight
Can be due to perceptions that meat has too much
fat and calories
Educate about optimal protein-alternative foods (dairy, legumes) or how to

combine foods to ensure complete proteins
Alert athlete to consume adequate nutrients such as iron, calcium, and zinc
Inquire about why this lifestyle is appealing to the athlete to ensure answer
isconsistent with balanced decision
The Female Athlete A combination of 3 disorders (or spectrums) that

includes low energy availability (ie, expend more
Triad
calories than consume), amenorrhea, and low
bonedensity
May be related to disordered eating, poor body
image, unrealistic body weight goals, and weightloss expectations
Often undetectable or not considered until stress
fracture occurs
Exists in all sports but especially in those with
weight or appearance requirements
Critical read for this area of evaluation is ACSM
Position Statement39
Encourage eating a diet with a wide variety of foods that will fuel the muscle
foroptimal performance
When in doubt, suggest evaluation by psychological professional and dietitian
Intervene early to increase chances for recovery
Use of
May be related to athletes desire to excel but
oftennot supported by evidence
performanceenhancing
Often used by athlete as a substitute for
supplements (legal adequatenutrition
and illegal)
Could be related to peer pressure and media
influences
There are no pediatric evidence-based clinical trials on the use or the adverse
effects of some supplements (herbals, ergogenic aids, etc.)
Recent review of supplement studies shows anabolic steroid use ranges from 1%
to 11.1% of adolescents surveyed and creatine use in reviewed studies ranged
from5.6% to 30%40
Supplements sought frequently for improving speed, decreasing weight, or
increasing size/bulk of athlete
Use of one multivitamin/mineral supplement daily has been suggested for all
individuals, not just athletes
Seek advice of certified sports dietitian (CSSD)
186
Table 17-6 Additional Exercise and Nutrition Resources

Topic
Resources
To find a Registered Dietitian (RD)

certified to work with athletes;
known as a Certified Specialist in
Sports Dietetics (CSSD)
General Sports Nutrition Information
American Dietetic Association (ADA) list of RDs

www.eatright.org
ADA Dietetic Practice Group for Sports, Cardiovascular, and Wellness Nutritionists (SCAN) list of CSSD RDs
www.scandpg.org
Position Papers:
American Dietetic Association41
www.eatright.org
American College of Sports Medicine25,41
www.acsm.org
National Athletic Trainers Association
www.nata.org/statements/
Books/Web sites:
Sports Nutrition; A Practice Manual for Professionals. 4th ed. Chicago, IL: American Dietetic Association; 2006
http://www.scandpg.org/cssd_promotion.php
Gatorade Sports Science Institute*
www.gssiweb.com
American College of Sports Medicine
www.acsm.org
NISMAT Exercise Physiology Corner*
www.nismat.org/physcor/index.html
Australian Institute of Sport*
www.ausport.gov.au/ais/nutrition
Gatorade Sports Science Institute*
www.gssiweb.com
Drug Free Sport*
www.drugfreesport.com/
IBIDS database
ods.od.nih.gov/Health_INformation/IBIDS.aspx
Natural Medicines Database
www.naturaldatabase.com
Consumer Labs third party quality testing
www.ConsumerLabs.com
*Many of the above Web sites have companion athlete links or at an appropriate level for athletes.
General Exercise Physiology

Information
Supplement Information
Digital Athlete Resources
1. How much carbohydrate as a minimum should the

young athlete include in the daily diet?
A. This is not important. It is the overall calories that
count.
B. 5 g/kg body weight
C. 15 g/kg body weight
D. Athletes only need about 35% of their diet as
carbohydrate.
2. When, relative to a strength-training session, is the
timing and amount of protein intake the most important for a young athlete trying to gain lean mass?
A. Protein should be the primary focus.
B. Carbohydrate only; no protein needed
C. 3:1 or 4:1 ratio of carbohydrate to protein
D. Athletes should not eat within 30 to 45 minutes of
exercise.
3. How much fluid should an athlete who requires 3500

kcal/d be aiming to consume?
A. 3.5 L along with evaluation of urine color for
hydration
B. Athletes should let thirst be their guide.
C. Athletes need 8 to 10 glasses of water per day.
D. All athletes should consume an electrolyte sports
drink during activities in the heat.
4. Which of the following are included spectrums of the
female athlete triad?
A. Amenorrhea or delayed menarche
B. Poor bone mineral acquisition compared with age
cohort
C. Low energy availability
D. All of the above
SPORTS NUTRITION
References
1. Hoffman JR, Faigenbaum AD, Ratamess NA, Ross R,

Kang J, Tenenbaum G. Nutritional supplementation and
anabolic steroid use in adolescents. Med Sci Sports Exerc.
2007;40(1):1524.
2. Andrew K. Practice tips (in children and young athletes). In:
L. Burke, V. Deakin, eds. Clinical Sports Nutrition. 3rd ed.
Sydney: McGraw Hill; 2006:620.
3. Walker JL. The energy cost of horizontal walking and running
in adolescents. Med Sci Sports Exerc. 1999;31(2):311.
Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty
Acids, Cholesterol, Protein, and Amino Acids (Macronutrients).
Washington, DC: National Academy Press; 2005:12.
5. Bass S, Inge K. Nutrition for special populations: children
and young athletes. In: L. Burke, V. Deakin, ed. Clinical Sports
Nutrition. 3rd ed. Sydney: McGraw Hill; 2006:605.
6. Jacobs K, Sherman W. The efficacy of carbohydrate supplementation and chronic high carbohydrate diets for improving
endurance performance. Int J Sports Nutr. 1999;9:92115.
7. Burke L, Cox G, Cummings N, Desbrow B. Guidelines for
daily carbohydrate intake: Do athletes achieve them? Sports
Med. 2001;31:267299.
8. Dunford M. Sports Nutrition: A Practice Manual for Professionals. 4th ed. Chicago, IL: American Dietetic Association;
2006:547.
9. Ali A, Williams C, Nicholas CW, Foskett A. The influence
of carbohydrate-electrolyte ingestion on soccer skill performance. Med Sci Sports Exerc. 2007;39(11):19691976.
10. Tipton KD, Witard OC. Protein requirements and
recommendations for athletes: relevance of ivory tower
arguments for practical recommendations. Clin Sports Med.
2007;26(1):1736.
11. Phillips SM. Dietary protein for athletes: from requirements to metabolic advantage. Appl Physiol Nutr Metab.
2006;31(6):647654.
12. Lemon PW. Beyond the zone: protein needs of active individuals. J Am Coll Nutr. 2000;19(5):513S521S.
13. Tarnopolsky MA. Protein and amino acid needs for training
and bulking up. In: L. Burke, V. Deakin, eds. Clinical Sports
Nutrition. 3rd ed. Sydney: McGraw Hill; 2006:95.
14. Lemon PW. Effects of exercise on dietary protein requirements. Int J Sport Nutr. 1998;8(4):426447.
15. Bolster DR, Pikosky MA, Gaine PC, et al. Dietary protein
intake impacts human skeletal muscle protein fractional
synthetic rates after endurance exercise. Am J Physiol Endocrinol Metab. 2005;289(4):E678E683.
16. Martin WF, Cerundolo LH, Pikosky MA, et al. Effects of
dietary protein intake on indexes of hydration. J Am Diet
Assoc. 2006;106(4):587589.
17. Borsheim E, Tipton KD, Wolf SE, Wolfe RR. Essential amino
acids and muscle protein recovery from resistance exercise.
Am J Physiol Endocrinol Metab. 2002;283(4):E648E657.
18. American Dietetic Association, Dietitians of Canada. Position
of the American Dietetic Association and Dietitians of Canada:
vegetarian diets. J Am Diet Assoc. 2003;103(6):748765.
187
19. Phillips SM. Protein requirements and supplementation in

strength sports. Nutrition. 2004;20(7-8):689695.
20. Tarnopolsky M. Protein requirements for endurance athletes.
Nutrition. 2004;20(7-8):662668.
21. Position of the American Dietetic Association and Dietitians of Canada: Dietary fatty acids. J Am Diet Assoc.
2007;107(9):15991611.
22. Stellingwerff T, Spriet LL, Watt MJ, et al. Decreased PDH
activation and glycogenolysis during exercise following fat
adaptation with carbohydrate restoration. Am J Physiol Endocrinol Metab. 2006;290(2):380388.
23. American Academy of Pediatrics: Climatic heat stress and the
exercising child and adolescent. Committee on Sports Medicine and Fitness. Pediatrics. 2000;106(1):158159.
24. Casa DJ, Armstrong LE, Hillman SK, et al. National Athletic
Trainers Association position statement: Fluid replacement
for athletes. J Athl Train. 2000;35(2):212.
25. American College of Sports Medicine. American College of
Sports Medicine position stand. Exercise and fluid replacement. Med & Sci Sports & Exerc. 2007;39(2):377390.
26. Bar-Or O. Temperature regulation during exercise in children
and adolescents. In: C. Gisolfi, DR Lamb, eds. Perspectives in
Exercise Sciences and Sports Medicine. Indianapolis, IN: Benchmark Press; 1989:335367.
27. Wilk B, Bar-Or O. Effect of drink flavor and NaCl on voluntary drinking and hydration in boys exercising in the heat. J
Appl Physiol. 1996;80(4):11121117.
28. Wilk B, Kriemler S, Keller H, Bar-Or O. Consistency in
preventing voluntary dehydration in boys who drink a flavored
carbohydrate-NaCl beverage during exercise in the heat. Int J
Sport Nutr. 1998;8(1):19.
29. Karp JR, Johnston JD, Tecklenburg S, Mickleborough TD,
Fly AD, Stager JM. Chocolate milk as a post-exercise recovery
aid. Int J Sport Nutr Exerc Metab. 2006;16(1):7891.
30. Bauman DE, Mather IH, Wall RJ, Lock AL. Major advances
associated with the biosynthesis of milk. J Dairy Sci.
2006;89(4):12351243.
31. Roy BD. Milk: The new sports drink? A review. J Int Soc Sports
Nutr. 2008;5:15.
32. Merson SJ, Maughan RJ, Shirreffs SM. Rehydration with
drinks differing in sodium concentration and recovery from
moderate exercise-induced hypohydration in man. Eur J Appl
Physiol. 2008;103(5):585594.
33. Stuempfle KJ, Drury DG. Comparison of 3 methods to assess
urine specific gravity in collegiate wrestlers. J Athl Train.
2003;38(4):315319.
34. Knez WL, Jenkins DG, Coombes JS. Oxidative stress in
half and full Ironman triathletes. Med Sci Sports Exerc.
2007;39:283288.
35. Baty JJ, Hwang H, Ding Z, et al. The effect of a carbohydrate
and protein supplement on resistance exercise performance,
hormonal response, and muscle damage. J Strength Cond Res.
2007;21(2):321329.
36. Ivy JL, Goforth HWJ, Damon BM, McCauley TR, Parsons
EC, Price TB. Early postexercise muscle glycogen recovery
is enhanced with a carbohydrate-protein supplement. J Appl
Physiol. 2002;93(4):13371344.
188
37. Tipton K, Sharp C. The response of intracellular signaling and

muscle-protein metabolism to nutrition and exercise. Eur J
Sport Sci. 2005;5(3):107121.
38. Zemel MB, Donnelly JE, Smith BK, et al. Effects of dairy
intake on weight maintenance. Nutr & Metab. 2008;5:28.
39. Nattiv A, Loucks AB, Manore MM, et al. American College of
Sports Medicine position stand. The female athlete triad. Med
Sci Sports Exerc. 2007;39(10):18671882.
40. Castillo EM, Comstock RD. Prevalence of use of performanceenhancing substances among United States adolescents.
Pediatr Clin N Am. 2007;54:663675.
41. American Dietetic Association; Dietitians of Canada; American College of Sports Medicine, Rodriguez NR, Di Marco
NM, Langley S. American College of Sports Medicine position stand. Nutrition and athletic performance. Med Sci Sports
Exerc. 2009;41(3):709731.
PART III
DISEASE STATES AND

NUTRITION
18. Developmental Delay. . . . . . . . . . . . . . . . . . . . . . . 191

27. Intestinal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . 311

19. Eating Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . 204

Betsy Hjelmgren, MS, RD, LDN, CSP
28. Pulmonary Disorders . . . . . . . . . . . . . . . . . . . . . . . 323

20. Food Allergies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213

Michael B. Levy, MD
21.Diabetes Mellitus and
Other Endocrine Disorders. . . . . . . . . . . . . . . . . . . 226
Diane Olson, RD, CNSD, CSP, LD
22. Inborn Errors of Metabolism . . . . . . . . . . . . . . . . . 232
Sandy van Calcar, PhD, RD, CD
23. Cardiac Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . 247
Anupama Chawla, DCH(UK), MD, CNSP
24. Renal Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
25. Gastrointestinal Disease. . . . . . . . . . . . . . . . . . . . 283
Donald George, MD
26. Hepatic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . 302
Renee A Wieman, RD, CSP, LD, CNSD
29. Organ Transplantation. . . . . . . . . . . . . . . . . . . . . . 337

Beth Lytle, RD, LDN
30.Oncology, Hematopoietic Transplant,
andSurvivorship. . . . . . . . . . . . . . . . . . . . . . . . . . . 349
Vinod K. Prasad, MD, MRCP (London)
David Henry, MS, BCOP
Susan Rheingold, MD
31. Trauma and Burns . . . . . . . . . . . . . . . . . . . . . . . . . 378
32. Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
18
Developmental Delay
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Nutrition Problems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
Undernutrition, Growth Failure, and Overweight
Micronutrient Deficiencies
Osteopenia
Nutrition Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194

Medical History
Growth and Anthropometric Measurements
Physical Examination
Meal Observation
Diagnostic Studies
Nutrition Support. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196

Nutrition Requirements
Positioning and Oral Feeding
Behavioral Modification
Enteral Tube Feeding
Feeding Intolerance
Ethical Considerations
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Learning Objectives
1. Identify the nutrition problems frequently diagnosed in

children with developmental delay.
2. Assess the nutrition status of the child with developmental delay.
3. Understand the approach to provide oral and enteral
support to the child with developmental delay.
Introduction
Undernutrition, growth failure, overweight, micronutrient

deficiencies, and osteopenia are nutrition comorbidities
that affect the child with developmental delay regardless
of the specific neurological disability. The epidemiology,
pathogenesis, assessment, and treatment of these disorders
in neurologically impaired children have been reviewed
elsewhere.13 This chapter examines further the principles
and practices associated with the nutrition management of
children with developmental disabilities that are characterized primarily by gross and fine motor dysfunction and with
or without cognitive or speech delay.
Early involvement by a multidisciplinary team of
physicians, nurses, dietitians, feeding therapists, psychologists, and social workers is essential to prevent the adverse
outcomes associated with poor nutrition status in the child
with developmental delay. Undernutrition and overweight
lead to more frequent hospital admissions and physician
visits and diminished participation in home and school
activities.4 Adequate nutrition support may restore linear
and ponderal growth, improve health and quality of life,
reduce the frequency of hospitalization, enhance neurological function and developmental progress, support wound
healing and peripheral circulation, decrease the frequency
of aspiration, and ameliorate gastroesophageal reflux in
191
192
these children. 59 Careful evaluation and monitoring of

children with severe disabilities is warranted because of the
risk of nutrition-related morbidity and mortality.10
Nutrition Problems
Undernutrition, Growth Failure, and Overweight
Prevalence
The true prevalence of undernutrition, growth failure,
and overweight in children with developmental delay is
unknown. Estimates are limited to disorders such as cerebral
palsy, myelodysplasia, spina bifida, spinal cord injury, and
Rett syndrome.1120 Undernutrition, based on weight-forheight and triceps skinfold thickness, has been documented
in 29% to 46%, linear stunting in 23%, and overweight in
8% to 40% of individuals with these disorders. The prevalence of undernutrition increases with increasing age,
lower intelligence, and increased severity of neurological
impairment.17
Pathophysiology
Non-nutrition factors including the type and severity of
neurological disability, ambulatory status, and cognitive ability contribute to growth failure in children with
developmental delay.21 Children with seizures or spastic
quadriplegia and those who are non-ambulatory have lower
height z scores than children who lack these disabilities.18
Children with spastic hemiplegia have smaller measures
of breadth and length on the affected side, suggesting that
neurological impairment influences growth.21 Inherent
genetic factors may be associated with permanent linear
stunting.22 Height-for-age z scores may decrease with
advancing age independently of weight-for-age z scores in
individuals affected with scoliosis or contractures.18
Nutrition factors contribute to growth failure in
children with developmental delay based on correlations
between height and weight z score deficits.23 Nutrition
status explains 10% to 15% of the variability of linear
growth in children with cerebral palsy. 23 Nutrition status
has a stronger effect on linear growth in younger than in
older children, attesting to the irreversible effects of longterm undernutrition on growth. Inappropriate dietary
intake relative to nutrient needs, oral motor dysfunction,
increased nutrient losses, and altered energy expenditure
may account for the poor nutrition status of children with
developmental delay.
Inappropriate dietary intake
Inappropriate dietary energy intake is the primary cause of

undernutrition, growth failure, and overweight in the neurologically impaired child.2428 Children with cerebral palsy
and myelomeningocele consume less dietary energy and
nutrients than unaffected children. They may be unable to
communicate hunger, food preferences, and satiety, leaving
caretakers responsible for regulating their dietary intake.
Caretakers often overestimate the childs energy intake and
underestimate the time spent feeding the child.26,29 Because
the task of feeding may be difficult and time-consuming,
the amount of food provided may be insufficient to meet
the childs growth needs. When adequate dietary energy is
provided by enteral tube feedings, nutritional therapy leads
to weight gain and linear growth.22 Careful monitoring may
be necessary to avoid overfeeding, and consequently overweight, in these children. 30
Oral motor dysfunction
Feeding problems associated with oral motor dysfunction

occur frequently in children with developmental delay.12,29
In one study, 90% of preschool children with cerebral palsy
had oral motor dysfunction during the first year of life; 57%
had sucking problems, 38% had swallowing problems, and
80% were fed non-orally at least once as infants. Severe
feeding difficulties preceded the diagnosis of cerebral palsy
in as much as 60% of patients. Poor suck, difficulty breastfeeding, problems with the introduction of solid foods,
difficulty drinking liquids, difficulty biting or chewing
solids, and coughing and choking with meals were common
parental complaints.
Dependency on a caretaker and the inefficiency of the
feeding process, including the amount of food spilled and
the time required for feeding, influence the childs nutrition
status.12,16,29 Children with cerebral palsy take 2 to 12 times
longer to swallow pureed food and up to 15 times longer
to chew and swallow solids than unaffected children. 31
In one report, 28% of parents required more than 3 hours
daily to feed their child and 3% required more than 6 hours
daily. 32 Longer mealtimes may not compensate for feeding
inefficiency. 31 Parents may perceive mealtime as a stressful,
unpleasant experience. 32 Parents perceptions of mealtime
are important because 60% of children with cerebral palsy
are totally dependent on a caretaker for feeding.29
Oral motor dysfunction usually correlates with the
severity of motor impairment.16,3335 Children may present
with inadequate lip closure, drooling, and persistent tongue
thrust, resulting in food loss through spillage. Bolus formation may be difficult to accomplish because of abnormal
DEVELOPMENTAL DELAY
oral sensation, uncoordinated or involuntary tongue movements, or delayed development of age-appropriate oral motor
skills. Initiation of the swallowing reflex may be delayed,
resulting in food accumulation in the vallecula or pyriform
sinuses and subsequent aspiration. Neurologically impaired
children with these findings have lower height-, weight-, and
weight-for-height z scores, body fat, and arm muscle area
than unaffected children.16,34,35 Children with more severe
impairment who are unable to lift their heads or feed themselves have a higher risk of aspiration. 36 Early, persistent,
and severe feeding difficulties are markers of subsequent
poor health, nutrition status, and growth and identify children who may benefit from gastrostomy feedings. 35,37
Increased nutrient losses
Children with developmental delay who feed themselves

may have poor hand-to-mouth coordination, leading to
loss of nutrients as a result of excessive spillage. The use of
adaptive utensils may enhance movement performance and
minimize food spillage in these individuals. 38 Gastroesophageal reflux, which affects 75% of developmentally impaired
children, and delayed gastric emptying may result in a loss
of nutrients because of frequent emesis.
Abnormal energy expenditure
Children with spastic quadriplegic cerebral palsy and

myelodysplasia may grow adequately with average energy
intakes as low as 50% to 61% of the dietary reference intake
(DRI) for age and gender because their lean body mass,
and hence resting energy expenditure (REE), is lower
than that of unaffected children.14,26,39,40 REE in children
with myelomeningocele is 96% of predicted, but total daily
energy expenditure is lower than predicted because of a
reduction in physical activity.41,42 Children with diplegia,
hemiplegia, and spina bifida have higher rates of energy
expenditure while walking compared with unaffected children.43 Dietary energy needs of children with cerebral palsy
who ambulate or have athetosis are higher than those who
do not.44 REE correlates poorly with body cell mass in some
developmentally impaired children, suggesting that central
nervous system injury may affect energy regulation. 39 REE
in well-nourished, non-ambulatory children with cerebral
palsy is lower than that predicted from equations based on
age, gender, and weight in healthy children. 39,45 The DRI
for energy in healthy children overestimates the energy
needs of children with spastic quadriplegic cerebral palsy in
whom a value of REE 1.1 may be sufficient.26 The ability
to estimate dietary energy needs of children with developmental delay is difficult because of the heterogeneity in their
193
clinical features. Altered body composition and reduced

physical activity make formulas used to calculate energy
needs in healthy children invalid for children with developmental delay.
Clinical Features
Height-for-age and weight-for-age growth standards of children with developmental delay are lower than those of the
reference population.11,12,23,4648 The median height-for-age
and weight-for-age for children with spastic quadriplegic
cerebral palsy and Rett syndrome range between the 5th and
10th percentiles for the National Center for Health Statistics (NCHS) reference population. The differences between
the observed growth pattern of children with spastic quadriplegic cerebral palsy or Rett syndrome and the NCHS
reference population become greater with increasing age.
Developmental impairment may adversely affect linear
growth even in the absence of undernutrition because of the
underlying genetic or medical condition. As a consequence,
growth failure may not be corrected completely by nutritional therapy.22
Children with developmental delay may have progressive weight deficits due to fat loss, while muscle and visceral
proteins are maintained. Some children lack weight gain in
the presence of linear growth, while others have progressive
muscle atrophy unresponsive to nutritional intervention.
Although children with developmental delay may be shorter
and weigh less than unaffected children, others may be
overweight based on weight-for-height, triceps skinfold
thickness, or underwater weighing1113 or have features
consistent with the metabolic syndrome (Chapter 14).19 The
prevalence of overweight may be underestimated because
weight-for-height gains are overlooked in the presence
of a small body size or an aberrant distribution of body
fat. Weight-for-height comparisons may be monitored
less frequently than weight alone because of the difficulty
obtaining accurate height measurements.
Micronutrient Deficiencies
Vitamin, trace element, and essential fatty acid (EFA)
deficiencies have been documented in children with developmental delay who have reduced dietary intakes.4951
Iron, selenium, zinc, EFAs, and vitamins C, D, and E were
reported to be deficient in 15% to 50% of the children.4952
Some may develop nutrient deficiencies because enteral
formulas provide adequate amounts of micronutrients only
when volumes that meet their age-related DRI for energy are
consumed. 53 Because many children with developmental
delay require lower energy intakes, their micronutrient
194
intakes are correspondingly lower. Replacement therapy

reverses these abnormalities.
Complementary and alternative medicine is administered frequently to children with chronic medical
conditions. 54 The use of dietary supplements, including
vitamins, minerals, herbs, or other botanicals, was reported
by 6% of families with children who have cerebral palsy. 55
Concerns have been raised because of potential interactions
between complementary or alternative medicines and antiepileptic drugs and consequently modification of seizure
risk. 56
Osteopenia
Osteopenia is prevalent in developmentally impaired children. 52,5759 Weight z score is the best correlate of bone
mineral density z score in children with developmental
delay. 58 Dietary calcium, vitamin D, and phosphorus intakes
are lower than the DRI in 50% to 80% of these children. 24,60
Non-ambulatory children have lower bone mineral content
than those who ambulate independently. 58 Limited ambulation, increased duration of anticonvulsant therapy, and
reduced sun exposure contribute to the pathogenesis of
osteopenia. 5760 Osteopenia is associated with an increased
fracture risk in developmentally impaired children. 5759
Supplemental calcium improves bone mineral density by
5% over 4 years in healthy children, but the effect of dietary
calcium in children with developmental delay is unknown.61
The use of bisphosphonates increased bone mineral density
by 89% over 18 months in children with cerebral palsy. 62
However, the relation between bisphosphonate use and
fracture risk or frequency in these children is unknown. The
use of bisphosphonates is limited because their indications
in childhood diseases are not well defined and their longterm effects on bone remodeling in children are unknown.
Nutrition Assessment
Nutrition assessment of the child with developmental

delay includes a thorough medical history, accurate growth
and anthropometric measurements, a complete physical
examination, meal observation and food record review, and
selected diagnostic studies.
Medical History
The medical history includes information about the
etiology, duration, and severity of neurological impairment
and its expected course. These factors correlate with the
risk of undernutrition and may affect the type of nutritional
intervention required. Although the neurological condition
itself may remain stable, manifestations of the disorder may

change over time and require periodic reassessment.
Medications
A review of medications is important because drugs
prescribed for gastroesophageal reflux, drooling, constipation, seizures, and spasticity may influence the childs
eating pattern. Gastric acid inhibitors and laxatives often
minimize gastrointestinal discomfort and reverse feeding
refusal. Valproic acid, gabapentin, topiramate, zonisamide,
and felbamate may affect appetite and result in weight gain
or loss. Many anticonvulsants impact the level of consciousness, thereby reducing oral motor skills and airway
protection. Glycopyrrolate may reduce pooling of oral
secretions, but may aggravate constipation. Baclofen and
trihexyphenidyl may reduce spasticity, and consequently,
energy expenditure.
Review of Systems
The review of systems identifies clinical problems that may
influence the type of nutritional intervention prescribed.
Respiratory and gastrointestinal problems impact all
aspects of nutrition support. Emesis, food refusal, anemia,
and intestinal blood loss suggest gastroesophageal reflux
and esophagitis. Acid reflux tends to be more frequent in
children with severe disabilities and those with scoliosis.
Irritability, infrequent bowel movements, and abdominal
distention suggest constipation. Chronic cough, poorly
controlled asthma, or recurrent pneumonia raises the possibility of aspiration.
Growth History
Birth weight and length and previous weight and length
measurements, when recorded on NCHS growth charts,
may be compared with the reference population to determine if growth faltering or abnormal weight gain or loss has
occurred. Height measurements may be erroneous if the
child has difficulty standing. The heights of the biological
parents may provide insight regarding the childs genetic
growth potential.
Social History
The child with developmental delay requires a considerable
amount of care, a factor that impacts the parents ability to
work and the familys social activities. Scheduled activities, such as school or physical therapy, and the siblings
school and parents work schedules require consideration
when planning nutritional interventions. Financial issues,
DEVELOPMENTAL DELAY
medical insurance, and the availability of home care require

exploration. All individuals involved in the care and feeding
of the child and all settings in which feeding occurs require
consideration to ensure that nutritional interventions can
be integrated into the family or institutional routines.
Growth and Anthropometric Measurements

Growth measures reflect the childs nutrition status.17
Accurate measures of height, length, or a proxy if these
measurements are not reliable, and weight are obtained,
using standardized techniques and equipment, at every
medical encounter. Length is obtained supine in children
less than age 2 years or in older children unable to stand.
Alternative measures such as upper arm length (UAL) or
lower leg length (LLL) may be used to estimate body length
in children who have contractures or scoliosis. Reference
standards are available for UAL and LLL in children age
2 years and older.63 Standing height, without shoes and
braces, is obtained in all other children. Weight is measured
with the child wearing little or no clothing. Children with
severe disabilities may be weighed while being held by a
parent, while seated in a wheelchair, or on a table scale. Body
mass index (BMI) can be calculated from height and weight
measurements of children age 2 years and older. Although
the inability to measure standing height theoretically
invalidates the calculation of BMI, estimates derived from
LLL serve as a practical alternative in the clinical setting.
Weight-for-length is determined for children less than age
2 years. Head circumference may be of limited use in the
presence of microcephaly. Height (length), weight, BMI,
and weight-for-length, when properly measured and plotted
on gender- and age-appropriate growth charts (http://www.
cdc.gov/growthcharts), can be compared with previous
measures and the reference population. Condition-specific
growth charts may be available, but often have limited
use because of small data sets that contributed to their
formation.
Any height or weight measurement that falls below the
5th percentile, is greater than the 95th percentile, or crosses
2 growth channels is considered to represent an abnormal
growth pattern. Serial measurements are obtained to
determine if the growth pattern is truly abnormal or if
these findings represent constitutional short stature or
the re-channeling of the genetic growth potential in children with neurological disabilities. Radiographic studies
of bone age may help to clarify the presence of abnormal
growth patterns because chronic undernutrition is one of
the causes of delayed bone maturation, and hence, delayed
linear growth.64
195
The BMI-for-age may be used to screen children with

neurological disabilities for underweight and overweight.
Children are classified as underweight if their BMI-for-age
is less than the 5th percentile, overweight if their BMI-forage is between the 85th and 95th percentile, and obese if
their BMI-for-age is greater than the 95th percentile. The
use of BMI-for-age may be problematic because of decreased
muscle mass, increased regional and total body fat, and/or
skeletal deformities in children with neurological disabilities. Nevertheless, an estimate of the BMI-for-age serves as
a useful guide for the approach to nutritional intervention.
Thus, nasogastric or gastrostomy tube feedings may be indicated if the BMI-for-age is less than 11 to 13 kg/m 2 because
of the increased morbidity and mortality associated with
these values.65 Conversely, an energy-deficit diet may be
implemented if the BMI-for-age is greater than 30 kg/m 2 ,
whereas a more restrictive diet such as a protein-sparing
modified fast may be necessary for a BMI-for-age greater
than 40 kg/m 2 .66 Body fat and arm muscle area can be
estimated from mid-upper arm circumference and triceps
skinfold thickness.11 Reliability is improved when the same
observer obtains the measurements. The values for triceps
skinfold thickness and arm muscle area may be compared to
reference standards.67 Body fat usually is reduced at all sites,
with the triceps being affected more than the subscapular
skinfold thickness in children with developmental delay.11,23
Measures of triceps skinfold thickness rather than weightfor-height percentiles may better identify those children
with undernutrition. Decreased triceps skinfold thickness
identifies 96% of children with depleted fat stores, while
weight-for-height less than the 10th percentile identifies
only 55%.46 Waist circumference may serve as an alternative
indicator of adiposity because this measure correlates well
with truncal fat.19
Physical examination focuses on signs of undernutrition,
linear stunting, overweight, and specific nutrient deficiencies. Muscle tone, activity level, and the presence of athetoid
movement are relevant because they influence dietary
energy needs. Contractures and scoliosis are noteworthy
for positioning during meals. Abnormal breath sounds may
be suggestive of chronic respiratory problems associated
with aspiration. Abdominal distention in conjunction with
palpable masses suggests constipation. Examination of the
skin may reveal the presence of decubitus ulcers. Pallor,
skin rashes, smooth tongue, gingival bleeding, petechiae,
bone deformities, or pedal edema may suggest other micronutrient deficiencies.
196
Meal Observation
A 24-hour recall of habitual food intake or a 3-day record
of food consumption reflects the adequacy of dietary
energy and nutrient intake. 34 Meal observation, with
emphasis on the childs ability to feed independently and
the efficiency of the feeding process, may reveal a reason
for poor weight gain.12,16,29,30 An evaluation of oral motor
skills, including inadequate lip closure, drooling, a persistent extrusion reflex, gagging and delayed swallowing, or
coughing and choking during meals reflects poor feeding
capabilities. Limited texture tolerance may indicate poor
oral ability to manage food, resulting in self-restricted
eating patterns, reduced nutrient intake, and poor weight
gain.68,69 Consumption of inappropriate food textures may
result in aspiration. Fatigue and lethargy during meals may
suggest hypoxemia.70 Meal observation shows that children
with developmental delay may be offered less, consume less,
and spill more food than unaffected children. Classification systems based on measures of growth and patterns of
food consumption, such as eating efficiency and oral motor
feeding skills, may be helpful to assess the effectiveness of
oral feeding interventions.71,72
Diagnostic Studies
Although isolated nutrient deficiencies may be present in
children with developmental delay, extensive laboratory
evaluation is not necessary.4951 A complete blood count and
serum ferritin may document anemia or iron deficiency.
Serum electrolytes and blood urea nitrogen (BUN) reflect
hydration status; however, BUN may be low because of
poor protein intake and low muscle mass. Serum albumin
and prealbumin, factors that correlate strongly with the
risk of morbidity and mortality, are less reliable indicators
of nutrition status.73 Abnormal serum phosphorus, alkaline
phosphatase, and 25-hydroxyvitamin D levels may coincide
with poor bone mineral status. Bone densitometry may be
considered in children who have pathologic fractures. Bone
quantitative ultrasonography may be more easily performed
than bone densitometry; however, normative data for children are not yet available.74
Additional diagnostic studies may be helpful, depending
on the childs symptoms and the need for permanent enteral
access. A videofluoroscopic assessment of chewing and
swallowing function, using different food and beverage
textures, determines the degree of oral motor dysfunction
and risk of aspiration. Positioning the child during the
evaluation is important because some children may not
aspirate when placed upright, but do so in a reclined position. A swallowing function study may demonstrate silent
aspiration in the absence of choking and coughing during

meals. Assessment of swallowing function at the end of a
meal is informative because feeding fatigue may lead to
aspiration. A swallowing function study may provide guidance for appropriate food textures and therapeutic feeding
techniques.
Gastroesophageal reflux may be apparent based on
symptoms of vomiting, chest or abdominal pain, feeding
refusal, or irritability. A 24-hour esophageal pH probe study
may be helpful if the diagnosis of acid reflux is not obvious. A
gastric emptying scan may detect delayed gastric emptying
which indirectly may contribute to gastroesophageal reflux
and aspiration. An upper gastrointestinal series may detect
gastroesophageal dysmotility or superior mesenteric artery
syndrome, both of which may interfere with feeding.
Episodic reflux occurring during the study may not be diagnostic of acid reflux disease. An abnormal location of the
stomach in the thorax of children with severe scoliosis may
influence the type of intervention used for enteral access.
The child with symptoms suggestive of chronic aspiration may require a chest x-ray and an evaluation by a
pulmonologist, especially if surgical intervention for enteral
access is considered. Monitoring O2 saturation during a meal
may be important because children with developmental
delay may have hypoxemia with feedings.70 Modifying food
textures and liquid consistencies with thickening agents
may help to reduce aspiration risk.
Nutrition Support
Nutrition support is provided enterally rather than parenterally, assuming competency of the gastrointestinal tract.
Enteral tube feedings are essential in children who cannot
meet their energy and nutrient needs orally.75 Evidence of
oral motor feeding difficulties, undernutrition (weight-forheight < 80% of expected, BMI < 5th percentile), growth
failure (height-for-age < 90% of expected), overweight
(BMI > 85th percentile), and individual nutrient deficiencies indicate the need for nutritional intervention.1
Energy requirements of children with developmental delay
vary with the severity of their neurological disability, their
mobility, the presence of feeding difficulties, altered body
composition, and the need for weight gain or loss and catchup growth. Dietary energy needs for the maintenance of
body weight may be estimated from either the DRI standards for basal energy expenditure (http://www.nal.usda.
gov/fnic/etext/000105.html), indirect calorimetry,76 or
height77 (Table 18-1). Dietary energy needs for catch-up
DEVELOPMENTAL DELAY
growth may approximate the DRI for basal energy expenditure 1.5. Monitoring the rate of weight gain or loss and
change in BMI is the best way to determine the adequacy of
diet in the child with developmental delay. Adequate provision of dietary protein, vitamins, and minerals is mandatory
when energy intakes are modified to obtain the desired rate
of weight change. In the absence of evidence-based nutrient
allowances for children with developmental delay, the
DRIs for protein, vitamins, and minerals in healthy children are recommended (http://www.nal.usda.gov/fnic/
etext/000105.html). Multivitamin and mineral supplements may be prudent for children with developmental
delay who rely primarily on table foods and beverages to
meet their nutrient needs, particularly in relation to the
need for improved vitamin D status.78
Table 18-1. Methods to Determine Dietary Energy Needs in Neurologically
Impaired Children
Dietary Reference Intake Standards for Basal Energy Expenditure
(http://www.nal.usda.gov/fnic/etext/000105.html)
Energy intake (kcal/d) = Basal Energy Expenditure (BEE) x 1.1
Age (y)
Basal Energy Expenditure (kcal/d)
Boys
Girls
38
1035
1004
913
1320
1186
1418
1729
1361
Indirect Calorimetry76
Energy intake (kcal/d)
= [basal energy expenditure (BMR) x muscle tone x activity] + growth
where:
BMR (kcal/d) = body surface area (m2) x metabolic rate (kcal/m2/h)
x 24 h
Muscle tone = 0.9 if decreased, 1 if normal, and 1.1 if increased
Activity = 1.1 if bedridden, 1.2 if wheelchair dependent or crawling,
and 1.3 if ambulatory
Growth = 5 kcal/g of desired weight gain (normal and catch-up
growth)
Height77
15 kcal/cm in children without motor dysfunction
14 kcal/cm in children with motor dysfunction who are ambulatory
11 kcal/cm in children who are non-ambulatory
Positioning and Oral Feeding

The feeding therapist can assist with oral motor skills,
correct positioning of the child, and the use of appropriate chairs and adapted utensils during meals. Therapy
to improve oral motor skills may be attempted, especially
before age 5 years. Oral feeding interventions may enhance
oral motor function, but are not effective in promoting
feeding efficiency and weight gain.79 VitalStim, a device
that administers electrical stimulation to the musculature
197
of the neck, has been used; however, improved feeding

efficiency in children has not been documented. 80 Periodic
reassessment of oral feeding skills is important to determine the potential for continued oral feeding.
Behavioral Modification
Behavioral therapy initiated by a skilled child psychologist
may improve the quantity of food consumed, the feeding
efficiency, and the range of textures accepted, as well as the
quality of feeding interactions between the caretaker and
the child.81

Oral feedings can be maintained in children with adequate
oral motor skills who have a low risk of aspiration. Adequate
positioning and adjustment of food and beverage consistency with thickening agents may improve feeding
efficiency. Increasing the energy density of food maximizes
energy intake. If oral intake is insufficient to promote
weight gain, linear growth, and adequate hydration, if the
amount of time to feed the child is excessive because of
chewing and swallowing dysfunction, or if aspiration is a
risk, enteral tube feedings may be considered. The type of
enteral access selected will depend upon the nutritional and
clinical status of the child and the anticipated duration of
enteral feedings. Parents will be concerned about the childs
loss of oral feeding skills, the risks and benefits of enteral
tube feeding, and the manner in which alternative feeding
methods fit the familys lifestyle. Enteral feeding regimens
that preserve oral feeding skills while providing adequate
nutrient intakes facilitate the transition back to oral feeds
when safe or after catch-up growth has been achieved.
Enteral Access
Nasogastric or nasojejunal tube feedings are minimally
invasive methods that may be used for short-term nutrition support in undernourished children or in those with
acid reflux or aspiration who are awaiting gastrostomy
placement. Nasogastric or nasojejunal tubes are not used
long-term because they may be dislodged easily, may stiffen
and cause intestinal perforation, or may result in nasal
congestion, sinusitis, otitis media, and skin and mucosal
irritation. Bedside placement of nasojejunal tubes can be
achieved by allowing the tube to migrate spontaneously
or in conjunction with a prokinetic drug. 8284 Newer techniques such as pH-assisted tube placement are available. 85
Fluoroscopic or endoscopic tube placement may be required
if these approaches are unsuccessful.
Gastrostomy feedings provide an option for children
198
with severe feeding problems who have poor weight gain,

although evidence-based practice guidelines with attendant risks and benefits are lacking.6,7 A gastrostomy tube
or button device is recommended for long-term enteral
nutrition (EN) because it is more comfortable for the child
and is less easily dislodged than a nasogastric tube. Gastrostomy feedings may promote weight gain, improve the childs
health, and reduce the time spent feeding the child.68,22 The
best clinical response is seen in children with the shortest
time between the neurological insult and gastrostomy
placement. Children who have a gastrostomy placed within
the first year of life are more likely to exceed the 5th percentile for height and weight. Gastrostomy feedings initiated
within 1 year of the neurological insult are associated with
improved weight-for-age, weight-for-length, and lengthfor-age. Nutritional intervention initiated 8 years after
the neurological insult does not normalize length-for-age,
despite improvement in weight-for-age. 86
Percutaneous endoscopic gastrostomy (PEG) placement, a minimally invasive non-surgical procedure, involves
little discomfort and the feeding device can be used within a
few hours of installation. 87 The higher death rate in children
fed by gastrostomy may reflect the severity of their neurological disability compared with those fed orally.7,88 The risk
of acid reflux or esophagitis after PEG placement in developmentally impaired children without previous symptoms
is increased.8993 Medical therapy for pre-existing acid reflux
often will be required after PEG placement. 88 An evaluation
for acid reflux before PEG placement may be warranted
because 5% of developmentally impaired children who have
a normal pH probe study eventually require an anti-reflux
procedure compared with 29% to 58% of those who have
an abnormal pH probe study.88,89 Acid reflux may improve
in some children after PEG placement and nutritional rehabilitation. Further evaluation with upper endoscopy and
esophageal biopsy does not predict clinical outcome after
PEG placement in children.94
Surgical gastrostomy placement is a safe alternative to
enteral access in the child with developmental delay. Laparoscopic gastrostomy placement is associated with less
morbidity, permits earlier EN, and has a cost advantage
compared with the open technique. Laparoscopic or open
surgical fundoplication may be required in as much as 25%
of neurologically impaired children.88,89,93,95,96 Although pyloroplasty improves gastric emptying, dumping syndrome
may occur and require long-term continuous infusions
until bolus feeds are tolerated.97,98 The risk of feeding difficulty, gas bloat, or dumping syndrome, and recurrence of
acid reflux after a fundoplication, varies in children with
developmental delay.95,98,99 Retching may be a disturbing

symptom after a fundoplication, but generally can be controlled by slowing the rate of formula administration.100
Surgical gastrojejunostomy or jejunostomy tube placement may be required in children who do not tolerate
gastric feeds, have severe gastroesophageal reflux, are at
risk for aspiration, are poor candidates for fundoplication,
or are high-risk for failure of a second anti-reflux procedure.
A surgical or laparoscopic loop or Roux-en-Y jejunostomy is
reserved for selected children in whom other options have
failed.101
Image-guided, retrograde or antegrade, percutaneous
placement of gastrostomy or gastrojejunostomy tubes is
an alternative, minimally invasive fluoroscopic method for
enteral feeding.102 The retrograde percutaneous technique
has a higher rate of successful placement than the PEG
method and has a lower rate of major complications than
PEG or surgical gastrostomy placement.
Formula Administration
The choice of enteral formula depends on the childs
age, medical condition, energy requirement, and mode of
enteral access. Standard, age-appropriate, infant or pediatric, casein-based formulas are administered routinely.
Whey-based formulas may be better tolerated because
they enhance gastric emptying.103 Children who manifest
symptoms associated with cows milk protein sensitivity
may require a protein hydrolysate or amino acid formula.
Nutrient deficiencies may occur as a consequence of enteral
feedings.2,6,17 Adult formulas may prevent hypoalbuminemia during periods of catch-up growth, but care should
be taken to avoid iron, vitamin D, calcium, and phosphorus
deficiency.24 If high energy density (1.5 or 2 kcal/mL)
formulas are used, monitoring hydration status and protein
and micronutrient intake is necessary. A fiber-containing
formula may ameliorate constipation, but may aggravate
intestinal gas bloating if the volume is increased rapidly.
Bolus formula feedings are preferred in children who
do not have acid reflux or delayed gastric emptying because
they mimic the physiologic responses associated with meals,
allow a more flexible feeding schedule, and are more convenient in ambulatory children. Continuous formula infusions
may be used throughout the day or night in children who
do not tolerate bolus feeds or have formula administered
directly into the jejunum. When large volumes are required,
bolus feeds can be combined with continuous nocturnal
infusions of formula. Continuous nocturnal infusions avoid
interruptions during daytime activities, but may interfere
with sleep.104
DEVELOPMENTAL DELAY
199
Feeding Intolerance
Acknowledgments
Feeding intolerance may be associated with recurrent

acid or non-acid reflux, delayed gastric emptying, diarrhea, or constipation.105 In the absence of progression of
the neurological disorder, intercurrent infection, or intestinal obstruction, the quality and quantity of the feeding
regimen requires periodic re-evaluation. Changing the
feeding schedule from bolus to continuous infusion,
decreasing the rate of infusion, concentrating the formula
to decrease the volume of feeds, or selecting an alternative
formula may ameliorate symptoms. If symptoms persist,
medical treatment of acid reflux or delayed gastric emptying
may be instituted before exploring laparoscopic or surgical
procedures. Medical management of acid reflux and delayed
gastric emptying consists of using whey hydrolysate
formulas and medications that promote acid suppression (histamine antagonists, proton pump inhibitors) and
motility (bethanechol, metoclopramide, erythromycin,
cisapride). Although the availability of cisapride is restricted
because of safety concerns, its use in neurological disorders
associated with QT wave abnormalities (eg, Rett syndrome)
is cautioned. Medical management of constipation consists
of single or multiple laxative agents with stool-softening
and stimulatory effects (polyethylene glycol-electrolyte
solution, magnesium hydroxide, senna extract, lactulose,
bisacodyl). Rectal inertia may require local treatment with
suppositories (bisacodyl) or enemas.106
The authors thank V. Moore for secretarial support. This

chapter is a publication of the USDA/ARS Childrens Nutrition Research Center, Department of Pediatrics, Baylor
College of Medicine, Houston, TX, and has been funded
in part with federal funds from the U.S. Department of
Agriculture, Agricultural Research Service, under Cooperative Agreement Number 58-6250-1-003. The contents
herein do not necessarily reflect the views or policies of
the U.S. Department of Agriculture, nor does mention of
trade names, commercial products, or organizations imply
endorsement by the U.S. government.
Ethical Considerations
Many families find the idea of a feeding gastrostomy difficult to accept.107 Caregivers believe that they have failed
to adequately care for the child when physicians insist on
gastrostomy placement. Starvation, quality of life, prolongation of life, and meaningful family interrelationships
constitute a framework for discussion. Although medical
opinions generally prevail, parental wishes should be
considered and respected.
Conclusion
Nutrition support is essential for the care of the child with

developmental delay. After a thorough evaluation, an individualized intervention plan that accounts for the childs
nutrition status, feeding ability, and medical condition may
be determined. Nutrition assessments may be performed
at least annually in the older child and more frequently in
the infant and toddler to document adequate growth and
nutrient intakes. The goal of nutrition assessment and intervention is to optimize the childs health, functional status,
and quality of life, while maintaining adequate growth and
nutrition status.
1. Which anthropometric measurements are most useful

to determine nutrition status of the child with developmental delay?
A. Height, length, and triceps skinfold
B. Weight, head circumference, and arm circumference
C. Head circumference, body mass index, and triceps
skinfold thickness
D. BMI, weight, and height
2. What are the most common reasons for poor weight
gain in the child with developmental delay?
A. Inadequate dietary intake and constipation
B. Increased basal metabolic rate
C. Chewing and swallowing dysfunction and inadequate dietary intake
D. Athetoid or repetitive motor movements and
aspiration
3. The best way to determine the adequacy of the diet for
children with developmental delay is to:
A. Calculate dietary energy needs based on the DRI
standards for basal energy expenditure.
B. Monitor the rate of weight gain or loss and change
in BMI.
C. Measure hemoglobin concentration and serum
albumin levels.
D. Provide a protein hydrolysate or amino acid formula
as the main source of nutrients.
References
1. Motil KJ. Enteral nutrition in the neurologically impaired

child. In: Baker SB, Baker RD Jr, Davis A, eds. Pediatric Enteral
Nutrition. New York, NY: Chapman & Hall; 1994:217237.
2. Thomas AG, Akobeng AK. Technical aspects of feeding
the disabled child. Curr Opin Clin Nutr Metab Care.
2000;3(3):221225.
200
3. Marchand V, Motil KJ, NASPGHAN Committee on Nutrition. Nutrition support for neurologically impaired children:
a clinical report of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr
Gastroenterol Nutr. 2006;43(1):123135.
4. Samson-Fang L, Fung E, Stallings VA, et al. Relationship of
nutritional status to health and societal participation in children with cerebral palsy. J Pediatr. 2002;141(5):637643.
5. Rogers B. Feeding method and health outcomes of children
with cerebral palsy. J Pediatr. 2004;145(2 Suppl):S28S32.
6. Sleigh G, Brocklehurst P. Gastrostomy feeding in cerebral palsy: a systematic review. Arch Dis Child. 2004;89(6):534539.
7. Samson-Fang L, Butler C, ODonnell M. Effects of gastrostomy feeding in children with cerebral palsy: an AACPDM
evidence report. Dev Med Child Neurol. 2003;45(6):415426.
8. Sullivan PB, Juszczak E, Bachlet AM, et al. Gastrostomy tube
feeding in children with cerebral palsy: a prospective, longitudinal study. Dev Med Child Neurol. 2005; 47(2):7785.
9. Craig GM, Carr LJ, Cass H, et al. Medical, surgical, and health
outcomes of gastrostomy feeding. Dev Med Child Neurol.
2006;48(5):353360.
10. Strauss D, Kastner T, Ashwal S, White J. Tubefeeding and
mortality in children with severe disabilities and mental retardation. Pediatrics. 1997;99(3):358362.
11. Stallings VA, Charney EB, Davies JC, Cronk CE. Nutritional
status and growth of children with diplegic or hemiplegic
cerebral palsy. Dev Med Child Neurol. 1993;35(11):9971006.
12. Dahl M, Thommessen M, Rasmussen M, Selberg T. Feeding
and nutritional characteristics in children with moderate or
severe cerebral palsy. Acta Paediatr. 1996;85(6):697701.
13. Mita K, Akataki K, Ono Y, Ishida N, Oki T. Assessment of
obesity of children with spina bifida. Dev Med Child Neurol.
1993;35:305311.
14. Bandini LG, Schoeller DA, Fukagawa NK, Wykes LJ, Dietz
WH. Body composition and energy expenditure in adolescents with cerebral palsy or myelodysplasia. Pediatr Res.
1991;29(1):7071.
15. Schultz R, Glaze DG, Motil KJ, et al. The pattern of growth failure in Rett syndrome. Am J Dis Child. 1993;147(6):633637.
16. Troughton KE, Hill AE. Relation between objectively
measured feeding competence and nutrition in children with
cerebral palsy. Dev Med Child Neurol. 2001;43(3):187190.
17. Sanchez-Lastres J, Eiris-Punal J, Otero-Cepeda JL, PavonBelinchon P, Castro-Gago M. Nutritional status of mentally
retarded children in north-west Spain. I. Anthropometric
indicators. Acta Paediatr. 2003;92(6):747753.
18. Stevenson RD, Hayes RP, Cater LV, Blackman JA. Clinical
correlates of linear growth in children with cerebral palsy. Dev
Med Child Neurol. 1994;36(2):135142.
19. Nelson MD, Widman LM, Abresch RT, et al. Metabolic
syndrome in adolescents with spinal cord dysfunction. J Spinal
Cord Med. 2007;30(Suppl 1):S127S139.
20. Fiore P, Picco P, Castagnola E, et al. Nutritional survey of
children and adolescents with myelomeningocele (MMC):
overweight associated with reduced energy intake. Eur J
Pediatr Surg. 1998;8(Suppl 1):3436.
21. Stevenson RD, Roberts CD, Vogtle L. The effects of nonnutritional factors on growth in cerebral palsy. Dev Med Child
Neurol. 1995;37(2):124130.
22. Motil KJ, Morrissey M, Caeg E, Barrish JO, Glaze DG. Gastrostomy placement improves height and weight in girls with Rett
syndrome. J Pediatr Gastroenterol Nutr. 2009;49:237242.
23. Stallings VA, Charney EB, Davies JC, Cronk CE. Nutritionrelated growth failure of children with quadriplegic cerebral
palsy. Dev Med Child Neurol. 1993;35(2):126138.
24. Fried MD, Pencharz PB. Energy and nutrient intakes of children with spastic quadriplegia. J Pediatr.
1991;119(6):947949.
25. Reilly S, Skuse D. Characteristics and management of
feeding problems of young children with cerebral palsy. Dev
Med Child Neurol. 1992;34(5):379388.
26. Stallings VA, Zemel BS, Davies JC, Cronk CE, Charney
EB. Energy expenditure of children and adolescents with
severe disabilities: a cerebral palsy model. Am J Clin Nutr.
1996;64(4):627634.
27. Hillesund E, Skranes J, Trygg KU, Bohmer T. Micronutrient status in children with cerebral palsy. Acta Paediatr.
2007;96(8):11951198.
28. Mathisen BA, Shepherd K. Oral-motor dysfunction and
feeding problems in infants with myelodysplasia. Pediatr
Rehabil. 1997;1:117122.
29. Reilly S, Skuse D, Poblete X. Prevalence of feeding problems
and oral motor dysfunction in children with cerebral palsy: a
community survey. J Pediatr. 1996;129(6):877882.
30. Sullivan PB, Alder N, Allison ME, et al. Gastrostomy feeding
in cerebral palsy: too much of a good thing? Dev Med Child
Neurol. 2006;48(11):877882.
31. Gisel EG, Patrick J. Identification of children with cerebral
palsy unable to maintain a normal nutritional state. Lancet.
1988;1(8580):283286.
32. Sullivan PB, Lambert B, Rose M, Ford-Adams M, Johnson A,
Griffiths P. Prevalence and severity of feeding and nutritional
problems in children with neurological impairment: Oxford
Feeding Study. Dev Med Child Neurol. 2000;42(10):674680.
33. Thommessen M, Heiberg A, Kase BF, Llarson S, Riis G.
Feeding problems, height and weight in different groups of
disabled children. Acta Paediatr Scand. 1991;80(5):527533.
34. Sullivan PB, Juszczak E, Lambert BR, et al. Impact of feeding
problems on nutritional intake and growth: Oxford Feeding
Study II. Dev Med Child Neurol. 2002;44:461467.
35. Fung EB, Samson-Fang L, Stallings VA, Rose M, Ford-Adams
ME, Johnson A. Feeding dysfunction is associated with poor
growth and health status in children with cerebral palsy. J Am
Diet Assoc. 2002;102(3):361368.
36. Strauss D, Ashwal S, Shavelle R, Eyman RK. Prognosis for
survival and improvement in function in children with severe
developmental disabilities. J Pediatr. 1997;131(5):712717.
37. Motion S, Northstone K, Emond A, Stucke S, Golding J. Early
feeding problems in children with cerebral palsy: weight
and neurodevelopmental outcomes. Dev Med Child Neurol.
2002;44(1):4043.
38. Van Roon D, Steenbergen B. The use of ergonomic
spoons by people with cerebral palsy: effects of food
spilling and movement kinematics. Dev Med Child Neurol.
2006;48(11):888891.
39. Azcue MP, Zello GA, Levy LD, Pencharz PB. Energy
expenditure and body composition in children with spastic
quadriplegic cerebral palsy. J Pediatr. 1996;129(6):870876.
DEVELOPMENTAL DELAY
40. Grogan CB, Ekvall SM. Body composition of children

with myelomeningocele, determined by 40K, urinary
creatinine and anthropometric measures. Am J Coll Nutr.
1999;18:316323.
41. Littlewood RA, Trocki O, Shepherd RW, Shepherd K, Davies
PS. Resting energy expenditure and body composition in children with myelomeningocele. Pediatr Rehabil. 2003;6:3137.
42. van den Berg-Emons HJ, Bussmann JB, Brobbel AS,
Roebroeck ME, van Meeteren J, Stam HJ. Everyday physical
activity in adolescents and young adults with meningomyelocele as measured with a novel activity monitor. J Pediatr.
2001;139:880886.
43. Duffy CM, Hill AE, Cosgrove AP, Corry IS, Graham HK.
Energy consumption in children with spina bifida and
cerebral palsy: a comparative study. Dev Med Child Neurol.
1996;38(3)238243.
44. Rose J, Medeiros JM, Parker R. Energy cost index as an
estimate of energy expenditure of cerebral-palsied children during assisted ambulation. Dev Med Child Neurol.
1985;27(4):485490.
45. Bandini LG, Puelzl-Quinn H, Morelli JA, Fukagawa NK.
Estimation of energy requirements in persons with severe
central nervous system impairment. J Pediatr. 1995;126(5 Pt
1):828832.
46. Samson-Fang LJ, Stevenson RD. Identification of malnutrition
in children with cerebral palsy: poor performance of weight for
height centiles. Dev Med Child Neurol. 2000;42(3):162168.
47. Stallings VA, Cronk CE, Zemel BS, Charney EB. Body composition in children with spastic quadriplegic cerebral palsy. J
Pediatr. 1995;126(5 Pt 1):833839.
48. Tarquinio D, Motil K, Hou W, et al. Growth charts for Rett
syndrome: Birth to 18 years of age. Neurology. 2009;72 (Suppl
3):A427A428. Platform presentation American Academy
of Neurology annual meeting, Seattle, WA. April, 2009. ID:
2740AAN09D1.
49. Hals J, Ek J, Svalastog AG, Nilsen H. Studies on nutrition in
severely neurologically disabled children in an institution.
Acta Paediatr. 1996;85(12):14691475.
50. Jones M, Campbell KA, Duggan C, et al. Multiple micronutrient deficiencies in a child fed an elemental formula. J Pediatr
51. Hals J, Bjerve KS, Nilsen H, Svalastog AG, Ek J. Essential fatty
acids in the nutrition of severely neurologically disabled children. Br J Nutr. 2000;83(3):219225.
52. Henderson RC, Lark RK, Gurka MJ, et al. Bone density and
metabolism in children and adolescents with moderate to
severe cerebral palsy. Pediatrics. 2002;110 (1 Pt 1):e51.
53. Piccoli R, Gelio S, Fratucello A, Valletta E.
Risk of low micronutrient intake in neurologically disabled children artificially
fed. J Pediatr Gastroenterol Nutr. 2002;35(4):583584.
54. Samdup DZ, Smith RG, Il Song S. The use of complementary
and alternative medicine in children with chronic medical
conditions. Am J Phys Med Rehabil. 2006;85(10):842846.
55. Hurvitz EA, Leonard C, Ayyangar R, Nelson VS. Complementary and alternative medicine use in families of children
with cerebral palsy. Dev Med Child Neurol. 2003;45:364370.
201
56. Kaiboriboon K, Guevara M, Alldredge BK. Understanding

herb and dietary supplement use in patients with epilepsy.
Epilepsia. 2009;50(8):19271932.
57. Chad KE, McKay HA, Zello GA, Bailey DA, Faulkner RA,
Snyder RE. Body composition in nutritionally adequate
ambulatory and non-ambulatory children with cerebral
palsy and a healthy reference group. Dev Med Child Neurol.
2000;42(5):334339.
58. Henderson RC, Kairalla J, Abbas A, Stevenson RD.
Predicting low bone density in children and young adults
with quadriplegic cerebral palsy. Dev Med Child Neurol.
2004;46(6):416419.
59. Motil KJ, Ellis KJ, Barrish JO, Caeg E, Glaze DG. Bone
mineral content and bone mineral density are lower in older
than in younger females with Rett syndrome. Pediatr Res.
2008; 64(4):435439.
60. Baer MT, Kozlowski BW, Blyler EM, Trahms CM, Taylor ML,
Hogan MP. Vitamin D, calcium, and bone status in children
with developmental delay in relation to anticonvulsant use and
ambulatory status. Am J Clin Nutr. 1997;65(4):10421051.
61. Matkovic V, Goel PK, Badenhop-Stevens NE, et al. Calcium
supplementation and bone mineral density in females from
childhood to young adulthood: a randomized controlled trial.
Am J Clin Nutr. 2005;81(1):175188.
62. Henderson RC, Lark RK, Kecskemethy HH, Miller
F, Harcke HT, Bachrach SJ. Bisphosphonates to treat
osteopenia in children with quadriplegic cerebral palsy:
a randomized, placebo-controlled clinical trial. J Pediatr.
2002;141(5):644651.
63. Spender QW, Cronk CE, Charney EB, Stallings VA. Assessment of linear growth of children with cerebral palsy: use
of alternative measures to height or length. Dev Med Child
Neurol. 1989;31(2):206214.
64. Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist. 2nd ed. Stanford, CA: Stanford
University Press, 1959.
65. Collins S. The limits of human adaptation to starvation. Nat
Med. 1995;1(8):810814.
66. Figueroa-Colon R, Franklin FA, Lee JY, von Almen TK,
Suskind RM. Feasibility of a clinic-based hypocaloric dietary
intervention implemented in a school setting for obese children. Obes Res. 1996;4(5):419429.
67. Frisancho AR. New norms of upper limb fat and muscle
areas for assessment of nutritional status. Am J Clin Nutr.
1981;34(11):25402545.
68. Isaacs JS, Murdock M, Lane J, Percy AK. Eating difficulties in
girls with Rett syndrome compared with other developmental
disabilities. J Am Diet Assoc. 2003;103(2):224230.
69. Gisel EG, Alphonce E. Classification of eating impairments
based on eating efficiency in children with cerebral palsy.
Dysphagia. 1995;10(4):268274.
70. Rogers BT, Arvedson J, Msall M, Demerath RR. Hypoxemia
during oral feedings of children with severe cerebral palsy.
71. Gisel EG, Alphonce E, Ramsay M. Assessment of ingestive
and oral praxis skills: children with cerebral palsy vs. controls.
Dysphagia. 2000;15(4):236244.
202
72. Gisel EG. Effect of oral sensorimotor treatment on

measures of growth and efficiency of eating in the moderately eating-impaired child with cerebral palsy. Dysphagia.
1996;11(1):4858.
73. Fuhrman MP, Charney P, Mueller CM. Hepatic
proteins and nutritional assessment. J Am Diet Assoc.
2004;104(8):12581264.
74. Hartman C, Brik R, Tamir A, Merrick J, Shamir R. Bone
quantitative ultrasound and nutritional status in severely
handicapped institutionalized children and adolescents. Clin
Nutr. 2004; 23(1):8998.
75. Axelrod D, Kazmerski K, Iyer K. Pediatric enteral nutrition. J
Parenter Enteral Nutr. 2006;30(1 Suppl):S21S26.
76. Krick J, Murphy PE, Markham JF, Shapiro BK. A proposed
formula for calculating energy needs of children with cerebral
77. Culley WJ, Middleton TO. Caloric requirements of mentally
retarded children with and without motor dysfunction. J
Pediatr. 1969;75(3):380384.
78. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M.
Vitamin D deficiency in children and its management: review
of current knowledge and recommendations. Pediatrics.
2008;122(2):398417.
79. Gisel EG, Applegate-Ferrante T, Benson JE, Bosma JF. Effect
of oral sensorimotor treatment on measures of growth, eating
efficiency and aspiration in the dysphagic child with cerebral
80. Chetney R, Waro K. A new home health approach to swallowing disorders. Home Health Nurse. 2004;22(10):703707.
81. Linscheid TR. Behavioral treatments for pediatric feeding
disorders. Behav Modif. 2006;30(1):623.
82. Kalliafas S, Choban PS, Ziegler D, Drago S, Flancbaum
L. Erythromycin facilitates postpyloric placement of
nasoduodenal feeding tubes in intensive care unit patients:
randomized, double-blinded, placebo-controlled trial. J
Parenter Enteral Nutr. 1996;20(6):385388.
83. Kittinger JW, Sandler RS, Heizer WD. Efficacy of metoclopramide as an adjunct to duodenal placement of small-bore
feeding tubes: a randomized, placebo-controlled, doubleblind study. J Parenter Enteral Nutr. 1987;11(1):3337.
84. Davies AR, Bellomo R. Establishment of enteral nutrition:
prokinetic agents and small bowel feeding tubes. Curr Opin
Crit Care. 2004;10(2):156161.
85. Krafte-Jacobs B, Persinger M, Carver J, Moore L, Brilli R.
Rapid placement of transpyloric feeding tubes: a comparison
of pH-assisted and standard insertion techniques in children.
Pediatrics. 1996;98(2 Pt 1):242248.
86. Sanders KD, Cox K, Cannon R, et al. Growth response to
enteral feeding by children with cerebral palsy. J Parenter
Enteral Nutr. 1990;14(1):2326.
87. Gauderer MW. Percutaneous endoscopic gastrostomy:
a 10-year experience with 220 children. J Pediatr Surg.
1991;26(3):288292.
88. Catto-Smith AG, Jimenez S. Morbidity and mortality
after percutaneous endoscopic gastrostomy in children
with neurological disability. J Gastroenterol Hepatol.
2006;21(4):734738.
89. Sulaeman E, Udall JN, Brown RF, et al. Gastroesophageal

reflux and Nissen fundoplication following percutaneous
endoscopic gastrostomy in children. J Pediatr Gastroenterol
Nutr. 1998;26(3):269273.
90. Khattak IU, Kimber C, Kiely EM, Spitz L. Percutaneous
endoscopic gastrostomy in paediatric practice: complications
and outcome. J Pediatr Surg. 1998;33(1):6772.
91. Behrens R, Lang T, Muschweck H, Richter T, Hofbeck M.
Percutaneous endoscopic gastrostomy in children and adolescents. J Pediatr Gastroenterol Nutr. 1997;25(5):487491.
92. Grunow JE, al-Hafidh A, Tunell WP. Gastroesophageal reflux
following percutaneous endoscopic gastrostomy in children.
JPediatr Surg. 1989;24(1):4244.
93. Isch JA, Rescorla FJ, Scherer LR 3rd, West KW, Grosfeld JL. The development of gastroesophageal reflux after
percutaneous endoscopic gastrostomy. J Pediatr Surg.
1997;32(2):321322.
94. Heikenen JB, Werlin SL. Esophageal biopsy does not predict
clinical outcome after percutaneous endoscopic gastrostomy
in children. Dysphagia. 2000;15(3):167169.
95. Cameron BH, Blair GK, Murphy JJ 3rd, Fraser GC. Morbidity
in neurologically impaired children after percutaneous
endoscopic versus Stamm gastrostomy. Gastrointest Endosc.
1995;42(1):4144.
96. Heine RG, Reddihough DS, Catto-Smith AG. Gastrooesophageal reflux and feeding problems after gastrostomy in
children with severe neurological impairment. Dev Med Child
Neurol. 1995;37(4):320329.
97. Farrell TM, Richardson WS, Halkar R, et al. Nissen fundoplication improves gastric motility in patients with delayed
gastric emptying. Surg Endosc. 2001;15(3):271-274.
98. Bufler P, Ehringhaus C, Koletzko S. Dumping syndrome: a
common problem following Nissen fundoplication in young
children. Pediatr Surg Int. 2001;17(56):351355.
99. Pimpalwar A, Najmaldin A. Results of laparoscopic antireflux procedures in neurologically impaired children. Semin
Laparosc Surg. 2002;9(3):190196.
100. Friedman JN, Ahmed S, Connolly B, Chait P, Mahant
S. Complications associated with image-guided gastrostomy and gastrojejunostomy tubes in children. Pediatrics.
2004;114(2):458461.
101. Richards CA, Milla PJ, Andrews PL, Spitz L. Retching and
vomiting in neurologically impaired children after fundoplication: predictive preoperative factors. J Pediatr Surg.
2001;36(9):14011404.
102. Neuman HB, Phillips JD. Laparoscopic Roux-en-Y feeding
jejunostomy: a new minimally invasive surgical procedure for
permanent feeding access in children with gastric dysfunction. J Laparoendosc Adv Surg Tech A. 2005;15(1):7174.
103. Fried MD, Khoshoo V, Secker DJ, Gilday DL, Ash JM,
Pencharz PB. Decrease in gastric emptying time and episodes
of regurgitation in children with spastic quadriplegia fed a
whey-based formula. J Pediatr. 1992;120(4 Pt 1):569572.
104. Holden CE, Puntis JW, Charlton CP, Booth IW. Nasogastric
feeding at home: acceptability and safety. Arch Dis Child.
1991;66(1):148151.
DEVELOPMENTAL DELAY
203
105. Del Buono R, Wenzl TG, Rawat D, Thomson M. Acid

and nonacid gastro-oesophageal reflux in neurologically
impaired children: investigation with the multiple intraluminal impedance procedure. J Pediatr Gastroenterol Nutr.
2006;43(3):331335.
106. Leibold S, Eckmark E, Adams RC. Decision-making for a
successful bowel continence program. Eur J Pediatr Surg.
2000;10(Suppl. 1):2630.
107. Isaacs D, Kilham HA, Somerville HM, OLoughlin EV,
Tobin B. Nutrition in cerebral palsy. J Paediatr Child Health.
2004;40(56):308310.
19
Eating Disorders
Christina Fitzgerald, MS, RD, LDN and Betsy Hjelmgren, MS, RD, LDN, CSP
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
Classification and Diagnosis of Eating Disorders. . . . . . 205
Physical Presentation
Etiology of Eating Disorders
Nutrition in Eating Disorders. . . . . . . . . . . . . . . . . . . . . . . 206

Laboratory Assessment
Nutrition Support in Eating Disorders . . . . . . . . . . . . . . . 208

Oral Nutrition and Meal-Planning Guidelines
Enteral Nutrition Support and Route of Feeding
Parenteral Nutrition
Monitoring Nutrition Interventions
Refeeding Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209

Definition and Incidence
Pathophysiology and Characteristics of StarvationandRefeeding
Prevention and Therapy
204
Learning Objectives
1. Discuss the basic macro- and micronutrient needs in

the eating-disordered patient.
2. Summarize the rationale for providing oral nutrition versus enteral nutrition or parenteral nutrition in
patients with eating disorders.
3. Identify patients at risk for refeeding syndrome and
identify key monitoring parameters in its prevention
and treatment.
Introduction
An eating disorder is an elusive disease that afflicts many

adolescents and young adults. It can be difficult to detect and
can go undiagnosed for extended periods while wreaking
havoc on the young growing body. Unfortunately, eating
disorders, specifically anorexia nervosa, have the highest
premature fatality rate of all mental illnesses.1 In the United
States alone, more than 10 million females and 1 million
males are battling an eating disorder such as anorexia
nervosa or bulimia nervosa. Of those females afflicted,
approximately 5 million are American girls.2 However, this
disease is not specific to the female gender; approximately
10% of those afflicted are males. Once thought of as a
white upper-class disease, eating disorders are seen across
all cultures and all socioeconomic classes. Robinson et al
found that among the leanest 25% of sixth- and seventhgrade girls, Hispanics and Asians reported significantly
more body dissatisfaction than did Caucasians. 3
This chapter reviews the classification, diagnosis, and
etiology of eating disorders; describes nutrition therapy and
monitoring of interventions for eating disorders; defines
and describes the pathogenesis of refeeding syndrome; and
discusses prevention and treatment of refeeding syndrome.
EATING DISORDERS
Classification and Diagnosis of Eating

Disorders
Anorexia nervosa, bulimia nervosa, binge-eating disorder,

and eating disorder not otherwise specified are eating
disorders with the commonalities of extreme emotion and
behaviors around food and body image. The American
Psychiatric Association recommends using a multiaxial
system in assessing and diagnosing mental disorders and
now lists the subcategories Anorexia Nervosa, Bulimia
Nervosa, Binge-Eating Disorder, and Eating Disorder Not
Otherwise Specified in its Diagnostic and Statistical Manual
of Mental Disorders (DSM) (Figures 19-119-4). These
subcategories are diagnosed and classified on Axis 1 of the
multiaxial system.4 Of note, amenorrhea (ie, the absence
of at least 3 consecutive menstrual cycles) is one of the
diagnostic criteria for anorexia nervosa listed in the DSM.
However, this may not be useful in the assessment of adolescent patients as healthy adolescent females may normally
have episodes of amenorrhea during the first 1 to 2 years
after the onset of menarche. 5
Psychiatric comorbidities, such as obsessive-compulsive disorder and affective disorder, are common and should
be treated alongside the eating disorder.6 Major depression
205
is the most common comorbid disease among persons with

anorexia nervosa7 and substance abuse prevalence is estimated at 30% to 70% in persons with bulimia. 8 It is often
these psychiatric comorbidities or other medical problems,
such as continued dizziness or fatigue, that are presented to
the physician prior to the eating disorder detection.
Physical Presentation
Physical presentation of a person with anorexia nervosa
includes lanugo-type hair, muscle wasting, dry skin,
cyanosis of extremities, bradycardia less than 60 beats/min,
and cachexia. When anorexia develops in childhood, the
first clinical sign may be failure to make weight gains while
continuing to grow in height as opposed to documented
weight loss. Growth charts should be evaluated for typical
growth patterns of the individual.9
Physical signs and symptoms of a person with bulimia
nervosa are more difficult to detect but may include parotid
gland enlargement, scarring of the hand used to stimulate
gag reflux (referred to as Russells sign), erosion of dental
enamel with increased dental caries, and sore red throat
Figure 19-2 American Psychiatric Association Diagnostic Criteria for
307.51 Bulimia Nervosa
A.Refusal to maintain body weight at or above a minimally normal

weight for age and height (ie, weight loss leading to maintenance
of body weight less than 85% of that expected; or failure to make
expected weight gain during period of growth, leading to body
weight less than 85% of that expected).
B.Intense fear of gaining weight or becoming fat, even though
underweight.
C.Disturbance in the way in which ones body weight or shape is
experienced, undue influence of body weight or shape on selfevaluation, or denial of the seriousness of the current low body
weight.
D.In postmenarcheal females, amenorrhea, ie, the absence of at least
three consecutive menstrual cycles. (A woman is considered to
have amenorrhea if her periods occur only following hormone, eg,
estrogen, administration.)
Restricting Type: During the current episode of anorexia nervosa, the
person has not regularly engaged in binge-eating or purging behavior
(ie, self-induced vomiting or the misuse of laxatives, diuretics, or
enemas).
Binge-Eating/Purging Type: During the current episode of anorexia
nervosa, the person has regularly engaged in binge-eating or purging
behavior (ie, self-induced vomiting or the misuse of laxatives, diuretics,
or enemas).
A.Recurrent episodes of binge eating. An episode of binge eating is

characterized by both of the following:
1.Eating, in a discrete period of time (ie, within any 2-hour period),
an amount of food that is definitely larger than most people
would eat during a similar period of time and under similar
circumstances;
2.A sense of lack of control over eating during the episode (ie, a
feeling that one cannot stop eating or control what or how much
one is eating).
B.Recurrent inappropriate compensatory behavior in order to prevent
weight gain, such as self-induced vomiting; misuse of laxatives,
diuretics, enemas, or other medications; fasting; or excessive
exercise.
C.The binge eating and inappropriate compensatory behaviors both
occur, on average, at least twice a week for 3 months.
D.Self-evaluation is unduly influenced by body shape and weight.
E.The disturbance does not occur exclusively during episodes of
anorexia nervosa.
Purging Type: During the current episode of bulimia nervosa, the
person has regularly engaged in self-induced vomiting or the misuse of
laxatives, diuretics, or enemas.
Nonpurging Type: During the current episode of bulimia nervosa, the
person has used other inappropriate compensatory behaviors, such
as fasting or excessive exercise, but has not regularly engaged in selfinduced vomiting or the misuse of laxatives, diuretics, or enemas.
Reprinted with permission from: American Psychiatric Association. Diagnostic

and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American
Psychiatric Association; 2000.


307.1 Anorexia Nervosa
206
secondary to excessive purging.10 Dependent on the degree

of purging, and if any restriction is utilized, the patient with
bulimia nervosa may meet all expected weight gains and
track normally along the growth chart percentiles.
Etiology of Eating Disorders

The etiology of eating disorders is complex but appears
to originate from not only predisposed genetic factors
but also serotonin dysfunction and psychological factors
surrounding childhood abuse and/or trauma.11 A 17-year
longitudinal study of 800 children found that eating
conflicts, struggles with food, and unpleasant meals were
additional risk factors for the development of an eating
disorder in this population.12 The role of heredity is still
unclear, as twin studies, often utilized to differentiate
between genetic factors and environment in familial studies,
have reported mixed data, with some demonstrating a
strong correlation while others little correlation.13
Figure 19-3 Research Criteria for Binge-Eating Disorder
A.Recurrent episodes of binge eating. An episode of binge eating is
characterized by both of the following:
1.Eating, in a discrete period of time (ie, within any 2-hour
period), an amount of food that is definitely larger than most
people would eat in a similar period of time under similar
circumstances;
2.A sense of lack of control over eating during the episode (ie, a
feeling that one cannot stop eating or control what or how much
one is eating).
B.The binge-eating episodes are associated with three (or more) of
the following:
1.Eating much more rapidly than normal,
2.Eating until feeling uncomfortably full,
3.Eating large amounts of food when not feeling physically hungry,
4.Eating alone because of being embarrassed by how much one
is eating,
5.Feeling disgusted with oneself, depressed, or very guilty after
overeating.
C.Marked distress regarding binge eating is present.
D.The binge eating occurs, on average, at least 2 days a week for
6months.
Note: The method of determining frequency differs from that used
for bulimia nervosa; future research should address whether the
preferred method of setting a frequency threshold is counting the
number of days on which binges occur or counting the number of
episodes of binge eating.
E.The binge eating is not associated with the regular use of
inappropriate compensatory behaviors (ie, purging, fasting,
excessive exercise) and does not occur exclusively during the course
of anorexia nervosa or bulimia nervosa.
Nutrition in Eating Disorders
Although nutritional rehabilitation and weight stabilization

are essential components in the treatment of and recovery
from eating disorders, research continues to be limited in
this population. The following recommendations should be
used as guidelines and not definitive treatment.
Macronutrients
Energy Requirements
Initial energy requirements for anorexia nervosa are 30

to 40 kcal/kg of current body weight.4 An elevated dietinduced thermogenesis (DIT) has been reported in anorexia
nervosa.14 In patients with an elevated DIT or patients who
are extremely anxious, energy requirements may be as high
as 80 to 100 kcal/kg before weight gain can be achieved.4 If
higher energy needs are required in a patient with anorexia
nervosa due to poor weight gain, the patient should be evaluated for manipulation of intake. In patients with bulimia
nervosa or binge-eating disorder, initial energy requirements for weight maintenance may start at 1.2 to 1.3
measured resting energy expenditure (REE) for sedentary
activity.15 It is recommended to avoid caloric levels that
promote weight loss until an eating pattern is stabilized,
because a restriction in calories in such a patient may trigger
a binging episode.
307.50 Eating Disorder Not Otherwise Specified
A.For females, all of the criteria for anorexia nervosa are met except
that the individual has regular menses.
B.All the criteria for anorexia nervosa are met except that, despite
significant weight loss, the individuals current weight is in the
normal range.
C.All of the criteria for bulimia nervosa are met except that the binge
eating and inappropriate compensatory mechanisms occur at a
frequency of less than twice a week or for duration of less than 3
months.
D.The regular use of inappropriate compensatory behavior by an
individual of normal body weight after eating small amounts of food
(ie, self-induced vomiting after the consumption of two cookies).
E.Repeatedly chewing and spitting out, but not swallowing, large
amounts of food.
F.Binge-eating disorder: recurrent episodes of binge eating in the
absence of the regular use of inappropriate compensatory behaviors
characteristic of bulimia nervosa.
EATING DISORDERS
Protein Requirements
Recommended protein intake is the recommended dietary

allowance (RDA) in g/kg ideal body weight for age (0.81.5
g/kg) or 15% to 20% of total calories from a high biologic
value source.4,15
Fat Requirements
Recommended fat intake is 25% to 30% of total daily calories from fat, with appropriate sources of essential fatty
acids.4,15
Micronutrients
A number of micronutrient deficiencies occur in patients
with eating disorders. In both anorexia nervosa and bulimia
nervosa, zinc deficiency is common and documented as
resultant from suboptimal intake attributed to severe
caloric restriction, avoidance of red meat, and/or the adoption of an inadequate vegetarian lifestyle.16 Additionally,
riboflavin, thiamin, calcium, B-vitamin, and magnesium
deficiencies are well documented and are of concern in
both anorexia nervosa and bulimia nervosa.11 It is recommended to routinely screen and subsequently supplement
207
anorectic patients with thiamin and magnesium in addition to addressing any other found deficiencies.17 At onset
of intervention, provide a 100% RDA multivitamin with
minerals.15
Laboratory Assessment
A detailed laboratory assessment is recommended at time of
initial assessment. Although a complete blood count (CBC)
and chemistry profile is recommended, these traditional
tests are typically normal and may underestimate the physical damage and degree of malnutrition. More targeted and
sensitive tests are recommended, including zinc, iron, prealbumin, transferrin, ferritin, 25-OH vitamin D, thiamin,
and complement 3 (C3) level.18 Refer to Figure 19-5 for a
complete recommendation of laboratory tests.
Despite these normal CBC panels, elevated serum
cholesterol and abnormal lipoprotein profiles are often
found in an anorectic patient regardless of consumption
of extremely low-fat and low-cholesterol diets. Arden et al
postulates that mild hepatic dysfunction, decreased bile
acid secretion, and/or hypothalamic dysfunction may
contribute to these abnormalities.19
Figure 19-5 Recommended Laboratory Tests

Standard
Complete Blood Count (CBC) with differential
Urinalysis
Complete Metabolic Profile: Sodium, Chloride, Potassium, Glucose, Blood Urea Nitrogen, Creatinine, Total Protein,
Albumin, Globulin, Calcium, Carbon Dioxide, AST, Alkaline Phosphates, Total Bilirubin
Serum magnesium
Thyroid Screen (T3, T4, TSH)
Electrocardiogram (ECG)
Special Circumstances
15% or more below ideal body weight (IBW)
Chest X-Ray
Complement 3 (C3)
24 Creatinine Clearance
Uric Acid
20% or more below IBW or any neurological sign
Brain Scan
20% or more below IBW or sign of mitral valve prolapse
Echocardiogram
30% or more below IBW
Skin Testing for Immune Functioning
Weight loss 15% or more below IBW lasting 6 months or longer at any time during course of eating disorder
Dual Energy X-Ray Absorptiometry (DEXA) to assess bone mineral density
Estradiol Level (or testosterone in males)
Adapted from http://www.nationaleatingdisorders.org/p.asp?WebPage_ID=758#Table1. Accessed January 2, 2009.
Copyright 2008 National Eating Disorders Association. www.nationaleatingdisorders.org.
208
Nutrition Support in Eating Disorders

In all eating disorders, the ultimate nutrition treatment goals
include non-restrictive eating that incorporates variety and
nutritional adequacy, and absence of purging behaviors.20
In bulimia, purging efforts are utilized in attempts to lose
weight, and patients will often request assistance during
treatment in achieving this goal. For patients suffering from
either bulimia or binge-eating disorder, although longterm weight loss may be reasonable and/or recommended,
the immediate goal should be interruption of the binge or
binge-purge cycle with stabilization of weight.9
For all eating disorder types, plan 4 to 6 eating opportunities per day. Allow no more than 4 hours between eating
opportunities in order to prevent hypoglycemia, extreme
hunger, and/or the temptation to binge.20 Each meal and
snack should contain a balance of sufficient carbohydrates
to prevent craving, and adequate protein and fat to promote
satiety.9
For patients with binge-eating disorder or bulimia,
the initial meal plan should not include any foods that
the patient is unwilling or unable to keep from vomiting.
Provide support to the patient during and after meals while
encouraging expression of feelings. Additionally, encourage
the patient to remain out of the bathroom for up to an hour
after meal consumption.20
easily purged.15 For the anorectic patient, several options are

appropriate: bolus feed appropriate supplemental calories
only at mealtimes, bolus feed only uneaten calories to meet
mealtime goal, or nighttime continuous feed of uneaten or
excessive calories.20
When EN is utilized, an isotonic, fiber-containing, polymeric formula is usually sufficient for nutritional repletion,
unless impaired digestion or absorption indicates use of an
elemental- or peptide-based product. Due to the high risk
of refeeding syndrome (discussed below) in an anorectic
patient, the initial infusion should not exceed 25 to 50 mL/h
and should be gradually increased 10 to 25 mL every 8 to 24
hours as tolerated until goal feeds are achieved.20
Manipulation behaviors may arise when utilizing EN
in the eating-disordered individual. Precautions need to be
taken. Sample behaviors used in tube feeding manipulation
include18:
lowering the delivery rate on the feeding pump;
using sharp objects to poke holes in the feeding tube;
filing the tube to reduce thickness, then bending the
tube at that point to spill the feeding;
removing the feeding bag from its hanging pole and
swinging it to create air pockets to clog the tube;
purging through the surgical opening of a percutaneous
endoscopic gastrostomy tube; and
placing the nasogastric tube in another place (in a plant,
out the window, in the mattress).
Enteral Nutrition Support and Route of Feeding
The decision to initiate enteral nutrition (EN) in a person

with an eating disorder is a complex one and should take
into account not only the patients immediate physical
health but also his or her psychological health. EN support is
indicated if a patient is refusing any oral intake, rapid weight
loss continues despite improved oral intake, or the patient
is hypermetabolic and unable to meet nutritional needs
orally. When choosing a route for EN, the nasogastric route
is preferred for the relative ease of administration; however,
a nasojejunal placement may alleviate discomfort from
delayed gastric emptying.15 If long-term enteral support is
needed, it is recommended that the tube ending be placed
in the duodenum to avoid problems with gastric reflux and
purging by the patient.18
When utilizing EN in an eating-disordered patient, it
is encouraged to provide the supplementation in a manner
that will continue to promote the persons ability to identify
natural hunger cues. In a patient with bulimia nervosa, a
continuous drip tube feeding is often recommended because
a bolus feeding may cause involuntary vomiting and is more
Parenteral nutrition (PN) is only indicated in cases of digestive inability as it leads to a continued loss of hunger cues in
the eating-disordered individual. 20 When PN is initiated in
severely malnourished patients, caution needs to be taken
due to the possibility that refeeding syndrome might occur.
Refer to the Refeeding Syndrome section in this chapter for
definitions and guidelines.
Oral Nutrition and Meal-Planning Guidelines
Monitoring Nutrition Interventions

The anthropometric status of patients with eating disorders
should be assessed and monitored regularly. Rehydration
and replenished glycogen stores contribute to weight gain
during the initial refeeding; thereafter, weight gain results
from increased lean and fat stores.9 In hospitalized patients
in whom weight restoration is a goal, 2 to 3 pounds per week
is reasonable.9
The hospitalized individual should be weighed daily,
gowned, preprandial and postvoid. Baseline height and
growth history should be obtained and monitored every
1 to 2 months in patients who still have growth potential.
EATING DISORDERS
Baseline anthropometric measurements (skinfolds, midarm

circumference, and midarm muscle circumference) should
be obtained at onset of intervention and monitored as medically indicated.9,15
Refeeding Syndrome
Definition and Incidence
Refeeding syndrome can be described as a cascade of
potentially fatal complications caused by shifts in fluid
and electrolytes as nutrition is reintroduced into the body,
taxing wasted and weakened tissues and demanding more
nutrients than are readily available.21,22 It is manifested in
an assemblage of symptoms that result from rapidly and
inappropriately refeeding (via oral, enteral, or parenteral
route) individuals who have been malnourished or starved
for a period of time, usually exceeding 7 to 10 days. 23
Other symptoms of refeeding syndrome include cardiac
dysfunction, edema, and neurological changes.24 Hypophosphatemia is the hallmark clinical sign of refeeding
syndrome, but hypomagnesemia and hypokalemia are also
common indicators. Glucose intolerance and thiamin deficiency are often present as well.25
The exact incidence of refeeding syndrome is unknown,
due in part to the lack of a universal definition 21 and also
poor recognition of the condition. It is known that 30% to
38% of previously unfed patients receiving PN containing
phosphorus experience hypophosphatemia, 26 and 100% of
these patients develop hypophosphatemia when no phosphorus has been added to the PN solution. It has also been
documented that when patients were vigorously refed,
80% experienced hypokalemia, hypomagnesemia, and/or
hypophosphatemia.27
Pathophysiology and Characteristics of

StarvationandRefeeding
In a normal, fed state, glucose and fatty acids are the preferred
energy substrates for the human body. During periods of
starvation exceeding 3 to 5 days, the body shifts glucose
metabolism to fat and protein metabolism and enters a state
of ketosis. The brain switches from glucose to ketones as
an energy source. The liver visceral protein stores and vital
organs, adipose tissue, and fluids also become depleted. The
wasting of muscle affects vital organ function, including
both respiratory capacity and cardiac mass and output.21,24
During starvation, the kidneys role is to decrease the
excretion of minerals as the bodys stores become depleted.
Serum electrolyte levels are maintained by decreased excretion through the kidneys and by volume constriction as
209
fluid shifts from extracellular to intracellular spaces.21 In

addition, because electrolytes, especially phosphorus, play
a major role in glucose metabolism, electrolyte demands are
diminished during ketosis and starvation.28
As nutrition is reintroduced to the body, a rapid spike
of insulin accompanies the introduction of carbohydrate,
which seems to be the driving force of refeeding syndrome.1
Insulin promotes the uptake of glucose, water, and electrolytes by the cells, and thus glycogen, protein, and fat
synthesis resume. Water and sodium are retained causing
extracellular fluid overload, which can lead to pulmonary
edema and cardiac decompensation.22 Hyperglycemia
may result from excess carbohydrate administration and
inadequate insulin output. Hyperglycemic complications
include osmotic diuresis, dehydration, metabolic acidosis,
and ketoacidosis.21 Anabolism is triggered by macronutrient intake and places demands on the body for a myriad
of other nutrients including phosphorus, potassium,
magnesium, and water-soluble vitamins. These nutrients
are now in short supply due to their depletion during the
prolonged period of fasting, and the bodys remaining
stores are exhausted quickly.21 Thus, hypophosphatemia,
hypokalemia, hypomagnesemia, and thiamin deficiency
may clinically present.
Phosphorous is involved in the intracellular processes
and structural integrity of all the cells.21 It is also required
for the production of energy in the form of adenosine
triphosphate (ATP), and is a structural component of
2,3-diphosphoglycerate (2,3-DPG).25 Hypophosphatemia
may cause clinical symptoms when serum levels reach 1.5
mg/dL, and severe hypophosphatemia ( 1 mg/dL) can
have devastating effects on multiple systems.22 Serum phosphorus levels typically reach a nadir around 2 to 3 days of
refeeding.1 Cardiovascularly, ATP depletion and cardiac
atrophy contribute to hypocontractility and ventricular
arrhythmia, which is complicated by volume overload.
Skeletal muscle weakness and sarcolema disruption lead
to rhabdomyolysis. Myopathy causes difficulty with ambulation and may additionally contribute to respiratory
dysfunction due to accessory muscle and diaphragmatic
weakness/catabolism. Hypophosphatemia affects the
hemo-immunologic system by inducing bone marrow
dysfunction, which can lead to decreased immune function evidenced by hemolytic anemia, thrombocytopenia,
hemolysis, and decreased oxygen delivery to peripheral
tissue. Hypophosphatemia influences the nervous system
via inadequate 2,3-DPG and/or ATP deficiency, which may
contribute to the incidence of delirium, coma, hallucinations, seizures, tetany, weakness, and parasthesias. 25
210
Hypokalemia may result as anabolism resumes and

cells take up potassium during fluid and electrolyte shifts.
Serum potassium levels < 2.5 mg/dL may cause devastating
paralysis, respiratory dysfunction, rhabdomyolysis, muscle
necrosis, and changes in myocardial contraction and signal
conduction.22 Serum magnesium levels < 1 mg/dL can
cause electrocardiographic changes, tetany, convulsions,
and seizures.29 Patients experiencing refeeding syndrome
may present with hypophosphatemia, hypokalemia, and/or
hypomagnesemia, thus illustrating the importance of close
electrolyte monitoring.
All vitamins may be deficient as a result of long-term
inadequate nutritional intake. However, due to its role in
carbohydrate metabolism, thiamin is of particular importance. Thiamin (vitamin B1) is a structural component of
nervous system membranes30 and thus its deficiency may
present with symptoms of beriberi such as parasthesia,
hypoesthesia, anesthesia, and lower extremity weakness,4 or
as Wernickes encephalopathy (ocular abnormalities, ataxia,
confusion, hypothermia, coma) or Korsakoffs psychosis
(retrograde and anterograde amnesia, confabulation). 31
Prevention and Therapy

Prevention of refeeding syndrome is the most effective
factor in its management, therefore an awareness and ability
to identify high-risk patients is key.22 Patients with a weight
loss of 10% within 2 to 3 months or those at or below
70% ideal body weight are at the greatest risk.22 Categories of patients who may meet these criteria include those
with anorexia nervosa, alcoholism, cancer, uncontrolled
diabetes, marasmus, malabsorptive syndrome (eg, pancreatitis, cystic fibrosis, short bowel), prolonged fasting, morbid
obesity with profound weight loss, prolonged antacid use
(due to binding of phosphorus), and long-term diuretic use
(due to electrolyte losses), as well as postoperative patients,
the elderly, and patients allowed nothing by mouth for
greater than 5 to 7 days.21
If a patient meets the preceding high-risk criteria
for refeeding syndrome, there are several acceptable
approaches for preventing or treating refeeding (Table
19-1). Importantly, baseline electrolytes (including potassium, phosphorus, magnesium, and calcium) should be
obtained and corrected if low prior to the initiation of feeds.1
Electrolyte monitoring should continue 1 to 4 times per day
depending upon the severity of malnutrition, for the first 3
days.24 During this time, calories may be introduced at 50%
of goal, not to exceed 20 to 25 kcal/kg/d.1,21,22,24 Macronutrient distribution should limit carbohydrate intake to
2 to 3 g/kg/d based on actual body weight. No restriction
is necessary for protein or fat intake, and common recommendations for each are 1 to 1.5g/kg/d1,22,24 and 1 g/kg/d,
respectively.1 Fluid should be restricted to 800 to 1000
mL/d due to the potential risk of fluid overload and cardiac
decompensation.22,24
TABLE 19-1 Timeline for Prevention and Therapy of Refeeding Syndrome1,21,22,24,25,32,33

Days 13
Days 47
Days 814
Calories
50% of goal, or 1520 kcal/kg/d
Carbohydrate
23 g/kg/d
Protein
Fat
Fluid
11.5 g/kg/d
1 g/kg/d
8001000 mL/d
Phosphorus
0.30.6 mmol/kg/d for normal

serum levels. Correct low serum
levels aggressively with 918 mmol
over 212 hours as indicated
24 mmol/kg/d. Correct low
serum levels as necessary
0.2 mmol/kg/d. Correct
moderately low serum levels with
0.5 mmol/kg x 24 hours. Correct
severely low levels with 24 mmol
over 6 hours
200300 mg daily
Multivitamin/mineral supplement
daily
Advance by 200300 kcal if

electrolytes stable
Advance to meet daily calorie
adjustments
11.5 g/kg/d
1 g/kg/d
Advance with calories if electrolytes
stable and no clinical signs of fluid
overload
0.30.6 mmol/kg/d. Continue
to correct low serum levels as
necessary
Advance every 3 days by 200300

kcal if electrolytes remain stable
Advance to meet daily calorie
adjustments
11.5 g/kg/d
1 g/kg/d
Advance with calories if electrolytes
stable and no clinical signs of fluid
overload
0.30.6 mmol/kg/d. Continue
to correct low serum levels as
necessary

0.2 mmol/kg/d if stable. 0.25
mmol/kg/d for patients who have
been hypomagnesemic

0.2 mmol/kg/d
200300 mg daily
daily
200300 mg daily until day 10

daily
Potassium
Magnesium
Thiamin
Other vitamins/minerals
EATING DISORDERS
During these first few days of renourishment, electrolytes, if low, should be corrected aggressively. Potassium
phosphate preferably, or sodium phosphate in the presence
of normal serum potassium, can be given intravenously for
moderate to severe hypophosphatemia.25 Different references recommend infusing 9 to 18 mmol over anywhere
from 2 to 12 hours.21,25,32 For orally fed patients with mild
to moderate hypophosphatemia, cows milk is an excellent
source of both phosphorus and potassium,25 and can be used
to treat mild electrolyte derangements. Oral sodium phosphate can also be used, at 500 mg 4 times per day until serum
phosphorus is stable, then decreased to 250 mg 3 times per
day for maintenance.22 Mild to moderate hypomagnesemia
can be treated with an initial dose of 0.5 mmol/kg over a
24-hour infusion, then maintained at 0.25 mmol/kg/d for
the next 5 days to maintain serum levels.21 For severe hypomagnesemia, infuse 24 mmol over 6 hours, then follow with
0.25 mmol/kg/d for the next 5 days as above.21
In addition to the attention paid to macronutrients and
electrolytes, patients at risk of refeeding should receive a
daily multivitamin/mineral supplement. Any signs or symptoms of thiamin deficiency can be treated with 200 to 300
mg of oral thiamin daily for 10 days to correct deficiency. 21
After electrolytes have stabilized and the patient has
received 72 hours of nutrition at 50% of goal, calories can
gradually be increased every 3 days by 200 to 300 kcal. 22,24,33
Continue to monitor and correct electrolytes as feedings
progress for the duration of the first 2 weeks of feeding. 21
With awareness and proper monitoring, refeeding
syndrome can be prevented or managed appropriately to
prevent serious complications and the potential of death.
Monitoring and correction of electrolytes, supplementation of nutrients, and conservative administration of
carbohydrate and fluid can save lives of those at highest risk
forrefeeding.
1. The following are common physical signs and symptoms of anorexia nervosa:
A. Lanugo-type hair, cyanosis of the extremities, and
erosion of the dental enamel
B. Cyanosis of the extremities, erosion of the dental
enamel, and Russells sign
C. Cachexia, cyanosis of the extremities, and muscle
wasting
D. Cachexia, Russells sign, and sore red throat
211
2. In an eating-disordered individual, parenteral nutrition

is only indicated
A. If the person is unwilling to consume food orally
B. In cases of digestive inability
C. If the person is < 75% of ideal body weight
D. If the person is manipulating the enteral tube
3. Persons at greatest risk for refeeding syndrome
include:
A. Weight loss 10% within 2 to 3 months or those at
or below 70% ideal body weight
B. Weight loss 10% within 6 to 8 months or those at
or below 70% ideal body weight
C. Weight loss 7% within 2 to 3 months or those at or
below 75% ideal body weight
D. Weight loss 7% within 2 to 3 months or those at or
below 70% ideal body weight
References
1. Skipper A, ed. Dietitians Handbook of Enteral and Parenteral

Nutrition. 2nd ed. Gaithersburg, MD: American Society for
Parenteral and Enteral Nutrition; 1998.
2. Crowther JH, Wolf EM, Sherwook N. Epidemiology of
bulimia nervosa. In: Crowther M, Tannenbaum DL, Hobfoll
SE, Stephens MAP, eds. The Etiology of Bulimia Nervosa: The
Individual and Familial Context. Washington, DC: Taylor +
Francis; 1992:126.
3. Robinson T, Killen J, Litt I, et al. Ethnicity and body dissatisfaction: are Hispanic and Asian girls at increased risk for
eating disorders? J Adolesc Health. 1996;19(6):384393.
4. American Psychiatric Association. Practice Guideline for the
Treatment of Patients with Eating Disorders. 2nd ed. Washington, DC: APA Press; 2000b.
5. Fischer M, Golden NH, Katzman DK, et al. Eating disorders in adolescents: a background paper. J Adolesc Health.
1995;16:420437.
6. Carney CP, Andersen AE. Eating disorders. Guide to medical
evaluation and complications. Psychiatr Clin North Am.
1996;19:657679.
7. Herzog DB, Nussbaum KM, Marmor AK. Comorbidity
and outcome in eating disorders. Psychiatr Clin North Am.
1996;19:843859.
8. Vastag B. Whats the connection? No easy answers for
people with eating disorders and drug abuse. JAMA.
2001;285:10061007.
9. Mahan LK, Escott-Stump S. Krauses Food, Nutrition, & Diet
Therapy. 11th ed. Philadelphia: WB Saunders Co; 2004.
10. Russell GFM. The changing nature of anorexia nervosa. J
Psychiatr Res. 1985;19:101109.
11. Patrick L. Eating disorders: a review of the literature with
emphasis on medical complications and clinical nutrition
Eating Disorders. Alternative Med Rev. FindArticles.com Web
site. http://findarticles.com/p/articles/mi_m0FDN/is_3_7/
ai_88823869/pg_3/ Accessed January 3, 2009.
212
12. Kotler LA, Cohen P, Davies M, Pine DS, Walsh BT. Longitudinal relationships between childhood, adolescent, and
adult eating disorders. J Am Acad Child Adolesc Psychiatry.
2001;40(12):14341440.
13. Fairburn CG, Cowen PJ, Harrison PJ. Twin studies
and the etiology of eating disorders. Int J Eat Disord.
1999;26:349358.
14. de Zwaan M, Aslam Z, Mitchell JE. Research on energy
expenditure in individuals with eating disorders: a review. Int
J Eating Disord. 2002;32:127134.
15. The Royal College of Psychiatrists. Guidelines for the nutritional management of anorexia nervosa. http://www.rcpsych.
ac.uk/files/pdfversion/cr130.pdf. Accessed December 15,
2008.
16. Bakan R, Birmingman CL, Aeberhardt L, Goldner EM.
Dietary zinc intake of vegetarian and nonvegetarian patients
with anorexia nervosa. Int J Eating Disord. 1993;13:229233.
17. Winston AP, Jamieson CP, Madira W, et al. Prevalence of
thiamin deficiency in anorexia nervosa. Int J Eat Disord.
2000;28:451454.
18. Woosley M. Eating Disorders: A Clinical Guide to Counseling
and Treatment. Chicago, IL: American Dietetic Association;
2002.
19. Arden MR, Weiselberg EC, Nussbaum MP, et al. Effect of
weight restoration on the dyslipoproteinemia of anorexia
nervosa. J Adolesc Health. 1990;11:199202.
20. Setnick JS. The Eating Disorders Clinical Pocket Guide: Quick
Reference for Healthcare Professionals. Snack Time Press;
2005.
21. Mehanna HM, Moledina J, Travis J. Refeeding syndrome:
What it is, and how to prevent and treat it. BMJ.
2008;336:14951498.
22. Tresley J, Sheean PM. Refeeding syndrome: recognition

is the key to prevention and management. J Am Diet Assoc.
2008;108:21052108.
23. Lagua RT, Claudio VS. Nutrition and Diet Therapy Reference
Dictionary. 4th ed. New York, NY: Chapman and Hall; 1996.
24. McCray S, Walker S, Parrish CR. Much ado about refeeding.
Practical Gastroenterology. 2005;23:2644.
25. Marinella MA. The refeeding syndrome and hypophosphatemia. Nutr Rev. 2003;61:320323.
26. Sacks GS, Walker J, Dickerson RN, et al. Observations of
hypophosphatemia and its management in nutrition support.
Nutr Clin Pract. 1994;9:105108.
27. Yantis M, Velander R. How to recognize and respond to
refeeding syndrome. Nursing. 2008;38:3439.
28. Brody T. Nutritional Biochemistry. San Diego, CA: Academic
Press; 1994.
29. Kraft MD, Btaiche IF, Sacks GS. Review of the refeeding
syndrome. Nutr Clin Prac. 2005;20:625633.
30. Itokaiva Y, Schulz RA, Cooper JR. Thiamine in nerve
membranes. Biochem Biophys Acta. 1972;266:293299.
31. Reuler JB, Girard DE, Cooney TG. Wernickes encephalopathy. N Engl J Med. 1985;312:10351039.
32. Dwyer K, Barone JE, Rogers JF. Severe hypophosphatemia in
postoperative patients. Nutr Clin Pract. 1992;7:279283.
33. Klein CJ, Stanek GS, Wiles CE. Overfeeding macronutrients
to critically ill adults metabolic complications. J Am Diet
Assoc. 1998;98:795806.
20
Food Allergies
Mary Beth Feuling, MS, RD, CD, CNSD, Michael B. Levy, MD, and Praveen S. Goday, MBBS, CNSP
Learning Objectives
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pathophysiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Major Food Allergens. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical Presentation. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
213
213
214
215
215
215
IgE-Mediated Diseases
Mixed IgE and Non-IgE Mediated Diseases
Non-IgE Mediated Disease
Allergy Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216

Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
Clinical and Laboratory Assessment
Nutrition Intervention
Nutritionally Complete Formulas
Milk Substitutes
Dietary Allowance Versus Dietary Restrictions
Micronutrient Supplementation . . . . . . . . . . . . . . . . . . . . 221

Two Special Scenarios
Prognosis and Follow-Up
Food Allergies and Nutrition Support. . . . . . . . . . . . . . . . 223

Enteral Nutrition
1. Understand the epidemiology, pathophysiology,

clinical presentation, and recognition of pediatric food
allergies.
2. Describe the nutrition assessment of children with food
allergies.
3. Summarize the nutrition management of children with
food allergies.
4. Understand the food and non-food allergy issues that
may impact the provision of nutrition support.
Introduction
Adverse reactions to foods are a growing public health

concern in the Western world. Food allergies are a greater
problem in children than in adults, with significant food
allergies being associated with poorer nutrition outcomes
in children. This chapter discusses the epidemiology,
pathophysiology, clinical presentation, management, and
prognosis of children with food allergies.
Definitions
Several terms may be used when defining adverse reactions to foods. An abnormal response to a food may include
allergy, hypersensitivity, or intolerance. Tolerance
usually refers to the ability to consume a food that may have
the potential for allergy or a food that previously caused
allergy and is now consumed without sequelae.
Adverse reactions to foods may occur within a spectrum of reactions ranging from immunoglobulin E (IgE)
to non-IgE mechanisms. Generally speaking, allergy or
hypersensitivity refers to IgE-mediated events and intolerance refers to non-IgE events. Other important definitions
that will be used in this chapter are outlined in Table 20-1.
213
214
Table 20-1 Definitions of Common Terms That Are Frequently Used in Association with Food Allergies
Term
Definition
Adverse food reaction

Allergen
Anaphylaxis
Antibodies
Antigen
Any undesired response to a food regardless of mechanism.

Substance foreign to the body that, on interaction with the immune system, causes an allergic reaction.
An acute, often severe, and sometimes fatal immune response that may affect one or more organ systems.
Immunoglobulins produced in response to an antigen or allergen.
Any substance (as a toxin or enzyme) that stimulates an immune response in the body (especially the production of
antibodies).
A disease characterized by chronic inflammation of the skin which is atopic, hereditary, and non-contagious.
Tendency toward the development of allergic diseases, determined genetically.
An eating plan that omits one or more foods suspected to cause an adverse food reaction.
An adverse food reaction that is mediated by an immunologic mechanism; the reaction occurs consistently after
consumption of a particular food and causes functional changes in target organs; IgE-mediated food hypersensitivity,
gluten sensitivity.
Administration of a food in increasing amounts performed in order to establish whether a patient is orally tolerant. This
may be performed in an open, single-blind, or double-blind fashion.
A subjective tool for recording food and drink consumed and onset, intensity, and duration of symptoms.
An adverse reaction to a food caused by toxic, pharmacologic, metabolic, or idiosyncratic reactions to the food or
chemical substances in the food.
Tissue cells that release histamine and other mediators that cause allergic symptoms.
A test in which an antigen is applied directly to the skin and is pricked with a specifically designed device. The localized
histamine and mediator release correlates to the presence of specific IgE.
Ability to consume a food that may have the potential for allergy or a food that previously caused allergy and is now
consumed without sequelae.
Atopic dermatitis (eczema)

Atopy
Elimination diet
Food allergy
(hypersensitivity)
Food challenge
Food and symptom diary
Food intolerance
Mast cells
Skin prick test
Tolerance
For many clinicians, defining a food reaction as IgE-mediated or non-IgE mediated has great utility. IgE reactions
have been well understood and chemically described as a
cascade of events which involves a process that results from
mast cell or basophil degranulation at mucosal surfaces
or the skin. Because IgE can be quantitatively measured,
levels of food-specific IgE may aid in the diagnosis of IgEmediated food allergy and serial food-specific IgE levels
may be followed to help determine the development of
clinical tolerance.
Non-IgE food intolerance may include immunologic
and non-immunologic reactions due to the effects of other
components within food (eg, lactose, seafood toxins, or
naturally occurring pharmacologically active compounds
such as tyramine). These substances may cause an adverse
reaction, but are differentiated from true food allergy
because they do not involve the IgE cascade.
Gastrointestinal diseases related to foods also may be

caused by IgE and non-IgE mechanisms. Some diseases
such as eosinophilic esophagitis may have both an IgE and
a non-IgE component. These diseases are characterized in
Table 20-2.
Epidemiology
Adverse reactions to foods have been reported in up to

15% to 20% of the population with the highest prevalence
in infancy and childhood. In 2007, the Centers for Disease
Control and Prevention (CDC) reported that an estimated
3 million children under age 18 years (3.9%) had a reported
food allergy. Higher rates were seen in children under age
5, as compared with children 5 to 17 years of age with boys
and girls showing similar rates of food allergy. Interestingly,
Hispanic children had lower rates than non-Hispanic black
or non-Hispanic white children.1
Table 20-2 Clinical Food Allergy Syndromes Associated with IgE or Non-IgE Mechanisms
IgE-Mediated Syndromes
Mixed IgE & Non-IgE-Mediated Syndromes
Non-IgE-Mediated Syndromes
Oral allergy syndrome

Anaphylaxis
Urticaria
Angioedema
Eosinophilic esophagitis
Eosinophilic gastritis
Eosinophilic gastroenteritis
Atopic dermatitis
Protein-induced enterocolitis
Protein-induced enteropathy
Food protein-induced enterocolitis syndrome (FPIES)
Dermatitis herpetiformis, gluten enteropathy
FOOD ALLERGIES
There has been a significant rise in atopic conditions

in westernized countries over the past 20 years. Results
from the third National Health and Nutrition Examination
Survey (NHANES III), which measured the prevalence of
positive skin prick test responses to common allergens in
the U.S. population from 19881994, showed a significant
rise in allergy skin prick test reactivity from the NHANES
II study of 19761980.2 In 2007, the reported food allergy
rate among all children younger than 18 years was 18%
higher than in 1997. During the 10-year period of 1997 to
2006, food allergy rates increased significantly among both
preschoolers and older children. In addition, from 2004 to
2006, there were approximately 9,500 hospital discharges
per year with a diagnosis related to food allergy among children under age 18 years.1
Most studies suggest that 6% to 8% of the pediatric
population and up to 1% to 3% of adults may have true food
allergy based on skin prick tests. The true prevalence in the
population is probably lower because of false-positive skin
prick tests and this fact has also been noted using random
telephone surveys. 3 Sicherer et al determined the prevalence of peanut and tree nut allergy to be 0.7% adults and
0.4% children in a New York telephone survey. 3,4
Children with food allergies are more likely to have
other allergic conditions including asthma and atopic
dermatitis when compared to children without food allergies. Asthma has been reported in 29% of children with food
allergies (12% in children without food allergies); respiratory allergy is noted in over 30% versus 9% without food
allergies while eczema is seen in 27% as compared with 8%
of children without food allergies.2 Patients with a peanut
allergy have asthma and atopic dermatitis prevalence rates
of 46% and 50%, respectively. 5
Pathophysiology
The production of IgE antibody may develop in the genetically predisposed individual through mechanisms that
involve multiple factors. Once allergen-specific IgE is
produced, binding to the high-affinity IgE receptor which
is present on mast cells and basophils occurs. Low-affinity
IgE receptors are present on eosinophils, monocytes, and
macrophages.6
There are multiple host, antigen, and allergen factors
that may be involved in the IgE-sensitization cascade which
may result in the subsequent development of clinical allergy.
These factors include the genetics of the host, immunologic
competence at the mucosal level, and allergen presentation by intact antigen-processing cells, as well as the route
of exposure to the allergen. Sensitization may occur via
215
ingestion, inhalation of airborne residue (eg, steam droplets

carrying antigen), or by skin contact. The allergenic properties of foods may be affected by product processing (eg,
heating or enzymatic digestion), which may affect changes
in the antigenic epitope conformation. This may render a
food more or less allergenic. The allergen threshold dose,
which is the dose that triggers a systemic allergic reaction
in the host, involves many factors and is an area of current
research interest.
IgE-mediated degranulation of effector cells occurs
after the food allergen contacts the food-specific IgE antibodies. Cross-linking of the IgE antibodies present on the
surface of these cells results in mediator release of histamine, leukotrienes, and prostaglandins. These mediators
cause the clinical manifestations of immediate hypersensitivity reactions including pruritus, vasodilatation, smooth
muscle contraction, mucus production, and inflammatory
cell recruitment to tissues.6
Major Food Allergens
Almost every major food allergen identified is a protein or

glycoprotein. They tend to resist denaturation by heat or acid
and may be more or less common depending on the society
or ethnicity of the population observed. In the United States,
milk, soy, egg, wheat, peanut, tree nut, fish, and seafood are
the most common allergens noted. However, other legumes,
sesame, poppy seed, sunflower seed, pine nuts, and spices
are allergens of increasing importance.
Clinical Presentation
IgE-Mediated Diseases
The major IgE-mediated allergic diseases are oral allergy
syndrome, anaphylaxis, urticaria, and angioedema.
The pollen-associated oral allergy syndrome presents
with pruritus of the lips, palate, tongue, and oropharynx
following oral mucosal contact with fresh fruits and vegetables. The reaction usually does not occur following a
cooking process because the cross-reactive allergen is very
heat sensitive. These symptoms usually resolve without
treatment and generally do not progress to cause more
systemic involvement. Cross-reactivity between plant
pollens and fruits is responsible for the clinical syndrome.
Specifically, patients with ragweed sensitivity may have
these symptoms after ingesting watermelon, cantaloupe,
banana, or honeydew while patients sensitive to birch
pollen may notice symptoms with apple, pear, celery,
carrot, or peach.
Food-induced anaphylaxis is the most severe form of
216
immediate hypersensitivity reaction. Symptoms may include

hypotension, urticaria, angioedema, respiratory compromise
including laryngeal edema, and gastrointestinal symptoms
of pain, vomiting, and diarrhea; although, food-induced
anaphylaxis can occur without any skin manifestations.
Near-fatal and fatal reactions often occur in the teenage to
35-year age range and are associated with a patient history of
asthma, an accidental ingestion of a known allergen, and the
delayed administration of epinephrine. The foods implicated
are usually peanut, tree nut, or seafood.7
Mixed IgE and Non-IgE Mediated Diseases

The gastrointestinal eosinophilic disorders listed in Table
20-2 have features that may best be described as mixed
IgE and non-IgE disorders. There may be evidence of IgE
present (eg, positive skin prick tests or serologic in vitro
IgE to the offending food) but other mechanisms may be
involved. These disorders are characterized by eosinophilic
infiltration of the esophageal, gastric, or intestinal mucosa.
These patients often present with vomiting, abdominal
pain, weight loss, or failure to thrive. Diagnosis is confirmed
with endoscopic examination and biopsy. Eosinophilic
esophagitis is discussed later in this chapter.
Non-IgE Mediated Disease

Efforts to define the mechanisms underlying the non-IgE
mediated diseases listed in Table 20-2 have shown varying
results. These conditions are thought to be caused by other
immunologic mechanisms not involving IgE. Typical
symptoms may include recurrent vomiting or diarrhea. In
infancy, this is most commonly related to cows milk or soy
protein. This condition is discussed in detail below.
Food protein-induced enterocolitis syndrome
(FPIES) is classified as a non-IgE mediated allergic disorder,
triggered by the ingestion of certain food proteins.8 Children
usually present at less than 12 months of age with vomiting
and/or diarrhea within hours of ingestion of the causative
food. The symptoms should mimic IgE-mediated anaphylaxis, however the clinical picture lacks the usual cutaneous
signs of urticaria, angioedema, or respiratory compromise.
Some children present in a moribund state, with shock and
metabolic acidosis.9 Typically, the offending food is either
cows milk or soy10,11 although meats, vegetables, and grains
have also been implicated.9 Tests for food-specific IgE by
either skin prick testing or serologic in-vitro methods are
negative.12 Awareness of the entity is important as the clinical presentation can be confused with other life-threatening
conditions. Multiple presentations before the true diagnosis
is established are the norm. Early diagnosis should be based
on the clinical history and presentation, and removal of the

offending food serves as a simple and effective therapy. The
age at which oral tolerance develops varies.
Allergy Testing
Allergy skin prick testing is commonly used by the practicing allergist-immunologist to determine the presence
of IgE to specific foods. Clinical correlation of the patient
history to the testing results is important. The skin prick
technique is highly reproducible and extracts for these
tests are commercially available for hundreds of airborne
and food allergens. These tests are performed by applying
the extracts by a prick or puncture technique to the palmar
surface of the forearm or upper back. The allergy prick test
is actually a localized mediator-release phenomenon which
occurs following allergen presentation to skin mast cells.
The reaction is a nearly immediate wheal and flare reaction characteristic of IgE-mediated allergy. The test is read
within 20 minutes and correlates closely with the presence
of specific IgE to the suspected allergen. Positive tests indicate the presence of IgE but not clinical reactivity with an
estimated false positive rate of approximately 50%. A negative test has high negative predicted value of nearly 95%,
thus excluding the role of IgE.13
In-vitro radioallergosorbent tests (RAST) are blood
tests that are available for the determination of serumspecific IgE with close correlation to skin prick testing
results. The Pharmacia ImmunoCAP system has been
studied with food challenge results showing a greater than
95% predictive value for reactions to peanut, egg, and milk.
There are a small number of false negative ImmunoCAP
tests for peanuts. The established values can be utilized by
clinicians to determine when a food challenge may be safe
to perform in the patient with IgE-mediated food allergy.14
Management
There is currently no cure available for the food allergic

individual. Strict avoidance of the allergy-causing food is
the only way to prevent a reaction. Future treatment horizons may include anti-IgE monoclonal antibody which has
already been trialed in peanut allergy, as well as newer forms
of allergen immunotherapy.15 Trials in oral desensitization
have been recently published and have shown efficacy in
inducing tolerance.16
Exclusion of foods may lead to nutrition problems that
require the expertise of a qualified dietitian. All patients
with anaphylaxis to foods (or other allergens) and patients
with severe food allergies should be educated regarding the
use of injectable epinephrine, which may be lifesaving in the
FOOD ALLERGIES
event of accidental exposure. Practically, all children with

multiple food allergies should be co-managed by an allergist
and a dietitian.
Because avoidance is the only proven treatment,17 children with food allergies need to avoid the foods to which they
are allergic. The goals of the dietitian are twofold: to provide
families and patients with guidelines, education, and suggestions for avoiding the allergenic foods and to monitor the
child to ensure a nutritionally adequate diet that will promote
appropriate weight gain and growth. There must be a multidisciplinary approach that is adopted in conjunction with the
allergist with accurate diagnosis of causative foods, assessment of nutrition status, institution of a diet that eliminates
the offending foods (elimination diet), prevention of adverse
reactions, development of proper emergency treatment with
an action plan in place, and treatment of associated atopic
217
disorders. There should be ongoing care by both the allergist

who periodically determines whether the child has developed
tolerance to any of the offending foods and the dietitian who
continues to monitor the nutrition status and growth of the
child. An algorithm for the management of the food-allergic
child is proposed in Figure 20-1.
Restriction of a childs diet due to the diagnosis of food allergies may have a severe impact on his or her nutrition intake.
This section provides a practical approach to identifying the
risk factors that can lead to nutrition deficiencies, undernutrition, and poor growth while providing guidelines for a
comprehensive nutrition assessment.
Because strict avoidance of the causative food is necessary, it is critical to clearly define the avoidance list. The
Figure 20-1: Algorithm for the Evaluation of Suspected Food Reactions
218
nutrition risk increases as the number of foods avoided

increases. This compounds the challenge for providing a
nutritionally complete diet. Any additional problems associated with feeding further compound the risk. It is crucial
to collaborate with the allergist and the family to clearly
define the foods to be avoided and prevent any unnecessary
restrictions. The degree of nutrition risk can be ascertained
by methods outlined in Table 20-3.
Table 20-3 Questions That Need To Be Asked To Determine the Degree of
Nutrition Risk in Children with Food Allergies
How many foods need to be avoided?
Risk increases with more foods being/needing to be avoided

What is the impact on nutrients?
Risk increases with more of the following nutrients being impacted

orfewer nutrients being severely impacted
Calories
Protein
Fat
Micronutrients
Are there other concerns about food intake?
Risk increases with other medical and psychological diagnoses

affecting intake
Swallowing/chewing difficulties
Psychological diagnoses affecting intake
Feeding disorder
When a diagnosis of food allergy has been made,

medical nutrition therapy with scheduled follow-up visits
can provide a way to monitor the overall health effects of
food elimination. Identifying individuals at risk may protect
and possibly improve the patients nutrition and overall
health status. Medical nutrition therapy with appropriate
food substitution(s) provides the tools necessary, giving the
food-allergic patient the specific focus needed for improved
nutrition self-care and food allergen avoidance.18
Table 20-4 provides a case scenario where 3 toddler
diets are presented. The first diet is a typical unrestricted
diet. Once the toddler is diagnosed with food allergies to
milk, egg, and peanut, the second diet that needs to be
followed puts him at a high risk for malnutrition and micronutrient deficiencies. The third diet provides the vital food
substitutions (for the foods that the child must avoid) to
ensure adequate nutrition.
Nutrient intake needs change over time throughout
the life cycle. This includes all of the macronutrient, micronutrient, and fluid needs, all of which play a key role in a
developing child. These intake guidelines can be found
in other chapters of this book. Nutrient requirements for
infants and children with food allergies are the same as the
requirements for healthy children. Occasionally they will

require increased caloric intake to provide catch-up growth
due to poor growth often associated with allergen restriction. In addition, children with moderate to severe atopic
dermatitis may have higher caloric and protein needs based
on the degree of skin involvement. The more medically
complex allergic child may have other nutrition needs due to
his or her other medical diagnoses and these are discussed
elsewhere in this book.
Clinical and Laboratory Assessment

Nutrient intake and growth are affected in children with
food allergies. Children with greater than 2 food allergies
have a lower height, weight, and body mass index (BMI)
than those with 1 food allergy.19 Diagnosis of food allergies often results in poor growth due to lack of caregiver
knowledge, inadequate intake due to lack of guidance for
substitutions to meet nutrition needs, and increased anxiety
associated with feeding. Failure to achieve normal growth
rates or growth velocity definitely suggests the need for
medical nutrition therapy but a multidisciplinary approach
involving a dietitian at the time of diagnosis of food allergy
may be able to prevent or attenuate problems associated with
growth. Accurate anthropometric data and use of growth
charts is critical to the evaluation of these children.
Based on the diet and feeding history, the clinician
must review the risk of micronutrient deficiency. Table 20-5
summarizes the micronutrients provided by the top 8 allergens and provides the most common food alternatives that
can be used when these foods need to be avoided.
Many children with multiple food allergies are at high
risk for inadequate essential amino acids and essential fatty
acids. Refer to Chapter 3 (Carbohydrates) and Chapter 4
(Fats) for a complete discussion of the goals for the pediatric
population. Often protein hydrolysate-based and/or amino
acid-based formulas can be used to supplement the diet to
meet these nutrition needs. Patients who present after being
on prolonged significantly restricted diets without concomitant multivitamin-multimineral use and patients who
present with significant malnutrition should be considered
for laboratory tests of micronutrient adequacy. The clinical
scenario should guide which laboratory tests are obtained
(eg, a vegetarian child who is sustained on rice milk should
be tested for anemia, zinc deficiency, essential fatty acid
deficiency, and vitamin D deficiency). Most patients in
the United States with minimal dietary restrictions can be
managed through judicious use of a multivitamin-multimineral supplement and without laboratory testing.
FOOD ALLERGIES
219
Table 20-4 Case Scenario

Diet 1
Diet 2
Diet 3
Breakfast
Lunch
Dinner
Breakfast
Lunch
Dinner
Breakfast
Lunch
Dinner
Whole milk
Whole milk
Whole milk
Whole milk
Whole milk
Whole milk
Cereal
Peanut
butter & jelly
sandwich
Cooked
carrots with
butter
Meatloaf
Cereal
Meatloaf
Peas
Banana
Peanut
butter & jelly
sandwich
Cooked
carrots
with butter
Enriched
soymilk
Cereal
Peas
Banana
Enriched
soy milk
Milk-free,
egg-free
meatloaf
Peas
Strawberries
Mashed
potatoes
Enriched
soymilk
Soynut butter
and jelly
sandwich
Cooked
carrots with
milk-free
margarine
Strawberries
Banana
Strawberries
Mashed
potatoes
Roll with
butter
Roll with
butter
Mashed
potatoes
made with
chicken broth
Milk-free roll
with milk-free
margarine
SNACK
SNACK
SNACK
SNACK
SNACK
SNACK
SNACK
SNACK
SNACK
Granola bar
Yogurt drink
Ice cream
Granola bar
Yogurt drink
Ice cream
Soy yogurt
Soy ice cream
Juice
Oatmeal
cookie
Juice
Oatmeal
cookie
Teddy
Grahams
Juice
FAAN Oatmeal
cookie*
*Food Allergy and Anaphylaxis Network recipe

(can be found at http://www.foodallergy.org/recipes.html)
Nutrition Analysis of Diet 1

Nutrient
Calories
Protein
Fat
1490 kcal
47 g
55 g
Calcium
Vitamin D
Iron
Zinc
1100 mg
203 IU
9.9 mg
8.9 mg

% Goal**
Nutrient
> 100
360
33% of
totalkcal
221
101
141
297
Calories
Protein
Fat
305 kcal
5g
2g
Calcium
Vitamin D
Iron
Zinc
98 mg
20 IU
4 mg
2.6 mg

% Goal**
Nutrient
25
41
6% of
totalkcal
20
10
59
87
Calories
Protein
Fat
1360 kcal
42 g
49 g
% Goal**
Calcium
Vitamin D
Iron
Zinc
754 mg
285 IU
10 mg
6 mg
> 100
321
32% of
totalkcal
151
285
147
201
**Based on DRI for age.20

Legend: D
iet 1: Sample menu for an 18-month-old child prior to diagnosis of food allergy.
Diet 2: Nutritionally depleted sample menu for the same child who has been diagnosed with milk, egg, and peanut allergy.
Diet 3: Revised nutritionally adequate menu for the child with acceptable food substitutions.
Table 20-5 Key Micronutrients Provided by the Most Common Food Allergens and Alternative Food Sources That Can Serve as Food Substitutes for the
Allergenic Foods
Allergenic Foods
Micronutrients Provided
Appropriate Food Substitutes
Milk
vitamin A, vitamin D, riboflavin, pantothenic acid, vitamin

B12, calcium, phosphorus
vitamin B12, riboflavin, pantothenic acid, biotin, selenium
meats, legumes, whole grains, nuts, fortified foods/

beverages (with B vitamins, calcium, and vitamin D)
meats, legumes, whole grains
meats, legumes
Wheat
thiamin, riboflavin, pyridoxine, folate, calcium, phosphorus,

magnesium, iron, zinc
thiamin, riboflavin, niacin, iron, folate if fortified
Peanut/Tree nut
vitamin E, niacin, magnesium, manganese, chromium
Fish/Shellfish
vitamin B6, vitamin E, niacin, phosphorus, selenium,

omega-3 fatty acids, folate, copper, zinc, potassium
Egg
Soy
alternative fortified grains (barley, rice, oat, corn, rye, quinoa,

soy) and potatoes
whole grains, vegetable oils
whole grains, meats, oils, soybean, flaxseed, nuts
220
Nutrition Intervention
Education provides a family and patient the pathway for
success with an elimination diet. This includes education
regarding dietary avoidance and consideration of nutrition
deficiencies that may result. In addition, they must receive
education regarding the nutrition goals for the patient in order
to avoid nutrition consequences of food allergies. They must
also be educated about resources for obtaining additional
information regarding living with food allergies (eg, support
groups, local retail establishments that sell allergen-free
foods, cookbooks, and other helpful tips for the elimination
diet). A list of food allergy resources is provided in Table 20-6.
Each food-allergic child/family must be given a list of substitutions in order to be successful with strict avoidance of the
food allergens. In addition, a nutritionally complete formula
or beverage, if possible, should be encouraged. This type of
information assists the patient and family in living a normal
and well-nourished life despite having food allergies. Without
education, the recommendation of an elimination diet can be
overwhelming and unsuccessful as families struggle to find
accurate and useful information.
the small fraction of children who are also allergic to the

protein hydrolysates. Both of these types of formulas are
generally less palatable than standard formulas and are
considerably more expensive. Significant advances in the
flavor and acceptability of the formulas have been made
which has improved the adherence to incorporating these
formulas as supplemental nutrition. The major categories
of formulas are enumerated in Table 20-7.
Table 20-7 Major Pediatric Formulas
Formula
Protein
Examples
Cows Milk
Casein, whey
Infant formulas
Similac Advance Early Shield

Enfamil Premium
Formulas for older children
PediaSure
Lactose-free
Infant formulas
Similac Sensitive
PediaSure
Soy
Soy
Infant formulas
Enfamil ProSobee
Similac Isomil Advance
Bright Beginnings Soy Pediatric Drink
Table 20-6 Food Allergy Resources

Resource
Website
Food Allergy & Anaphylaxis Network

American Academy of Allergy,
Asthma& Immunology
American Dietetic Association
Asthma and Allergy Foundation
ofAmerica
American Partnership For
Eosinophilic Disorders
American College of Allergy,
Asthma& Immunology
http://www.foodallergy.org
http://www.aaaai.org
http://www.eatright.org
http://www.aafa.org
http://www.apfed.org
http://www.acaai.org
Hydrolysate
Peptides,
amino acids
Infant formulas
Nutramigen
Similac Alimentum
Vital jr
Peptamen Jr
Elemental
Amino acids
Infant formulas
Neocate
EleCare
Nutramigen AA
older children (ELEMENTAL)
Neocate Jr
EleCare
EO28 Splash
Nutritionally Complete Formulas

Identification of formulas is dependent upon the known
food allergens. Most standard formulas are free of wheat,
egg, peanut, tree nut, fish, and shellfish. It is common
to substitute a soy protein-based formula for the cows
milk protein-allergic patient. In patients who are allergic
to both cows milk and soy, a protein hydrolysate or
elemental formula is recommended. These formulas
exploit the concept that intact proteins are allergenic and
with increasing breakdown of the intact protein, the allergenicity can be reduced. Protein hydrolysates are made
by hydrolysis of proteins into mostly di- and tri-peptides
and can be tolerated by the vast majority (80% 90%) of
patients with allergies to milk and soy. Elemental formulas
are made up of individual amino acids and are tolerated by
Most children with food allergies can be managed

through judicious food substitutions. When faced with an
extensive array of food allergies that span multiple food
groups, protein hydrolysate and elemental formulas become
the primary option. Infants under the age of 4 to 6 months
usually accept these less-palatable formulas without difficulty but with increasing age acceptability of these formulas
becomes a problem. In toddlers or preschool children, when
elemental formulas are the sole or major source of nutrition
and the patient will not consume enough to sustain nutrition, tube feeding may become necessary.
Patients who are extremely malnourished at presentation may need to be admitted to the hospital to monitor for
refeeding syndrome (Chapter 19); otherwise, most patients
FOOD ALLERGIES
with food allergies can be managed in the outpatient

setting.
221
supplements, medications, bath products, lotions, pet foods,

and cosmetics as young children may accidentally or voluntarily consume these products.
The Food Allergen and Consumer Protection Act
(FALCPA), which became effective in January 2006,
mandates that foods (including spices and flavorings)
identify the 8 major allergens on the food label. Voluntary
allergen advisories or may contain statements are also
appearing on an increasing number of products. 22 These
statements are voluntary; companies elect when to use the
statements and what language to use. The statements are
used by some companies to indicate there may be a risk of
cross-contact with an allergen in another product. Recent
efforts to increase public awareness and strides made in
labeling of food products are encouraging. However, there
is also a concern that food companies may choose to make
voluntary statements regarding cross-contamination in an
attempt to avoid accidental exposures to allergens. If this
practice does occur, it may decrease food choices for patients
with food allergies. Table 20-9 provides some examples of
hidden food allergens in common foods.
Milk Substitutes
Milk substitutes must be used in combination with nutrition assessment and monitoring. There are many different
milk products in the marketplace that continue to
provide alternatives for the allergic patient. However, each
product should only be used with careful consideration of
the nutritional quality of the milk product. Many provide
adequate micronutrients such as vitamin D, calcium, and B
vitamins; however most provide minimal fat and protein.
Children under the age of 2 are at high risk for malnutrition
if one of the incomplete milk substitutes is used in place of
whole cows milk. See Table 20-8 for a list of the nutritional
constituents of various milk substitutes.
Dietary Allowance Versus Dietary Restrictions

The diagnosis of food allergy impacts the patient and family
in many different ways including grocery shopping, cooking,
socializing, travel/vacations, eating out, and family relationships. It is essential to provide education regarding all
of these topics. One of the cornerstones of management is
education about reading food labels.21 Labels must be read
every time a food product is purchased as the ingredients
may change without warning. Labels must also be read for
Micronutrient Supplementation
The benefit of early intervention is to avoid micronutrient

deficiency by recommending adequate substitutions and
supplementation. The DRIs20 for vitamins, minerals, and
Table 20-8 Nutrition Comparisons of Various Milk Substitutes with Whole Milk
Nutrient per 8 oz.
Rice Milk,
Non-Enriched
Rice Milk,
Enriched,
Refrigerated
Soy Milk,
Enriched
Whole Milk
PediaSure
Almond
Milk
Hazelnut
Milk
Calories
120
120
130
150
237
70
110
7.1
2
2
Protein (g)
1
1
7
8
Carbohydrate (g)
25
25
17
11
26
11
18
11.8
2.5
3.5
Fat (g)
2
2
4
8
3.5
3
7.4
2.5
3.5
Unsaturated fat (g)
2
2
0.5
5
3.1
0
0
Saturated fat (g)
0
0
Calcium (mg)
20
300
300
294
230
300
300
1.8
0.1
3.3
0.36
0.36
Iron (mg)
NS
NS
Zinc (mg)
0.29
0.29
0.6
1
2.8
5.4
Selenium (mcg)
NS
NS
9
NS
0.12
0.15
0.107
0.64
NS
Thiamin-B1 (mg)
NS
0.07
0.447
0.5
0.5
0.5
Riboflavin-B2 (mg)
Niacin-B3 (mg)
0.8
0.8
0.8
0.261
4
NS
0.23
0.4
0.883
2.4
NS
Pantothenic acid-B5 (mg) NS

1.5
60
12
88
NS
Folate (mcg)
1.5
1.5
3
1.07
1.4
NS
Vitamin B12 (mcg)

Vitamin A ( IU)
NS
500
500
300
610
500
500
Vitamin D (IU)
NS
100
100
100
120
100
100
NS Not a significant source
Legend: These are typical nutrition values for various milk substitutes. Individual brands may have varying amounts of nutrients.
Oat Milk
Multigrain
Milk
130
4
24
2.5
2.5
0
300
0.36
0.5
500
100
160
5
30
2
2
0
300
1.08
0.5
500
100
222
Table 20-9 Common Sources of Hidden Food Allergens

Egg
Milk
Nuts
Soy
Wheat
Rice
Pasta
Bread/bread crumbs
Bread/bread crumbs
Cereals
Baby food
Bread/bread crumbs
Egg Beaters
Breakfast cereals
Frozen desserts
Breakfast cereals/
granola bars
Egg rolls
Cakes/cookies
Waffles
Crackers
Bread/bread crumbs
Cake/muffin mixes
Candy/chocolate
Candy/chocolate
Frozen desserts
Marshmallows
Canned tuna
Nut butters
Chicken hot dogs/

low-fat beef franks
Cakes/muffins
Gluten-free products
Chicken hot dogs/
low-fat beef franks
Soy sauce
Waffles
Processed meats
Sauces/chili
Bouillon cubes
trace elements can be used for children with food allergies because the vast majority of these children are normal
except for their food allergies and atopic problems. Chapter
6 (Minerals), Chapter 7 (Water-Soluble Essential Micronutrients), and Chapter 8 (Fat-Soluble Vitamins) discuss these
topics. Recommendations for supplementations should be
made based on foods that need to be eliminated and the
patients nutrition status. There are several hypo-allergenic
multivitamin-multimineral supplements that are appropriate for children with food allergies (Table 20-10).
Table 20-10 Allergen-Free Multivitamins
All of these products are free of milk, soy, egg, wheat, peanut,
tree nut, fish, and shellfish.
One-A-Day Kids Scooby-Doo! Complete Multivitamin

One-A-Day Bugs Bunny Complete Multivitamin
Flintstones Complete-Childrens Chewable Multivitamin
NanoVM (13 yrs and 48 yrs)*# Multivitamin
Natures Plus Animal Parade Childrens Chewable Multivitamin
*This product is only available online.
# This is the only allergen-free vitamin that contains selenium.
Note: Products can change at any time and labels should be read
beforeuse.
Two Special Scenarios

Cows Milk-Protein Allergy
Cows milk-protein allergy (CMPA) is the most common
food allergy in early childhood with an incidence of 2%
to 3% in the first year of life.23 Most infants with CMPA
develop symptoms before 1 month of age, often within a
week after introduction of cows milk-based formula. The
majority have 2 or more symptoms with symptoms from
2 or more organ systems: cutaneous symptoms (urticarial
rash, atopic eczema), gastrointestinal symptoms (blood in
the stool, diarrhea, vomiting, protein-losing enteropathy),
Barbecue-flavored
potato chips
Modified food starch
Waffles
Soups
and respiratory symptoms (allergic rhinoconjunctivitis,

asthma).24 This condition can also develop when an infant is
exclusively breastfed, through the passage of the offending
antigens from food consumed by the mother through the
breast milk.
The diagnosis is usually made through the history of
clinical symptoms in young infants that develop soon after
birth or shortly after starting cows milk-based formula in
an infant with a family history of atopy. If the reaction is
IgE-mediated, then the specific IgE levels may be elevated.
Up to 80% to 90% of these infants will do well with a
protein hydrolysate and the rest will require an elemental
formula.25 In breastfed infants, the mother should initially
avoid cows milk; if there is no improvement, she may also
need to exclude some of the other common food allergens.
These children, particularly infants with gastrointestinal symptoms, have a good prognosis. Approximately 50%
of infants are able to tolerate cows milk by the age of 1 year
and the vast majority remits by the age of 3 years.23
Eosinophilic esophagitis
Eosinophilic esophagitis (EE) is a disorder of the esophagus
characterized by upper gastrointestinal tract symptoms in
association with esophageal mucosal eosinophilia. 26 EE
tends to be a chronic disease with persistent or relapsing
symptoms and appears to be becoming more prevalent.
Children under the age of 5 years commonly present
with food refusal, regurgitation, and emesis. Abdominal
pain and failure to thrive may also be seen. Dysphagia
and food impaction tend to be increasingly common with
age. There is a strong association between EE and allergic
rhinitis, asthma, and eczema as well as food allergies. All
patients with EE must be managed with coordinated care
between a gastroenterologist, allergist, and dietitian.
Systemic and topical corticosteroids effectively resolve
acute features of EE; however, when discontinued, the
FOOD ALLERGIES
disease generally recurs. Three types of nutrition intervention have met with varying degrees of success in EE. First,
specific food elimination can be based on allergy testing
and clinical history.27 Even when allergy testing does not
reveal specific food allergens, elimination diets can be used.
Simply removing the 8 most common allergenic foods (milk,
soy, egg, wheat, peanut, tree nut, fish, and seafood) from
the diet has significant efficacy.28 Finally, a 100% amino
acid-based formula diet can be utilized, thus removing all
potential food allergens; this approach has been extremely
effective.29,30
Hence, medical nutrition therapy should be considered
as an effective treatment in all children diagnosed with EE.
When deciding on the use of a specific nutrition therapy,
the patients lifestyle and family resources also need to be
considered. This requires comprehensive education and
nutrition monitoring by a dietitian.
Prognosis and Follow-Up

There is a good possibility that many young children diagnosed with allergies to foods such as milk, egg, wheat, and
soybeans will outgrow the sensitivity after several years. 31
There is a trend for non-IgE-mediated milk allergy to be
outgrown more quickly than IgE-mediated allergy with
both forms of the allergy having a good prognosis. 31 Children who develop a food allergy after 3 years of age are less
likely to lose the food reactions over a several-year period. 25
Peanut allergy is a lifelong disorder for most but not all
patients. 31 Individuals with allergies to foods such as tree
nuts, fish, and seafood seem likely to retain their allergic
sensitivity for a lifetime. 31
Follow-up visits with the allergist-immunologist are
important for the management of food allergies. Because
pediatric patients have the potential for outgrowing a food
allergy, the follow-up visits can re-assess the allergic status
and determine if any food allergens may be re-introduced.
Re-introduction of a food allergen should only be considered if managed and directed by the allergist. Introduction
of previously avoided allergens may increase food options,
decrease cost if the patient is drinking a specialty formula
and/or eating specialty allergen-free foods, and decrease
the stress around preparing meals for the child.
Food Allergies and Nutrition Support
There are two possible scenarios wherein food allergies

are associated with nutrition support. The first is when a
child with known food allergies requires nutrition support
and the second is where allergies to formula or parenteral
nutrition (PN) components become apparent only after the
223
commencement of nutrition support.
Enteral Nutrition
Enteral nutrition support of children presenting with food
allergies can be straightforward. Because most enteral
formulas contain cows milk protein, children with cows
milk protein allergies can be managed with soy-based,
protein hydrolysate, or elemental formula using the principles outlined earlier in this chapter.
Some of the formula intolerances that occur in young
children receiving nutrition support are probably secondary
to food allergies and are usually not recognized at the first
instance. Since one of the management strategies for formula
intolerances during nutrition support includes a transition to a protein hydrolysate/elemental formula, the acute
situation usually resolves. Often, food allergy is diagnosed
retrospectively when the child cannot be transitioned back
to a more standard formula.
There are minimal data on PN support in children with
documented allergies to foods. Egg allergy can be a cause
for concern because these proteins can be found in intravenous lipid solutions. In patients with documented allergies
to eggs, 3 options could be consideredconsultation with
an allergist who may or may not do a skin prick test, lipidfree PN, or the use of Liposyn II. 32 There is a theoretical
risk with extremely soy-allergic patients needing PN. Most
of these patients probably tolerate intravenous lipid, but the
first 2 options outlined above should be considered.
A variety of allergies to PN have been described
through case reports in the literature. 3238 As with other
allergies, they appear to be more common in children. 3638
Skin rashes appear to be the most common manifestation.
However, they can present with dyspnea, cyanosis, nausea,
vomiting, headache, flushing, fever, and chest pain. Anaphylaxis can occur. 3739 All of these reactions can occur at the
first administration, after several days of administration, or
after reinstitution following a hiatus.
These reactions have been attributed to intravenous
lipid preparations, 32,34 crystalline amino acid solutions, 37
and multivitamin mixtures (either due to stabilizers and
emulsifiers in the M.V.I. Pediatric or due to vitamin
K). 3537,39
When these reactions occur, PN needs to be stopped and
appropriate drug treatment for the allergic reaction started.
If the reaction is severe and the patient is going to continue
to require PN, a multidisciplinary approach utilizing an
allergist, pharmacist, nutrition-support physician, and/
224
or dietitian should be pursued. Two approaches may be

considered when the reaction is mild and resolves after
PN is discontinued. The first is to have skin prick testing
of the lipid, multivitamin, and amino acid components and
removal of the offending agent(s) before PN is restarted.
The other approach has been to identify the offending agent
through trial and error.
One micronutrient that may be added to PN solutions
and cause significant allergic reactions is intravenous iron.
All 3 parenteral iron compoundsiron dextran, sodium
ferric gluconate complex in sucrose, and iron sucrose
can be associated with allergic reactions.40,41 It appears that
iron sucrose is associated with the lowest risk of allergy.41
Iron dextran is the least expensive preparation, and a test
dose should always be given with the thought of routinely
pre-treating patients with diphenhydramine and acetaminophen to minimize adverse events. Both sodium
ferric gluconate and iron sucrose offer safe alternatives to
patients intolerant of iron dextran but at a higher cost.40,41
Iron dextran-sensitive patients and patients with multiple
allergies who receive one of the newer preparations should
receive test doses prior to therapy.
1. A 7-year-old boy with an enterocutaneous fistula

develops an urticarial rash the day that he is started on
parenteral nutrition. All of the following constituents of
his parenteral nutrition could cause the rash EXCEPT:
A. Intravenous lipid
B. Amino acid solution
C. Pediatric multivitamin solution
D. Dextrose
2. An 18-month-old vegetarian girl with presumed
milk and soy protein allergy is drinking 32 ounces of
enriched rice milk per day. She also eats rice, wheat,
corn, fruits, and vegetables but does not consume any
egg or meat products. She does not receive any vitamin
or mineral supplementation. You are concerned about
her intake of all of the following EXCEPT:
A. Fat
B. Vitamin D
C. Energy
D. Zinc
3. A 6-year-old Asian boy is seen by a dietitian for followup nutrition assessment and education. His parents
report he is allergic to milk, soy, and peanuts. He has
a history of anaphylaxis while eating peanut butter one
year ago. His current intake includes tofu stir-fry and
milk chocolate candy bars. Parents report he eats these
foods at least once a week without any problems. He
does not drink a milk substitute. All of the following

must be done or considered at this visit EXCEPT:
A. Assessment of growth and nutrient intake
B. Suggesting an age-appropriate beverage
C. Recommending follow-up with allergist as patient
is tolerating milk and soy
D. Suggesting food challenge of peanut butter at home
4. A 6-month-old breastfed infant has significant
vomiting and diarrhea within hours of being given a
bottle of cows milk-based formula. His mother reports
that this has happened each time he has been fed the
formula. She denies any skin rashes. RAST testing for
IgE directed against cows milk protein is negative. All
of the following are true about this child EXCEPT:
A. This is consistent with IgE-mediated anaphylaxis.
B. This is most likely food protein-induced enterocolitis syndrome.
C. Cows milk protein must be eliminated from the
childs diet.
D. In addition to breastfeeding, a protein hydrolysate
formula may be appropriate.
References
1. Branum AM, Lukacs SL. Food allergy among U.S. children:

trends in prevalence and hospitalizations. NCHS data brief, no
10. Hyattsville, MD: National Center for Health Statistics;
2008.
2. Arbes SJ Jr, Gergen PJ, Elliott L, Zeldin DC. Prevalences
of positive skin test responses to 10 common allergens in
the US population: results from the third National Health
and Nutrition Examination Survey. J Allergy Clin Immunol.
2005;116(2):377383.
3. Sicherer SH, Muoz-Furlong A, Burks AW, Sampson HA.
Prevalence of peanut and tree nut allergy in the US determined by a random digit dial telephone survey. J Allergy Clin
Immunol. 1999;103(4):559562.
4. Sicherer SH, Muoz-Furlong A, Sampson HA. Prevalence of seafood allergy in the United States determined
by a random telephone survey. J Allergy Clin Immunol.
2004;114(1):159165.
5. Sicherer SH, Furlong TJ, Burks AW, Sampson HA. A
voluntary registry for peanut and tree nut allergy: characteristics of the first 5149 registrants. J Allergy Clin Immunol.
2001;108(1):128132.
6. Sampson HA, Burks AW. Mechanisms of food allergy. Annu
Rev Nutr. 1996;16:161177.
7. Bock SA, Muoz-Furlong A, Sampson HA. Fatalities due
to anaphylactic reactions to foods. J Allergy Clin Immunol.
2001;107(1):101103.
8. Sicherer SH. Food protein-induced enterocolitis syndrome:
clinical perspectives. J Pediatr Gastroenterol Nutr. 2000;30
Suppl:S4549.
FOOD ALLERGIES
9. Sicherer SH, Eigenmann PA, Sampson HA. Clinical features

of food protein-induced enterocolitis syndrome. J Pediatr.
1998;133(2):214219.
10. Powell GK. Milk- and soy-induced enterocolitis of infancy.
Clinical features and standardization of challenge. J Pediatr.
1978;93(4):553560.
11. Burks AW, Casteel HB, Fiedorek SC, Williams LW, Pumphrey
CL. Prospective oral food challenge study of two soybean
protein isolates in patients with possible milk or soy protein
enterocolitis. Pediatr Allergy Immunol. 1994;5(1):4045.
12. Nowak-Wegrzyn A, Sampson HA, Wood RA, Sicherer SH.
Food protein-induced enterocolitis syndrome caused by solid
food proteins. Pediatrics. 2003;111(4)Pt 1:829835.
13. Bock SA, Lee WY, Remigio L, Holst A, May CD. Appraisal of
skin tests with food extracts for diagnosis of food hypersensitivity. Clin Allergy. 1978;8(6):559564.
14. Sampson HA. Utility of food specific IgE concentrations in
predicting symptomatic food allergy. J Allergy Clin Immunol.
2001;107(5):891896.
15. Burks W, Bannon G, Lehrer SB. Classic specific immunotherapy and new perspectives in specific immunotherapy for
food allergy. Allergy. 2001;56(Suppl 67):121124.
16. Jones SM, Pons L, Roberts JL, et al. Clinical efficacy and
immune regulation with oral peanut immunotherapy. J
Allergy Clin Immunol. 2009;124:292230.
17. Sicherer SH. Diagnosis and management of childhood food
allergy. Curr Probl Pediatr. 2001;31(2):3557.
18. Hubbard S. Nutrition and food allergies: the dietitians role.
Ann Allergy Asthma Immunol. 2003;90(6 Suppl 3):115116.
19. Christie L, Hine RJ, Parker JG, Burks W. Food allergies in
children affect nutrient intake and growth. J Am Diet Assoc.
2002;102(11):16481651.
reference intakes: recommended intakes for individuals; 2009
(2/5):7.
http://iom.edu/en/Global/News%20Announcements/~/media/Files/Activity%20Files/Nutrition/DRIs/
DRISummaryListing2.ashx. Accessed November 23, 2009.
21. Joshi P, Mofidi S, Sicherer SH. Interpretation of commercial
food ingredient labels by parents of food-allergic children. J
Allergy Clin Immunol. 2002;109(6):920922.
22. Food Allergy Issues Alliance. Food Allergen Labeling Guidelines. Washington, DC: National Food Processors Association;
2001.
23. Hst A. Frequency of cows milk allergy in childhood. Ann
Allergy Asthma lmmunol. 2002;89(Suppl):3337.
24. Hst A. Cows milk protein allergy and intolerance in infancy.
Some clinical, epidemiological and immunological aspects.
Pediatr Allergy Immunol. 1994;5(Suppl):136.
25. Atkins D. Food allergy: diagnosis and management. Prim
Care. 2008;35(1):119140.
26. Furuta GT, Liacouras CA, Collins MH et al. First
International Gastrointestinal Eosinophil Research Symposium

(FIGERS) Subcommittees. Eosinophilic esophagitis in
children and adults: a systematic review and consensus
recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):13421363.
225
27. Spergel JM, Andrews T, Brown-Whitehorn TF, Beausoleil

JL, Liacouras CA. Treatment of eosinophilic esophagitis
with specific food elimination diet directed by a combination
of skin prick and patch tests. Ann Allergy Asthma Immunol.
2005;95(4):336343.
28. Kagalwalla AF, Sentongo TA, Ritz S et al. Effect of sixfood elimination diet on clinical and histologic outcomes
in eosinophilic esophagitis. Clin Gastroenterol Hepatol.
2006;4(9):10971102.
29. Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA,
Sampson HA. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based
formula. Gastroenterology. 1995;109(5):15031512.
30. Markowitz JE, Spergel JM, Ruchelli E, Liacouras CA.
Elemental diet is an effective treatment for eosinophilic
esophagitis in children and adolescents. Am J Gastroenterol.
2003;98(4):777782.
31. Wood RA. The natural history of food allergy. Pediatrics.
2003;111(6):16311637.
32. Buchman AL, Ament ME. Comparative hypersensitivity
in intravenous lipid emulsions. J Parenter Enteral Nutr.
1991;15(3):345346.
33. Nagata MJ. Hypersensitivity reactions associated with parenteral nutrition: case report and review of the literature. Ann
Pharmacother. 1993;27(2):174177.
34. Weidmann B, Lepique C, Heider A, Schmitz A, Niederle
N. Hypersensitivity reactions to parenteral lipid solutions.
Support Care Cancer. 1997;5(6):504505.
35. Scolapio JS, Ferrone M, Gillham RA.
Urticaria associated with parenteral nutrition. J Parenter Enteral Nutr.
2005;29(6):451453.
36. Bullock L, Etchason E, Fitzgerald JF, McGuire WA. Case
report of an allergic reaction to parenteral nutrition in a pediatric patient. J Parenter Enteral Nutr. 1990;14(1):98100.
37. Pomeranz S, Gimmon Z, Ben Zvi A, Katz S. Parenteral
nutrition-induced anaphylaxis. J Parenter Enteral Nutr.
1987;11(3):314315.
38. Market AD, Lew DB, Schropp KP, Hak EB. Parenteral nutrition-associated anaphylaxis in a 4-year-old child. J Pediatr
39. Andersen HL, Nissen I. Presumed anaphylactic shock after infusion of Lipofundin. Ugeskr Laeger. 1993;155(28):22102211.
40. Silverstein SB, Rodgers GM. Parenteral iron therapy options.
Am J Hematol. 2004;76(1):7478.
41. Bailie GR, Clark JA, Lane CE, Lane PL. Hypersensitivity
reactions and deaths associated with intravenous iron preparations. Nephrol Dial Transplant. 2005;20(7):14431449.
Diabetes Mellitus and

Other Endocrine Disorders
21
Diane Olson, RD, CNSD, CSP, LD and W. Frederick Schwenk II, MD
CONTENTS
Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
Type 1 Diabetes Mellitus
CF-Related Diabetes Mellitus
Consequences of Hyper/Hypoglycemia
in the CriticallyIll Child. . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Glucose Control in Healthy Children with Diabetes. . . . .228
Short-Term Implications
Long-Term Complications
Glucose Control in Children with Diabetes

Mellitus on Parenteral Nutrition. . . . . . . . . . . . . . . . . . . . 228
Choice of Dextrose Solution
Use of an Insulin Infusion
Addition of Insulin to Parenteral Nutrition Solutions

Mellitus onEnteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . 229
Choice of Formula
Administration of Insulin
Nutrition Support in CF-Related Diabetes . . . . . . . . . . . . 229

Choice of Formula
Control of Blood Glucose
Nutrition Support in Other Endocrine Conditions . . . . . . 229

Central Diabetes Insipidus
Panhypopituitarism
Future Research. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
226
Learning Objectives
1. Define the different types of diabetes mellitus that

occur in childhood.
2. Relate how to create a parenteral formulation or choose
an enteral formula in a child with diabetes mellitus
receiving nutrition support.
3. Report the optimal way to administer insulin in a
child with diabetes on parenteral or enteral nutrition
support.
4. State how to prevent hypo- or hypernatremia in a child
with central diabetes insipidus on nutrition support.
Diabetes Mellitus
Diabetes mellitus is one of the most common chronic

illnesses in the pediatric-aged population. It results from an
absolute or relative lack of insulin, with or without insulin
resistance. While there are a number of different causes
of diabetes in children, all untreated forms of diabetes
mellitus are associated with elevated plasma glucose and
lipid concentrations.
Definitions
The most common form of diabetes in children remains
type 1 diabetes mellitus. This disorder is usually an autoimmune destruction of the beta cells of the pancreas, resulting
in an absolute deficiency of insulin.14 Incidence of type 1
diabetes mellitus in the United States and other western
countries has been increasing. In the United States, the
prevalence of type 1 diabetes mellitus at 18 years of age is 2
to 3 per 1000.1 The incidence of type 1 diabetes mellitus is
about 1.5 times greater in the American non-Hispanic white
DIABETES MELLITUS AND OTHER ENDOCRINE DISORDERS
population than in African Americans or Hispanic Americans. Children with type 1 diabetes mellitus are at risk for
developing ketoacidosis and require insulin to prevent
hyperglycemia.2 Because of a risk for developing low blood
glucose concentrations, current recommendations from the
American Diabetes Association (ADA) are to keep target
blood glucose goal ranges in children somewhat higher than
what is recommended for adults.2,4

In the last 20 years, there has been an epidemic of childhood obesity in developed countries. 5 Associated with this
increase in childhood obesity has been a marked increase in
the incidence of children with type 2 diabetes mellitus. 69
The etiology of type 2 diabetes remains to be established,
but appears to be caused not only by a relative insufficiency
of insulin secretion by the pancreas but also by insulin resistance. In the United States, depending upon the geographic
location, between 8% and 43% of new-onset cases of diabetes
are type 2 diabetes mellitus. Children with type 2 diabetes
mellitus rarely develop ketoacidosis.8 Optimal treatment
of children with type 2 diabetes mellitus remains controversial.9 The incidence of type 2 diabetes mellitus varies by
ethnic group, with higher rates (in order) in Native Americans, African Americans, Hispanic Americans, and Pacific
Islanders/Asian children.9
CF-Related Diabetes Mellitus

Children with cystic fibrosis (CF) and pancreatic insufficiency are at increased risk of developing CF-related
diabetes.1013 The prevalence of this condition in children
with CF and pancreatic insufficiency less than 18 years of
age has been reported to be between 5% and 15%, while in
similar adults the prevalence may be as high as 50%.12,13
These children do not typically develop ketoacidosis and
may have increased insulin resistance, particularly at
time of intercurrent illness.10,14 Children with CF-related
diabetes may not exhibit the classic symptoms of polyuria
and polydipsia associated with other types of diabetes
mellitus.15
Consequences of Hyper/Hypoglycemia in the

CriticallyIll Child
Hyperglycemia appears to be common in pediatric intensive care units (ICUs) regardless of whether the child has
known diabetes mellitus.1619 In one retrospective study
involving 152 children in a pediatric ICU, blood glucose
concentrations greater than 125 mg/dL were observed in
over half of the patients within 24 hours of admission and
227
in almost 90% of the patients sometime during the admission.16 In a second retrospective study, almost 70% of 192
critically ill children had blood glucose concentrations
greater than 120 mg/dL within 24 hours of admission to a
pediatric ICU.17
Hyperglycemia has been linked to poor outcome. In
a study of 184 children less than 1 year of age who had
undergone cardiac surgery, hyperglycemia in the postoperative period was associated with increased mortality and
morbidity.18 However, in a fourth retrospective study of
1094 admissions to a pediatric intensive care unit, the risk of
having a blood glucose value over 200 mg/dL was less than
the risk of having a blood glucose value less than 65 mg/dL.18
Furthermore, the risk of dying was 6 times greater if the child
had a blood glucose less than 110 mg/dL than if all blood
glucose values were greater than 110 mg/dL.19
There are many reasons why hyperglycemia might affect
mortality and morbidity in critically ill patients. In vitro, high
glucose concentrations have been shown to cause abnormalities in several aspects of immune function, including
intracellular killing, complement function, granulocyte
adhesion, chemotaxis, phagocytosis, and respiratory burst
function.20 Glucose attaches itself to the third component of
complement, affecting this components ability to attach itself
to microbes and impairing opsonization of the microbe.21
On the other hand, it is not difficult to understand why low
blood sugars might affect mortality and morbidity in critically ill children. More than 60% of the basal metabolic rate
in an infant is estimated to be related to brain metabolism,
compared with less than 30% in an adult.22
Numerous studies in adult patients with diabetes have
shown increased morbidity and mortality associated with
hyperglycemia.23,24 These studies formed the backdrop for
a large retrospective study in surgical patients showing that
intensive insulin therapy reduced in-hospital mortality rates
by 34% and had a profound effect on a variety of morbidities.21
A similar retrospective study in non-surgical patients also
showed reductions in mortality and morbidity, although the
results were not as striking.25 These reports led many intensive care units to modify their management of hyperglycemia
in diabetic and non-diabetic patients. Since those initial
studies, there have been a plethora of additional reports, with
varying conclusions.26,27 Additional studies have focused on
the increased morbidity and morality associated with hypoglycemia in adult hospitalized patients,28,29 consistent with
the findings in children.
The optimal control of blood glucose in the adult hospitalized patient with or without diabetes remains controversial.
There are very limited data in children. While one recent
228
randomized, prospective study of intensive insulin therapy

in critically ill children did show improved morbidity and
mortality in a subgroup of patients,30,31 near normal plasma
glucose concentrations, regardless of whether the child has
pre-existing diabetes, are not set as goals by many pediatric
practitioners.
Glucose Control in Healthy Children with

Diabetes
Short-Term Implications
The current recommendations of the ADA are that target
blood glucose concentrations be individualized for each
child with diabetes.4 In general, children less than the age
of 7 years often have a form of hypoglycemic unawareness
due to limited cognitive ability and immature counterregulation, making them more susceptible to severe
hypoglycemia.4 Children less than 5 years of age appear to be
at risk for permanent cognitive impairment after episodes of
severe hypoglycemia. 3234 In addition, severe hypoglycemia
occurs in younger children most frequently during sleep. 35
Consequently, blood glucose targets for younger children
are usually higher than for adolescents or adults.2,4,36 While
ketoacidosis continues to be a concern in undiagnosed children with type 1 diabetes mellitus, it is rarely a problem
in children known to have type 1 diabetes mellitus unless
inadequate or no insulin is given.4 Overall, the incidence of
short-term adverse events in children, such as hospitalization and severe hypoglycemia, is high. 37
Long-Term Complications
In contrast to some older children with type 2 diabetes,
children with type 1 diabetes rarely have complications at
the time of diagnosis.38 A large prospective, randomized
study called the Diabetes Control and Complications Trial
(DCCT) established that the major risk factor for microvascular complications is glycemic control.3941 What appears to
be important is the exposure to elevated glucose concentrations over time.38 However, despite marked improvement in
treatment options, 12 years after diagnosis more than 50% of
patients with type 1 diabetes had developed complications or
comorbities.39,42 Persistently high blood glucoses over time
also appear to increase the risk of macrovascular complications, but these rarely occur in childhood.

Mellitus on Parenteral Nutrition
Choice of Dextrose Solution
There are no data to suggest that children with diabetes
require a special formulation for parenteral nutrition (PN).
The composition of the PN solution should be determined
independent of whether the patient has diabetes. This includes
the choice of the final concentration of dextrose. However,
it should be noted that many children with diabetes have
hyperlipidemia,4 so that the triglyceride levels in children
with diabetes on PN need to be monitored carefully.
Use of an Insulin Infusion

When an infusion containing a high concentration of
dextrose is given intravenously in a child (or adult) with
diabetes, blood glucose concentrations are most safely
controlled using a separate intravenous (IV) insulin infusion.43 If insulin is given intravenously, the infusion can
easily be changed if the rate of IV glucose administration
is changed. In adults, insulin is often directly added to the
PN, beginning with a dose of 0.1 units of regular insulin
per gram of dextrose in the infusate (eg, 10 units/L of
10% dextrose; 20 units/L of 20% dextrose).43 Additional
subcutaneous regular insulin or an IV insulin infusion may
be needed to supplement the insulin in the PN. This ratio
of insulin to dextrose is unlikely to cause hypoglycemia
and minimizes the need to discard a bag of PN because it
contains too much insulin.43
While a similar protocol may be used in children, a
strong case can be made to control blood glucose concentrations using a separate infusion of insulin. Using a syringe
pump, the insulin infusion can be directly piggy-backed
into the IV line. A reasonable rate to begin such an infusion
would be 0.05 units of regular insulin per kilogram body
weight per hour. The rate of insulin administration can be
changed to optimize blood glucose control.
As mentioned previously, there is no consensus as to
how tightly to control the plasma glucose concentration in
a critically ill child, with or without a previous diagnosis of
diabetes. However, most practitioners would suggest that
blood glucose concentrations between 100 mg/dL and
200 mg/dL might be a reasonable goal, preventing both
hypoglycemia and ketoacidosis.
Whatever method is chosen to administer the IV
insulin, blood glucose concentrations need to be checked
frequently. This is often done at least hourly in children on
an insulin infusion until there appears to be stability in the
blood glucose concentrations. Blood glucose concentrations
are easiest to control if the PN is given as a continuous infusion, rather than being cycled. It should also be mentioned
that even if the IV infusion of dextrose is stopped, patients
with type 1 diabetes mellitus will continue to need some
insulin to inhibit hepatic gluconeogenesis and prevent the
child from developing ketoacidosis.
Addition of Insulin to Parenteral Nutrition Solutions

If a separate IV insulin infusion is used to control blood
glucose concentrations and both the rate of insulin infusion
and blood glucose concentrations have remained stable over
24 hours, the separate insulin infusion can be discontinued
and insulin added directly to the PN. In such cases, one can
easily calculate the amount of insulin that is required to
control blood glucose concentrations during the administration of the PN by totaling the amount of insulin infused
with the separate infusion. Previously, albumin was also
added to the PN to prevent the insulin from binding to the
bag and tubing being used to administer the PN. However,
adequate blood glucose control can be obtained without
such an addition.44

Mellitus onEnteral Nutrition
Choice of Formula
The use of enteral formulas designed for patients with
diabetes has not been studied in children with diabetes.
Therefore, the current recommendations are to use a standard age-appropriate formula.45
Administration of Insulin
Blood glucose concentrations in children with diabetes on
enteral nutrition (EN) support can usually be adequately
controlled by using subcutaneous injections of insulin.
Guidelines for adults have been published for the administration of insulin at the initiation of tube feedings, as the rate
of tube feedings increases, and for continuous intermittent
and nocturnal feeding schedules.44 By dosing the insulin on
a per kilogram body weight basis, these recommendations
can also be utilized in children. Of course, careful monitoring of blood glucose concentrations is required.
Nutrition Support in CF-Related Diabetes

Choice of Formula
PN support is rarely required in children with CF.46 If EN
support is being considered, no evidence suggests that one
enteral formulation is superior to another.47 There are data
229
in adults that patients who develop CF-related diabetes

have lower body mass indices and are more likely to require
enteral feedings from 2 years prior to diagnosis compared to
adults who do not develop CF-related diabetes.48
Control of Blood Glucose

Blood glucose concentrations in children with CF and
CF-related diabetes receiving EN support can usually be
managed with subcutaneous insulin.1013 However, with
intercurrent illness, children with CF have increased insulin
resistance, requiring larger doses than the typical 1 unit of
insulin per kilogram body weight per day requirements of
children with type 1 diabetes mellitus.10,14
Nutrition Support in Other Endocrine

Conditions
Central Diabetes Insipidus
Central or neurogenic diabetes insipidus is a relatively rare
condition in children resulting from an inability to secrete
active vasopressin from the posterior pituitary gland.49
While genetic defects in vasopressin synthesis have been
described, the usual etiology of this condition is a hypothalamic or posterior pituitary lesion.49 There are multiple
causes of this condition including tumors, inflammatory
lesions, vascular diseases, and cranial malformations.49
Outpatient treatment for this condition in children
with intact thirst sensation involves giving an analogue of
vasopressin either orally or intranasally. Such children are
allowed to drink to thirst. Fluid intake in children without
an intact thirst mechanism must be monitored carefully to
prevent hypo- or hypernatremia.
There do not appear to be any published guidelines as
to how to manage a child with central diabetes insipidus
who might require PN or EN. Because of the large volumes
of fluid associated with such therapy, the child is at risk for
both hypo- and hypernatremia.
One option for managing such a patient is to use a
low-dose IV infusion of aqueous vasopressin, as has been
described for use in children who are receiving additional
fluid as part of a chemotherapy regimen. 50 To maintain
adequate hydration and serum sodium concentrations, a
dilute infusion of aqueous vasopressin is given at a starting
rate of 0.08 to 1 mU/kg/h. During the infusion, fluid intake,
urine output, body weight, urine specific gravity, and serum
electrolyte concentrations are monitored carefully.
230
Panhypopituitarism
Another relatively uncommon endocrine condition that
might affect nutrition support is panhypopituitarism. Again,
no guidelines exist for how to manage nutrition support in
such patients. Children with panhypopituitarism are unable
to secrete a number of anterior pituitary hormones, including
growth hormone and corticotropin. This condition can be
the result of intracranial surgery, but can also be idiopathic.
Children with this condition often present with hypoglycemia and are at continuing risk for low blood sugars. The
hypoglycemia is due to an inability to counterregulate. 51 To
prevent hypoglycemia in a critically ill child with this condition, additional glucocorticoids are administered. In such
patients, a strong case can also be made for administering
nutrition support as a constant infusion, rather than giving
enteral feeds as boluses or cycled PN.
Future Research
Research in children is difficult, not only because they

cannot give informed consent but also because mortality
is quite low, requiring large numbers of patients to do
outcome studies. Consequently, many of the above recommendations are extrapolated from adult recommendations.
Future studies will hopefully answer what is the optimal
blood glucose concentration for a critically ill child. It is also
hoped that new strategies will be developed to help children
with diabetes mellitus achieve improved blood glucose
control when they are receiving PN or EN.
1. When creating a parenteral formulation to use in a child with

diabetes mellitus, the dextrose concentration should be:
A. Kept to a minimum
B. No greater than 15%
C. At least 20%
D. Chosen without regard to whether the child has
diabetes mellitus
2. To prevent hyperglycemia, hospitalized children with
CF-related diabetes mellitus and acute infections may
require:
A. An increased amount of insulin
B. A decreased amount of insulin
C. Their usual doses of insulin
D. Frequent doses of short-acting insulin
3. In children with diabetes mellitus on EN, insulin should
usually be:
A. Discontinued
B. Given parenterally
C. Given subcutaneously
D. Given enterally
4. Serum sodium concentrations can be safely maintained in

a child with diabetes insipidus on EN or PN support by:
A. Limiting oral fluids
B. Administering a vasopressin analogue orally
C. Doubling the patients usual dose of a vasopressin
analogue
D. Using an intravenous drip of aqueous vasopressin
References
1. Cooke DW, Plotnick L. Type 1 diabetes mellitus in pediatrics.

Pediatr Rev. 2008;29:374 385.
2. Silverstein J, Klingensmith G, Copeland K, et al. Care of children
and adolescents with Type 1 diabetes: a statement of the American Diabetes Association. Diabetes Care. 2005;28(1):186212.
3. American Diabetes Association. Diagnosis and classification of
diabetes. Diabetes Care. 2006;20(suppl 1):S4S25.
4. American Diabetes Association. Clinical Practice Recommendations 2009. Diabetes Care. 2009;32(suppl 1):S13S61.
Pediatric obesity. In: Kleinman RE, ed. Pediatric Nutrition
Handbook. 6th ed. Elk Grove Village, IL: American Academy
of Pediatrics; 2009:733782.
Pediatric dietary management of diabetes mellitus in children. In: Kleinman RE, ed. Pediatric Nutrition Handbook. 6th
2009:673697.
7. Sinha R, Fisch G, Teague B, et al. Prevalence of impaired glucose
tolerance among children and adolescents with marked obesity.
N Engl J Med. 2002;346(22):802810.
8. American Diabetes Association. Type 2 diabetes in children
and adolescents. Diabetes Care. 2000; 23(3):381389.
9. Kaufman F. Type 2 diabetes in youth: rate, antecedents, treatment, problems and prevention. Pediatr Diabetes. 2007:8(suppl
9):46.
10. Moran A, Hardin D, Rodman, et al. Diagnosis, screening
and management of cystic fibrosis related diabetes mellitus:
a consensus conference report. Diabetes Res Clin Pract.
1999;45(1):6173.
11. Hardin DS, Moran A. Diabetes mellitus in cystic fibrosis. Endocrinol & Metab Clin North Am. 1999;28(4):787800.
12. Solomon MP, Wilson DC, Corey M, et al. Glucose intolerance
in children with cystic fibrosis. J Pediatr. 2003;142(2):128132.
13. Moran A, Doherty L, Wang X, Thomas W. Abnormal glucose
metabolism in cystic fibrosis. J Pediatr. 1998;133(1):1017.
14. Brennan AL, Geddes DM, Gyi KM, Baker EH. Clinical
importance of cystic fibrosis-related diabetes. J Cyst Fibros.
2004;3(4):209222.
Nutrition in cystic fibrosis. In: Kleinman RE, ed. Pediatric
Nutrition Handbook. 6th ed. Elk Grove Village, IL: American
Academy of Pediatrics; 2009:10011020.
16. Srinivasan V, Spinella PC, Drott HR, Roth CL, Helfaer MA,
Nadkarni V. Association of timing, duration, and intensity of
hyperglycemia with intensive care unit mortality in critically ill
children. Pediatr Crit Care Med. 2004;5(4):329336.
17. Faustino EV, Apkon M. Persistent hyperglycemia in critically ill
children. J Pediatr. 2005;146(1):57.
18. Yates AR, Dyke PC 2nd, Taeed R, et al. Hyperglycemia is a
marker for poor outcome in the postoperative pediatric cardiac
patient. Pediatr Crit Care Med. 2006;7(4):351355.
19. Wintergerst KA, Buckingham B, Gandrud L, Wong BJ, Kache S,
Wilson DM. Association of hypoglycemia, hyperglycemia, and
glucose variability with morbidity and death in the pediatric
intensive care unit. Pediatrics. 2006;118(1):173179.
20. Van den Berghe G, Wouters P, Weeker F, et al. Intensive
insulin therapy in the critically ill patients. N Engl J Med.
2001;345(19):13591367.
21. McMahon MM, Bistrian BR. Host defenses and susceptibility
to infection in patients with diabetes mellitus. Infect Dis Clin
North Am. 1995;9(1):19.
22. Haliday MA. Metabolic rate and organ size during growth from
infancy to maturity and during late gestation and early infancy.
Pediatrics. 1971;47(1):167179.
23. Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyper
glycemia and increased risk of death after myocardial infarction
in patients with and without diabetes: a systematic overview.
Lancet. 2000:355(9206):773778.
24. Capes SE, Hunt D, Malmberg K, Pathak P. Stress
hyperglycemia and prognosis of stroke in nondiabetic
and diabetic patients: a systematic overview. Stroke.
2001;32(10):24262432.
25. Van den Berghe G, Wilmer A, Hermans C, et al. Intensive insulin therapy in the medical ICU. N Engl J Med.
2006;345(5):449461.
26. Inzucchi Se, Slegel MD. Glucose control in the ICUhow tight
is too tight? N Engl J Med. 2009;360(13):13461349.
27. The NICE-SUGAR Study Investigators. Intensive versus
conventional glucose control in critically ill patients. N Engl J
Med. 2009;360(13):12831297.
28. Turchin A, Matheny ME, Shubina M, et al. Hypoglycemia and
clinical outcomes in patients with diabetes hospitalized in the
general ward. Diabetes Care. 2009;32(7):11531157.
29. Arabi Y, Tamim HM, Rishu AH. Hypoglycemia with intensive insulin therapy in critically ill patients: Predisposing
factors and association with mortality. Crit Care Med.
2009;37(9):25362544.
30. Vlasselaers D, Milants I, Desmet L, et al. Intensive
insulin therapy for patients in paediatric intensive care:
a prospective, randomized controlled study. Lancet.
2009;373(9663):547556.
31. Agus MSD, Hirshberg EL. Pediatrics: Intensive insulin therapy
in critically ill children. Nature Rev Endo. 2009;5(7):360362.
32. Northam EA, Anderson PJ, Werther GA, Warne GL, Adler
RG, Andrewes D. Neuropsychological complications of
IDDM in children 2 years after disease onset. Diabetes Care.
1998;21(3):379384.
33. Rovet J, Alvarez M. Attentional functioning in children and
adolescents with IDDM. Diabetes Care. 1997;20(5):803810.
231
34. Bjorgaas M, Gimse R, Vik T, Sand T. Cognitive function in type

1 diabetic children with and without episodes of sever hypoglycaemia. Acta Paediatr. 1997;86(2):148153.
35. Ryan C, Gurtunca N, Becker N. Hypoglycemia: a complication of diabetes therapy in children. Pediatr. Clin North Am.
2005;52(6):17051733.
36. Ryan CM, Becker DJ. Hypoglycemia in children with type 1
diabetes mellitus. Pediatr Endocrinol. 1999;28(4):883900.
37. Levine B, Anderson BJ, Butler DA, et al. Predictors of glycemic
control and short-term adverse outcomes in youth with type 1
diabetes. J Pediatr. 2002;139(2):197203.
38. Gallego PH, Wiltshire E, Donaghue KC. Identifying children
at particular risk of long-term diabetes complications. Pediatric
Diabetes. 2007;8(suppl 6):4048.
39. The Diabetes Control and Complications Trial Research Group.
The effect of intensive treatment of diabetes on the development
and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977986.
40. Diabetes Control and Complications Trial Research Group.
Effect of intensive therapy on the microvascular complication
of type 1 diabetes mellitus. JAMA. 2002;287(19):25632569.
41. Writing Team for the DCCT and EDIC Research
Group. Sustained effect of intensive treatment of type
1 diabetes mellitus on development and progression of
diabetic nephropathy: the Epidemiology of Diabetes
Interventions and Complications (EDIC) study. JAMA.
2003;290(16):21592167.
42. Danne T, Kordonouri O. Current challenges in children with
type 1 diabetes. Pediatr Diabetes. 2007;8(Suppl 6):35.
43. McMahon MM. Diabetes mellitus. In: Merritt T, ed. A.S.P.E.N.
Nutrition Support Practice Manual. 2nd ed. Silver Spring,
MD: American Society for Parenteral and Enteral Nutrition.
2005:317323.
44. Weber SS, Wood WA, Jackson EA. Availability of insulin
from parenteral nutrient solutions. Am J Hosp Pharm.
1977;34:353357.
45. American Diabetes Association. Nutrition principles and
recommendations in diabetes. Diabetes Care. 2004;27(Suppl
1):S3646.
46. Jelalian E, Stark LJ, Reynolds L, Seifer R. Nutrition intervention for weight gain in cystic fibrosis: a meta analysis. J Pediatr.
1998;132(3 Pt 1):486492.
47. Erskine JM, Lingard C, Sontag M. Update on enteral
nutrition support in cystic fibrosis. Nutr Clin Pract.
2007;22(7):223232.
48. White H, Pollard K, Etherington C, et al. Nutritional decline in
cystic fibrosis related diabetes: the effect of intensive nutritional
intervention. J Cyst Fibros. 2009;8(3):179185.
49. Ghirardello S, Garre ML, Rossi A, Maghnie M. The diagnosis
of children with central diabetes insipidus. J Pediatr Endocrinol
Metab. 2007;20(3):359375.
50. Bryant WP, OMarcaigh AS, Ledger GA, Zimmerman D.
Aqueous vasopressin infusion during chemotherapy in patients
with diabetes insipidus. Cancer. 1994;74(9):25892592.
51. Bolli GB, Fanelli CG. Physiology of glucose counterregulation to hypoglycemia. Endocrinol Metab Clin North Am.
1999;28(3):467493.
Inborn Errors of Metabolism
22
Bridget Reineking, MS, RD, CD and Sandy van Calcar, PhD, RD, CD
CONTENTS
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
Phenylketonuria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
Natural History
Maternal Phenylketonuria
Acute Management
Chronic Management
Methylmalonic Acidemia. . . . . . . . . . . . . . . . . . . . . . . . . . 237

Natural History
Acute Management
Chronic Management
Ornithine Transcarbamylase Deficiency. . . . . . . . . . . . . . 239

Natural History
Acute Management
Chronic Management
Very Long Chain Acyl-CoA Dehydrogenase Deficiency. . . 240

Natural History
Acute Management
Chronic Management
Galactosemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
Natural History
Acute Management
Chronic Management
232
Learning Objectives
1. Understand the basic principles of treating inborn

errors of metabolism.
2. Understand the biochemistry and medical nutrition
therapy for phenylketonuria.
therapy for methylmalonic acidemia.
therapy for ornithine transcarbamylase deficiency.
therapy for very long-chain acyl Co-A dehydrogenase
deficiency.
therapy for classic galactosemia.
Background
Inborn errors of metabolism (IEM) are genetic disorders

caused by deficient production or function of specific
enzymes, transport proteins, or enzyme cofactors in
protein, lipid, carbohydrate, or micronutrient metabolism.
The deficiency in enzyme activity results in accumulation
of various abnormal metabolites that can cause detrimental
symptoms. Presentation of disease varies greatly depending
on the disorder, but severe forms of many disorders can
include overwhelming illness in the newborn period with
hypotonia, seizures, and coma associated with poor feeding
(Table 22-1). Many of these disorders can be fatal or cause
profound developmental delay if not treated promptly and
aggressively.
INBORN ERRORS OF METABOLISM
Table 22-1 Various Signs and Symptoms of Inborn Errors of Metabolism

Overwhelming illness in the newborn period
Recurrent vomiting
Poor growth
Failure to thrive
Developmental delay
Mental retardation
233
devoid of the amino acid(s) that cannot be fully metabolized, but will provide all other amino acids, carbohydrates,
fat sources, vitamins, and minerals. Medical foods often
provide a significant portion of a childs nutrition needs. 35
Figure 22-1 Basic Principles of Nutrition Management of Inborn Errors
ofMetabolism
Loss of previously acquired skills

Hypotonia
Hypertonia
Seizures
Infantile spasms
Unusual odor
Episodes of rhabdomyolysis with intense exercise
Cardiomyopathy
Newborn screening is an important public health

program that can detect many IEM in the neonate, which
allows for early diagnosis and initiation of treatment.1
Newborn screening was initiated in the 1960s with detection of phenylketonuria (PKU). PKU is often referred to as
the model for newborn screening because the methodology
is reliable and cost-effective and there are clear benefits
from early intervention with medical nutrition therapy.
With the recent introduction of tandem mass spectrometry,
more than 30 IEM can now be detected from blood spots
collected at 24 to 48 hours of age.1 The number of screened
disorders varies by state, although a national uniform panel
has been recommended.2 Infants with abnormal screening
results are referred to specialized clinics with medical
geneticists, metabolic dietitians, and genetic counselors to
assure prompt clinical evaluation and confirmatory testing.
When the diagnosis is confirmed, appropriate medical and
nutrition management is initiated.
The overall goal of treatment for IEM is to improve and
maintain metabolic homeostasis. Medical nutrition therapy
plays a large role to achieve this goal. The basic principles
of medical nutrition therapy for IEM include prevention
of catabolism with adequate caloric intake, restriction of
the offending substrate, supplementation of deficient products, and/or supplementation with the enzymes cofactor
(Figure 22-1). In order to meet nutrient needs but prevent
excessive intake of substrates, specialized formulas, which
are termed medical foods, have been developed for treatment of numerous IEM. Medical foods do not contain the
substrate(s) that cannot be metabolized. For instance, a
medical food designed for an amino acidopathy will be
In disorders where the blocked substrate is an essential

amino acid, a limited but sufficient quantity of substrate
must be provided to allow for growth and protein maintenance. This is accomplished by providing a source of intact
protein from regular infant formula or, for some disorders, a
limited quantity of breast milk is allowed. However, excessive intake of the substrate(s) results in elevations in the
offending metabolites and can lead to detrimental symptoms. Careful laboratory monitoring and proper nutrition
education is essential to treat IEM. 35
This chapter provides a basic overview of 5 disorders
to illustrate different types of IEM and their nutrition
management. Various references are available that provide
detail about the biochemistry and treatment of the wide
range of IEM. 57 For any IEM, different phenotypes are
possible and treatment can vary greatly depending on the
severity of the disorder. Presentation of a disorder can occur
in infancy, childhood, or for some disorders, in adults. The
patients age, growth, and other clinical factors influence
the nutrition prescription. For many of these disorders, lifelong monitoring and treatment changes are required. The
involvement of a metabolic dietitian trained to manage IEM
is imperative for successful treatment of these conditions.
234
Phenylketonuria
Natural History
PKU is an inborn error of phenylalanine (phe) metabolism
caused by a deficiency of the hepatic enzyme phenylalanine
hydroxylase (PAH), which catalyses the hydroxylation
of phe to tyrosine (Figure 22-2). PKU is an autosomal
recessive disorder with a carrier frequency of 1 in 50 and
incidence of approximately 1 in 10,000 to 15,000 births in
those of European ancestry. More than 500 mutations have
been identified in the PAH gene, but genotype/phenotype
correlations have not proven to predict outcome. 8
which 211 subjects with PKU were randomized at age 6 to

continue or discontinue the PKU diet.9 Results from this
study demonstrated that individuals with PKU who discontinued the diet developed significant reductions in IQ and
academic performance by age 12 years.9 A follow-up study
of 70 adults who participated in the PKU Collaborative
Study found significantly fewer adverse medical, cognitive,
and psychological outcomes in those who were randomized to remain on diet compared with those who stopped
diet treatment at age 6.12 Conclusions from these and other
studies led to the recommendation of life-long treatment for
PKU.1315
Figure 22-2 Phenylketonuria (PKU) results from a deficiency of

phenylalanine hydroxylase (PAH) with elevated phenylalanine
concentrations and tyrosine deficiency. PAH requires the cofactor
tetrahydrobiopterin (BH4).
Maternal Phenylketonuria
Adapted from Acosta PB, Yannicelli S. The Ross Metabolic Formula System
Nutrition Support Protocols. 4th ed. Columbus, OH: Ross Products
Division/Abbott Laboratories; 2001. Copyright 2001 with permission
from Abbott Nutrition.
Acute Management
PKU is often classified based on the degree of phe

elevation in blood prior to initiation of treatment. Those
with classic PKU show blood phe elevations > 20 mg/dL
(normal phe is < 2 mg/dL). Untreated classic PKU results
in profound mental retardation, seizures, and autistic-like
behavior. Treatment with a phe-restricted diet ameliorates
this outcome and those with classic PKU can have similar
intelligence quotient (IQ ) and developmental potential as
their unaffected siblings.9 On the other end of the spectrum,
phe elevations in those with mild hyperphenylalaninemia
(HPA) remain < 10 mg/dL and may not require any diet
modification. 35
Treatment recommendations for PKU have evolved since
diet treatment was first described in the 1950s.10 Initially,
metabolic specialists discontinued the phe-restricted diet at
6 years of age because it was felt that brain development was
complete and continuation of the diet could cause nutrition deficiencies.11 This practice was formally evaluated
in the National PKU Collaborative Study (19681984) in
Phenylalanine is a known teratogen and in utero exposure

to elevated phe concentrations interferes with embryonic
development.16 Infants born to women with uncontrolled
phe levels during pregnancy are at risk for low birth weight,
microcephaly, congenital abnormalities, and mental retardation. The National Maternal PKU Collaborative Study
(19842000) found that these detrimental effects to the
fetus could be prevented if maternal plasma phe concentrations remained below 6 mg/dL prior to conception and
throughout pregnancy.17,18 Education about the risks of
elevated phe concentrations during pregnancy should begin
early in adolescence for all females with PKU.
Initial Presentation
When an infant with PKU is identified by newborn
screening, treatment should be initiated as soon as possible.
Depending on the degree of elevation in plasma phe, dietary
phe is eliminated or greatly reduced in the diet until blood
phe levels decrease to the treatment range of 2 to 6 mg/dL.
This can be accomplished by feeding exclusively a phe-free,
but otherwise nutritionally complete, medical food. Once
plasma phe concentrations are reduced to < 6 mg/dL, a
limited quantity of an intact protein is added to the medical
food to meet minimum phe needs for growth and protein
maintenance (Table 22-2). 35 The intact protein source can
be provided by a standard infant formula or breast milk.
Phe concentrations may increase during times of illness
or severe injury. Prevention of catabolism can minimize
these elevations. During illness, individuals with PKU are
encouraged to reduce phe intake but continue to consume
the phe-free medical food. If gastrointestinal symptoms
develop, the medical food can be discontinued and carbohydrate-based beverages can be provided to increase caloric
intake to help slow catabolism. 3 Efforts should be made to
select medications that are phe-free. The source of phe in

pediatric medications is typically in the flavoring agents
which may contain aspartame (Nutrasweet) as the sweetener. Aspartame is a dipeptide derived from aspartic acid
and phenylalanine.19
TABLE 22-2 Recommended Daily Nutrient Intakes for Phenylketonuria
Age
PHE
(mg/kg)
Nutrient
TYR
Protein
(mg/kg)
(g/kg)
Energy
(kcal/kg)
Infants
0 to < 3 mo
25 70
3 to < 6 mo
20 45
6 to < 9 mo
15 35
9 to < 12 mo
10 35
Girls and Boys
(mg/d)
1 to < 4 yr
200 400
4 to < 7 yr
210 450
7 to < 11 yr
220 500
120
(145 95)
120
300 350 3.50 3.00
(145 95)
110
250 300 3.00 2.50
(135 80)
105
250 300 3.00 2.50
(135 80)
(g/d)
(g/d)
(kcal/d)
1,300
1.72 3.00
30
(900 1800)
1,700
2.25 3.50
35
(1300 2300)
2,400
2.55 4.00
40
(1650 3300)
300 350
3.50 3.00
Women
11 to < 15 yr
250 750
3.45 5.00
50
15 to < 19 yr
230 700
3.45 5.00
55
19 yr
220 700
3.75 5.00
60
11 to < 15 yr
225 900
3.38 5.50
55
15 to < 19 yr
295 1100 4.42 6.50
65
19 yr
290 1200 4.35 6.50
70
2,200
(1500 3000)
2,100
(1200 3000)
2,100
(1400 2500)
Men
2,700
(2000 3700)
2,800
(2100 3900)
2,900
(2000 3300)
Chronic Management
The goal of chronic management for PKU is restriction of
dietary phe to maintain blood phe concentrations within
the recommended treatment range of 2 to 6 mg/dL from
infancy to age 12 years and 2 to 10 mg/dL in adolescents.14
However, with the concern of maternal PKU, adolescent girls should be encouraged to maintain levels below
6 mg/dL. Additional treatment goals include maintenance
of adequate growth velocity and weight gain, prevention
of protein deficiency, and achieving adequate macro- and
micronutrient status. 35
235
Figure 22-3. Calculating a Low-Phe Formula

An infant weighing 3.6 kg is diagnosed with PKU with an initial blood phe
concentration of 15 mg/dL. Determine an appropriate formula for this
infant.
Answer:
Provide a phe-free formula until phe concentrations are < 6 mg/dL. Then
add an intact protein source to meet nutrition needs.
Determine Needs
1) Determine Phe Requirement Using Table 22-2.
3.6 kg 45 mg of phe*/kg = 162 mg of phe per day
*Phe requirements range from 25-70 mg/kg. Given the moderate
elevation in blood phe of 15 mg/dL, phe requirements are estimated
at 45 mg/kg.
2) Determine Tyrosine (Tyr) Requirement
3.6 kg 325 mg of tyr/kg = 1170 mg
3) Determine Protein (Pro) Requirement
3.6 kg 3.2 g of pro/kg = 1112 g of pro
4) Determine Calorie (kcal) Requirement
3.6 kg ~ 120 kcal/kg = 430450 kcal
Calculate Formula
1) Determine the Amount of Infant Formula Needed to Meet Phe Needs
Infant formula A contains 330 mg of phe in 100 g
162 mg of phe needed per day
100 g of infant formula
330 mg of phe
= 49 g of Infant
Formula A Needed
2) Determine Amount of Kcals and Protein in Infant Formula

Infant formula A contains 10.8 g of protein and 518 kcal in 100 g
49 g infant formula A 10.8 g protein
49 g of infant formula A 518 kcal
= 5.3 g of protein
= 254 kcals
3)Determine Amount of Phe-Free Medical Food B Needed to Meet

Protein Needs
Phe-free medical food B contains 15 g of protein in 100 g
11.5 g total protein needs 5.3 g of protein from Infant formula A =
6.2 or ~6 g of protein needed
6 g of protein needed 100 g of
medical food B
15 g of protein
= 40 g of phe-free
medical food
4) Determine Kcal from Phe-Free Medical Food B

40 g of medical food B 480 kcal
100 g of phe free medical food
= 192 kcal
Final Recipe
Product
Infant Formula A
Phe-free medical
food B
Total
Amount
Phe (mg)
Pro (g)
Calories
49 g
162 mg
5g
254 kcal
40 g
0 mg
6g
192 kcal
162 mg
11 g
446 kcal
Volume required at 20 kcal/oz = 22 fl oz (625 mL)
236
Dietary phe must be quantified to achieve blood phe

control. Phe needs vary between individuals and change
with age, weight, and growth velocity (Table 22-2). In
infancy, the phe requirement is supplied by a standard
infant formula or breast milk (Figure 22-3). Adjustments
in the phe prescription are based on frequent monitoring of
blood phe concentrations. If blood phe concentrations are
elevated above the treatment range, the amount of intact
protein must be decreased incrementally until phe concentrations are within the treatment range. 35
Breastfeeding is possible in the treatment of PKU;
metabolic control in infants allowed to breastfeed is similar
to those consuming a regular infant formula as their phe
source.20,21 To maintain phe concentrations within the
treatment range, adjustments are made in the prescribed
volume of phe-free medical food to effectively increase or
decrease the infants intake of breast milk. Medical food
may be provided prior to each breastfeeding or feedings of
medical food and breastfeeding may be alternated.20,21 The
average phe content of breast milk is known and is higher in
colostrum than mature milk by approximately 60%.22,23
Total protein needs for infants and children with PKU
may be greater than protein needs for the general population (Table 22-2) because of rapid amino acid absorption
and utilization when free amino acids rather than an intact
protein are given as the source of protein. 24 Caloric requirements should be determined using dietary reference intake
(DRI) estimates and adjusted based on frequent growth
measurements.25
An individuals phe requirement is the same regardless of
the source of intact protein consumed (formula, breast milk,
or solid food). When an infant transitions to solids, the infant
formula or breast milk is decreased and replaced by an equivalent amount of phe from foods. Caregivers are instructed
to count milligrams of phe or use an exchange system (1
exchange = 15 mg phe). References are available that list the
phe content of various foods and beverages.3,26,27 Accuracy in
measuring medical food, infant formula, and foods is imperative for successful management of PKU. The use of a gram
scale is recommended because small measurement errors can
lead to significant changes in blood phe concentrations.
Phe is found in any food containing protein. Meat,
legumes, nuts, and dairy products are too high in phe and
are not allowed in the phe-restricted diet. Grains, fruits, and
vegetables must be precisely measured and the phe content
carefully calculated to ensure proper blood phe control
(Table 22-3). For the PKU diet, free foods and beverages
are those that contain no protein (and no phe) such as sugars
and fats. 3,27
Table 22-3 Example of Daily Meal Plan for Classic Phenylketonuria

Age: 3 years, 9 months
Weight: 15.2 kg
Height: 101 cm
Sex: Female
Medical Food Prescription: 125 g of Phenex-2 unflavored + 18 fl oz of
water = 20 fl oz total volume
Daily Phenylalanine Prescription from Foods: 200 mg
Estimated Needs: Protein: > 30 g/d Kcal: 900 1800 kcal/d
Food or Liquid
Offered
Amount
Eaten
Phe
Protein
Calories
Medical Food
Froot Loops
Crackles
Low-Protein
Cereal
Blueberries,
fresh
Medical Food
French Fries,
Ore-Ida
Golden Fries
Broccoli,
cooked
Thousand
Island
Dressing
Peaches,
canned
Cantaloupe,
fresh
Medical Food
Sweet Potato,
with skin,
baked
Green beans,
canned
Pears, canned
Zoo Animal
Crackers,
Farleys
Sorbet,
strawberry
6 oz
6g
0 mg
17 mg
11 g
0.4 g
154 kcal
25 kcal
30 g
7 mg
0.2 g
120 kcal
32 g
8 mg
0.2 g
18 kcal
7 oz
0 mg
13 g
179 kcal
56 g
50 mg
1.4 g
80 kcal
28 g
14 mg
0.6 g
6.0 kcal
16 g
6 mg
0.1 g
59 kcal
57 g
8 mg
0.3 g
42 kcal
27 g
8 mg
0.2 g
9 kcal
7 oz
0 mg
13 g
179 kcal
22 g
25 mg
0.4 g
23 kcal
28 g
14 mg
0.4 g
6 kcal
90 g
8 mg
0.2 g
66 kcal
22 g
20 mg
1.6 g
94 kcal
122 g
15 mg
0.4 g
119 kcal
Total
200
mg
43.4 g
1179
kcal
% from
medical
food
0%
85.3%
43.4%
Meal
Breakfast
Lunch
Snack
Dinner
Snack
Low-protein food products, made primarily from wheat

starch (instead of wheat flour), are available to increase variety
and meet the caloric needs of individuals with PKU. Products
include low-protein baking mixes, bread, rice, pasta, peanut
butter, cereals, and snack chips. Some food companies also
market low-protein specialty items such as chicken nuggets,
hamburgers, egg replacers, and cheese. Several lowprotein cookbooks for PKU are also available.28,29
In PKU, decreased PAH activity reduces the production
of tyrosine; thus, tyrosine becomes an essential amino acid
for this population (Figure 22-2). Medical foods for PKU
are supplemented with tyrosine and additional tyrosine
supplementation is indicated only if the combination of
intact protein and medical food does not meet tyrosine
requirements. Plasma tyrosine concentrations should be
routinely monitored in individuals with PKU. 3,4
Some micronutrients may be insufficient in the low-phe
diet, particularly in those consuming a suboptimal amount
of medical food. Inadequate intake of iron, folate, vitamin
B12 , calcium, and vitamin D has been reported. 3032 Dietary
intake should be analyzed for micronutrient content and
additional supplementation prescribed as needed. 33 In addition, intake of essential fatty acids (EFAs) may be low even
with sufficient intake of medical food and erythrocyte EFA
profiles should be routinely assessed. 3436 If low concentrations are found, vegetable oils such as canola or walnut oil or
a docosahexaenoic acid (DHA) supplement can be added to
the diet. Some medical formulas designed for PKU are now
supplemented with arachidonic acid (ARA) and DHA.
Large neutral amino acids (LNAAs): Phenylalanine
and other LNAAs (leucine, valine, isoleucine, methionine,
tyrosine, tryptophan, and threonine) share common transporters at the blood-brain barrier and intestinal mucosa. In
PKU, competitive inhibition from high concentrations of
phe reduce the transport of other LNAAs into the cerebral
cells, which may reduce synthesis of various neurotransmitters. 37 Supplementation with high doses of LNAAs
can reduce both blood and brain concentrations of phe;
improved executive function skills have been measured
in those with poor dietary control who were treated with
LNAA supplements. 38,39 Several LNAA formulations are
now commercially available.
Cofactor supplementation: A newer therapy for the treatment of PKU is supplementation with a synthetic form
of tetrahydrobiopterin, the cofactor for the PAH enzyme
(sapropterin dihydrochloride, Kuvan) (Figure 22-2).
For some individuals, administration of sapropterin can
improve PAH activity and, thus, lower blood phe levels.40,41
In a phase III randomized, placebo-controlled, double-blind
study, 44% of those taking sapropterin for 6 weeks showed
a reduced phe concentration of 30% or greater.40 Response
to sapropterin needs to be individually assessed as not all
individuals with PKU will respond to supplementation and
the degree of response to the drug varies. Supplementation
with sapropterin rarely allows for complete liberalization of
237
the low-phe diet or eliminates the need for medical food.42

Continued involvement of a trained dietitian and geneticist is
imperative.
Methylmalonic Acidemia
Natural History
Methylmalonic acidemia (MMA) is an inborn error of
isoleucine (ile), methionine (met), threonine (thr), valine
(val), and odd-chain fatty acid metabolism caused by a
deficiency of the enzyme methylmalonyl-CoA mutase,
which converts methymalonyl CoA to succinyl-CoA with
eventual oxidation in the citric acid cycle (Figure 22-4). In
MMA, methylmalonyl CoA is not metabolized and leads
to accumulation of various methylmalonate metabolites.
The degree of deficiency in the mutase enzyme affects
the clinical outcome of this disorder.6,7,43 Those classified with mut-deficiency have some residual activity and
often a less severe clinical course than those with mut0
deficiency who have no remaining enzyme activity.43,44
Methylmalonyl-CoA mutase requires the cofactor 5-dehydroxyadenosylcobalamin, which is produced from vitamin
B12 . Defects in the production of the cobalamin cofactor can
also cause MMA. The estimated prevalence of MMA is 1 in
80,000 births.45,46
Infants with classic MMA caused by a severe deficiency
of the mutase enzyme often present in the first week of life
with overwhelming illness. Symptoms include poor feeding,
failure to thrive, hypotonia, vomiting, and dehydration with
ketosis, acidosis, hyperammonemia, and hypoglycemia.43,44
Acute episodes are often fatal without aggressive management. Screening for MMA is now included in the expanded
newborn screening panel, which is expected to improve
early diagnosis and clinical outcomes of this disorder.47
Individuals with a deficiency in the mutase enzyme
require medical nutrition therapy, described below. Despite
treatment, those with severe mutase deficiency often have
impaired developmental and medical outcomes.48,49 For
patients with MMA caused by a mild, late-onset mutase
deficiency or a defect in cofactor production, supplementation with high doses of vitamin B12 may improve metabolic
control and allow for more normal development. This is
particularly true for those with a cbl A defect.43 Other
cofactor deficiencies, such as cbl B and cbl C defect, can
have a more complicated clinical course and require both
medical nutrition therapy and vitamin B12 supplementation.43,50 Liver transplantation is now an option for treatment
of this disorder, particularly for those with severe enzyme
deficiency. 5153
238
Figure 22-4 Methylmalonic acidemia is caused by a defect in methylmalonyl CoA mutase. Two of 6 known cobalamin cofactor synthesis defects are
shown, which also cause methylmalonic acidemia.
Adapted from Nyhan WL, Barshop BA, Ozand PT. Atlas of Metabolic Diseases. 2nd ed. New York, NY: Oxford University Press Inc; 2005. Reproduced by
permission of Edward Arnold (Publishers) Ltd.
Acute Management
Initial Presentation
Infants with MMA presenting in an acute episode require
immediate medical attention to control acidosis, hyperammonemia, and hypoglycemia.43,54,55 Nutrition management
during the acute phase of illness concentrates on delivery of
nonprotein calories to help slow catabolism. Typically, intravenous (IV) dextrose at the maximum glucose infusion rate
with additional lipid is provided to achieve maximal caloric
intake. 55 IV carnitine may also be indicated.6
Medical foods for the treatment of MMA are available
which contain all amino acids except ile, met, thr, and val.56
If enteral feedings are poorly tolerated, specialized parenteral
solutions are available that lack the offending amino acids.
As metabolic control improves, a standard infant formula
or standard total parenteral nutrition solution is added to
provide a complete source of protein and meet the individuals
met, val, ile, and thr needs.3,5 Monitoring of ammonia, prealbumin, bicarbonate, and plasma amino acids is necessary to
adjust the dietary prescription to achieve optimal metabolic
control.
Illness
During illness and injury, an increase in the metabolic rate
leads to catabolism of protein. In MMA, the offending
amino acids cannot be utilized and a metabolic episode,
with symptoms similar to those observed during the initial
episode in infancy, can develop. Metabolic crisis associated
with illness or injury can occur at any age and can be life
threatening if not managed aggressively.48,55
For management of illness at home, a sick-day diet

is prescribed to reduce intact protein and increase caloric
intake. If tolerated, medical food is continued to provide
adequate amino acids and kilocalories to promote protein
anabolism. For individuals with less severe febrile illness,
the sick-day diet may prevent the need for further medical
intervention. For severe illness, aggressive medical intervention is required.6,55 Caretakers need to be educated about the
signs of metabolic decompensation and provided with an
emergency protocol that includes contact information for
the metabolic team.
Chronic Management
The long-term medical nutrition therapy for individuals
with mutase deficiency includes restriction of the amino
acids ile, met, thr, and val with adequate caloric intake to
prevent catabolism. 3,5,56 Often, a medical food restricted in
these 4 amino acids provides the primary source of calories, other amino acids, and micronutrients. Intact protein
from infant formula or expressed breast milk is added
to provide adequate intake of ile, val, thr, and met. This
allows for adequate growth and protein maintenance, but
prevents excessive intake of these amino acids, which can
lead to excessive production of methylmalonic acid and its
metabolites. 57 The amount of intact protein allowed in the
diet depends on the individuals tolerance for the offending
amino acids. Supplementation with individual amino acids,
particularly ile and/or val, may be required to meet needs of
these offending amino acids without increasing the concentration of other offending amino acids. 3,56 Depending on the
childs clinical status, foods such as fruits, vegetables, and
239
grains can replace the amino acids provided by the standard

infant formula or breast milk.
For those responding to vitamin B12 supplementation,
typical oral doses include 1000 to 2000 mcg/d or similar
doses given 1 to 2 times per week via intramuscular (IM)
injection. 58 Hydroxycobalamin may be better metabolized
than cyanocobalamin in these disorders. 50
L-carnitine is often deficient in individuals with
MMA. 59 Carnitine binds to the metabolites produced
in this disorder; thus, individuals with MMA can have a
higher requirement for this nutrient. Supplementation
with prescription-strength L-carnitine (Carnitor) is
common practice, especially if plasma carnitine deficiency
is observed. Doses for carnitine supplementation range
from 60 to 200 mg/kg.6 Side effects from excessive carnitine intake include diarrhea and a fishy odor.
Laboratory monitoring is required to assess metabolic
status and determine dietary prescription changes. Labs
typically include plasma or serum concentrations of amino
acids, carnitine, acyl carnitine profile, methylmalonic acid,
ammonia, and/or urine organic acid analysis.54,56 In addition to these indicators, labs to assess general nutrition status
such as iron indices, calcium, vitamin D, EFAs, and albumin/
prealbumin concentrations should be routinely assessed. 3
Ornithine Transcarbamylase Deficiency
Acute Management
Natural History
The most common inborn error of metabolism of the urea cycle
is deficiency of the enzyme ornithine transcarbamylase (OTC)
(Figure 22-5). OTC deficiency impairs urea cycle function,
resulting in hyperammonemia as conversion of ammonia to
nontoxic urea is impaired. Production of arginine is decreased,
and arginine becomes an essential amino acid in this disorder.6,7
OTC deficiency is an X-linked disorder; therefore, males are
often more severely affected than females. However, there is
a wide range of clinical presentations, including adult-onset
OTC deficiency in affected women.60
The severe form of the disease is characterized by
overwhelming hyperammonemia (> 400 mol/L) in the
newborn period causing recurrent vomiting, lethargy,
irritability, and seizures, which can quickly cause coma
and death if not treated aggressively. Mental retardation
is common in those surviving the initial episode.60 Milder
forms of the disorder may not present until later in life after
a severe illness and can include neurological complications,
such as psychosis.61 Long-term outcome with treatment
varies greatly and often depends on the ability to prevent
further episodes of hyperammonemia.
Figure 22-5 Nitrogen metabolism in the urea cycle. Ornithine

transcarbamylase (OTC) deficiency results in hyperammonemia, elevated
L-glutamine concentrations, and deficiency of L-arginine. Other enzymes in
the urea cycle include angininosuccinate synthetase (AS), argininosuccinate
lyase (AL), and arginase.
Acute management may be necessary at the time of initial

presentation or with any intercurrent illness or injury. The
goal of acute management of OTC deficiency is to slow
protein catabolism and, thus, reduce ammonia production
by providing a nonprotein, high-calorie nutrition source
via enteral or parenteral nutrition. 55,62,63 As clinical status
improves, essential amino acids are provided to prevent
further protein breakdown. Essential amino acids can be
provided with specialty total parenteral nutrition solutions
or enteral medical foods designed for treatment of urea
cycle disorders. Providing essential amino acids promotes
protein anabolism, yet restricts intake of the nonessential
amino acids that can contribute to the nitrogen load.62,63
Since arginine is an essential amino acid in OTC deficiency, supplementation with oral or IV L-arginine is often
indicated during illness. Arginine bypasses the enzymatic
block to allow for conversion of urea rather than further
ammonia production. Acute medical management often
includes use of nitrogen-scavenger drugs, which are available in both oral (Buphenyl) and IV forms (Ammunol).
These medications bind to accumulated precursors to
reduce toxicity.64,65 Liver transplantation is now an option
for treatment of this disorder.66,67
240
Chronic Management
Figure 22-6. Fatty Acid Oxidation and VLCAD Deficiency.
There is a wide range of clinical phenotypes in OTC

deficiency and, thus, dietary management needs to be
individualized. Chronic management of OTC deficiency
includes dietary restriction of total protein; approximately
50% of total protein from intact sources and 50% from a
medical food containing essential amino acids as the protein
source is typically recommended. 5,62,63,68 Often, the protein
prescription for OTC deficiency is lower than the protein
requirements outlined in the DRIs. In infancy, the intact
protein source can include infant formula or expressed breast
milk with transition to lower protein foods in childhood.
The use of specialty low-protein food products is necessary
to meet caloric needs, increase satiety, and provide variety in
the diet. In addition, citrulline is routinely supplemented up
to 170 mg/kg as it is the precursor for arginine and utilizes
additional nitrogen via aspartate in the urea cycle.62
To assess metabolic control, frequent monitoring of
ammonia and plasma amino acids is necessary. Of particular interest are citrulline and arginine to evaluate citrulline
supplementation and glutamine which increases with excessive protein intake (Figure 22-5).69 Additionally, assessment
of leucine, valine, and isoleucine is required as chronic use
of a nitrogen-scavenging medication may reduce concentrations of the branched-chain amino acids. 64 Additional
indices of nutrition status such as albumin/prealbumin and
iron status should be routinely monitored. 3
Fatty acid oxidation requires entry of long-chain fatty acids (LCFAs) into the
mitochondria. This process requires L-carnitine. Carnitine cycle enzymes
include acyl-CoA synthetase (AS), carnitine palmitoyltransferase I and II
(CPT I and CPT II), and acylcarnitine/carnitine translocase (CT). Once in the
mitochondria, the -oxidation spiral sequentially oxidizes the fatty acyl-CoA
to the 2-carbon unit acetyl-CoA. Oxidation of LCFA requires very long-chain
acyl-CoA dehydrogenase (VLCAD) and a trifunction protein which includes
3 enzyme activities. In treatment of LCFA, supplementation with medium
chain triglycerides (MCTs) bypasses the long-chain fatty acid enzymes and
utilizes enzymes that oxidize medium and short-chain fatty acids including
medium-chain acyl-CoA dehydrogenase (MCAD) and short-chain acyl-CoA
dehydrogenase (SCAD) enzymes.
Very Long Chain Acyl-CoA Dehydrogenase

Deficiency
Natural History
Very long chain acyl-CoA dehydrogenase deficiency
(VLCADD) is an inborn error in the first step of mitochondrial -oxidation of long-chain fatty acids (LCFAs) (14 to
20 carbons in length) resulting in disturbed energy production with hypoglycemia, reduced ketone production, and
production of abnormal long-chain fat metabolites (Figure
22-6).6,7 Severe forms of this disorder can cause cardiomyopathy and myopathy and can be fatal in infancy without
medical intervention. Milder forms of this disorder may not
present until later in life with episodes of muscle pain and
rhabdomyolysis, especially after intense and/or prolonged
exercise or during illness.70,71 Newborn screening can now
detect infants with VLCADD. This disorder appears to
be more common than earlier estimates since screening is
identifying those with milder forms of this disorder.72 Longterm development and outcome of those diagnosed and
treated early can be favorable.73,74
Adapted from Nyhan WL, Barshop BA, Ozand PT. Atlas of Metabolic
Diseases. 2nd ed. New York, NY: Oxford University Press Inc; 2005.
Reproduced by permission of Edward Arnold (Publishers) Ltd.
Acute Management
The primary goal of acute management of VLCADD is to
provide sufficient kilocalories to prevent or reduce catabolism of fat stores.6,7 A dextrose infusion at the upper threshold
of the glucose infusion rate is typically provided to reverse
catabolism.55,75 As enteral feeding becomes possible, sources
of glucose and medium-chain triglycerides (MCTs) can be
given to meet calorie demands. Intralipid is contraindicated in
VLCADD because it is a source of LCFAs.
Chronic Management
Long-term management of VLCADD includes prevention of fasting, restriction of long-chain fat intake, and
supplementation with MCTs. 5,74,76,77 Prevention of fasting,
especially in the newborn period when energy stores are
limited, is imperative to prevent breakdown of fat stores.
Fasting guidelines need to be individualized, but typically
fasting is limited to 4 hours for infants up to 4 months of
age.74,78 Longer periods of fasting can be allowed as the
infant ages, but often a feeding during the night is recommended during the first year.76
Nutrition therapy for VLCADD includes modification of fat sources to restrict intake of long-chain fat and
supplement with MCTs. Depending on the severity of the
disorder, long-chain fat intake may need to be reduced
below 20% of total kilocalories during infancy. 5,74,76,77 The
remaining fat kilocalories are supplied by MCTs, which
include fatty acids of 8 to 12 carbons in length and thus can
bypass the enzymatic block in LCFA oxidation. There are
several medical foods available for treatment of VLCADD
which contain limited amounts of long-chain fats and are
supplemented with MCTs. In mild forms of this disorder,
limited breastfeeding may be allowed.74,76,77
With the restriction in long-chain fat, it is important
to assess the intake of the EFAs linoleic acid (LA) and
alpha-linolenic acid (ALA). Supplementation with walnut,
flax, or safflower oil may be necessary to meet LA and ALA
needs.79 Some medical foods are supplemented with ARA
and DHA.
In older children with severe LCFA disorders, restriction of long-chain fat to approximately 10% of total calories
may be necessary to maintain metabolic control.77,80 All
fat from food should be considered long-chain fat since
medium- and short-chain fats are limited in natural
foodsources. Supplementation of low- or nonfat foods and
beverages with a commercial MCT source (available in
oil and powder) provides the remaining calories from fat.
With intense exercise, consuming MCT prior to activity
may be beneficial as an energy source during activity. 81
Addition of raw cornstarch to the nighttime feed may
be indicated in some children with VLCADD. Cornstarch
is a slowly digested source of glucose and is employed in
the treatment of glycogen storage disease to prevent hypoglycemia. 82 Cornstarch supplementation may be helpful
in fatty acid oxidation disorders to prevent low glucose
concentrations and reduce production of abnormal fat
metabolites during fasting.75 Because of poor digestion,
cornstarch is contraindicated before 9 months of age. 82
Routine monitoring to assess metabolic control
241
typically includes measurement of fasting serum glucose,

creatine phosphokinase (CK), plasma carnitine and acylcarnitine profiles, and erythrocyte essential fatty acids. 5,83
Galactosemia
Natural History
Classic galactosemia is an autosomal recessive disorder
caused by the enzymatic deficiency of galactose-1-phosphate uridyl transferase (GALT) resulting in elevations of
galactose-1-phosphate (Gal-1-P), galactitol, and galactonate (Figure 22-7).6,7 The incidence of classic galactosemia
is approximately 1 in 60,000 births. Various mutations
have been identified in the GALT gene. In the Caucasian
population, a common mutation is Q188R; homozygosity
of this mutation results in a severe phenotype, often with
0% enzyme.84 Another common mutation is S135L, which
results in a milder clinical course and is prevalent in the
African American population. Another form of galactosemia
is the Duarte variant, which results in a mild phenotype that
may not require dietary intervention. 85
Figure 22-7 Classic galactosemia is a caused by a deficiency of
galactose-1-phosphate uridyl transferase (GALT). Elevations in galactose1-phosphate, galactose, galactitol and galactonate are present in this
disorder.
242
Galactosemia is detected by newborn screening; however,

infants with severe galactosemia can present with symptoms before newborn screening results are available. Acute
symptoms include cataracts, jaundice, failure to thrive,
vomiting, sepsis, hepatomegaly, and liver failure. These
symptoms resolve quickly with medical intervention and a
diet restricted in galactose. 5,6,7
Treatment of classic forms of galactosemia requires a
life-long galactose-restricted diet. Despite nutrition management, long-term complications of classic galactosemia can
include mental retardation, neurological abnormalities,
speech delay, and ovarian failure in females.86,87,88 Abnormal
bone metabolism has also been described in this population.89 The specific cause of these complications remains
unknown, although endogenous production of galactose
has been implicated.90
Acute Management
Infants identified with classic galactosemia should be
immediately placed on a soy-based infant formula. Soy
formulas, which contain soy protein isolate as the protein
source, have a very low galactose content compared to
cows milk-based formulas or breast milk. If an infant
does not tolerate enteral feeds, standard total parenteral
nutrition may be used. Efforts should be made to choose
medications that are free of lactose extenders. Unlike
some disorders of amino acid and fat metabolism, those
with galactosemia do not develop metabolic episodes
associated with illness.
Chronic Management
Long-term management of classic galactosemia requires
restriction of galactose in the diet. Galactose is primarily
derived from lactose.91 During infancy, powdered soy
formula is provided and breastfeeding is not allowed.
Powdered soy formula is recommended over ready-to-feed
or concentrated liquid soy formulas. Liquid soy formulas
contain a higher galactose content from the addition of
carageenan, although the digestive availability of galactose
from carageenan is unclear.92 Use of lactose-free elemental
formulas, which contain no galactose, have been used to
treat some infants with classic galactosemia with Gal-1-P
concentrations that have not decreased into the treatment
range by 4 to 6 months of age.93
When starting solids, all dairy products are contraindicated. Caregivers are instructed to check food labels
for lactose- and galactose-containing foods and ingredients (Table 22-4). Galactose is also found in organ meats
and some legumes. Fruits and vegetables contain varying
amounts of both free and bound galactose.9496 It remains

unclear if the minimal intake of galactose from some fruits
and vegetables contributes excessive dietary galactose and
need to be eliminated from the diet.97 Calcium and vitamin
D intake needs to be assessed in those on a galactoserestricted diet. Supplementation is typically required for
children who do not consume a soy-based formula or fortified soy milk. 3,5
Table 22-4 Foods and Ingredients That Contain Lactose or Galactose*
Milk
Casein
Milk solids
Calcium caseinate
Nonfat dry milk
Sodium caseinate
Nonfat dry milk solids
Lactose
Dry milk
Hydrolyzed whey protein
Butter
Whey and whey solids
Buttermilk and buttermilk solids
Lactalbumin
Cream
Lactoglobulin
Garbanzo beans
Dry peas/beans
Organ meats
Milk chocolate
Ice cream
Sour cream
Sherbet
Yogurt
Cheese
* These foods and ingredients are eliminated in the dietary management
of classic galactosemia.
Erythrocyte Gal-1-P is the primary metabolite

monitored in galactosemia and maintenance of Gal-1-P
concentrations below 4 mg/dL is considered optimal.91
When evaluating Gal-1-P concentrations, patient-specific
comparisons should be made; some individuals maintain
Gal-1-P concentrations above 4 mg/dL even with strict
dietary management. Gal-1-P is not a sensitive measure
of treatment compliance; however, a significant increase
above a patients typical Gal-1-P concentrations should be
investigated for possible dietary indiscretions.98
1. PKU is often referred to as the model for newborn

screening because:
A. Screening is economically feasible and results are
reliable.
B. Early medical nutrition therapy is available.
C. Nutrition therapy prevents mental retardation associated with untreated PKU.
D. All of the above.
2. When is total parenteral nutrition indicated for an individual with methylmalonic acidemia (MMA)?
A. Standard total parenteral nutrition solutions should
never be given to patients with this disorder.
B. Only specialty total parenteral nutrition solutions

containing no isoleucine, methionine, threonine,
and valine should be provided.
C. Depending on a patients clinical status, a combination of specialty total parenteral nutrition and
standard total parenteral nutrition can be provided.
D. Total parenteral nutrition is always contraindicated
in this disorder.
3. In very long chain acyl CoA dehydrogenase deficiency
(VLCADD),
is/are contraindicated
because
:
A. Medium chain triglycerides; they cannot be
metabolized
B. Intralipid; of its long chain fat content
C. Carbohydrates; they interfere with oxidation of
fatty acids
D. Cornstarch; it helps prevent hypoglycemia and
rhabdomyolysis
References
1. Garg U, Dasouki M. Expanded newborn screening of

inherited metabolic disorders by tandem mass spectrometry: clinical and laboratory aspects. Clin Biochem.
2006;39:315332.
2. Watson AS, Mann MY, Lloyd-Puryear MA, Rinaldo P, Howell
RR. Newborn screening: toward a uniform panel and system.
Executive summary. Genet Med. 2006;8:111S.
3. Acosta PB, Yannicelli S. The Ross Metabolic Formula System
Nutrition Support Protocols. 4th ed. Columbus, OH: Ross
Products Division/Abbott Laboratories; 2001.
4. Elsas LJ, Acosta PB. Inherited metabolic disease: amino acids,
organic acids, and galactose. In: Shils ME, Shike M, Ross AC,
Caballero B, Cousins RJ, eds. Modern Nutrition in Health and
Disease, 10th ed. Philadelphia, PA: Lippincott, Williams &
Wilkins; 2006:909959.
5. Acosta PB, ed. Nutrition Management of Patients with Inherited
Metabolic Disorders. Sudbury, MA: Jones & Bartlett; 2009.
6. Nyhan WL, Barshop BA, Ozand PT. Atlas of Metabolic Diseases.
2nd ed. New York, NY: Oxford University Press Inc; 2005.
7. Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Online Metabolic & Molecular Bases of Inherited Disease. New York, NY:
McGraw-Hill, 2007. Available from http://www.ommbid.com.
8. Guldberg P, Romano V, Ceratto N, et al. Mutational spectrum
of phenylalanine hydroxlyase deficiency in Sicily: implications
for diagnosis of hyperphenylalaninemia in southern Europe.
Hum Mol Genet. 1993;2:17031707.
9. Koch R, Azen C, Friedman EG, Williamson ML and Writing
Committee for the PKU Collaborative Study. Paired comparisons between early treated PKU children and their matched
sibling controls on intelligence and school achievement test
results at eight years of age. J Inherit Metab Dis. 1984;7:8690.
243
10. Bickel H, Gerrard J, Hickmans EM. The influence of phenylalanine intake on phenylketonuria. Lancet. 1953; 265:812813.
11. Berry HK, Wright S. Conference on treatment of phenylketonuria. J Pediatr. 1967;70:142147.
12. Koch R, Burton B, Hoganson G, et al. Phenylketonuria
in adulthood: a collaborative study. J Inherit Metab Dis.
2002;25:333346.
13. Azen CG, Koch R, Friedman EG, et al. Intellectual development in 12-year-old children treated for phenylketonuria. Am
J Dis Child. 1991;145:3539.
14. National Institutes of Health. Phenylketonuria (PKU):
Screening and Management. NIH Consensus Statement.
Washington DC; 2000.
15. Waisbren SE, Noel K, Fahrbach K, et al. Phenylalanine blood
levels and clinical outcomes in phenylketonuria: a systematic literature review and meta-analysis. Mol Genet Metab.
2007;92:6370.
16. Levy H, Ghavami M. Maternal phenylketonuria: A metabolic
teratogen. Teratology. 1996;53:176184.
17. Waisbern SF, Hanley W, Levy HL, et al. Outcomes at age
4 years in offspring of women with maternal phenylketonuria: the Maternal PKU Collaborative Study. JAMA.
2000;283:756762.
18. Waisbren SE, Azen C. Cognitive and behavioral development in maternal phenylketonuria offspring. Pediatrics.
2003;112:15441547.
19. Yagasaki M, Hashimoto S. Synthesis and application of
dipeptides; current status and perspectives. Appl Microbiol
Biotechnol. Epub. 2008;81:1322.
20. van Rijn M, Bekhof J, Dijkstra T, Smit PG, Moddermam P, van
Spronsen FJ. A different approach to breast-feeding of the infant
with phenylketonuria. Eur J Pediatr. 2003;162:323326.
21. Greve LC, Wheeler MD, Green-Burgeson DK, Zorn EM.
Breast-feeding in the management of the newborn with
phenylketonuria: a practical approach to dietary therapy. J Am
Diet Assoc. 1994;94:305309.
22. Lawrence RL. Breastfeeding: A Guide for the Medical Profession.
5th ed. St. Louis, MO: C.V. Mosby Co; 2005.
23. Leamons JA, Reyman D, Moye L. Amino acid composition
of preterm and term breast milk during early lactation. Early
Hum Dev. 1983;8:323329.
24. Gropper SS, Acosta PB. Effect of simultaneous ingestion of
L-amino acids and whole protein on plasma amino acid and
urea nitrogen concentrations in humans. J Parenteral Enteral
Nutr. 1991;15:4853.
25. Otten JJ, Helwig JP, Meyers LD. Dietary Reference Intakes: The
Essential Guide to Nutrient Requirements. Washington, DC: The
National Academies Press; 2006.
26. Singh R, Lesperance E, Crawford K. PKU Food List. 2nd ed.
Atlanta, GA: Emory University, Department of Human
Genetics, Division of Medical Genetics; 2006.
27. Schuett V. Low Protein Food List for PKU. 2nd ed. Seattle, WA:
National PKU News; 2002.
28. Schuett V. Low Protein Cookery for PKU. 4th ed. Madison, WI:
The University of Wisconsin Press; 1996.
29. Schuett V, Corry D. Apples to Zucchini: A Collection of Favorite
Low Protein Recipes. Seattle, WA: National PKU News; 2005.
244
30. Acosta PB, Yannicelli S, Singh RH, Elsas LJ, Mofidi S, Steiner
RD. Iron status of children with phenylketonuria undergoing
nutrition therapy assessed by transferrin receptors. Genet Med.
2004;6:96101.
31. Robinson M, White FJ, Cleary MA, et al. Increased risk of
vitamin B12 deficiency in patients with phenylketonuria on an
unrestricted or relaxed diet. J Pediatr. 2000;136:545547.
32. Acosta PB, Yannicelli S. Plasma micronutrient concentrations
in infants undergoing therapy for phenylketonuria. Biol Trace
Elem Res. 1999;67:7584.
33. Hvas AM, Nexo E, Nielsen JB. Vitamin B12 and vitamin B6
supplementation is needed among adults with phenylketonuria (PKU). J Inherit Metab Dis. 2006;29:4753.
34. Moseley K, Koch R, Moser AB. Lipid status and long-chain
polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-restricted diet. J
Inherit Metab Dis. 2002;25:5664.
35. Koletzko B, Beblo S, Demmelmair H, Hanebutt FL. Omega-3
LC-PUFA supply and neurological outcomes in children
with phenylketonuria (PKU). J Pediatr Gastroenterol Nutr.
2009;48(suppl):S27.
36. Beblo S, Reinhardt H, Demmelmair H, Muntau AC, Koletzko
B. Effect of fish oil supplementation on fatty acid status, coordination, and fine motor skills in children with phenylketonuria.
J Pediatr. 2007;150:479484.
37. Puglisi-Allegra S, Cabib S, Pascucci T, et al. Dramatic brain
aminergic deficit in a genetic mouse model of phenylketonuria. Neuroreport. 2000;11:13611364.
38. Matalon R, Michals-Matalon K, Bhatia G, et al. Double blind
placebo controlled trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine. J Inherit Metab
Dis. 2007;30:153158.
39. Schindeler S, Ghosh-Jerath S, Thompson S, et al. The effects
of large neutral amino acid supplements in PKU: an MRS and
neuropsychological study. Mol Genet Metab. 2007;91:4854.
40. Levy HL, Milanowski A, Chakrapani A, et al. Efficacy of
sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4)
for reduction of phenylalanine concentrations in patients with
phenylketonuria: a phase III randomized placebo-controlled
study. Lancet. 2007;370:504510.
41. Burton BK, Grange DK, Milanowski A, et al. The response
of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride
(6R-tetrahydrobiopterin): a phase II, multicentre, open-label,
screening study. J Inherit Metab Dis. 2007;30:700707.
42. Singh R, Jurecki E, Rohr F. Recommendations for personalized dietary adjustments based on patient response to
tetrahydrobiopterin (BH4) in phenylketonuria. Top Clin Nutr.
2008;23:149157.
43. Merinero B, Perez C, Perez-Cerda A, et al. Methylmalonic
acidemia: examination of genotype and biochemical data in
32 patients belonging to mut, cbIA or cbIB complementation
group. J Inherit Metab Dis. 2008;31:5566.
44. Shevell M, Matiaszuk N, Ledley F, Rosenblatt D. Varying
neurological phenotypes among mut0 and mut patients
with methylmalonyl CoA mutase. Am J Med Genet.
1993;45:619624.
45. Sniderman LC, Lambert M, Giguere R, et al. Outcome of

individuals with low-moderate methylmalonic aciduria
detected through a neonatal screening program. J Pediatr.
1999;134:675680.
46. Chace D, DiPerna J, Kalas T, Johnson R, Naylor E. Rapid diagnosis of methylmalonic and propionic acidemias: quantitative
tandem mass spectrometric analysis of propionylcarnitine in
filter-paper blood specimens obtained from newborns. Clin
Chem. 2001;47:20402044.
47. Dionisi-Vici C, Deodato F, Rschinger W, Rhead W, Wilcken
B. Classical organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: Long-term outcome and
effects of expanded newborn screening using tandem mass
spectrometry. J Inherit Metab Dis. 2006;29:383389.
48. Van der Meer SB, Poggi F, Spada M, et al. Clinical outcome of
long-term management of patients with vitamin B12-unresponsive methylmalonic acidemia. J Pediatr. 1994;125:903908.
49. de Baulny HO, Benoist JF, Rigal O, Touati G, Rabier D,
Saudubray JM. Methylmalonic and propionic acidaemias: management and outcome. J Inherit Metab Dis.
2005;28:415423.
50. Andersson HC, Shapira E. Biochemical and clinical response
to hydroxocobalamin versus cyanocobalamin treatment in
patients with methylmalonic acidemia and homocystinuria
(cblC). J Pediatr. 1998;132:121124.
51. Nyhan WL, Gargus JJ, Boyle K, Selby R, Koch R. Progressive neurologic disability in methylmalonic acidemia despite
transplantation of the liver. Eur J Pediatr. 2002;161:377379.
52. Morioka D, Kasahara M, Horikawa R, Yokoyama S, Fukuda
A, Nakagawa A. Efficacy of living donor transplantation
for patients with methylmalonic acidemia. Am J Transplant.
2007;7:27822787.
53. McGuire PJ, Lim-Melia E, Diaz GA, et al. Combined liverkidney transplant for the management of methylmalonic
aciduria: A case report and review of the literature. Mol Genet
Metab. 2008;93:2229.
54. Lee NC, Chien YH, Peng SF, et al. Brain damage by mild
metabolic derangements in methylmalonic acidemia. Pediatr
Neurol. 2008;39:325329.
55. Prietsch V, Lindner M, Zschocke J, Nyhan WL, Hoffmann
GF. Emergency management of inherited metabolic diseases.
J Inherit Metab Dis. 2002;25:531546.
56. Yannicelli S. Nutrition therapy of organic acidaemias with
amino acid-based formulas: emphasis on methylmalonic and
propionic acidaemia. J Inherit Metab Dis. 2006;29:281287.
57. Ney DM, Bay C, Saudubray JM, et al. An evaluation of protein
requirements in methylmalonic acidaemia. J Inherit Metab
Dis. 1985;8:132142.
58. Wedel U, deBaulny HO. Branched-chain organic acidurias/
acidemias. In: Fernandes J, Saudubray JM, van den Berghe G,
Walter JH, eds. Inborn Metabolic Diseases: Diagnosis and Treatment, 4th ed., rev. Heidelberg Germany: Springer Medizen
Verlag, 2006:245260.
59. Chalmers RA, Roe CR, Stacey TE, Hoppel CL. Urinary
excretion of L-carnitine and acylcarnitines by patients with
disorders of organic acid metabolism: evidence for secondary
insufficiency of L-carnitine. Pediatr Res. 1984;18:13251328.
60. Maestri N, Clissold D, Brusilow S. Neonatal onset ornithine

transcarbamylase deficiency: a retrospective analysis. J Peds.
1999;134:268-272.
61. Bachmann C. Outcome and survival of 88 patients with urea
cycle disorders: a retrospective evaluation. Eur J Pediatr.
2003;162:410416.
62. Leonard JV. The nutritional management of urea cycle disorders. J Pediatr. 2001;138:S4045.
63. Singh RH. Nutritional management of patients with urea
cycle disorders. J Inherit Metab Dis. 2007;30:880887.
64. Scaglia F, Carter S, OBrien W, Lee B. Effect of alternative pathway therapy on branched chain amino acid
metabolism in urea cycle disorder patients. Mol Genet Metab.
2004;81:7985.
65. Batshaw ML, MacArthur RB, Tuchman M. Alternative
pathway therapy for urea cycle disorders: twenty years later. J
Pediatr. 2001;138:S4654.
66. Puppi J, Tan N, Mitry RR, et al. Hepatocyte transplantation
followed by auxiliary liver transplantationa novel treatment
for ornithine transcarbamylase deficiency. Am J Transplant.
2008;8:452457.
67. McBride K, Miller G, Carter S, et al. Developmental outcomes
with early orthotopic liver transplantation for infants with
neonatal-onset urea cycle defects and a female patient with
late-onset ornithine transcarbamoylase deficiency. Pediatrics.
2004;114:523526.
68. Acosta PB, Yannicelli S, Ryan AS, et al. Nutritional therapy
improves growth and protein status of children with a urea
cycle enzyme defect. Mol Genet Metab. 2005;86:448455.
69. Wilson CJ, Lee PJ, Leonard JV. Plasma glutamine and
ammonia concentrations in ornithine carbamoyltransferase deficiency and citrullinaemia. J Inherit Metab Dis.
2001;24:691695.
70. Pons R, Cavadini P, Baratt S, et al. Clinical and molecular
heterogeneity in very-long chain acyl-coenzyme A dehydrogenase deficiency. Pediatr Neurol. 2000;22:98105.
71. Smelt A, Poorthuis B, Onkenhout W, et al. Very long chain
acyl-coenzyme A dehydrogenase deficiency with adult onset.
Ann Neurol. 1998;43:540544.
72. Liebig M, Schymik I, Mueller M, et al. Neonatal screening for
very long-chain acyl-CoA dehydrogenase deficiency: enzymatic and molecular evaluation of neonates with elevated
C14:1-carnitine levels. Pediatrics. 2006;118:10651069.
73. Vianey-Saban C, Divry P, Brivet M, et al. Mitochondrial
very-long-chain acyl-coenzyme A dehydrogenase deficiency:
clinical characteristics and diagnostic considerations in 30
patients. Clin Chim Acta. 1998;269:4362.
74. Spiekerkoetter U, Lindner M, Santer R, et al. Treatment
recommendations in long-chain fatty acid oxidation
defects: consensus from a workshop. J Inherit Metab Dis.
2009;32:498505.
75. Vockley J, Singh RH, Whiteman DA. Diagnosis and management of defects of mitochondrial beta-oxidation. Curr Opin
Clin Nutr Metab Care. 2002;5:601609.
76. Rohr F, van Calcar S. Very long chain acyl CoA dehydrogenase deficiency (VLCADD). Genetic Metabolic Dietitians
International, 2008. Available at: http://www.gmdi.org/
guidelines. Accessed September 4, 2008.
245
77. Arnold GL, Van Hove J, Freedenberg D, et al. A Delphi

clinical practice protocol for the management of very long
chain acyl-CoA dehydrogenase deficiency. Mol Genet Metab.
2009;96:8590.
78. Walter J. Tolerance to fast: rational and practical evaluation in children with hypoketonaemia. J Inherit Metab Dis.
2009;32:214217.
79. Roe CR, Roe DS, Wallace M, Garritson B. Choice of oils for
essential fat supplements can enhance production of abnormal
metabolites in fat oxidation disorders. Mol Genet Metab.
2007;92:346350.
80. Gillingham M, Connor W, Matern D, et al. Optimal dietary
therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase
deficiency. Mol Gen Metab. 2003;79:114123.
81. Gillingham MB, Scott B, Elliott D, Harding CO. Metabolic
control during exercise with and without medium chain
triglycerides (MCT) in children with long-chain 3-hydroxy
acyl-CoA dehydrogenase (LCHAD) or trifunctional protein
(TFP) deficiency. Mol Genet Metab. 2006;89:5863.
82. Goldberg T, Slonim AE. Nutrition therapy for hepatic glycogen
storage diseases. J Am Diet Assoc. 1993;93:14231430.
83. Spiekerkotter U, Schwahn B, Korall H, Trefz FK, Andresen
BS, Wendel U. Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency: monitoring of treatment by
carnitine/acylcarnitine analysis in blood spots. Acta Paediatr.
2000;89:492495.
84. Elsas LJ, Langley S, Paulk EM, Hjelm LN, Dembure PP.
A molecular approach to galactosemia. Eur J Pediatr.
1995;154:S217.
85. Ficicioglu C, Thomas N, Yager C, et al. Duarte (DG)
galactosemia: A pilot study of biochemical and neurodevelopmental assessment in children detected by newborn
screening. Mol Genet Metab. 2008;95:206212.
86. Waggoner DD, Buist NMR, Donnell GN. Long-term prognosis in galactosemia: results of a survey of 350 cases. J Inherit
Metab Dis. 1990;13:802818.
87. Ridel KR, Leslie ND, Gilbert DL. An updated review of the
long-term neurological effects of galactosemia. Pediatr Neurol.
2005;33:153161.
88. Bosch A. Classical galactosaemia revisited. J Inherit Metab
Dis. 2006;29:516525.
89. Panis B, Forget P, van Kroonenburgh MJPG, et al. Bone
metabolism in galactosemia. Bone. 2004;35:982987.
90. Berry GT, Moate PJ, Reynolds RA, et al. The rate of de
novo galactose synthesis in patients with galactose-1phosphate uridyltransferase deficiency. Mol Genet Metab.
2004;81:2230.
91. van Calcar S, Wolff J. Galactosemia. In: Ekval S, Ekval VK,
eds. Pediatric Nutrition in Chronic Disease and Developmental
Disorders. 2nd ed. New York, NY: Oxford University Press.
2005:335339.
92. Acosta PB, Gross K. Hidden sources of galactose in the environment. Eur J Pediatr. 1995;154:16.
93. Ficicioglu C, Hussa C, Yager C, Segal S. Effect of galactose
free formula on galactose-1-phosphate in two infants with
classical galactosemia. Eur J Pediatr. 2008;167:595596.
246
94. Gross K, Acosta PB. Fruits and vegetables are a source of

galactose: implications in planning the diets of patients with
galactosaemia. J Inherit Metab Dis.1991;14:253258.
95. Scaman C, Jin Wai Jim V, Hartnett C. Free galactose
concentrations in fresh and stored apples (malus domestica) and processed apple products. J Agric Food Chem.
2004;52:511517.
96. Gropper S, Weese S, West P, Gross K. Free galactose content
of fresh fruits and strained fruit and vegetable baby foods:
more foods to consider for the galactose-restricted diet. J Am
Diet Assoc. 2000;100:573575.
97. Kim H, Hartnett C, Scaman CH. Free galactose content in

selected fresh fruits and vegetables and soy beverages. J Agric
Food Chem. 2007;55:81338137.
98. Hutchesson AC, Murduck-Davis C, Green A, et al. Biochemical monitoring of treatment for galactosemia: biological
variation in metabolic concentrations. J Inherit Metab Dis.
1999;22:139148.
23
Cardiac Disease
Anupama Chawla, MD, CNSP, DCH (UK) Janice Antino, RD, MS, CNSD, CSP, and Mindy Freudenberg, RD, MS, CNSD
CONTENTS
Congenital Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . 247
Malnutrition and Growth
Complications After Congenital Heart Disease Surgery
Cardiovascular Disease in the PediatricPatient. . . . . . . 252

Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
Learning Objectives
1. Identify factors contributing to growth failure in children with congenital heart disease.
2. Summarize the components of nutrition assessment
and optimal methods of nutrient delivery in children
with congenital heart disease.
3. Recognize and manage postoperative complications
and prescribe appropriate nutrition therapy.
Congenital Heart Disease
Congenital heart diseases are abnormalities in the heart

structure that are present at birth. Approximately 8 out of
every 1,000 infants are born with congenital heart disease.
Congenital heart disease can be classified into 2 major categories, cyanotic and acyanotic1 (Table 23-1).
Pediatric heart disease can be a congenital or an acquired
condition. This population is presented with unique challenges in meeting their energy requirements for optimal
Table 23-1 Two Major Categories of Congenital Heart Disease
Acyanotic
Cyanotic
Atrial septal defect (ASD)

Interrupted aortic arch
Ventricular septal defect (VSD)
Pulmonary atresia
Patent ductus arteriosus (PDA)
Ebsteins anomaly
Common A-V canal (CAVC)
Pulmonary stenosis*
Coarctation of aorta*
Aortic stenosis
Tetralogy of Fallot*
Transposition of the great vessels*
Total anomalous pulmonary venous return*
Truncus arteriosus*
Tricuspid atresia*
Hypoplastic left heart syndrome*
* These conditions may transition to cyanotic state.
247
248
growth and development. Depending on the congenital heart

disease lesion and its severity, a child with cogenital heart
disease may face feeding difficulties and malnutrition during
a critical developmental period.
Malnutrition and Growth

Failure to thrive and malnutrition is well documented
in infants and children with congenital heart disease. 24
Malnutrition has been identified in both acyanotic and
cyanotic congenital heart disease however the degree of
growth delay is often related to the severity of the anatomical lesion and tends to be most severe in lesions associated
with congestive heart failure (CHF). Cyanotic heart disease
patients usually tend to be more undernourished due to
their chronic hypoxic state and relatively prolonged course
until final correction, as these infants require surgery in
several stages.
At birth, the weight of infants with congenital heart
disease is usually appropriate for gestational age. Despite
normal or near-normal birth weights, infants with congenital heart disease commonly experience a rapid decline in
weight for age percentiles reflecting acute malnutrition. If
malnutrition persists, height velocity will be affected within
a few months, resulting in stunting. Weight gain can be
considerably less than expected to maintain normal growth
patterns. 5 Cameron et al reported the prevalence of acute
and chronic malnutrition to be as high as 33% and 64%,
respectively.6
Surgical correction has emerged as the most efficient
method to improve the nutrition status of these infants.
Surgical correction eliminates the cardiac factors contributing
to malnutrition. Mitchell et al evaluated the nutrition status
of 48 children with congenital heart disease before corrective
surgery.7 Significant undernutrition was evident in all children
irrespective of the cardiac lesion or the presence or absence of
cyanosis. Fifty-two percent of the children had a weight under
the third percentile for age, 83% had abnormal biochemical
and hematological measurements reflecting compromised
nutrition status, and 33% had abnormally high 3-methyhistidine suggesting a degree of active muscle wasting.
Corrective surgery is usually not performed until a
patient achieves an ideal weight and appropriate age or when
growth failure or defect requires early correction. Eskedal
et al also emphasized the role of nutrition in this population during the postoperative period. 8 They evaluated the
growth of 2 groups of infants with congenital heart disease
who underwent cardiac corrective surgery. Children who
survived past the thirtieth postoperative day but subsequently died were compared to children who were long-term
survivors. Children who died had impaired weight gain

postoperatively compared to the long-term survivors who
showed a mean increase in weight age z scores.
Depending on the type of cardiac lesion, an infant with
congenital heart disease may undergo complete corrective
surgery or a staged palliative intervention leading to complete
repair. The type of surgical treatment and the remaining
cardiac defect can have a profound impact on the nutrition rehabilitation process. The age and timing of corrective
surgery may affect the potential for growth and nutrition
recovery in infants with congenital heart disease.8 Infants
with congenital heart disease will experience fewer deficits
in weight and height if corrective surgery is performed in the
first 10 days of life compared to infants undergoing surgery
after the newborn period.9 Vaidyanathan et al evaluated the
nutrition status of infants with congenital heart disease who
underwent corrective surgery. Significant catch-up growth
was evident after 3 months, suggesting that correction of the
cardiac anomaly favorably influences the nutrition status of
infants with congenital heart disease.4 Corrective and timely
surgical intervention has been proposed as critical to avoid
the long- and short-term consequences of malnutrition.4,9
Although somatic growth is often impaired before surgical
intervention, growth usually dramatically improves to normal
or near-normal values after corrective surgery. In most infants
catch-up growth is largely complete within 6 to 12 months of
surgery.4
Etiology of Growth Impairment
The exact etiology for growth impairment in children with
congenital heart disease remains unclear. Many factors have
been identified as contributing to growth failure in this population (Table 23-2).
Table 23-2 Factors Contributing to Growth Failure in Congenital Heart
Disease
Etiology
Increased energy requirements

Decreased energy intake
Increased nutrient losses
Insufficient utilization of nutrients
Malabsorption
Tachypnea and tachycardia can

increase metabolic demands
Anorexia, dysphagia, reflux,
fatigue during feeding
Protein-losing enteropathy, renal
electrolyte losses
Acidosis, hypoxia
Gut edema
Decreased Nutrient Intake and Utilization

Inadequate caloric intake, increased metabolic demands,
or a combination of both may be responsible for significant growth impairment.9 Energy imbalance is a major
factor contributing to malnutrition in these patients, and it
CARDIAC DISEASE
influences outcomes after corrective cardiac surgery.

Feeding difficulties and intolerances are common
during the first year of life in infants with congenital heart
disease. Vomiting occurs frequently in this population and
has been identified as the most common feeding intolerance.10,11 The energy intake of infants with congenital heart
disease is often insufficient and loss of nutrients as a result of
vomiting can further decrease the amount of energy available for growth. It has been estimated that vomiting after
feeding can result in a loss of 12% of the infants energy
intake.11 Utilization of nutrients is compromised in the
setting of chronic hypoxia and acidosis is often seen in
infants with congenital heart disease.
Schwarz et al assessed the growth and energy intake of 19
infants with congenital heart disease who were not candidates
for early corrective surgery.12 Anthropometric measurements
began to improve only when energy intakes reached 150 kcal/
kg. Considering the diversity of the population and varying
degrees of anomalies, an infant with congenital heart disease
may require energy intakes of 140 to 200 kcal/kg body weight
to induce growth.4
Energy Expenditure
Infants with congenital heart disease have increased requirements of energy and protein needed to promote growth and
development. Studies examining an energy deficit whether
due to a decreased intake or increased energy expenditure
can be difficult to interpret due to the heterogenicity of the
congenital anomaly, severity of illness, and age.2
Several studies have been performed to evaluate the
methods traditionally used to determine the energy requirements in this patient population. Leitch et al used respiratory
calorimetry to measure resting energy expenditure (REE)
and total energy expenditure (TEE) in 12 infants with uncorrected cyanotic congenital heart disease and compared them
to a group of age-matched controls at 2 weeks and again at 3
months of age. No significant differences in REE were identified at either time, however a significant increase in TEE
was identified at 3 months of age.2,3 Therefore an increased
TEE but not an increased REE may be a primary factor in
the reduced growth of infants with cyanotic congenital heart
disease. This suggests that the use of REE should not be
extrapolated to determine TEE, and that caloric recommendations determined by indirect calorimetry may significantly
underestimate the actual energy needs of these patients.
Nydegger et al used indirect calorimetry to assess the
energy expenditure of 108 infants with various forms of
congenital heart disease.9 When compared to healthy controls
an increased REE was observed in infants with congenital
249
heart disease and normalized within 1 week after corrective

surgery. It was also observed that standard equations fail to
accurately predict REE in this population. When utilizing
the gold standard of measuring energy expenditure, using
the doubly labeled water technique, TEE was considerably
and consistently elevated compared to healthy controls.5,11
Although this method is considered the gold standard to
measure energy expenditure it is costly, requires specialized
equipment, and is rarely used.
Therefore, indirect calorimetry and predictive equations should be used cautiously as both may underestimate
the energy needs of children with congenital heart disease.
A thorough and accurate nutrition assessment is the primary
step for early recognition of feeding difficulties and growth
delay in children with congenital heart disease. This will result
in early intervention to help prevent nutrition deficiencies and
optimize growth. A complete nutrition assessment includes a
combination of methods that should include an accurate feeding history, visual clinical assessment, anthropometric evaluation, and biochemical indices (Table 23-3). Anthropometric
data such as weight, length/height, weight-for-length, and head
circumference can be evaluated using published growth charts
from the Centers for Disease Control and Prevention (CDC)
or the World Health Organization (WHO) (see Chapter 33).
Measurements should be plotted and monitored over time
to determine growth velocity and degree of growth failure.
Congenital heart disease may be present in conjunction with
an underlying chromosomal abnormality. In these condi
tions anthropometric data can be evaluated using specialized
growthcharts as available for children with trisomy 21, trisomy 18, Turners syndrome, and for infants born preterm.
Table 23-3 Components of Nutrition Assessment
in Congenital Heart Disease
Medical history
Type of lesion (cyanotic vs. acyanotic),
current medications, other medical
conditions
Feeding history
Type of formula, concentration of formula,
preparation methods, and amount
consumed; duration of feeds
Physical exam
Fluid status/edema, cyanosis, respiratory
rate (tachypnea)
Biochemical indices
Serum electrolytes, albumin, prealbumin.
Total lymphocyte count and stool for alpha1-antitrypsin if suspicious of protein-losing
enteropathy
Anthropometric data
Weight, length/height, weight-for-length,
triceps skinfolds, mid-arm circumference
Evaluation of growth
Monitor weight gain and linear growth
overtime
Gastrointestinal function
Evaluation of bowel pattern (eg, frequency
and consistency), GI reflux
250
Biochemical evaluation should include prealbumin,

serum albumin, and serum electrolytes including calcium,
magnesium, and phosphorus. Serum albumin results must
be interpreted with caution as it is highly sensitive to the
patients hydration status. Prealbumin is influenced by infection, sepsis, inflammation, and operative course and should be
evaluated with consideration of non-nutrition factors. Fluid
overload secondary to congestive heart failure, or dehydration
secondary to diuretics, can alter fluid and electrolyte balance
and may affect renal function. If the serum albumin is low then
protein-losing enteropathy (PLE) is a consideration and stool
for alpha-1-antitrypsin and total lymphocyte count should be
obtained to assess for PLE (see Protein-Losing Enteropathy in
this chapter).
longer than 8 weeks) then placing a gastrostomy tube should

be considered. A gastrostomy tube is better accepted socially
and also decreases the risks associated with prolonged nasogastric tube feeds. Dislodgement of the tube, stenting of the
lower esophageal sphincter with increased reflux, sinusitis,
and nasal skin and cartilage breakdown are associated with
long-term use of nasogastric tubes.13
For specialized infant formulas check manufacturers guidelines.
Adequate nutrition intake is not always easily achieved in

infants and children with congenital heart disease. These
infants require increased energy intakes to achieve significant
growth but are often unable to achieve their nutrition goal due
to anorexia and increased fatigue during feeding.
Nutrient Delivery
The primary goal is to maximize energy intake orally. When
oral intake alone fails to support growth and development,
alternative methods of nutrition delivery are indicated and
should be initiated relatively early. Tube feedings should be
considered to supplement inadequate oral intake.
In an effort to maintain the infants hunger and satiety
cycle, intermittent bolus tube feeds may be used to supplement oral nutrition intake. In order to preserve the infants oral
motor function and desire to eat, supplemental feeds should
be delivered after allowing the infant to feed orally for 10 to 15
minutes duration at each feed time.
Infants and children with CHF often need to be fluid
restricted. Concentrating formula helps provide adequate
calories while limiting fluid intake. Increasing the formula
concentration from 20 cal/oz to 24 or 27 cal/oz can be
achieved by the addition of modular components or by
reducing the water-to-powder ratio (Table 23-4). If intermittent bolus feeds are not tolerated because of compromised
motility, reflux, or concomitant respiratory distress, then
continuous feeds should be considered. Continuous feeds
allow delivery of daily requirements with smaller hourly
volumes with decreased energy expenditure.12 Continuous,
24-hour nasogastric feedings are a safe and effective method
of achieving increased nutrient intake resulting in improved
overall nutrition status. If it is anticipated that the infant will
require supplemental feeds for a prolonged duration (eg, for
Table 23-4 Concentrating Term Infant Formula

When using most infant powder: Preparing smaller volumes
Desired Concentration
(cal/oz)
24
27*
Level Scoop from

Can
3
3
Water (fl oz)

5
4.25
Concentrating liquid formula with term infant powder
Starting
Concentration
20 cal/oz
(breast milk,
ready-to-feed
formula)
24 cal/oz
Volume
Desired
Concentration
Term Infant
Formula
Powder
3 oz
24 cal/oz
1 teaspoon
4 oz
27* cal/oz
1 teaspoon
Using modulars to concentrate formulas

To prepare 24 to 28 cal/oz from 20 cal/oz formula
Modular
Duocal (14 kcal/

tsp) (Nutricia)
Vegetable Oil
(9 kcal/5 mL)
Triglyceride
Oil (MCT Oil)
(7.7 kcal/mL)
(Nestle)
Polycose (8 kcal/
tsp) (Abbott)
Volume of
Formula
20 cal/oz
To Prepare
2425 cal/oz
Formula
(amount of
modular)
To Prepare
2728* cal/oz
Formula
(amount of
modular)
3 oz
1 teaspoon
1 teaspoons
3 oz
1.5 mL
2.5 mL
3 oz
2 teaspoons
3 teaspoons
*2728 cal/oz may not supply enough water for some infants. Hydration
status and renal solute load should be carefully monitored.
Infants and children who are unable to meet their nutrition needs via the enteral route should be considered for
parental nutrition (PN). PN can be initiated pre- or postoperatively with a therapeutic goal of restoring or maintaining
nutrition status and inducing somatic growth. The optimal
timing for initiating PN is dependent on the childs baseline
nutrition status and disease acuity. In view of the relatively
CARDIAC DISEASE
high prevalence of malnutrition in infants and children with

congenital heart disease, aggressive nutrition support via
PN is an appropriate approach to prevent a further decline in
their nutrition status. PN formulation in children with congenital heart disease requires close electrolyte monitoring,
especially in patients on diuretics and digoxin therapy.
Growth impairment is frequently documented in children
with congenital heart disease. It has been well documented
that growth in children with congenital heart disease can be
significantly improved with adequate caloric intake.14 Significant caloric intake not only considerably impacts the surgical
outcomes but also the ultimate growth and development in
children with congenital heart disease.
Complications After Congenital Heart Disease Surgery

Feeding Difficulties
Infants and children often experience feeding difficulties
following cardiac surgery. Increased risk adjusted congenital heart surgery (RACHS) score, prolonged intubation,
and intraoperative transesophageal echocardiography have
been identified as risk factors associated with feeding difficulties among infants and children with congenital heart
disease after surgery.15 Problems encountered may include
a prolonged time to reach feeding goals, prolonged transition to oral feeds requiring tube feeding at discharge, and
aspiration or reflux.15 Postoperative vocal cord dysfunction is also a clinically important complication following
cardiac surgery and may increase the risk of aspiration due
to an impaired airway protection. In a study by Sachdeva
et al patients whose surgery involved manipulation of the
laryngeal nerves were at greater risk for vocal cord injury
with the presumed cause being injury to the vagus nerve.
An infant or child with vocal cord dysfunction may benefit
from a swallowing evaluation to identify the presence of
aspiration.16 Although in this particular study only 1.7%
were identified as having vocal cord dysfunction, of these
patients 100% had abnormal swallowing study results.
Most of these patients need modified oral feeds and or
nutrition support.
Patients who undergo cardiac surgery with the use
of transesophageal echocardiography have been associated with a high risk of dysphagia as well. Transesophageal
echocardiography has been identified to cause airway obstruction, common pulmonary vein compression, vascular
compression, tracheal extubation, esophageal perforation,
gastric perforation, and dental injury. Transesophageal
echocardiography probe size in relation to the patients
weight was identified as a risk factor for dysphagia. In
251
infants weighing less than 3 kg transesophageal echocardiography should be used cautiously.17

Protein-Losing Enteropathy
Protein-losing enteropathy (PLE) is an abnormal loss of protein from the digestive tract or the inability of the digestive
tract to absorb proteins. The prevalence of PLE in infants
and children with congenital heart disease seems most
prominent after the Fontan procedure (anastomosis of the
inferior vena cava to the pulmonary artery, preferred surgical correction for tricuspid atresia, hypoplastic left heart,
and single ventricle physiology). PLE can be a life-threatening complication with onset of the disease occurring from
2 months to 10 years postoperatively.18 Within 10 years of
Fontan procedure surgery, approximately 13% of patients
will develop PLE. Forty-six percent of PLE patients develop
significant morbidity and mortality within 5 years.18 Children with PLE lose protein molecules from the blood into
the intestinal tract resulting in changes in bowel habits,
abdominal discomfort, and diarrhea. Over time the concentrations of serum protein can become severely depleted,
resulting in hypoproteinemia and especially hypoalbuminemia. Hypocalcemia and lymphocytopenia are often
seen in this condition as well. The loss of serum proteins
decreases the vascular oncotic pressure and promotes the
development of edema, ascites, and pleural as well as pericardial effusion. Edema of the intestinal wall secondary to
chronic hypoalbuminemia may result in poor absorption of
nutrients and promote worsening of the diarrhea.19
Nutrition management of infants and children with PLE
should be tailored to the severity of bowel dysfunction,
diarrhea, and malabsorption. Dietary changes should
include increasing protein intake and transition from longchain triglycerides (LCTs) to a medium-chain triglyceride
(MCT) based diet. The use of a MCT-enriched diet is based
on the understanding that enterocytes directly absorb
MCTs into circulation, allowing delivery of adequate calories while reducing lymphatic flow to allow for healing.
MCTs are rapidly absorbed and reduce the amount of highprotein lymph fluid moving through the vessels within the
intestines, thereby reducing the quantity of protein loss. 20
Specialized nutrition support with the use of very high
MCT (80% to 90% of the total fat content) containing
formulas (Table 23-5) should be provided to infants and
children with intractable diarrhea who are unable to maintain their nutrition status with standard formula.20 When
using these formulas for long-term use, essential fatty acid
252
(EFA) deficiency should be monitored. In severe cases the

use of total parenteral nutrition may be implemented to
allow complete enteric rest to minimize lymphatic flow and
promote healing.
Table 23-5 Medium Chain Triglyceride Formulas for Infants
and Children > 1 Year of Age
MCT FORMULAS FOR INFANTS
Formula
Pregestemil (Mead Johnson)
Alimentum (Abbott)
Portagen (Mead Johnson)
Monogen (Nutricia)
EleCare (Abbott)
Enfaport (Enfamil)
MCT:LCT ratio
55:45
33:67
87:13
90:10
33:67
84:16
MCT FORMULA FOR CHILDREN > 1 YEAR OF AGE
Formula
Vivonex Pediatric (Nestle Nutrition)
Peptamin Junior (Nestle Nutrition)
Vital jr (Abbott)
Neocate One + (Nutricia)
Neocate Junior (Nutricia)
Pepdite Junior (Nutricia)
MCT:LCT ratio
69:31
60:40
50:50
35:65
35:65
35:65
Chylothorax
Chylothorax, a known complication of pediatric cardiac
surgery, requires special nutrition support considerations.
Chylothorax is the accumulation of chyle within the pleural
space. The chyle leak can be the result of injury to the
thoracic duct, disruption of accessory lymphatics, or from
an increased systemic venous pressure exceeding that in the
thoracic duct.2124 Studies have suggested that the increase
in postoperative chylothorax complications from 1% or less
in the 1970s and 1980s to 2.5% to 4.7% currently may be
due to the increased complexity of the surgeries performed
and possibly to the earlier initiation of enteral feeds. 21 Chan
reported an incidence of 3.8% from 2000 to 2002 with a
higher percentage occurring after heart transplant and the
Fontan procedure.
The challenge in managing chylothorax is in maintaining fluids and electrolytes while minimizing the
lymphatic leak. Chylothorax can be corrected surgically
but the results are not always favorable and not always
feasible for children who are possibly already compromised
after having had congenital heart surgery. Adverse affects
of chylothorax include immunosuppression, need for longterm chest tubes and intravenous access, and prolonged
hospitalization. 22 Postoperative length of stay is reported
to be significantly longer with a median of 22 days versus
8 days if a chylous leak develops. 23 Conservative management is usually attempted prior to surgery for the resolution
of the leak.
Conservative management includes pleural space
evacuation, the use of low-fat diets with MCTs, or total
parenteral nutrition for complete enteric rest. The use
of a MCT-enriched diet is based on the understanding
that MCTs are readily absorbed by the enterocytes into
circulation, providing adequate calories and minimizing
lymphatic flow to allow for healing. 23 For formula feedings, a high-MCT low-LCT formula may be used (Table
23-5). To prevent EFA deficiency, 2% to 4% of total calories
should be in the form of linoleic acid with 0.25% to 0.5%
from linolenic acid. 24 If patients are on oral feedings and
adequate calories can be consumed, a low-fat diet may be
sufficient. In the study by EH Chan 34 of 48 patients (71%)
had resolution with changes to their enteral diet. 23
Octreotide, a long-acting synthetic analogue of somatostatin, has been used as a treatment for chylothorax
drainage that did not respond to dietary manipulations
alone. In a study conducted between 19812004, 83% of
patients receiving octreotide responded with complete
resolution of their chylothorax after approximately 15
days of treatment and no side effects from the octreotide
therapy were noted after 2 weeks of treatment. 20 In a study
by EH Chan et al the patients had variable results. There
was no decrease in drainage over the treatment period
in 4 of 5 patients and it was thought that octreotide has a
better outcome with a low-flow leak versus higher drainage
patterns noted in patients in this study.
The early diagnosis and treatment of chylothorax can
reduce the length of the chylous leak. At present, dietary
management is the mainstay of treatment when managing
these patients conservatively.
Cardiovascular Disease in the

PediatricPatient
Obesity is a rising epidemic in children. As obesity rises

there is a potential for the increase of early onset coronary
artery disease. Childhood obesity significantly increases
morbidity and mortality from cardiovascular disease
(CVD). 24 Freedman et al studied obese children using
the Bogalusa Heart Study database, and found a relationship between obesity and blood pressure, low-density
lipoprotein (LDL) cholesterol, triglycerides, insulin
concentration, and low levels of high-density lipoprotein
(HDL) cholesterol, all of which are risk factors for CVD.
There is evidence that atherosclerosis, the progressive narrowing and hardening of the arteries, begins in childhood. 25
CARDIAC DISEASE
Preventive measures must be taken in children who have

been identified at risk for CVD. Table 23-6 helps identify
these children.
Table 23-6 Classification of Total and LDL Cholesterol Levels in Children
and Adolescents From Families With Hypercholesterolemia or Premature
Cardiovascular Disease
Category
Total Cholesterol (mg/dL)
LDL Cholesterol (mg/dL)
Acceptable
Borderline
High
< 170
170199
> 200
< 110
110129
> 200
Adapted from American Academy of Pediatrics Policy Statement.

Cholesterol in Childhood (RE9805). Pediatrics. 1998;101(1):141147.
The National Cholesterol Education Program (NCEP)

discusses the effects of early elevated lipid levels on adult
atherosclerosis and coronary heart disease risk. The program
focuses on prevention and lowering of lipids in children and
adolescents. Eating behavior and genetics affect cholesterol
levels. Behavioral changes require intervention at several
levels. Individual approach by itself is less effective. The key
to success requires both a population and also an individualized approach.
One of the goals of lowering cholesterol levels in
children and adolescents is through changing the eating
behaviors on a population-wide basis. The panel concurs
with the recommendations issued by the National Cholesterol Education Program Expert Panel on Population
Strategies for Blood Cholesterol Reduction, as well as the
guidelines of the American Heart Association.27 It is recommended to include a variety of food and consume calories
adequate to support growth and maintain an ideal body
weight while keeping fat intakes at the recommended levels
(Table 23-7).
Table 23-7* Recommendations for Fat and Cholesterol Intake in Children
> 2 Years of Age
Saturated fat
Total fat intake
Cholesterol
*Step I Diet
< 10% of total calories

< or equal to 30%
of total calories
< 300 mg/d
Infants require additional calories and fat to support

growth and development and therefore restricting fat intake
is not recommended for children less than 2 years of age.
To support their efforts for population-wide changes, the
NCEP also provides recommendations for organizations
that influence the eating behaviors of children such as
schools, health professionals, government agencies, and the
food industry.
253
The individualized approach aims to identify and treat

children and adolescents who are at the greatest risk of CVD.
This approach aims at screening children who are from families with a history of premature CVD or at least one parent
with high cholesterol. Universal screening is not cost effective and may impose an unnecessary stigma on a child.27
Children identified with an elevated cholesterol level at
an early age should be treated. Initial therapy should always
be diet modification accompanied by life-style changes,
minimizing sedentary life style and promoting physical
activity. Once identified through the screening protocol as
having elevated LDL levels, diet therapy should be initiated.
The Step I Diet mimics the recommendations of the population approach (Table 23-7). If LDL levels remain elevated
after 3 months of adhering to the Step I Diet, the Step II
Diet should be initiated. The Step II Diet reduces saturated
fat to less than 7% of calories and cholesterol to less than
200 mg/d. Drug therapy is suggested in children 10 years
or older if diet fails after 6 to 12 months for those with LDL
levels greater than 190 mg/dL or > 160 mg/dL if other risk
factors are also present.
In 2006 the American Academy of Pediatrics came
out with a policy statement on cardiovascular risk reduction in high-risk pediatric populations. This policy outlines
CVD risk stratification based on existing comorbidities
and assesses cardiovascular risk factors to stratify patients
into At Risk, Moderate Risk, and High Risk categories.
Life-style changes to include diet, exercise, and cessation
of smoking as well as disease-specific management are the
basis of its recommendations in all 3 groups. Pharmacologic
intervention is recommended only if goals are not met. 28
Reis et al looked at risk factors in children and investigated whether families at risk for CVD can be identified.29
The authors looked at children to see if identification of
risk factors in them would help predict risk factors in their
parents. This population was targeted as children are more
likely to receive regular primary care than adults. The
participants underwent assessment of cardiovascular risk
factors: obesity, hypertension, dyslipidemia, and metabolic
syndrome. Parent-child association was strong for BMI,
waist circumference, systolic blood pressure, triglyceride,
and total cholesterol. Risk factors in children were found to
be significant predictors for the same risk factors for their
parents. This study suggests that CVD risk factors in children can predict elevated CVD risk factors in parents.
Obesity, hypertension, insulin resistance, and dyslipidemia, also known as the metabolic syndrome or syndrome
X (Chapter 14), are risk factors for childhood CVD. Studies
suggest that obese children with risk factors for CVD
254
become obese adults with increased risk of morbidity

from CVD. Prevention and early intervention should
be a primary goal of health professionals and government agencies. The NCEP has reported on these issues
and implemented recommendations for dietary changes,
screening, and treatment of children and adolescents who
are identified as at risk for CVD and for developing into an
adult withCVD. 30
Summary
Children with congenital heart disease often have difficulty

achieving adequate caloric intake to support their growth
and development. A child should be provided with nutrition support to maximize growth and development prior to
corrective surgery. Enteral or parenteral nutrition support
may be needed postoperatively until the childs condition
allows for adequate oral intake. Surgical outcomes and
catch-up growth rates have significantly improved with
adequate calories being delivered to this population.4,9
Postsurgical complications may occur depending on
the complexity of the defect and surgical intervention.
Complications that may arise postoperatively include
protein-losing enteropathy and chylothorax, which require
specialized nutrition modifications.
Pediatric cardiac disease over the past two decades has
extended to include CVD. Preventing, recognizing, and
treating these children holds promise of impacting CVD
and its complications in the adult population. CVD risk
factors have been well identified in children. The NCEP has
put forth recommendations and guidelines for early identification and intervention in children at risk for CVD.
1. The potential for growth and nutrition recovery in children with congenital heart disease seems to be most
affected by:
A. Degree of growth impairment
B. Feeding difficulties
C. Energy intake/expenditure
D. Age and timing of corrective surgery
2. Infants with congenital heart disease may require
caloric intake of
to thrive.
A. 100 kcal/kg/d
B. 120 kcal/kg/d
C. 90 kcal/kg/d
D. 140200 kcal/kg/d
3. Failure to thrive in infants with congenital heart disease

is secondary to:
A. Poor caloric intake
B. Increased energy expenditure
C. Hypoxia
D. All of the above
4. When selecting a formula for treatment of infants with
a chylous leak the following characteristics should be
considered:
A. Only long-chain triglycerides (LCTs)
B. Only medium-chain triglycerides (MCTs)
C. Fat blend (high MCT and low LCT)
D. Fat blend (high LCT and low MCT)
References
1. Prsa M, Saroli T et al. Birth prevalence of congenital heart

disease. Epidemiology. 2009;20:466468.
2. Leitch C, Karn C, Peppard R, et al. Increased energy expenditure in infants with cyanotic congenital heart disease. J
Pediatr. 1998;133(6):755760.
3. Leitch C. Growth, nutrition and energy expenditure in pediatric heart failure. Prog Pediatr Cardiol. 2000;11:195202.
4. Vaidyanathan B, Nair S, Sundarum KR, et al. Malnutrition in
children with congenital heart disease (CHD): determinants
and short-term impact of corrective intervention. Indian
Pediatr. 2008;45:541546.
5. Barton JS, Hindmarsh PC, Scrimgeour CM, Rennie MJ,
Preece MA. Energy expenditure in congenital heart disease.
Arch Dis Child. 1994;70:59.
6. Cameron JW, Rosenthal A, Olsen AD. Malnutrition in hospitalized children with congenital heart disease. Arch Pediatr
Adolesc Med. 1995;149(10):10981102.
7. Mitchell IM, Logen RW, Pollock JCS, Jamieson MPG. Nutritional status of children with congenital heart disease. Br
Heart J. 1995;73:277283.
8. Eskedal LT, Hagemo PS, Seem E, et al. Impaired weight gain
predicts risk of late death after surgery for congenital heart
disease. Arch Dis Child. 2008;93:495501.
9. Nydegger A, Bines JE. Energy metabolism in infants with
congenital heart disease. Nutrition. 2006;(22):697704.
10. da Silva VM, de Oliveira Lopes MV, de Araujo TL. Growth
and nutritional status of children with congenital heart
disease. J Cardiovasc Nurs. 2007;22(5):390396.
11. van der Kuip M, Hoos MB, Forget PP, Westerterp KR, Gemke
RJ, de Meer K. Energy expenditure in infants with congenital heart disease, including a meta-analysis. Acta Paediatr.
2003;92:921927.
12. Schwartz MS, Gewitz HM, See CC, et al. Enteral nutrition in
infants with congenital heart disease and growth failure. Pediatrics. 1990;86(3):368373.
CARDIAC DISEASE
13. Durai R, Venkatraman R, Ng P. Nasogastric tubes 2: risks and

guidance on avoiding and dealing with complications. Nurs
Times. 2009;105(17):1416.
14. Sy K, Dipchand A, Atenafu E, et al. Safety and effectiveness
of radiologic percutaneous gastrostomy and gastrojejunostomy in children with cardiac disease. Am J Roentgenol.
2008;191(4):11691174.
15. Kogon BE, Ramaswamy V, Todd K, et al. Feeding difficulty in
newborns following congenital heart surgery. Congenit Heart
Dis. 2007 Sep; 2(5):332337.
16. Sachdeva R, Hussain E, Moss M, et al. Vocal cord dysfunction
and feeding difficulties after pediatric cardiovascular surgery.
J Pediatr. 2007;151:312315.
17. Kohr LM, Dargan M, Hague A, et al. The incidence of
dysphagia in pediatric patients after open heart procedures
with transesophageal echocardiography. Ann Thorac Surg.
2003;76:14501456.
18. Feldt RH, Driscoll DJ, Offord KP, et al. Protein-losing
enteropathy after the Fontan procedure. J Thorac Cardiovasc
Surg. 1996;112:672680.
19. Ostrow MA, Hudsen F, Rychik J. Protein-losing enteropathy
after Fontan operation: investigations into possible pathophysiologic mechanisms. Ann Thorac Surg. 2006;83(2):695700.
20. Parrish RC, Krenitky J, Willcutts K, Radigan A. Gastrointestinal disease. In: Gottschlich MM, DeLegge MH, Mattox
T, Mueller C, Worthington P, eds. The A.S.P.E.N. Nutrition
Support Core Curriculum: A Case-based Approach The Adult
Patient. Silver Spring, MD: American Society for Parenteral
and Enteral Nutrition; 2007:524525.
21. Chan S, Lau W, Wong W, et al. Chylothorax in children after congenital heart surgery. Ann Thorac Surg.
2006;82:16501656.
255
22. Pelletier GJ. Invited commentary. Ann Thorac Surg.

2005;80:18701871.
23. Chan EH, Russell JL, Williams WG, et al. Postoperative
chylothorax after cardiothoracic surgery in children. Ann
Thorac Surg. 2005;80(5):18641879.
24. Hise M, Brown C. Lipids. In: Gottschlich MM, DeLegge
MH, Mattox T, Mueller C, Worthington P, eds. The A.S.P.E.N.
Nutrition Support Core Curriculum: A Case-based Approach
The Adult Patient. Silver Spring, MD: American Society for
Parenteral and Enteral Nutrition; 2007:4870.
25. Zalesin KC, Franklin BA, Miller WM, et al. Impact of obesity
on cardiovascular disease. Endocrinol Metab Clin N Am.
2008;37:663684.
26. Freedman DS, Khan LK, Dietz WH, et al. Relationship of childhood obesity to coronary heart disease risk
factors in adulthood: The Bogalusa Heart Study. Pediatrics.
2001;108(3):712718.
27. American Academy of Pediatrics Policy Statement.
Cholesterol in Childhood. (R E9805). Pediatrics.
1998;101(1):141147.
28. American Academy of Pediatrics Policy Statement. Cardiovascular risk reduction in high-risk pediatric populations.
Pediatrics. 2007;119(3):618621.
29. Reis EC, Kip KE, Marroquin OC, et al. Screening children to
identify families at increased risk for cardiovascular disease.
Pediatrics. 2006;118:17891797.
30. National Cholesterol Education Program (NCEP): highlights
of the report of the Expert Panel on Blood Cholesterol Levels
in Children and Adolescents. NCEP Expert Panel on Blood
Cholesterol Levels in Children and Adolescents. Pediatrics.
1992;89:496501.
24
Renal Disease
Christina L. Nelms, MS, RD, CSP, CNSC, LD, Marisa Juarez, MPH, RD, LD, and Bradley A. Warady, MD
CONTENTS
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256
Kidney Development and Function . . . . . . . . . . . . . . . . . . 257
Chronic Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . 258
Hemodialysis
Peritoneal Dialysis
Growth and Development
Fluid and Electrolyte Balance
Cardiovascular Disease and Lipid Management
Renal Transplant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268

Acute Kidney Injury (AKI) . . . . . . . . . . . . . . . . . . . . . . . . . 269
Continuous Renal Replacement Therapy
Neonatal Issues
Enteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272

Infant and Toddler Feeding
Tube Feeding for Older Children
Parenteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274

Intradialytic Parenteral Nutrition
Nephrotic Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274

Nephrolithiasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
Hypercalciuria and Calcium-Based Stones
Other Kidney Stones
Renal Tubular Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . 276

Renal Tubular Acidosis
Bartters Syndrome
Nephrogenic Diabetes Insipidus
Other Renal Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . 278

Oxalosis
Other
256
Learning Objectives
1. Describe normal kidney physiology and causes of pediatric renal failure.

2. Discuss nutrition care for chronic kidney disease and
acute kidney injury in pediatric patients.
3. Review nutrition needs and specifications for infants,
children, and adolescents receiving supplemental
enteral and parenteral nutrition.
4. Discuss specific nutrition needs for other kidney disorders in pediatrics, including nephrotic syndrome,
nephrolithiasis, and renal tubular disorders.
Background
Kidney disease in children is rare, with an incidence of about

75 per million of the age-related population for all stages of
chronic kidney disease (CKD).1 Children may have acute
kidney injury (AKI) from infections such as Escherichia coli
or from other comorbid conditions, such as sepsis or multisystem organ failure. CKD is often progressive in nature
and may develop as a result of congenital or autoimmunetype conditions. Pediatric patients with CKD are more
commonly male because congenital posterior urethral
valves, which only occurs in males, is a leading cause of
CKD.2 However, CKD may present acutely at an advanced
stage. Many children only exhibit mild symptoms such as
fatigue or flu-type illness until there has been a substantial
progression of the kidney damage. Irrespective of the cause
of kidney injury, these patients typically have a variety of
nutrition issues that should be addressed for optimal patient
management. This chapter is intended to review those issues
for the clinician.
RENAL DISEASE
Kidney Development and Function
Human kidney development, or nephrogenesis, begins

during week 5 of gestation. The first functioning nephrons
are formed by week 9 and the entire process is completed
by 32 to 34 weeks gestation. Once nephrogenesis has been
completed, the kidney is unable to respond to injury by de
novo generation of nephrons. Key components of nephrogenesis include formation of the pelvicalyceal system, renal
tubular development, and glomerulogenesis. Urine production begins at about 10 weeks gestation and by 20 weeks
gestation, it accounts for approximately 90% of amniotic
fluid. 3 The fraction of cardiac output received by the kidneys
is only 2.5% during late gestation. It increases to nearly
20% during the initial 6 weeks of life.4 Kidney function, as
measured by creatinine clearance, doubles during the first
2 weeks of life in term infants and reaches adult values by 2
years of age. 5 Normal serum creatinine values also increase
with age.6 Most important from the clinical perspective is
the fact that the kidney is key to a variety of functions that,
if impaired, may significantly alter body homeostasis. These
functions influence solute removal, fluid/electrolyte/water
status, calcium, phosphorus and vitamin D metabolism,
erythropoietin production, acid-base balance, and blood
pressure, all of which must be addressed medically if kidney
function is decreased on an acute or chronic basis.
Acute renal failure, more accurately called AKI, is
commonly characterized as an abrupt (hours to weeks) and
prolonged loss of kidney function that is reversible in most
cases.7 It is typically accompanied by a change in creatinine
clearance and possibly in urine output. The causes of AKI are
divided into 3 categories: prerenal, renal, and postrenal. The
categories localize the predominant site of injury and help
describe the mechanism of injury. For example, prerenal AKI
primarily includes the state of reduced renal blood flow that
might result from diarrhea and vomiting, burns, bleeding,
or congestive heart failure. Insults to the renal glomeruli
or tubules can give rise to renal or intrinsic AKI. Sources
of injury include glomerulonephritis (eg, postinfection,
257
systemic lupus erythematosus, membranoproliferative

diseases, and Henoch-Schnlein purpura); nephrotoxins
(eg, aminoglycosides, amphotericin B, and heavy metals);
interstitial nephritis; hemolytic-uremic syndrome; or acute
tubular necrosis (ATN). Finally, postrenal or obstructive
AKI can be the sequela of disorders such as nephrolithiasis,
neurogenic bladder, hemorrhage, renal tumors, or posterior
urethral severe valves in newborns. Strict attention to the
etiology of AKI and prompt therapeutic intervention often
result in a return to baseline kidney function.
In contrast to the reversible nature of AKI, CKD is a
manifestation of irreversible renal injury. It often progresses
to end-stage renal disease (ESRD), also known as CKD5,
and the need for dialysis (CKD5D) and/or transplantation. The National Kidney Foundation Kidney Disease
Outcomes Quality Initiative (NKF KDOQI) guidelines
classify CKD in children greater than 2 years of age, adolescents, and adults by the presence of kidney damage and the
level of estimated glomerular filtration rate (GFR) (Table
24-1).8
A variety of disorders are associated with the development of CKD in pediatrics, as reflected by data from more
than 7,000 patients enrolled in the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS)
registry (Table 24-2).2 The 2 most common diagnoses are
obstructive uropathy and a/hypo/dysplastic kidneys and
only 4 diagnoses individually represent greater than 4% of
the patients enrolled in the registry. There is clear evidence
from clinical studies that both hypertension and protein
uria play a key role in the progression of CKD to ESRD.9,10
The developmental abnormalities of the urinary tract that
account for the largest percentage of patients with CKD
stages I-IV logically account for the largest (eg, 30%50%)
number of children with ESRD (stage V CKD), resulting
in the affected children having a life-long experience with
their respective kidney disorders and the requirement for
long-term medical and nutrition intervention. 2
Table 24-1 NKF KDOQI Classification of the Stages of Chronic Kidney Disease8
Stage
GFR (mL/min/1.73 m2)
Description
1
2
3
4
5
> 90
6089
3059
1529
< 15 (or dialysis)
Kidney damage with normal or increased GFR

Kidney damage with mild reduction of GFR
Moderate reduction of GFR
Severe reduction of GFR
Kidney failure
GFR = Glomerular Filtration Rate
258
Table 24-2 CKD Primary Diagnosis2

All Patients
Total
7037
100.0
1454
1220
613
594
278
193
158
141
114
111
104
99
90
82
75
75
66
47
43
37
32
30
26
25
14
11
7
6
1110
182
20.7
17.3
8.7
8.4
4.0
2.7
2.2
2.0
1.6
1.6
1.5
1.4
1.3
1.2
1.1
1.1
0.9
0.7
0.6
0.5
0.5
0.4
0.4
0.4
0.2
0.2
0.1
0.1
15.8
2.6
Primary Diagnosis
Obstructive uropathy
A/hypo/dysplastic kidney
Focal segmental glomerulosclerosis
Reflux nephropathy
Polycystic disease
Prune Belly
Renal infarct
Hemolytic uremic syndrome
SLE nephritis
Familial nephritis
Cystinosis
Pyelo/interstitial nephritis
Medullary cystic disease
Chronic glomerulonephritis
Congenital nephrotic syndrome
Membranoproliferative glomerulonephritis Type I
Bergers (IgA) nephritis
Idiopathic crescentic glomerulonephritis
Henoch-Schnlein nephritis
Membranous nephropathy
Wilms tumor
Membranoproliferative glomerulonephritis Type II
Other systemic immunologic disease
Wegeners granulomatosis
Sickle cell nephropathy
Diabetic glomerulonephritis
Oxalosis
Drash syndrome
Other
Unknown
Chronic Kidney Disease
CKD is a permanent condition that involves a progressive

loss of kidney function. The National Kidney Foundation
describes 5 stages of CKD partially defined according to
GFR that apply to children > 2 years of age11 (Table 24-1). A
GFR of 90 or greater is considered normal. Stage 1 is a GFR
of > 90 mL/min/1.73 m 2 with evidence of kidney damage,
such as protein in the urine. There are added clinical signs of
impaired kidney function as GFR decreases. At stage 5, the
final stage defined by a GFR of < 15 mL/min/1.73 m 2 , the
child requires dialysis or transplantation.
According to the 2009 NKF KDOQI Clinical Practice

Guideline for Nutrition in Children with CKD, the energy
requirements for CKD stages 3 to 5 should be the estimated
energy requirements (EER), with an adjustment for physical activity and body size.12 There is no evidence suggesting
patients with CKD stages 3 to 5 have higher energy needs
compared to healthy controls. However, these patients need
regular assessments to adjust for inappropriate weight gain
or loss. If energy needs cannot be met with regular solid
food intake, consider oral supplementation with a product
that meets any electrolyte, mineral, and/or fluid restrictions. Supplementation can include modulars of glucose
polymers, protein, or fat if necessary to meet nutritional
needs. Many of the metabolic complications of CKD are
similar to those of AKI and ESRD, which will be discussed
later.
Hemodialysis
Hemodialysis (HD) is the use of a machine to dialyze soluble
substances and water from the blood by diffusion through a
semipermeable membrane, using a catheter placed centrally
or a fistula. It is often done for 3 to 5 hours, 3 or more times
per week for patients in CKD5 who cannot live without
regular dialysis.
Malnutrition is a significant complication of CKD and
a strong predictor for morbidity and mortality for adults
receiving maintenance HD.1315 Protein-energy malnutrition (PEM) produces profound effects on growth and
development and may be associated with increased risk of
hospitalization and mortality in children on HD.13,16,17
In addition to dry weight, length/height, weight-forlength, body mass index (BMI)-for-age, head circumference,
dietary intake, and serum albumin, the 2009 NKF KDOQI
nutrition guidelines now include recommendations on
monitoring normalized protein catabolic rate (nPCR) for
children on HD. The primary biochemical marker of nutrition status has been albumin. However, recent studies
indicate nPCR is superior to albumin as a marker of nutrition status in children on maintenance HD.16,18,19 These
studies show serum albumin to be a poor indicator of nutrition status. Research also demonstrates that intradialytic
parenteral nutrition (IDPN) significantly improves weight
gain and nPCR in malnourished patients on HD.16,18 A
nPCR of < 1 g/kg/d is a strong predictor of weight loss in
adolescent patients.19
The protein catabolic rate (PCR) is a measure of protein
intake. The nPCR is the PCR normalized to a function of
body weight, measured in grams of protein per kilogram
per day. nPCR is determined by first calculating the urea
generation rate (G):
RENAL DISEASE
G (mg/min) = {(C2 V2) (C1 V1)}/t

where
C2 = predialysis blood urea nitrogen (BUN) (mg/dL)
C1 = postdialysis BUN
V2 = predialysis total body water (dL; V2 = 5.8 dL/kg
predialysis weight in kg)
V1 = postdialysis total body water (dL; V1 = 5.8 dL postdialysis weight in kg)
t = time (minutes) from end of the dialysis treatment to the
beginning of next treatment.
Then, using a modified Borah equation, nPCR is calculated:
nPCR (g/kg/d) = 5.43 est G/V1 + 0.17
where
V1 = postdialysis total body water (L; V1 = 0.58 postdialysis weight in kg)
Peritoneal Dialysis
Peritoneal dialysis (PD) is typically recommended for
infants, toddlers, and approximately 50% of adolescents
needing dialysis treatment. It is usually a nightly process. PD
involves infusion of a glucose-based solution through a catheter surgically inserted into the peritoneal cavity. Diffusion
allows for waste products to cross the peritoneal membrane.
Fluid is then drained from the peritoneal cavity and fresh
fluid is infused. In most children, this process occurs over
10 to 12 hours while they sleep. A daytime dwell is often
left in the cavity during the day and drained before nightly
dialysis is resumed. The peritoneal membrane transport
capacity can be determined by conducting the Peritoneal
Equilibration Test (PET). Patients may be classified as
high, high-average, low-average, or low transporters
depending on how rapid solute (eg, creatinine, glucose)
moves across the peritoneal membrane during a 4-hour test
exchange. High transporters tend to have more porous peritoneal membranes and thus rapidly remove waste products
such as creatinine, but also tend to lose significant amounts
of potassium and protein across the peritoneum. The rapid
absorption of glucose from the dialysate decreases the
osmotic gradient and results in less fluid removal from these
same patients. In contrast, low transporters tend to remove
less kidney waste, but also lose less protein and potassium
and remove fluid well. The nutrition prescription for the
peritoneal dialysis patient is, in turn, often influenced by
what kind of transporter the PD patient is.
259
Children receiving PD typically have a poor energy

intake, often taking in less than 75% of needs.20 Even after
accounting for glucose calories derived from the dialysis
fluid, energy intake is still often insufficient. On the other
hand, protein intake is generally sufficient. Reduced height,
weight, and muscle mass are common findings, although
the reduced weight and muscle mass for age may be consistent with overall short stature and size as these patients
are often proportional. Many plasma proteins, including
albumin, total protein, transferrin, and individual amino
acids, are found to be decreased in patients undergoing PD.
Although these patients do lose about 7% to 10% of protein
intake (depending on body surface area) into the dialysis
effluent, inadequate caloric intake or uremia can affect
amino acid and protein profiles.20,21 Infants on PD have
twice the protein losses per square meter of body surface
area than adult-sized adolescents22 and thus may need
greater protein supplementation per kilogram. However, it
is important not to provide excessive protein intake. Excess
protein has been shown to increase body acidity, creating
poor bone mineralization. Sometimes patients may have
extreme protein losses in urine or through the peritoneum.
Increasing protein far above the dietary reference intake
(DRI) may just exacerbate further protein loss in these
patients and create a high acid load. Use clinical judgment when assessing protein-related laboratory values to
determine if added protein will benefit hypoalbuminemic
patients. Adequate, but not excessive, amounts of protein
are important in this population.23
Serum triglycerides and cholesterol are often elevated,
likely due to dextrose infusion of PD. Younger children
(<10 years of age) often have more lipid abnormalities than
older children.20
Similar to nPCR in HD, protein equivalent of nitrogen
appearance (PNA) has been recommended to assess dietary
protein intake in adults receiving PD. In adults PNA is
calculated by measuring urea nitrogen content of both urine
and dialysate, and then multiplying the result by 6.25 with
a modification for pediatrics. However, it is only valid when
the patient is not anabolic or catabolic and can have great
variability.12 Protein metabolism is age dependent, with
younger children having greater differences. Due to these
factors and limited pediatric data, PNA is not routinely
performed in pediatric patients.24

Poor growth is a common manifestation of CKD in children. Growth velocity suffers as GFR declines. Many
factors contribute to growth failure, including decreased
260
appetite with poor energy intake, acidosis, excessive urinary

sodium losses, renal osteodystrophy, and abnormalities of
the growth hormone-insulin-like growth factor (GH-IGF)
axis.25 Steroid therapy may also contribute to poor growth.
One of the goals of nutrition intervention in the pediatric
CKD patient is to promote growth.
Linear Growth and Growth Hormone
There are many factors that may affect growth, such as age at
onset of kidney disease, the primary renal disease, and the
quantity of residual kidney function. However, adequacy of
nutrition and treatment of growth hormone resistance are

treatable components and will be discussed in this context.
Linear growth in children with CKD is often impacted
by the nutrition status of the patient. Adequacy of nutrition should be assessed prior to consideration of growth
hormone (GH) therapy (Figure 24-1).12,26 Evidence suggests
that improved dialysis, as indicated by better solute clearance, along with caloric and protein intake at or above the
recommended intake for age, helps prevent growth failure.27
Supplementation by gavage feedings may be needed to meet
nutrition needs.
Figure 24-1 Short Stature Assessment and Treatment Algorithm26
Reprinted with permission from: Mahan JD, Warady BA. Assessment and treatment of short stature in pediatric patients with chronic kidney disease: a
consensus statement. Pediatr Nephrol. 2006;21:917930.
RENAL DISEASE
In young children, growth failure is primarily mediated

by inadequate nutrition. Adequate caloric intake, adjusting
calories based on height and weight gains, is essential for
adequate growth in infants and toddlers. Common causes of
CKD in infants and toddlers are congenital disorders, such
as obstructive uropathy and renal dysplasia, with associated
sodium wasting and polyuria. In children with these disorders, supplementation of water and 2 to 4 mEq of sodium
(as chloride, bicarbonate, or both) per 100 mL of formula
is recommended.28 KDOQI pediatric nutrition guidelines
recommend correcting the serum bicarbonate level to at
least 22 mmol/L.12,26 Adequate sodium supplementation
and correction of acidosis is essential for growth.
GH insensitivity/resistance and alterations in the
somatotropic hormone axis are other significant factors
influencing the growth of children with CKD. Typically,
growth occurs as a result of the action of insulin-like growth
factor 1 (IGF-1), a product released from the liver following
stimulation by endogenous GH. In children with CKD,
serum levels of IGF-1 binding proteins may be increased
seven- to tenfold, due to a reduction in renal filtration.
The increase in IGF-1 binding proteins decreases the free
or bioactive levels of IGF-1 and, as a result, limits growth
despite normal or elevated levels of circulating GH. Additionally, inadequate protein or caloric intake may impair
GHs ability to stimulate IGF-1. In this situation, therapeutic
doses of recombinant human growth hormone (rhGH)
may be given to patients with CKD, resulting in improved
height velocity.29 The KDOQI Clinical Practice Guideline
for Nutrition in Children with CKD indicates that children
with CKD (including transplant patients) and a height or
height velocity standard deviation score (SDS) < 1.88 or
height-for-age < 3rd percentile qualify for treatment with
rhGH.12
A Cochrane review of studies assessing GH in children
with CKD, including predialysis, dialysis, and transplant
patients, indicates that treated children had a significant
increase in height SDS and height velocity at 1 year after
starting therapy. The reported side effects are similar
to control patients. 30 Despite the safety and efficacy of
the therapy, rhGH is currently used in only a minority of
growth-retarded children with CKD, which is especially
concerning for those who could benefit the mostyoung
children and those in the early stages of CKD. Some of the
reasons for the underutilization of rhGH include family
refusal, secondary hyperparathyroidism, and noncompliance, as recently reported by Greenbaum et al. 31 However, in
this study 51% of patients with short stature did not receive
GH and 25% of those patients did not have an apparent
261
explanation. According to the authors, many of the factors

leading to nonuse may have been resolved with intervention.
Although kidney transplantation may improve the growth
of younger children, many older children do not achieve
adequate catch-up growth with transplantation alone. This
situation may change with the introduction of steroid-free
immunosuppressive regimens. Most important is that
poor final adult height affects quality of life, and there may
be other psychosocial implications for short children and
adolescents. Although likely not a direct relationship, poor
height has been associated with increased mortality and
hospitalizations. Figure 24-1 reviews the process of growth
evaluation and rhGH initiation and monitoring, including
the essential assessment of nutrition parameters prior to its
initiation.26 A dose of 0.35 mg/kg/wk is suggested for children with renal disease.
Adequacy of Weight Gain
Weight gain should be monitored often, with the most
frequent assessments occurring with infants and toddlers
with CKD. Dry weight should be used when assessing
weight parameters (see Dry Weight, below). If poor weight
gain occurs, contributing factors should be identified and
corrected. Many patients with CKD have a compromised
and/or restricted dietary intake, and nutritional supplements are required to meet age-appropriate nutrition goals.
Oral supplements should be provided first, followed by tube
feeding (nasogastric or gastrostomy) if deemed necessary.
Infants with significant CKD typically demonstrate delays
in feeding and often require enteral tube-feeding support
for an extended period of time.16 In fact, tube feeding may
provide relief to parents and caretakers concerned about
their childs poor intake. Some children may require more
aggressive nutrition therapy (eg, IDPN) to help reverse
a catabolic state (see Intradialytic Parenteral Nutrition,
below). It is important to recognize that all infants receiving
a substantial portion of their daily nutrition needs by a
non-oral route need continued oral stimulation to promote
normal oral motor development. Finally, there is some
preliminary evidence suggesting intensified and daily HD
may be associated with improved growth and nutrition
status. 32,33 More research on this subject is needed.
Malnutrition is a serious complication of CKD, especially
in CKD5D. There is no single measurement to adequately
define nutrition status in CKD.25,16 It is challenging to assess
this population due to the metabolic and growth complexities that are present. Early nutritional intervention may be
262
critical in optimizing growth and development. KDOQI

recommends routine monitoring of the following parameters in children with CKD.12 The recommended frequency
of assessment can be found in the KDOQI guidelines.
Dry Weight: Dry weight is the patients weight at a
euvolemic state. Dry weight should be assessed regularly and used when assessing growth, including
weight-for-age and BMI-for-age. In oliguric or anuric
patients requiring dialysis, fluid overload will influence
weight as well as will other anthropometric measures
such as head circumference and mid-arm circumference. Fluid overload is the most common source of error
in measuring anthropometric data in this population. 34
In other renal diseases in which urine-concentrating
capacity is impaired and volume depletion is common,
dry weight is equally important in assessing growth.
Length/Height: Length or height should be measured
as in other pediatric populations. Length- and heightfor-age trends are an indication of the chronic nutrition
status. Height velocity can be assessed using reference
data from the Fels Longitudinal Study. 34 This can be
assessed in 6-month intervals.
Weight-for-Length: This calculation is used for children
< 2 years to assess weight-to-length proportion.
BMI-for-age: BMI should be used in patients with
kidney disease as with assessment of other pediatric
populations. Dry weight should be used when calculating BMI-for-age. Because there is a predisposition
for stunted growth and developmental delays in CKD,
BMI-for-height age (the age at which height is at the
50th percentile) may be more appropriate in assessing
BMI and ideal body weight. Using chronological age to
assess BMI and ideal body weight may actually overestimate ideal body weight. 35 Studies have shown a
U-shaped curve in BMI-for-age versus mortality risk,
meaning that both a very high and a very low BMI is
associated with an increased risk of mortality in kidney
disease. 36
Head Circumference: As described in the nutrition
assessment chapter (Chapter 33), regular measurements should be taken through 3 years of age and
plotted on the 2006 World Health Organization head
circumference-for-age curve.12 Note any variance not
associated with a comorbidity.
Dietary Intake: Dietary intake should be assessed regularly. A 3-day food diary or 3 24-hour diet recalls with at
least 1 weekend day are acceptable methods to measure
intake. Both have limitations, but they can be useful in
gaining a better understanding of actual intake patterns

and eating behaviors.12
Serum Albumin: The 2000 KDOQI pediatric nutrition guidelines include serum albumin as a marker of
nutrition status. However, recent studies highlight the
limitations of using albumin in this manner, including
its long half-life and the dilutional effect of excess fluid.
Also, lower levels are often a manifestation of inflammation, increasing the association of increased risk of
mortality with hypoalbuminemia. 37 Therefore, serum
albumin may be used as a nutrition status marker, but
with caution if hypoalbuminemic factors such as acute
physiological stress or fluid overload are present. 35
Specifics on nutrition assessment (Table 24-3) are included
in the chapter on nutrition assessment (Chapter 33). Unless
specifically described, the calculation and assessment of
these measurements apply to patients with renal disease as
well as other populations.
Table 24-3 Nutrition Assessment12,34-37
Anthropometrics
Dry
(Target) Weight & Weight-for-age percentile
Length
or Height-for-age percentile
Length
or height velocity-for-age percentile
Weight/Length

percentile (for < 2 years)
BMI-for-age

percentile (for > 2 years)*
Body Weight*
Ideal

Head

circumference-for-age percentile (for < 3 years)
* BMI-for-height age percentile and ideal wt based on BMI-for-height
age may be more appropriate
Medical History
Assess

for conditions relevant to nutrition status and care
Intake Assessment Tools
Food diary
Diet
recall: 24-hour recall x 3
Labs
Electrolytes:

Na, K, Cl, bicarbonate
Minerals:

Ca, Phos, Mg
Glucose

Lipids:

Triglycerides, cholesterol
Renal

Function: BUN, Cr
Malnutrition signs
nPCR (HD)
Fluid Status
Blood

pressure
Urine

output
I/O

HD:
non-invasive monitoring, intradialytic weight gain
Medications
Assess

for medications that may influence nutrition parameters
RENAL DISEASE
Macronutrients
Energy
The estimated energy requirement (EER) for energy is the

recommended starting point for pediatric patients with
CKD stages 3 to 5.12 A balance of calories from all 3 macronutrientscarbohydrate, protein, and fatis desirable.
The recommended range of 45% to 65% of energy
from carbohydrate and 30% to 40% from fat as set by the
Institute of Medicine (IOM) is acceptable for children
with CKD. Because cardiovascular disease (CVD) is a
significant and frequent complication of CKD in children,
carbohydrate and fat sources should be closely monitored
and altered in the setting of dyslipidemia. Diet management of dyslipidemia should include heart-healthy fats such
as monounsaturated and polyunsaturated fat rather than
saturated or trans fats. 38,39 Complex carbohydrates should
replace simple sugars. If carbohydrate and fat modules
are needed to increase calories to promote growth while
conforming to fluid restrictions, add them proportionally
to keep the macronutrient content consistent with the base/
standard formula. (See Cardiovascular Disease and Lipid
Management section, below, for further discussion.)
Protein
Children with CKD may demonstrate lower dietary protein

intakes compared to healthy children. If children are unable
to consume adequate amounts of protein to meet their
needs, protein modulars or concentrated formula may be
used. However, if there is evidence of a high protein intake,
it may be beneficial to restrict protein intake to 100% to
140% of the DRI in children with CKD stage 3 and up
to 100% to 120% of the DRI in CKD stages 4 and 5.12 By
restricting protein, phosphorus is also restricted which may
prove beneficial in terms of preventing CVD and helping to
control renal osteodystrophy, the so-called chronic kidney
diseasemetabolic bone disorder (CKD-MBD). Because
CVD increases mortality and an abnormal calcium and
phosphorus balance is a nontraditional risk factor for CVD
(see section on Cardiovascular Disease), regularly evaluate
protein intake as a source of excessive phosphorus intake.
Patients on HD may only require 0.1 g/kg/d more
than the DRI to account for dialytic losses. PD patients
may only require 0.2 g/kg/d to 0.3 g/kg/d more than the
DRI.12 However, other factors, such as inflammation or
recent infection, which may contribute to protein catabolism should be considered when making recommendations
on protein needs.
263
Micronutrients
Children with CKD are at risk for micronutrient deficiencies due to poor intake, poor absorption, abnormal renal
metabolism, medication interactions, and potential dialysis
losses. Adequate intake of fat-soluble and water-soluble
vitamins, zinc, and copper should be encouraged. There is
risk to growth and overall health if these micronutrients are
deficient. Supplementation of these vitamins and minerals
is necessary if dietary intake is low or if there is clinical
evidence of a deficiency and/or low blood levels. Because
excess losses of water-soluble vitamins are possible in all
dialysis patients, all children with stage 5D CKD should
take a water-soluble vitamin supplement.12
Both dialysis and predialysis patients with significant

renal impairment have high retinol levels, despite having
a normal intake of vitamin A. This may be because of
increased retinol-binding protein found in renal failure.
Although elevated retinol levels are not found to be toxic
to these patients, supplemental vitamin A to patients with
renal impairment is not recommended.4042 There has been
some concern that excess vitamin A levels may be associated
with altered calcium homeostasis and hyperparathyroid
bone disease in adults with CKD. More evidence indicates
the association is not a concern and oral intake from food
should not be limited.43
Vitamin D has a significant and unique role when
discussed in the context of CKD. It is well known that
vitamin D synthesis from the inactive to active form takes
place in the kidney, and patients with CKD typically
need supplementation with the active form of vitamin
D, calcitriol. As GFR declines, plasma concentrations of
1,25-dihydroxyvitamin D (1,25-(OH)2D) decline concurrently. There usually is a concurrent increased parathyroid
hormone (PTH) level, inducing secondary hyperparathyroidism.44 Limitation of dietary phosphorus can improve
1,25-(OH)2D levels, which will be discussed later.45
Recent research indicates that dietary or inactive vitamin D (25-hydroxyvitamin D) may also have
an important role in bone metabolism. Low plasma
25-hydroxyvitamin D is an independent and major risk
factor for hyperparathyroidism, infection, and autoimmune
diseases, even in healthy children.46,47 Recent evidence also
indicates that 25-hydroxyvitamin D may be necessary for
bone metabolism and is often deficient in children with
CKD. The KDOQI Clinical Practice Guideline for Nutrition in Children with CKD suggests measuring serum
25-hydroxyvitamin D levels at least once per year and
264
supplementing with vitamin D2 (ergocalciferol) or vitamin

D3 (cholecalciferol) if levels are < 30 ng/mL. Once levels
are replete, a maintenance supplement of up to 800 International Units and yearly serum levels are appropriate.12
Serum vitamin E levels are often elevated in CKD and
vitamin E is not cleared well by dialysis.42 However, recent
evidence suggests that vitamin E may be beneficial in the
treatment of anemia. In one centers study of 10 children on
HD, patients given 15 mg/kg/d of vitamin E had improved
hemoglobin and hematocrit when compared to control
patients on epogen alone. Vitamin E therapy was also found
to reduce oxidative stress and insult. Some vitamin E supplementation may be beneficial for patients who are anemic.48
However, excessive vitamin E intake is not recommended
due to poor renal clearance.
Vitamin K is synthesized by the intestine and there is
no evidence of dialysis losses. Unless a patient is receiving
long-term antibiotic therapy, there is no need for supplementation in CKD.12
Water-Soluble Vitamins
A water-soluble vitamin supplement may be appropriate

for children with CKD stages 3 to 5 if dietary intake and/
or laboratory values are low. Supplementation is recommended for CKD stage 5D due to potential dialysis losses.
Low intakes of many water-soluble vitamins are common
in patients with CKD, often because of dietary phosphorus
restrictions and poor intake due to uremia. Additionally,
many water-soluble vitamins are lost during dialysis treatments. Adult patients who receive continuous ambulatory
peritoneal dialysis (CAPD) have been documented to have
low levels of vitamin B1 (thiamin), vitamin B6 (pyridoxine),
folic acid, and vitamin C.42 Vitamin B12 (cyanocobalamin)
and B2 (riboflavin) were normal. Low intakes of vitamins
B1, B6, and B12 were also noted. Supplementation of watersoluble vitamins produced increased levels of B6, folic acid,
and vitamin C. Similar vitamin losses have been noted in
HD patients. Biotin, riboflavin, and vitamin B12 have been
found to be normal in these same HD patients. Vitamin C
and folic acid levels, while low, have been easily corrected
with low-dose supplementation. Vitamin B6 and vitamin B1
are typically low, requiring supplementation.49
Hyperhomocysteinemia is common in children with
CKD. However, only a small percentage of these have low
folate levels, and a smaller percentage have low vitamin B12
levels. 50 Treatment with 1 mg of folic acid has been shown to
improve homocysteine levels significantly and to increase
serum folic acid levels in pediatric patients. 51 Whether there
is improved morbidity and morbidity outcomes is unknown.
A large study of adult patients treated with high-dose folic

acid, vitamin B6, and vitamin B12 did have lower serum
homocysteine levels, but no evidence was found of improved
cardiovascular morbidity or mortality. This study was
consistent with studies in the general population regarding
cardiovascular risk with homocysteine. High doses of folic
acid can potentially mask a vitamin B12 deficiency. 52
Another consideration for folic acid supplementation
is to improve erythropoietin-resistant anemia. Five milligrams of folic acid has been found to improve hemoglobin
and reduce epogen requirements in pediatric and adolescent
HD patients. 53 In light of this evidence, folic acid supplementation is likely beneficial to pediatric patients in moderate
doses as part of a standard renal multivitamin supplement.
It may not be as critical as earlier research indicated.
Although vitamin B6 losses are minimal in children
on PD, intake is typically limited due to poor appetite and
dietary restrictions, resulting in low serum levels. Supplementation of 2 mg/d is considered appropriate. 54
Intake of vitamin C, like the B vitamins noted above,
is often poor in CKD. Vitamin C is also lost through dialysis treatment. Supplementation of vitamin C, as part of
a water-soluble vitamin supplement, is recommended for
CKD patients stages 3 to 5 who are at risk for deficiency and
for all CKD stage 5D patients. However, excess amounts
of vitamin C may be detrimental. Ascorbic acid and amino
acids are precursors to oxalate. High doses of vitamin C may
contribute to higher blood oxalate levels which, along with
the reduced oxalate clearance common in renal damage,
can contribute to secondary oxalosis. Therefore, it is key to
assess predialysis patients for adequate vitamin C intake to
determine need for supplementation, remembering vitamin
C excretion is not impaired with declining renal function.
For dialysis patients supplement only to approximately the
DRI or slightly higher, enough to replace dialysis losses.12,55
There are currently no pediatric renal vitamins available on the market in the United States. However, many
adult-formulated vitamins are appropriate for older children and adolescent patients. The goal is to find a vitamin
with a content that is close to or slightly above the DRI for
age for the patient in question. Adult preparations of liquid
renal vitamins are also available and smaller doses can be
titrated to more closely meet the DRI requirements for
younger children and infants.12 Many adult renal vitamins
provide much more than the DRI for younger children and,
consequently, supplemented children may have normal or
above-normal serum concentrations of vitamins, including
thiamin, riboflavin, vitamin B6, and folic acid. Because these
vitamins are water soluble, it is not likely to cause harm.41
RENAL DISEASE
265
Infants may receive more vitamins and minerals than older

children due to the use of infant formula. 56 However, a small
dose of a renal-appropriate vitamin may still be necessary to
replenish dialysis losses.
disease, and serum levels. Fluid control is important to

minimize interdialytic weight change in dialysis patients.
An intradialytic change of < 5% is optimal.12 Fluid control is
also necessary to control blood pressure.
Minerals
Sodium
An inadequate intake of zinc and copper is frequently found

in patients with CKD due to diet restrictions, dialysis
losses, and poor oral intake. Zinc metabolism has been
noted in chronic renal disease and nephrotic syndrome
with low serum levels, especially in the face of proteinuria
and uremia. 57 Zinc levels typically improve within one year
of renal transplant. Zinc deficiency can cause impaired
wound healing, skin changes, anemia, taste changes, and
growth retardation, among other problems. Children on
PD have been found to have losses of zinc across the peritoneum with resultant low serum levels. These levels improve
with supplementation of zinc. 58 A small, single-center study
indicates that copper levels may be low in CKD stage 5D
patients due to medication interaction. 59 Thus, assess both
zinc and copper levels on a regular basis in dialysis patients;
semi-annually is suggested. Supplementation to the DRI if
low, or to therapeutic levels if critically low, may improve
serum values. Nondialysis patients may need to have zinc
levels checked if they present with poor intake or show clinical symptoms of zinc deficiency.
Abnormalities of selenium metabolism have also been
noted in patients with CKD. In a study of adult HD patients,
plasma selenium levels were found to be significantly lower
than controls, but corrected with supplementation. 60 Selenium is noted to be involved with the regulation of thyroid
function, and low thyroid-stimulating hormone (TSH)
levels and increased T3 levels were found in these patients.
However, there have been no studies of selenium in children
with CKD and supplementation is not recommended at this
time.12
Iron deficiency, manifesting as anemia, is typical in
CKD. The primary cause is insufficient production of erythropoietin (EPO) by the impaired kidneys. Iron deficiency,
blood loss from medical procedures, hyperparathyroidism,
and acute or chronic inflammation may all contribute.
Anemia is typically managed with therapeutic doses of EPO
and iron supplementation, as needed. 61 However, the intricacies of anemia require medical management and thus are
outside the scope of this chapter.
Sodium is often restricted to help control volume overload and blood pressure. According to the 2005 Dietary
Guidelines for Americans older than 2 years, all individuals with hypertension should limit sodium intake to
<1500 mg/d.62 This is complicated by the environmental
cues and peer pressures that promote high sodium intake,
especially where fast food is concerned. Stringent sodium
restrictions are challenging. A more reasonable sodium
restriction of 2000 to 3000 mg/d may be better accepted
and hence adhered to in older children or adolescents. The
amount of sodium restriction needed should be based on
individual patient parameters such as blood pressure, fluid
gains, and nutrition intake. Most sodium in the diet comes
from processed foods. Therefore, an increased intake of
fresh foods versus processed or canned foods will decrease
dietary sodium intake. Using natural herbs and spices
to season foods versus table salt is extremely helpful in
reducing sodium content in foods. It is not only important
to educate patients on low-sodium foods, but also on how
to read nutrition facts labels. According to the U.S. Department of Agriculture (USDA), foods with < 5 mg sodium per
serving are considered sodium- or salt-free. Foods with < 35
mg sodium per serving are considered very low sodium; and
foods with <140 mg sodium per serving are low sodium.62
The use of salt substitutes is often contraindicated in CKD
patients because potassium chloride is typically substituted
for sodium chloride. Potassium chloride can cause hyperkalemia in those at risk for the condition. Some PD patients
may lose large amounts of potassium across their peritoneal membrane and may actually benefit from additional
potassium.
Infants and children with CKD often have primary
disorders such as posterior urethral valves that cause
polyuria and salt wasting. These children must have supplemental sodium and free water to maintain proper balances.
Fluid and Electrolyte Balance

Fluid and electrolyte restrictions will vary among individuals according to urine output, stage of CKD, primary
Potassium
Dietary potassium is often restricted to prevent hyperkalemia

because as kidney failure progresses, the ability to excrete
potassium is decreased. Hyperkalemia can, in turn, lead to
impaired muscle function, including the heart, resulting in
cardiac death. When dietary management is not sufficient to
keep serum potassium levels acceptable, medication may be
266
necessary to prevent or treat hyperkalemia. It is important

to remember that certain medications, such as steroids and
ace-inhibitors, have a drug-nutrient interaction that causes
hyperkalemia.
Hypokalemia can occur in certain diseases such
as Fanconis syndrome in which a renal tubular defect
is present. CKD5D patients on PD may filter out large
amounts of potassium, often requiring a high-potassium
diet to maintain normal serum levels.12,63 Adult patients are
typically advised to limit potassium to 2000 to 3000 mg/d.
There is no direct evidence for appropriate amounts for children. However, an extrapolation of the 2000- to 3000-mg
recommendation is < 30 to 40 mg/kg/d or 0.8 to 1 mmol/
kg/d. However, for infants and young children, 1 to 3 mmol/
kg/d may be an appropriate place to start.12 Restriction can
be adjusted based on individual tolerance and serum lab
values.
Phosphorus
It is well known that elevated phosphorus levels increase

PTH levels in patients with CKD, even as early as stage 3
CKD. Elevated PTH levels lead to high bone turnover,
increasing risk for bone calcium loss and consequent
calcium deposition in organs and small vessels (CKDMBD). A low oral intake of phosphorous in the diet can help
prevent elevated serum phosphorus and PTH levels. Even
when phosphorus levels are normal in the earlier stages of
CKD, limiting oral phosphorus intake can improve PTH
values and increase 25-hydroxyvitamin D levels.45 Low
levels of active Vitamin D (calcitriol) exacerbate phosphate
retention, which increases calcium bone loss. Supplementation of vitamin D is necessary to increase calcium uptake
by the gut and suppress the parathyroid to prevent calcium
bone loss. The downside of vitamin D therapy is that it
also increases phosphorus absorption, possibly increasing
serum phosphorus levels.64 Consequences of excess phosphorus intake in patients with advanced stages of CKD
are increased cardiovascular morbidity and mortality. An
elevated calcium X phosphorus product can result in calcification of soft tissues and small vessels. In adult patients,
a phosphorus level above 6.5 mg/dL is correlated with an
increased risk of death, and those with the highest calcium
X phosphorus product have the greatest risk.65 The KDOQI
Clinical Practice Guidelines for Bone Metabolism and
Disease in Children With Chronic Kidney Disease indicate
that the calcium X phosphorus product in pediatric patients
should be < 65 mg2/dL2 in children 12 years of age and
younger and < 55 mg2/dL2 in adolescents > 12 years of age.65
These guidelines also recommend that serum phosphorus
levels should be maintained within age-appropriate reference ranges for CKD stages 1 to 4; and between 4 to 6 mg/
dL for ages 1 to 2 years and 3.5 to 5.5 mg/dL for adolescents
for CKD stage 5 and 5D. Hypophosphatemia that arises
due to phosphate wasting disorders, overcorrection, or
other causes should be corrected by liberalization of diet or
medication changes. Hypophosphatemia is associated with
increased morbidity or mortality and poor growth.
The KDOQI pediatric bone guidelines also suggest
that when PTH levels are elevated for the given stage of
CKD, dietary phosphorus should be limited to the DRI for
age. When phosphorus values and PTH values exceed reference ranges for age and stage of CKD, phosphorus should
be limited to 80% of the DRI.12,66 However, this guideline
can equate to low intake in children younger than age 8. It
should be noted that less than 500 mg of phosphorus, even
in young children, may not allow for adequate caloric intake.
An exception are children who get a controlled amount of
phosphorus via a set amount of enteral formula by mouth or
feeding tube.
Limiting phosphorus in the pediatric diet may be a challenge, especially as fast food and convenience food increases
in the usual diet of children and adolescents. About 60% of
dietary phosphorus is absorbed from the typical naturalfood mixed diet. Assuming natural foods are consumed, the
average adult man consumes an average of 1550 mg of phosphorus per day, with over half consuming more than 1600
mg daily. The average woman consumes about 1000 mg
daily. Foods high in protein typically contribute the most
phosphorus in a natural diet with dairy and meats, including
fish, providing 20% to 30% each of the usual daily intake.
These numbers are increasing as more instant and restructured foods as well as colas, which have phosphate additives,
are on the market. Foods made with phosphate additives,
including many instant and restructured foods, have almost
100% absorption of phosphate content. Estimates are that
these foods could contribute to dietary phosphorus intake by
about 1 gm daily, even with unchanged protein and calcium
intakes.67 Additionally, Sullivan et al looked at chicken
products with phosphate-containing additives and found
that the phosphorus content of these products was higher
in every instance than the phosphorus content expected
from a nutrient database, averaging 84 mg/100 g of product
or greater. This study concludes that standard nutrition
databases do not currently account for the recent influx of
phosphate additives in foods. This, coupled with the great
variation of phosphorus content between products, makes
it difficult to estimate phosphorus content of foods and to
advise patients who need to limit dietary phosphorus. The
RENAL DISEASE
increase in processed foods with phosphate additives on

the market makes controlling phosphorus and having a
healthful diet difficult for CKD patients as well as practitioners who advise them.68
A common treatment for elevated serum phosphate
levels is phosphorus binders. These medications induce
excretion of phosphorus through fecal elimination when
taken with meals. Phosphorus binders that are available
include calcium-based binders, notably calcium carbonate
and calcium acetate (Phoslo), sevelamer carbonate
(Renvela), and lanthanum carbonate (Fosrenol).
Lanthanum carbonate is not recommended for pediatric
patients at this time as long-term bone effect is not known.
Sevelamer has been shown to be as effective in lowering
serum phosphorus levels as calcium-based binders and,
because it does not contribute to calcium intake, it is much
less likely to increase serum calcium levels.69 The KDOQI
guidelines indicate that phosphorus binders should be used
when the serum phosphorus level is elevated and does not
normalize with dietary restriction alone. The guidelines also
indicate calcium-based binders should be the initial therapy
in infants and young children, but noncalcium-based binders
may be used if further correction of hyperphosphatemia is
needed.66 Either type may be used in adolescents. Calciumbased binders are discussed below.
Factors such as residual kidney function and dialysis
also play a large role in determining serum phosphorus
levels. Creatinine clearance provides a good estimate
of phosphorus clearance. If creatinine levels are higher,
patients typically have less phosphorus losses through urine
and dialysis. High transporters receiving PD also enjoy
greater phosphorus clearance than patients who are low or
average transporters.70 Increased dialysis time also improves
phosphorus clearance. Patients receiving nocturnal HD,
which is typically 6 to 10 hours nightly while the patient is
sleeping, typically have twice the phosphorus clearance of
patients who receive standard 3 times per week HD.71
Calcium
Insufficient dietary calcium intake may result in poor bone

mineralization. However, excess intake may contribute to
an increased risk for CVD. Consequently, a balance of an
adequate, but not excessive, intake of calcium is important
for children with CKD. Although at least 100% of the DRI
for age is recommended for children with CKD, there are
many sources that may contribute to calcium intake. The
total elemental calcium intake derived from dietary intake,
enteral supplementation, and calcium-based phosphorus
binders should not provide more than 200% of the DRI for
267
calcium, or 2500 mg for adolescents in which twice the DRI

would exceed 2500 mg.66
If intake is inadequate, a calcium supplement is useful.
It should be offered away from mealtime and iron supplements to allow maximum calcium absorption. Calcium
gluconate, lactate, acetate, or carbonate are all alternatives
and should be given in doses < 500 mg at a time for best
absorption. Calcium citrate should not be given as it can
increase aluminum absorption. Calcium chloride should
also be avoided as it can contribute to metabolic acidosis.12
If patients are hypocalcemic (< 8.8 mg/dL), calcium and
vitamin D therapy should be considered.66 The KDOQI
pediatric bone guidelines indicate that serum calcium levels
should not exceed norms for age in CKD, and should be on
the lower end of normal in ESRD.
As noted above, calcium carbonate (TUMS or others)
and calcium acetate (Phoslo) are often used as phosphorus
binders in children with CKD. Research indicates that use
of calcium-based binders may contribute to hypercalcemia,
and as mentioned previously, may contribute to the development of soft tissue calcification with organ and small vessel
damage. Calcium acetate has a higher binding capacity than
calcium carbonate. Forty-five milligrams of phosphorus is
bound by 667 mg of calcium acetate as opposed to 39 mg of
phosphorus per 1250 mg of calcium carbonate. Twenty-five
percent of calcium is absorbed from calcium acetate versus
40% from calcium carbonate, resulting in a lower calcium
load from calcium acetate.72
Intestinal calcium absorption is suboptimal in patients
with CKD, especially as renal failure advances, due to low
levels of 1,25-(OH)2D. Low dietary intake due to poor
appetite and dietary restrictions is also common.73 Consequently, higher doses of active vitamin D can decrease the
patients need for calcium supplements.12
Elevated serum calcium levels are also a concern. If
PTH is low, bone is not turning over at a rate necessary for
proper growth and bone maintenance, a state known as
adynamic bone disease. In this case, or if serum calcium
levels exceed 10.2 mg/dL on 2 consecutive measurements,
excess calcium is not appropriate as the bone cannot incorporate calcium appropriately. In these cases excess vitamin
D therapy or calcium supplementation should be lowered or
ceased. If discontinuation of binders and vitamin D therapy
is not enough to lower serum calcium levels, low-calcium
dialysate should be considered but is not the preferred
option.66,74
268
Other Electrolytes of Concern
Magnesium metabolism is often altered in patients with

CKD resulting in low ionized levels and high total circulating levels.75 Typically, serum magnesium levels will be
elevated or high-normal in dialysis patients; however, at this
time, dietary alterations are not generally recommended.
Other minerals of concern are those that may be impacted
by ongoing dialysis treatments. Minerals such as lead,
mercury, and cadmium have been noted to be elevated in
long-term dialysis patients. Contamination of dialysis fluids
may contribute to these mineral abnormalities.76
Aluminum has been found very harmful to patients
with renal impairment, and toxicity historically has caused
severe bone disease and encephalopathy in patients with
kidney disease. Prevention of excess aluminum intake by
choosing non-aluminum-based medications and avoiding
aluminum contamination in dialysate or parenteral solutions is critical.
Cardiovascular Disease and Lipid Management

CVD is the major cause of mortality in patients with CKD,
accounting for about 25% of deaths.77 Children with ESRD
have a 1000-fold higher risk of cardiac death compared to
non-ESRD children.77 Additionally, children with CKD
are among the American Heart Associations (AHAs) list
of high-risk pediatric populations. 39 Traditional risk factors
including hypertension (HTN), left ventricular hypertrophy (LVH), and dyslipidemia are highly prevalent in
adult CKD patients. However, recent data show that nontraditional markers or uremic factors are also contributing to
CVD in adult patients. These factors include dyslipidemia,
abnormal calcium and phosphorus levels, vascular injury
due to vascular calcifications and arteriosclerosis, inflammation, anemia, fluid overload, and proteinuria.78
Uncontrolled HTN is the most significant risk factor
for CVD and develops early in CKD. As CKD progresses,
HTN becomes more profound. Therefore, HTN control
should be a major goal in decreasing not only CVD risk, but
the risk of CKD progression as HTN exacerbates the rate of
kidney failure. Volume and pressure overload contribute to
the HTN and LVH present in many children with CKD. 38 If
uncontrolled, LVH may lead to cardiomyopathy and cardiac
failure. Therefore, blood pressure and volume control are
needed to help reduce manifestations of CVD.
Dyslipidemia also typically occurs as CKD progresses.
It is characterized by hypertriglyceridemia, and elevated
levels of very low-density lipoproteins (VLDL), low-density
lipoproteins (LDL), and total cholesterol. Low levels of highdensity lipoprotein (HDL) are present as well. According
to the AHA, treatment starts with lifestyle changes of diet

and exercise. Drug therapy is added when diet and exercise
are not sufficient to keep lipids at acceptable levels. 38 The
KDOQI guidelines do not recommend dietary intervention for dyslipidemia in malnourished children with CKD.
However, in non-malnourished children, a change to a
heart-healthy fat, increased fiber, and a limitation in sugar
intake are recommended.12,39
Obesity, especially in the posttransplant population,
contributes to CVD risk and the development of other risk
factors for CVD including dyslipidemia, HTN, and diabetes
mellitus. Therefore, weight management should be included
in the nutrition intervention (see Renal Transplant section).
A non-traditional risk factor for CVD is abnormal
calcium and phosphorus levels. Calcifications form in the
vessels and soft tissues, including the heart. As many as 60%
of pediatric patients on dialysis have soft-tissue calcifications
at time of death (see Phosphorus and Calcium sections).79
Inflammation is another non-traditional risk factor that
appears to contribute to CVD risk. Systemic inflammation
is often characterized by elevated serum c-reactive protein
(CRP) levels. Evidence suggests an elevated CRP level is
associated with cardiac morbidity and mortality in CKD
patients.80 Causes of inflammation include the presence
of uremic toxins increasing oxidative stress, chronic infections, increased presence of proinflammatory cytokines,
and abnormal calcium and phosphorus metabolism.81
There is also evidence of reverse epidemiology for low
serum cholesterol levels, low serum homocysteine levels,
and low BMI.78,82 Just as hypercholesterolemia, possibly
high serum homocysteine levels, and a high BMI can be risk
factors for CVD, low cholesterol, low homocysteine, and a
low BMI can be risk factors, suggesting that malnutrition is
a risk factor for CVD.
A syndrome known as MIA (malnutrition, inflammation, and atherosclerosis syndrome) is thought to be the
main cause of mortality in adults. This syndrome is based
on evidence of a strong link between these 3 factors and
an increased risk of mortality in CKD patients. 80 There are
not significant data in the pediatric literature to suggest the
same parameters increase the risk of mortality in pediatric
patients. More studies in this area are needed.
Renal Transplant
The ultimate medical goal for children with ESRD is renal

transplantation, either from a living donor or a deceased
organ donor. However, transplantation is considered a treatment modality and not a cure for CKD. Children who have
received a renal transplant should be considered to have
RENAL DISEASE
CKD. Unfortunately, until advances in medicine provide

improved medication treatment or alternatives to human
organs, slow deterioration of a renal transplant is probable.
Close attention to the nutrition and overall health care of
the transplant recipient is often paramount to the longevity
of the transplanted kidney.
CVD is not only a significant risk for mortality in pediatric and young adult ESRD patients, but is also much more
common in kidney transplant patients of this age group than
in the general population. The reduction of risks for CVD,
infection, and psychosocial issues compared to patients
on dialysis typically makes transplant the more desirable alternative for renal replacement therapy. However,
hyperlipidemia, hyperhomocysteinemia, inflammation,
malnutrition, anemia, and hyperglycemia or insulin resistance can all occur in the transplant patient and are factors
that may contribute to the development of CVD.
Several medications used for immunosuppression
and prevention of graft loss may have side effects that are
damaging to the kidney and to the overall health of the
recipient. Although many centers have developed protocols that minimize corticosteroid usage, these medications
are still frequently used in transplant recipients. Adverse
effects of transplant medications include HTN, hyperlipidemia, hyperglycemia, increased appetite leading to weight
gain, peptic ulcer disease, osteoporosis, muscle wasting,
and an increased risk of infection. Calcineurin inhibitors
(CNIs) such as cyclosporine and tacrolimus can cause
hyperglycemia, hypomagnesemia, hyperkalemia, HTN,
and nephrotoxicity. T-cell receptor (mTOR) inhibitors
such as sirolimus have potential side effects of hypertrigly
ceridemia, hypercholesterolemia, diarrhea, delayed wound
healing, and mouth ulcers. The use of antiproliferative
agents such as mycophenolate mofetil and azathioprine
may result in gastrointestinal side effects such as nausea and
diarrhea, sore throat, or altered taste acuity.83 A clinician
must be aware of these potential side effects and work with
the patient to optimize nutrition intake while minimizing
side effects.
Transplant patients should be advised to limit concentrated sweets, especially when medication doses are highest,
such as soon after transplant or when treating rejection.
Unless patients are underweight, water and other fluids low
in simple sugars are recommended to control weight gain,
limit hyperglycemia, and promote good dental health. After
transplant, patients often need to continue to limit their
sodium intake to prevent or control HTN. Correction of
abnormal mineral or electrolyte concentrations is recommended if needed.12,84
269
Adequate intake of calcium is important for bone health,

not only given the potential for transplant medicationrelated side effects such as osteoporosis, but also because
of bone damage that may have already occurred related to
CKD. Calcium and vitamin D intakes of at least 100% of
the DRI are usually suggested. However, if transplant function has deteriorated such that serum phosphorus and PTH
levels are elevated, total elemental calcium intake should
not exceed 200% of the DRI, as indicated for other CKD
patients at a similar stage.12,84 Dietary inclusion of highmagnesium foods and limitation of high-potassium foods
may be warranted if laboratory values dictate. However,
pharmacological management may be necessary with
treatment of hypomagnesemia with magnesium oxide, or
less frequently gluconate-based magnesium preparations.
Persistent or severe hyperkalemia can be treated with medications such as fludrocortisone or with Kayexalate-treated
formula. Hyperlipidemia can be treated with diet modification (eg, increase in polyunsaturated fats and decrease in
saturated fat) and medication. The use of 3 to 4 grams of
omega-3 fatty acids daily may also lower serum lipids.84
Fluid intake is key for the transplant recipient to assure
adequate perfusion and renal artery flow to the transplanted
kidney. In pediatric patients, this is typically 1.5 to 4 L/d
depending on the size and activity of the child. 84 Intake
of 2 to 3 L is typical for adult-sized adolescents. In young
children, including infants and toddlers, adequate fluid
intake may be especially important to prevent ATN, graft
thrombosis, and graft nonfunction. Transplant success in
this age population is best when adult-sized kidneys are
used. However, due to a childs small heart, blood volume,
and blood vessels, the need for a large blood flow may be
difficult to meet, resulting in loss of kidney function. One
centers experience indicates that total fluid intake (enteral
formula and water orally and via tube feeding) of 2500
mL per body surface area (2500 mL/cm2/d) and sodium
intake of 8 to 10 mEq/kg/d prevented these complications.
Salvatierra et al describe an increased sodium and fluid
protocol that reversed a high creatinine in one infant who
had a low sodium and fluid intake. Lower GFRs were noted
in the non-protocol patients.85,86 This type of protocol may
be necessary for 6 months to a year after transplant.85
Acute Kidney Injury (AKI)
AKI, formerly referred to as acute renal failure (ARF), is a

temporary condition of kidney dysfunction typically characterized by electrolyte imbalances, an increase in blood
urea nitrogen (BUN) and serum creatinine, and a decrease
in urine output.87 (For further discussion of physiology,
270
refer to the section on Kidney Development and Function.) Although kidney function is usually restored once
the etiology of AKI is eliminated or corrected, supportive
therapy is required in the interim. Therapy may or may not
include temporary dialysis. If dialysis is required, there is no
standard treatment modality. PD, HD, and continuous renal
replacement therapy (CRRT) are all used. CRRT is chosen
by an increasing number of pediatric centers because of the
safety and efficacy of the technique, even in those patients
who are experiencing hemodynamic instability.87,88
Nutrition assessment and planning for the patient with
AKI typically follow the same guidelines for CKD5D and
critical illness. There are no set standards for estimating
caloric and protein needs in the setting of AKI, either
with or without the use of dialysis. Needs are based on
the age-related needs of the patients, in addition to modifications based on comorbid medical conditions such as
sepsis. Hypercatabolism and alterations in metabolism are
common in AKI. Some of the alterations of metabolism
include decreased protein synthesis and inefficient use
of proteins by the cells, altered amino acid pools, hyper
glycemia secondary to insulin resistance, lipid alterations
caused by impaired lipolysis, acidosis, and electrolyte imbalances. The primary goal of nutrition therapy in patients with
AKI is to prevent catabolism as much as possible.
The patient with AKI and not on dialysis may need
more rigid electrolyte and fluid restrictions. If a nutritional supplement is required, use a renal supplement,
such as Suplena or Nepro, that is nutrient dense and has
a low renal solute load. For infants, Similac PM 60/40 is
usually the most appropriate choice. Once renal function is
restored, a regular diet and/or supplement is appropriate.
However, when dialysis is performed, depending on the
modality, restrictions may vary (see sections on Continuous
Renal Replacement Therapy, Hemodialysis, and Peritoneal
Dialysis). Nutrition guidelines in AKI when patients are
provided HD or PD are similar to those for CKD and HD
and PD. However, fluid and electrolyte concerns as well as
prevention of catabolism take priority to more long-term
concerns associated with CKD, such as CVD, growth, and
renal osteodystrophy.
Continuous Renal Replacement Therapy

CRRT is an umbrella term that can include continuous
arteriovenous hemofiltration (CAVH), continuous
venovenous hemofiltration (CVVH), slow continuous
ultrafiltration (SCUF), continuous arteriovenous hemodiafiltration (CAVHDF), continuous venovenous
hemodiafiltration (CVVHDF), continuous arteriovenous
hemodialysis (CAVHD), and continuous venovenous

hemodialysis (CVVHD). CRRT replaces kidney function
on a continuous or nearly continuous basis in terms of solute
and fluid removal and has been found to increase survival in
critically ill children, even infants less than 10 kg.89 Because
CRRT is a relatively new technology, there is little literature
regarding nutrition needs associated with it, especially in
children.
Consistent with adult studies, enteral nutrition is the
first choice for the route of nutrition support in children
receiving CRRT. Because CRRT efficiently improves
clearance of solutes, phosphorus, potassium, sodium, and
other electrolytes or minerals typically do not need to be
limited. They may actually need to be supplemented. A
renal formula may increase gastrointestinal complications,
such as diarrhea or emesis, due to high osmolality, and use
of a standard formula is appropriate. Gastric emptying can
be problematic in this population with slow gut motility.
It may be alleviated by using transpyloric feeding. A standard tube-feeding formula started at a slow, continuous rate
and monitored for tolerance is optimal, even in children on
vasoactive and sedative drugs.90
Caloric needs of the primary condition should determine caloric needs during CRRT. Acute renal failure,
itself, is typically not thought to increase calorie needs.
Oftentimes CRRT is used to support patients with AKI
secondary to conditions such as burns or sepsis in which
caloric requirements may be markedly increased. Although
dialysis may cause some inaccuracies in measurement of
caloric needs due to carbon dioxide removal by the dialysis
membrane, indirect calorimetry (IC) is still considered the
gold standard and has been used in studies to determine
caloric needs of pediatric patients receiving CRRT.91
Protein losses may be very high in patients receiving
CRRT. Maxvold et al91 attempted to assess nitrogen
balance and amino acid loss in pediatric patients. In this
study, children receiving 120% to 130% of IC-predicted
resting energy expenditure (REE) and 1.5 g/kg protein
were in negative nitrogen balance. That amount of protein
seemed inadequate for this population. A recent study with
adult patients indicated that at least 2.5 g/kg protein may
be necessary to achieve a positive nitrogen balance.92 Thus,
protein needs for children receiving CRRT are likely to be
at least as high, if not higher because the baseline protein per
kilogram needs are greater in children than adults. Studies
in both adults and pediatrics demonstrate a 10% to 25% loss
of amino acids in CRRT via the dialysis filter.93
There are no published studies assessing the micronutrient needs for children receiving CRRT. However, adult
RENAL DISEASE
studies indicate micronutrient loss is high in this patient

population. High losses of trace elements and vitamins,
such as selenium, copper, and thiamin, are common. It is
speculated that other water-soluble vitamins are lost in a
similar fashion.94,95 Experts recommend doubling the standard trace element preparations for adult patients receiving
CRRT plus an additional 100 mg of thiamin and 100 mcg
of selenium supplementation.96 It is likely that additional
micronutrient supplementation, proportional to the DRI
for age, would also be appropriate for children.
Neonatal Issues
AKI is common in the neonatal intensive care unit and
may be of primary origin, such as congenital renal disease,
or secondary to conditions such as sepsis, drug toxicity,
obstruction, hypoxia, or respiratory distress. Twenty
percent of new dialysis cases are reported to be newborns.97
Mortality is high (46%) in neonates and low-birth-weight
infants with AKI.98 Dialysis, including PD, CRRT, or less
commonly HD, may be used to maintain fluid, acid-base,
and electrolyte balance as well as remove toxins in the short
or long term. It is important to remember that serum laboratory values, such as phosphorus and potassium, may have
higher normal limits for neonates than for older infants and
children. Fluid balance is important because patients may
have high urine output due to sodium and fluid-wasting
renal disorders, stomas, emesis, or suction. This may necessitate a high fluid intake, replacing losses and providing
maintenance needs. Poor urine output or additional
sources of fluids, such as medication drips, may lead to fluid
restrictions, and the need to concentrate formula with additives or to use parenteral nutrition (PN).99 Oliguric and
anuric infants typically should receive 25 to 30 mL/kg/d,
with infants < 26 weeks gestational age possibly needing
more.100
Controlling HTN and edema are often critical in this
population. Maintenance fluid needs are a good starting
point, with adjustment based on clinical conditions.101 Often
children with high fluid and sodium losses require sodium
supplementation of 1 to 3 mEq/kg/d.100 Correct acidosis
with supplementation of sodium bicarbonate.97 Sodium
bicarbonate supplementation of 1 to 2 mEq/kg/d may be
needed to prevent hyperkalemia. If serum potassium levels
are high, limit potassium to 1 to 2 mEq/kg/d.100
It is important to be aware of medications that may
affect nutrition. Pressors or narcotics may decrease gastric
motility and may affect tolerance to enteral feeding. Continuous jejunal or transpyloric feedings may be better tolerated
than nasogastric feedings. Anti-hypertensives can increase
271
serum potassium levels. Diuretics may cause potassium and

chloride losses that need to be replaced. Antibiotic therapy
may result in the need for vitamin K supplementation, especially as gut flora and vitamin K production may not be
established in the neonate.99
The energy and protein needs for a neonate with AKI
are estimated to be 120 kcal/kg/d and 2.5 g/kg/d, respectively.99 Another proposed guideline has been 8 to 12 kcal/
cm/d.99 Patients on PD may receive some carbohydrate
calories from dialysate solution.100 A patient on dialysis
may need greater amounts of protein because of urine and
dialysate protein losses. Whereas the above recommendations are a good starting place, the quantity of protein
administered may need to be adjusted based on laboratory
values and individual needs. For example, a child with poor
urine output not receiving renal replacement therapy will
need reduced amounts of protein in contrast to the child
receiving continuous dialysis.99
Often, nutrition needs are not able to be met by oral
intake alone and tube feeding is a commonly used alternative. It should be emphasized that neonates who are tube
fed should still be encouraged to take at least a portion of
their feedings by mouth. Breast milk is the optimal choice
and partial breastfeeding or bottle-fed breast milk should
be considered. If oral intake is not well tolerated, regular
oral stimulation is necessary. If breast milk is not an option,
a whey-based formula, especially a low-electrolyte, lowaluminum, and vitamin A formula, discussed later, is the
next best option. Caloric density of breast milk or formula
can be gradually increased from 20 kcal/oz to more than
30 kcal/oz as needed if there is volume intolerance or
restriction. Typically it is done with glucose polymer or fat
modulars as opposed to volume concentration to reduce
renal solute load.99 Some concentration of formula may be
acceptable in premature infants with increased needs for
calcium and phosphorus for bone accretion, especially if
serum phosphate levels are appropriate. However, phosphate retention related to renal failure should be kept in
mind. Calcium needs should especially be assessed and
supplementation may be needed.100 However, calciumbased medications and vitamin D that patients with kidney
disease may be receiving may increase calcium uptake and
lessen the need for calcium supplementation to the level
that other premature infants need. Increasing formula
concentration may not be appropriate even if higher phosphate and calcium load is needed as aluminum and other
solute concentration also increases.
Feeding tolerance should be closely monitored.
Reflux and delayed gastric emptying are common in renal
272
impairment and should be treated if needed. Treatment

options include decreasing concentration of the formula
with a slow increase back to desired concentration, slowing
the rate of delivery, using continuous feeds, and possibly
adding medications to enhance gastric motility.99 Bolus
feeds, if tolerated, are most physiologic. Some infants may
do best with a combination of bolus feeds during the day
and continuous feeds overnight.
In some cases, oral and/or tube feeding cannot meet
the nutrition needs of the neonate, mandating the use of
parenteral nutritional (PN) support. Glucose monitoring
with PN is mandatory, with consideration for the use of an
insulin drip if needed to provide adequate carbohydrate
calories while keeping serum glucose levels normal. Use
of a neonatal amino acid solution, such as Trophamine,
is appropriate as is the use of 20% intralipids to provide
energy and essential fatty acids. Lipids are started at 1 g/kg
and then increased to increase calorie intake, but typically
not greater than 3 g/kg. Triglycerides should be monitored
and lipids should be advanced only if triglyceride values
are < 250 mg/dL. If triglyceride values are > 300 mg/dL,
lipids should be reduced or stopped.99 Parenteral solution additives, particularly micronutrients cleared renally,
should be based on an individual patients response. Small
amounts of potassium in the parenteral solution, especially
if the patient is on dialysis, are often still appropriate. Start
with half or less of standard amounts for neonates without
renal impairment. Likewise, the reduction of magnesium
and phosphorus in PN to one-third or one-half the normal
amount may be beneficial and prevent low serum levels.
Selenium, chromium, and molybdenum may need to be
intermittently given or avoided due to impaired renal clearance and liver impact. Zinc and copper intakes should
remain standard, unless liver impairment is present, in
which case copper may need to be limited. In high-output
renal failure, additional zinc may be needed and assessing
serum values may be beneficial.97,100 A multivitamin is
needed to provide water-soluble vitamins while limiting the
quantity of fat-soluble vitamins99 (see discussion on micronutrients in Chronic Kidney Disease section).
Close follow-up of a neonate with previous or ongoing
renal impairment is important, and growth and feeding
tolerance should be monitored postdischarge. Easy-to-read
formula mixing instructions in household measurements as
well as demonstration of mixing is important.99 Preterm or
low-birth-weight infants who suffered AKI may be at particular risk for medical complications later in life, likely due to
the loss of renal mass from the early insult or as a result of
failure to complete glomerulogenesis.98 Problems that may
occur include high blood pressure and proteinuria associated with a low GFR. Height and weight gains tend to be
impaired in these patients and mandate close monitoring/
supervision of their nutrition status. Growth goals are the
same as other neonates. Further discussion of the neonate is
found in the chapter on nutrition, growth, and development
(Chapter 13).
Enteral Nutrition
Inadequate intake is common in children with CKD.

Gastroesophageal reflux, medication taste, uremia, as well
as thirst for water instead of formula may contribute to
this problem. The KDOQI Clinical Practice Guidelines for
Nutrition for Children indicate that supplemental nutrition
support should be considered in CKD stages 3 to 5 or 5D
to meet energy needs if the child is not growing or gaining
weight well. Additionally, oral intake of an energy-dense
diet and/or supplements is the preferred source of nutrition
support, followed by tube feeding, if energy needs are not
met orally.12
The majority of infants and young children who receive
PD as treatment for ESRD require supplemental enteral
feedings for adequate growth. There is some concern that
the use of a gastrostomy may be a risk for peritonitis. Peritonitis is the most significant risk of PD and can permanently
damage or alter a patients peritoneal cavity and limit the
use of this dialysis modality in the future. Consequently,
most experts recommend placement of a percutaneous
gastrostomy (PEG) or an open gastrostomy if an anti-reflux
procedure is needed, prior to the initiation of PD. If a gastrostomy is needed after initiating dialysis, an open gastrostomy
has a lower risk of peritonitis than a PEG placement.101
When supplemental feedings are given via tube feeding,
intake needs can typically be met in young children. In one
study, both caloric and protein needs were met or exceeded
in infants and young children receiving gastrostomy feeding
with 61% of needs coming from supplemental feeding.100
However, whether intake from supplemental feedings,
even if meeting estimated nutrition needs, improves
height and weight standard deviation scores remains
controversial.102,103
Infant and Toddler Feeding

Frequent nutrition assessment and revision of plan of care
is essential for optimal management of the infant and
young child with CKD or on dialysis. One dialysis centers
experience reports that dietetic contacts, including
direct, phone, and patient-related activities such as school
contacts, averaged about 6 per month for children < 5
RENAL DISEASE
years of age, as opposed to about 3 per month for children

> 5 years of age.104
Breast milk, which is low in phosphorus, calcium, and
other minerals, is an optimal food source for infants with
CKD. As a second choice, a whey-based formula is most
appropriate for this population. Of note, the potential for
aluminum toxicity is an important concern for patients with
kidney impairment. Breast milk has the lowest content of
aluminum and infants fed breast milk have the lowest serum
aluminum levels.105 Whey-based formulas have the nextlowest aluminum concentration, followed by whey-based
formula fortified with carbohydrate and lipid modulars.
Preterm formulas are higher yet in aluminum followed by
casein hydrolysate formulas. Consequently, soy and casein
hydrolysate formulas are not recommended for children
with renal impairment.
As noted in the discussion of neonates, concentrating
formula with a reduction of the water-to-formula ratio is not
an ideal approach for patients with CKD due to the electrolyte and renal solute load. Adding fat and carbohydrate
modulars, as well as protein modulars as needed based upon
the protein needs of the infant, is the most appropriate way
to increase caloric intake or to concentrate the formula
density in this population.
Infants often require supplemental tube feeding to meet
nutrition needs, as discussed above. Infants may benefit from
continuous overnight feeding and bolus feedings during
the day.12,106 Renal wasting disorders such as renal dysplasia
are a common cause of renal impairment in this age group,
and sodium supplementation using sodium bicarbonate or
sodium chloride is often needed.107 Sometimes phosphate
additives are also needed to correct serum phosphate levels
in patients who use a low-phosphorus formula.
Introducing solids at age-appropriate times is important, limiting but not avoiding foods high in electrolytes or
protein based on the childs underlying renal condition.12
Children with CKD may have oral hypersensitivity and
food-aversive behavior. It is important to offer a wide array
of foods, increasing texture gradually and allowing infants
to experience food exploration and other good feeding
habits such as family mealtimes. Many of these children
exhibit aversive tendencies. Speech, occupational, or child
psychology therapists as part of a multidisciplinary team
may aid normal feeding skill advancement. Need for intervention should be identified in a timely manner to prevent
more lengthy feeding delays. Even for children who are tube
fed, oral stimulation, including non-threatening contact
with food or pacifier use, is beneficial to encourage oral
development. It is recommended to positively reinforce
273
oral feeding acceptance and ignore feeding refusal. Gradual

introduction of oral feeding in children with food aversion
is preferred to rapidly stopping tube feeding to promote
growth and adequate intake as well as appropriate advancement to a regular diet. Many children advance to an oral
diet after transplantation, when factors such as uremia,
excess thirst, or gastrointestinal reflux may be reduced.12,106
The latter problem may occur in as many as 70% or more
of infants with chronic renal disease and may result in
impaired intake, increased feeding refusal, and excess
emesis. The potential need for standard reflux precautions,
medication, or even surgical intervention (fundoplication)
should be assessed in this situation.108
Infants and toddlers often suffer from high potassium
levels. One method to reduce potassium content of the
formula is to treat it with sodium polystyrene sulfonate
(Kayexalate). Work by Bunchman et al indicates that
adding Kayexalate to formula and allowing it to precipitate for 30 minutes in a refrigerator, and then pouring off
the formula from the residue that has settled to the bottom
of the container, is an effective way to reduce potassium
content of liquid beverages including breast milk and
formula.109 Although potassium content reduces significantly (and calcium and magnesium to lesser degrees),
sodium content greatly increases. In these experiments,
sodium content of the treated liquids increased an average
of 234%. The greatest removal of potassium coupled with
the lowest addition of sodium was found to be at the
30-minute time point. This sodium exchange may be of
benefit in the infant with wasting disorders, and should be
taken into account. The Bunchman group used Kayexalate
in the amount of 1 g/mEq of potassium in the formula;
however, this approach may overcorrect potassium levels if
potassium is only moderately elevated, and the dose should
be adjusted on an individualized basis per patient tolerance
and requirement.
Tube Feeding for Older Children

Older children and adolescents may benefit from tube
feeding to meet their nutrition needs, but social and
cosmetic reasons often prevent initiation of tube feedings in this age group. However, some children who were
infants or toddlers with CKD or on dialysis remain on
tube feeding past toddler years because of both parent and
patient desires or where inadequate intake is an issue. In
this situation, it may be best to only provide tube feeding
overnight to allow for hunger during daytime hours to help
advance feeding skills and transition to a completely oral
feeding regimen.12
274
Malnutrition is caused by multiple factors including

anorexia, poor food intake, the catabolic effects of dialysis,
and the demands of growth.15,16 Because of these issues,
meeting the needs of catch-up growth can be challenging
with oral and enteral supplementation alone. Network 14
data suggest that 4.5% to 7.5% of the dialysis population has
malnutrition to a degree that requires a greater nutrition
intervention than nutrition counseling, diet liberation, and
oral or enteral supplementation can provide. 33
In the case of mild to severe intolerance of oral or enteral
supplements due to gastrointestinal dysfunction, PN may
be necessary to ensure adequate nutrition. Patients with
CKD5 often have a fluid restriction. Hence, this approach
to therapy requires central venous access to accommodate
the concentrated high osmolar parenteral solution.
These guidelines provide general recommendations
for CKD and AKI patients. For specific recommendations
for PN for neonates or in CRRT, see sections on Neonatal
Issues and Continuous Renal Replacement Therapy.
Intradialytic Parenteral Nutrition

Intradialytic parenteral nutrition (IDPN) is a non-invasive
method of providing carbohydrate, protein, and lipids to
undernourished patients during HD via venous access. It is
supplemental to other forms of nutrition, including PN. The
main goals of this therapy are to replace nutrients lost during
HD, increase dry body weight, prevent further muscle
wasting, improve the patients appetite and strength, increase
albumin and nPCR, and decrease hospital admissions.
IDPN is typically composed of a concentrated dextrose
and amino acid solution and a separate lipid solution.110 The
solution must be formulated based on the patients needs
and tolerance. Concentrate dextrose is used to minimize
the amount of free water given but keep glucose infusion
rate to 5 to 9 mg/kg/min. While the energy provided may
seem minimal, its purpose is to maximize protein utilization. Serum glucose levels must be monitored because of the
potential for hyperglycemia. Serum glucose levels should
be maintained at < 200 mg/mL, using insulin if needed.
Because of increased insulin levels, there is a potential for
hypokalemia and hypophosphatemia; therefore, serum
potassium and phosphorus levels should be monitored as
well. Amino acids typically provide about 1.3 g protein per
kilogram per treatment. Lipids are given as a 20% intralipid
solution. Triglycerides must be monitored before and after
the initial lipid infusion to assure tolerance. If there is a 50%
rise above baseline levels, there may be inadequate clearance of fat and lipids should be discontinued.
IDPN is shown to be an effective and safe treatment

for adults on chronic hemodialysis with PEM.93,111113 The
updated KDOQI nutrition guidelines now provide recommendations for its use in children.12
Nephrotic Syndrome
Nephrotic syndrome (NS) is a combination of symptoms

occurring in association with various renal and systemic
diseases; it is not a single disease. NS is characterized by
proteinuria, hypoalbuminemia, hyperlipidemia, anasarca,
and oliguria. Weakness, anorexia, and headaches are
common. Most children with NS have what is known as
minimal change disease. The cause of minimal change
disease is unknown. Most patients will have more than one
episode of severe proteinuria, but most will outgrow the
disease and not develop permanent kidney damage.114
The main treatment goals are to increase urine output
and decrease/correct proteinuria. The major rationale for
making diet changes in the patient with NS is to diminish
manifestations of the syndrome, replace nutrients lost in
urine, and reduce the risk of causing further renal damage.
The dietary reference intake (DRI) for age based on ideal
body weight (IBW) is the appropriate standard to be used
for energy and protein needs. Although proteinuria and
hypoalbuminemia may be present, a high-protein diet is not
recommended because it can contribute to further kidney
damage. Edema and diuretic therapy make the patients
weight parameters unreliable. Patients are usually sodium
and fluid restricted to control edema. As a guide to sodium
restriction, a sodium content of 1 to 2 mEq/kg is used in
most circumstances (Table 24-4). Fluids are restricted if a
patient is fluid overloaded.114
Nephrolithiasis
Nephrolithiasis refers to kidney stones or calculi within the

urinary tract. Calcium and oxalate, sometimes with phosphate, are the primary components of the most common
kind of stone in all age groups (50% to 75%), followed by
uric acid stones (10% to 20%), struvite (ammonium-magnesium phosphate) stones (5% to 10%), and cystine stones
(1% to 2%). Nephrolithiasis is most common in Caucasians
and males. Being overweight, having HTN, and living in a
warm climate are additional risk factors for stone formation.
Although the majority of stones are primary and idiopathic
in nature, a variety of kidney or urinary tract disorders can
be associated with the development of stones; they include
medullary sponge kidney, distal tubular acidosis, secondary
hyperuricemia, and obstructive uropathy. Other disorders
such as sarcoidosis, Crohns disease, thyroid or parathyroid
RENAL DISEASE
disease, disorders of calcium or vitamin D metabolism, and

drug ingestion may contribute as well. Nephrolithiasis may
lead to CKD with some conditions, such as infection stones
and primary hyperoxaluria, being particularly troublesome,
potentially causing scarring.1,115
Renal stone disease appears to be increasing in pediatric patients. In one center, the overall incidence of kidney
stones increased more than fourfold from the 1990s to the
2000s, with the most significant increase present in children
younger than 10. There was distinct familial tendency for
stone formation, and obese children comprised 31% of the
patients with stones.113 Hypercalciuria and hypocitraturia
are found in pediatric stone formers116,117 and are common
metabolic abnormalities in these patients. Changing societal and environmental dietary habits in children, such as
increased sodium and animal protein intake, as well as a
decreased fruit and vegetable intake, may play a role. Such
habits reduce potassium and citrate and increase sodium
and acid load in the typical childhood diet. Children who
form kidney stones are likely to have repeat kidney stones.
However, proper nutrition care is paramount in treatment
and may significantly reduce or eliminate recurrence of
stone formation.1,116
275
citrate increases the solubility of urine calcium.118,119 Fruit

and vegetable intake has an integral role in decreasing some
of these risk factors. Research indicates that increasing fruit
and vegetable intake not only increases potassium intake,
an important protective factor, but also increases citrate
intake. Additionally, fruits and vegetables confer an alkali
load, reducing the risk of calcium loss and stone formation.
A high sodium intake is another important risk factor
for stone formation. Sodium increases urinary calcium
losses and may lower urinary citrate. It may also interfere
with the actions of some medications used to treat hypercalciuria.119 Of interest, although excessive calcium intake
is not advised, restriction of calcium is detrimental to stoneformers. Patients with hypercalciuria have bone calcium
loss, and limiting calcium intake can put patients at further
risk for poor bone status. Additionally, many calcium-rich
foods are high in potassium. Finally, limiting calcium may
increase the stone-forming factor oxalate in the urine, due to
decreased availability of calcium to bind with oxalate.119,120
Potassium citrate may be recommended as a medication if
compliance with diet is poor. A high magnesium intake may
also be a protective factor as well as limiting cola-containing
beverages, however both interventions mechanisms of
action are unknown.1
Fluid intake is an important preventive measure for
all types of kidney stones. Adequate fluid intake has been
shown to almost eliminate super-saturation of stoneforming agents.119 Urine output, and thus fluid intake,
appears to be inadequate in more than half of pediatric
patients, in one centers experience. It has been suggested
that a urine output of 1 mL/kg/h is adequate to avoid saturation of stone components in the urine, thus limiting stone
formation.117 Other recommendations are that the urine
output should be as high as 35 mL/kg/d. The 1 mL/kg/h
rule can be equated, for practical purposes and to account
for insensible losses, to a recommendation of 1 oz/kg of
Hypercalciuria and Calcium-Based Stones

Hypercalciuria, or an excessive loss of calcium in the urine,
predisposes a patient to calcium-based kidney stones.
Hypercalciuria is thought to be both familial and related
to environmental factors.115 In this type of stones, calcium
typically combines with oxalate or phosphate. Preventing
the loss of calcium is key to reducing the incidence of
kidney stone formation. Acid may contribute to this kind
of stone formation. Diets high in animal protein can reduce
urine citrate and increase acid load, predisposing bones to
calcium loss. Some patients who form calcium-based stones
and have hypocitraturia have a higher risk of stones because
Table 24-4 Nutrition for Kidney Stone Management1,115121
Increase Fluid
(at least 1 oz/kg)
Increase Fruit and

Vegetable Intake
Limit Acid-Based
Foods
Limit Meats
and Protein
Limit
Oxalate
Limit
Sodium
DRI Calcium
Intake*
X
X
X
X
Calcium-based stones
Oxalosis or hyperoxaluria
with calcium-based stones
Uric acid stones
X
X
X
X
X
X
X
X
Cystine stones
Struvite stones
Other kidney stones
X
X
X
DRI, especially
limit purines
X
*Although DRI calcium intake is appropriate general medical management for general pediatric health, including patients with a variety of kidney stone
disorders, avoidance of excessive or inadequate intakes of calcium are especially important in the types of kidney stones notated.
276
body weight or more per day.117 Another guideline for fluid

intake is 2 L or more for adults or adult-sized adolescents.119
A more general qualitative guideline is that a child or teen
should be encouraged to consume enough fluid so that their
urine is near colorless.1,117
Reducing protein intake may also be helpful to prevent
kidney stones but does not seem to be as critical as high
fluid and potassium intake and limited sodium. Although
limiting meat intake may be difficult for some, certainly
discouraging particularly high-protein intake is a goal at
minimum.1
In turn, practical dietary recommendations would
indicate the need to limit sodium to 2000 to 2400 mg daily;
provide 100% of the DRI for potassium with at least 5 fruits
and vegetables, particularly those high in potassium; 100%
of the DRI for calcium; and adequate fluid intake for size
and age.
children to reduce cystine concentration. A patient ideally

should drink prior to bedtime, upon waking, and also at
night. Neutral or alkali beverages are recommended. Additionally, limiting methionine intake, which is metabolized
to cystine, is helpful. Limiting protein-rich foods including
meat, fish, eggs, soy, and wheat can reduce methionine intake
and thus urinary cystine excretion. However, strict protein
restriction is not advised in children. Protein to the DRI
in children is appropriate for growth and may limit excess
cystine production. Unfortunately, adherence to a lowsodium and lower-protein diet may be poor. High vitamin
C intake is often recommended for treatment of cystinuria,
but it is controversial. Cystinuric patients often produce
other types of kidney stones and excess ascorbic acid may
increase oxalate production. In the absence of other types of
stones, 3 g of vitamin C has been recommended for adolescents with cystinuria.121
Oxalate
Primary hyperoxaluria is rare, and will be discussed further
below. However, secondary hyperoxaluria may result from
fat malabsorption or idiopathic increased absorption of
oxalate. Oxalate intake may need to be restricted in hyperoxaluric stone formers.119 Because hyperoxaluria is rare,
reported at only 6% of stone formers in one pediatric study,
it may be unnecessary to restrict oxalate to prevent stones in
hypercalciuria alone or in other types of kidney stones.117 In
fact, limiting oxalate in hypercalcuric patients is not shown
to reduce stone formation in a study of adult patients.120
Other Kidney Stones
Cystinuria
Cystinuria is an autosomal-recessive disorder and is the
cause of about 10% of kidney stones in children. The disorder
is related to impaired transport of the amino acids cystine,
ornithine, lysine, and arginine. Of these, cystine is insoluble
in the urine and thus it can cause stone formation. Recurrent
stone formation is common without medical management,
but even with medical management adherence may be poor
due to side effects and lack of treatment efficacy. Cystinuria
often leads to renal insufficiency, including ESRD, due to
recurrent stone formation and frequent intervention. Male
patients tend to be more severely affected. Medications
are often used in treatment; however, dietary interventions may be beneficial as well. As in other types of stones,
high fluid intake, low-sodium diet, and foods high in alkali,
such as fruits and vegetables, are recommended. Limiting
acid load by limiting excess protein intake is appropriate. A
2g sodium diet has been shown to reduce urinary cystine
concentration. A fluid intake of 3 L/d is recommended in
Uric acid stones, found in 2% to 4% of pediatric stone

formers, are often a consequence of a high purine load. Limitation of animal protein and other high-purine foods should
be considered. Meat, including fish, should be reduced to
the DRI for protein. Other foods that should be limited
include meat extracts such as bullion, meat gravies, cocoa,
mushrooms, high-yeast products, peas, and beans. Organ
meat should be avoided.1, 119
Struvite calculi consist of magnesium ammonium
phosphate or a calcium phosphorus mix and are often called
infection stones as they frequently result from urinary
tract infections. Unlike other stone disease, these stones
form in an alkali environment and increasing urine acidity
may help. Ascorbic acid is suggested as a treatment.1
Other stones include 2,8-dihydroxyadenine calculi,
which should be treated with purine restriction, and
xanthine stones, which should be treated with increased
fluid intake.1
Renal Tubular Disorders

Renal Tubular Acidosis
Renal tubular acidosis in characterized by an inability to
acidify urine and, left untreated, growth impairment is
common as are nephrolithiasis and nephrocalcinosis, or
calcium deposits in the kidney. Typical treatment of this
condition is alkali therapy.122 In clinical practice, monitoring
for failure to thrive and for renal stone disease is imperative.
Metabolic bone disease and bone calcium loss may require
nutrition monitoring as well.1
RENAL DISEASE
277
Bartters Syndrome
Nephrogenic Diabetes Insipidus
Bartters syndrome is an autosomal-recessive disorder

with symptoms of poor growth, hypokalemia, and metabolic alkalosis. Some mixed forms of Gitelman syndrome
and Bartters syndrome may include hypomagnesemia.
Gitelman syndrome resembles Bartters but is a milder
disorder. Lack of sodium, chloride, and water reabsorption
cause urine losses in the 4 to 8 L/m 2/d range. Chloride loss
causes alkalosis, increasing potassium wasting. Sometimes
calcium absorption is impaired, creating hypercalciuria.
Treatment includes replacement of sodium, chloride, potassium, and often magnesium. Monitoring for growth failure
is important.1
Nephrogenic diabetes insipidus (NDI) is typically an

X-linked autosomal recessive disorder and impairs water
reabsorption in the kidney. It manifests as vomiting,
anorexia, failure to thrive, and constipation in young infants.
Hypernatremia is common. Aggressive water supplementation is needed, and infants will often need overnight tube
feedings to meet fluid needs. The amount of fluid needed
may inhibit adequacy of caloric intake, and growth and
intake should be carefully monitored in this population.1
The NDI Foundation recommends a sodium intake of 500
mg daily and potential benefit from a low-protein diet. The
low-sodium diet, however, is the cornerstone of treatment.
The goal of this diet is to reduce solute load on the kidneys
and thus the amount of urine the kidneys must excrete.123
Table 24-5 General Nutrition Management of Renal Dysfunction

Nephrotic
Syndrome
ARF
No dialysis
ARF
PD or HD
ARF
CRRT
CKD
(Stage 3-5)
CKD5
HD
CKD5
PD
Energy*
DRI
EER for age or

original disease
state
At least 2.5 g/
kg or greater
EER for age
EER for age
DRIdo not
supplement
to replace
urinary losses
EER for age

or original
disease state
DRI with
0.2 g/kg
increases for
hemo, 0.4 g/
kg increases
for PD
EER for age
Protein
EER for age

or original
disease state
DRI or less
per BUN
monitoring
DRI + 0.1**
g/kg IBW
DRI + 0.150.3** g/
kg IBW
(dependent on
age)
Sodium
13 mEq/kg
will vary
according to
edema or HTN
Will vary.
Consult with
renal/primary
team to
determine.
Will vary.
Consult with
renal/primary
team to
determine.
Typically no
restriction; may
need electrolyte
supplementation
Potassium
Restriction not
needed
Tightly limit
Limit
Stage 3:
100%140% x
DRI/kg IBW
Stage 4-5:
100%120% x
DRI/kg IBW
13 mEq/
kg will vary
according to
edema or HTN
unless sodium
wasting
Most will
tolerate > 3
mEq/kg/d
Phosphorus
Restriction not
needed
Will vary
according to
UOP. Consult
with renal
team to
determine.
DRI
Tightly limit
Limit
13 mEq/
kg will vary
according to
edema or HTN
unless sodium
wasting
Generally
unrestricted
unless low
transporter.
Will need to be
monitored.
Limit to 80%100% x DRI to keep serum levels WNL.
Will vary
according to
UOP. Consult
with renal
team to
determine.
Tightly limit
fat-soluble
vitamins
Will vary
according to
UOP. Consult
with renal
team to
determine.
Limit fatsoluble
vitamins
May need
additional
replacement
fluids.
Generally
unrestricted
Replace UOP,
insensible
losses, + UF
May need
supplementation
especially
selenium and
thiamin.
100% DRI.
Supplement
water soluble if
needed.
100% DRI. Water-soluble vitamin

supplement is recommended.
Fluids
Micronutrients
*DRI typically
appropriate unless
specific notation.
13 mEq/
kg will vary
according to
edema or HTN
unless sodium
wasting
13 mEq/kg
but will vary
according to
serum levels
and age
Replace UOP,
insensible
losses, + ~1
L/d
*Energy requirements may need to be adjusted for physical activity level and/or based on rate of weight gain or loss.
**Protein requirements may need to be adjusted according to dialytic protein and amino acid losses.
278
In clinical practice, growth may be impaired with limited

caloric intake from such a strict diet. Sodium allowance
should be adjusted according to the patients tolerance,
growth, and clinical picture, but should be limited as much
as possible.
Other Renal Dysfunction

Oxalosis
Primary hyperoxaluria (type 1) is an autosomal-recessive disorder characterized by a deficiency in glyoxalate
aminotransferase. Oxalosis is the final stage of primary
hyperoxaluria in which calcium oxalate accumulates in the
blood and tissues due to an abundance of oxalate production
and deposition of crystals in the kidneys. This accumulation in the kidneys is known as nephrocalcinosis and causes
progressive renal failure. As renal failure progresses, oxalate
accumulates because of the continued excessive production
and the impaired renal excretion. While frequent HD can
help clear oxalate and attempt to control oxalate deposition,
success is often limited and further buildup in the tissues
can occur. Oxalate can deposit in the bones, eyes, heart,
vessels, and nerves. The optimal treatment is a combined
liver-kidney transplantation. A kidney transplant alone is
not recommended because the liver continues to produce
oxalate and can cause renal failure in the transplanted
kidney. Typically, the treatment protocol during the immediate posttransplantation period will include hyperdilution
or hyperdiuresis through superhydration methods to keep
the concentration of urine crystals at low levels. A lowoxalate diet is recommended. Excessive vitamin C intake
may increase risk of oxalate stone formation and should be
avoided. Secondary hyperoxaluria can occur in the context
of fat malabsorption because unabsorbed fat binds with
calcium making it unavailable to bind oxalate. A low-fat diet
with increased calcium intake is recommended. A high fluid
intake is important for urine oxalate removal. Potassium
citrate, pyridoxine, magnesium citrate, and other medications may be helpful.1
Other
There are many other renal disorders, including phosphate
metabolism disorders, cystinosis, Fanconis syndrome,
Liddle syndrome, Gordon syndrome, and others that are too
numerous to discuss in this context. Other disorders may
be primary renal disorders or renal disease secondary to a
systemic disease. In either case, the nutrition needs of these
patients should routinely be assessed because of the impact
that they have on the growth and development of these
children. Close attention to electrolytes and growth are

often the primary role of nutrition care in these diseases.
1. What is the optimal feeding route for children in acute

renal failure receiving CRRT that need supplemental
nutrition?
A. Parenteral nutrition
B. Nasogastric feeding of a renal formula
C. Transpyloric feeding of a standard tube feeding
formula
D. Nasogastric feeding of a standard tube feeding
formula
2. Which of the following vitamins or minerals may be
beneficial to supplement to pediatric patients receiving
dialysis treatments?
A. Vitamin B6
B. 25-hydroxyvitamin D
C. Folic acid
D. All of these
3. Which of the following comorbid diseases is responsible for 25% of deaths in CKD patients?
A. ESRD
B. Respiratory arrest
C. Cardiovascular disease
D. Diabetes mellitus
4. Which of the following statements regarding nPCR is
false?
A. Recent studies show that serum albumin is a better
nutrition marker than nPCR.
B. KDOQI does not recommend monitoring nPCR in
chronic hemodialysis patients.
C. It is a measure of protein intake in g/kg/d.
D. nPCR is an algebraic equation.
References
1. Kher KK, Schnaper HW, Makker SP, eds. Clinical Pediatric

Nephrology. 2nd ed. London, UK: Informa Healthcare; 2007.
2. North American Pediatric Renal Trials and Collaborative
Studies. NAPRTCS 2008 Annual Report. www.naprtcs.org.
Accessed December 9, 2008, and February 2009.
3. Vanderheyden T, Kumar S, Fisk NM. Fetal renal impairment.
Semin Neonatol. 2003;8(4):279289.
4. Paton JB, Fisher DE, DeLannoy CW, Behrman RE.
Umbilical blood flow, cardiac output, and organ blood
flow in the immature baboon fetus. Am J Obstet Gynecol.
1973;117(4):560566.
5. Bueva A, Guignard JP. Renal function in preterm neonates.
Pediatr Res. 1994;36(5):572577.
RENAL DISEASE
6. Ceriotti F, Boyd JC, Klein G, et al. Reference intervals for

serum creatinine concentrations: assessment of available data
for global application. Clin Chem. 2008;54(3):559566 and
Erratum in Clin Chem. 2008;54(7):1261.
7. Lameire N, Van Biesen W, Vanholder R. Acute renal failure.
Lancet. 2005;365(9457):417430.
8. National Kidney Foundation. K/DOQI Clinical Practice
Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis. 2002 (suppl 1)
10;39:S1S266.
9. Wong CS, Pierce CB, Cole SR, et al. Association of proteinuria
with race, cause of chronic kidney disease, and glomerular
filtration rate in the Chronic Kidney Disease in Children
Study. Clin J Am Soc Nephrol. 2009;4(4):812819.
10. Flynn JT, Mitsnefes M, Pierce C, et al. Blood pressure
in children with chronic kidney disease: report from the
Chronic Kidney Disease in Children Study. Hypertension.
2009;52(4):631637.
11. National Kidney Foundation. Glomerular Filtration Rate (GFR).
http://www.kidney.org/kidneydisease/ckd/knowGFR.
cfm#what. Accessed February 22, 2009.
12. National Kidney Foundation. KDOQI Clinical Practice
Guideline for Nutrition in Children with CKD: 2008 update.
Am J Kidney Dis. 2009;53(suppl 2):S1S124.
13. Goldstein SL, Baronette S, Gambrell TV, et al. nPCR assessment and IDPN treatment of malnutrition in pediatric
hemodialysis patients. Pediatr Nephrol. 2002;17:531534.
14. Kopple JD. Effect of nutrition on morbidity and mortality
in maintenance dialysis patients. Am J Kidney Dis.
1994;24:10021009.
15. Wolfson M. Management of protein and energy intake in
dialysis patients. J Am Soc Nephrol. 1999;10:22442247.
16. Brewer ED. Pediatric experience with intradialytic parenteral
nutrition and supplemental tube feeding. Am J Kidney Dis.
1999;33:205207.
17. Krause I, Shamir R, Davidovitis M, et al. Intradialytic
parenteral nutrition in malnourished children treated with
hemodialysis. J Ren Nutr. 2002;12:5559.
18. Orellana P, Juarez-Congelosi M, Goldstein SL. Intradialytic parenteral nutrition treatment and biochemical marker
assessment for malnutrition in adolescent maintenance hemodialysis patients. J Ren Nutr. 2005;15:312317.
19. Juarez-Congelosi M, Orellana P, Goldstein SL. Normalized
protein catabolic rate versus serum albumin as a nutrition
status marker in pediatric patients receiving hemodialysis. J
Ren Nutr. 2007;17:269274.
20. Salusky IB, Fine RN, Nelson P, Blumenkrantz MJ, Kopple JD.
Nutritional status of children undergoing continuous ambulatory peritoneal dialysis. Am J Clin Nutr. 1983;38:599611.
21. Kaiser BA, Polinsky MS, Stover J, Morgenstern BZ, Baluarte
HJ. Growth of children following the initiation of dialysis:
a comparison of three dialysis modalities. Pediatr Nephrol.
1994;8:733738.
22. Quan A, Baum M. Protein losses in children on continuous
cycler peritoneal dialysis. Pediatr Nephrol. 1996;10:728731.
23. Azocar MA, Cano FJ, Marin V, Delucchi MA, Rodrigues EE.
Body composition in children on peritoneal dialysis. Adv Perit
Dial. 2004;20:231236.
279
24. Mendley SR, Majkowski NL. Urea and nitrogen excretion in pediatric peritoneal dialysis patients. Kidney Int.
2000;58:25642570.
25. Rees L, Shaw V. Nutrition in children with CRF and on dialysis. Pediatr Nephrol. 2007;22:16891702.
26. Mahan JD, Warady BA. Assessment and treatment of short
stature in pediatric patients with chronic kidney disease: a
consensus statement. Pediatr Nephrol. 2006;21:917930.
27. Tom A, McCauley L, Bell L, et al. Growth during maintenance
hemodialysis: impact of enhanced nutrition and clearance. J
Pediatr. 1999;134:464471.
28. Parekh RS, Flynn JT, Smoyer WE et al. Improved growth
in young children with severe chronic renal insufficiency
who use specified nutritional therapy. J Am Soc Nephrol.
2001;12:24182426.
29. Tonshoff B, Kiepe D, Ciarmatori S. Growth hormone/
insulin-like growth factor system in children with chronic
renal failure. Pediatr Nephrol. 2005;20:279289.
30. Vimalachandra D, Hodson EM, Willis NS, Craig JC, Cowell C,
Knight JF. Growth hormone for children with chronic kidney
disease. Cochrane Database Syst Rev. 2006;3:CD003264.
pub003262.
31. Greenbaum, LA, Hidalgo G, Chand D, et al. Obstacles to
the prescribing of growth hormone in children with chronic
kidney disease. Pediatr Nephrol. 2008;23:15311535.
32. Tom A, McCauley L, Bell L, et al. Growth during maintenance
hemodialysis: impact of enhanced nutrition and clearance. J
Pediatr. 1999;134:464471.
33. Fischbach M, Terzic J, Menouer S, et al. Intensified and daily
hemodialysis in children might improve statural growth.
Pediatr Nephrol. 2006;21:17461752.
34. Baumgartner RN, Roche AF, Himes JH. Incremental growth
tables: supplementary to previously published charts. Am J
Clin Nutr. 1986;43:711722.
35. Foster BJ, Leonard MB. Measuring nutritional status in
children with chronic kidney disease. Am J Clin Nutr.
2004;80:801814.
36. Wong CS, Gipson DS, Gillen DL, et al. Anthropometric
measures and risk of death in children with end-stage renal
disease. Am J Kidney Dis. 2000;36:811819.
37. Wong CS, Hingorani S, Gillen DL, et al. Hypoalbuminemia
and risk of death in pediatric patients with end-stage renal
disease. Kidney Int. 2001;61:630637.
38. Kavey RW, Allada V, Daniels SR, et al. Cardiovascular Risk
Reduction in High-Risk Pediatric Patients: A Scientific Statement from the American Heart Association Expert Panel on
Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention,
Nutrition, Physical Activity and Metabolism, High Blood
Pressure Research, Cardiovascular Nursing, and the Kidney
in Heart Outcomes Research: Endorsed by the American
Academy of Pediatrics. Circulation. 2006;114:27102738.
39. American Academy of Pediatrics Endorsed Policy Statement.
Cardiovascular risk reduction in high-risk pediatric populations. J Pediatr. 2007;119:618621.
280
40. Vannucchi MTI, Vannucchi H, Humphreys M. Serum levels

of vitamin A and retinol binding protein in chronic renal
patients treated by continuous ambulatorial peritoneal dialysis. Int J Vitam Nutr Res. 1992;62:107112.
41. Kriley M, Warady BA. Vitamin status of pediatric patients
receiving long-term peritoneal dialysis. Am J Clin Nutr.
1991;53:14761479.
42. Blumberg A, Hanck A, Sander G. Vitamin nutrition in patients
on continuous ambulatory peritoneal dialysis (CAPD). Clin
Nephrol. 1983;20(5):244250.
43. Cundy T, Earnshaw M, Heyen G, Kanis JA. Vitamin A and
hyperparathyroid bone disease in uremia. Am J Clin Nutr.
1983;38:914920.
44. Portale AA, Booth BE, Tsai HC, Morris RC Jr. Reduced
plasma concentration of 1,25-dihydroxyvitamin D in
children with moderate renal insufficiency. Kidney Int.
1982;21:627632.
45. Portale AA, Booth BE, Halloran BP, Morris RC Jr. Effect
of dietary phosphorus on circulating concentrations of
1,25-dihydroxyvitamin D and immunoreactive parathyroid
hormone in children with moderate renal insufficiency. J Clin
Invest. 1984;73:15801589.
46. Ghazali A, Fardellone P, Pruna A. Is low plasma 25-(OH)
vitamin D a major risk factor for hyperparathyroidism
and Loosers zones independent of calcitriol? Kidney Int.
1999;55:21692177.
47. Wagner CL, Greer FR. Prevention of rickets and vitamin D
deficiency in infants, children, and adolescents. Pediatrics.
2008;122:11421152.
48. Nemeth I, Turi S, Haszon I, Bereczki C. Vitamin E alleviates
the oxidative stress of erythropoietin in uremic children on
hemodialysis. Pediatr Nephrol. 2000;14:1317.
49. Descombes E, Hanck AB, Fellay G. Water soluble vitamins in
chronic hemodialysis patients and need for supplementation.
Kidney Int. 1993;13191328.
50. Canepa A, Carrea A, Caridi G, et al. Homocysteine, folate,
vitamin B12 levels, and C677T MTHFR mutation in children
with renal failure. Pediatr Nephrol. 2003;18:225229.
51. Kang HG, Lee BS, Hahn H, et al. Reduction of plasma homocysteine by folic acid in children with chronic renal failure.
52. Sunder-Plassmann G, Winkelmayer, WC, Fodinger M.
Approaching the end of the homocysteine hype? Am J Kidney
Dis. 2008;51(4):549553.
53. Bamgbola OF, Kaskel F. Role of folate deficiency on erythropoietin resistance in pediatric and adolescent patients on
chronic dialysis. Pediatr Nephrol. 2005;20:16221629.
54. Stockberger RA, Parrott KA, Alexander SR, Miller LT,
Leklem JE, Jenkins RD. Vitamin B-6 status of children undergoing continuous ambulatory peritoneal dialysis. Nutr Res.
1987;7:10211030.
55. Rolton HA, McConnell KM, Modi KS, Macdougall
AI. The effect of vitamin C intake on plasma oxalate in
patients on regular haemodialysis. Nephrol Dial Transplant.
1991;6:440443.
56. Warady BA, Kriley M, Alon U, Hellerstein S. Vitamin status
of infants receiving long-term peritoneal dialysis. Pediatr
Nephrol. 1994;8:354356.
57. Mahajan, SK. Zinc in kidney disease. J Am Coll Nutr.

1989;8(4):296304.
58. Tamura T, Vaughn WH, Waldo FB, Kohaut EC. Zinc and
copper balance in children on continuous ambulatory peritoneal dialysis. Pediatr Nephrol. 1989;3:309313.
59. Warady BA, Nelms C, Jennings J, Johnson S. Copper deficiency: a common cause of erythropoietin (rHuEPO)
resistant anemia in children on hemodialysis? Hemodial Int.
2005;9(1):99.
60. Napolitano G, Bonomini M, Bomba G, et al. Thyroid function
and plasma selenium in chronic uremic patients on hemodialysis treatment. Biol Trace Elem Res. 1996;55:221230.
61. National Kidney Foundation. K/DOQI clinical practice
guidelines and clinical practice recommendations for anemia
in chronic kidney disease. Am J Kidney Dis. 2006;47(Suppl
3):S1S146.
62. US Department of Health and Human Services and US
Department of Agriculture. Dietary Guidelines for Americans
2005. 6th ed. Washington, D.C. U.S. Government Printing
Office. 2005. http://www.health.gov/DietaryGuidelines/.
63. Council of Renal Nutrition of the National Kidney Foundation. L McCann, ed. Pocket Guide to Nutrition Assessment of the
Patient with Chronic Kidney Disease, 3rd ed.. New York, NY:
National Kidney Foundation; 2002.
64. Combe C, Aparicio M. Phosphorus and protein restriction
and parathyroid function in chronic renal failure. Kidney Int.
1994;46:13811386.
65. Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium X phosphate product
with mortality risk in chronic hemodialysis patients: a national
study. Am J Kidney Dis. 1998;31(4):607617.
66. National Kidney Foundation Kidney Disease Outcomes
Quality Initiative. Clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease: Am
J Kidney Dis. 2003;42(4 suppl 3):S1S201.
67. Uribarri J, Calvo MS. Hidden sources of phosphorus in the
typical American diet: does it matter in nephrology? Semin
Dial. 2003;16(3):186188.
68. Sullivan CM, Leon JB, Sehgal AR. Phosphorus-containing
food additives and the accuracy of nutrient databases: implications for renal patients. J Ren Nutr. 2007;17(5):350354.
69. Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the
progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002;62:245252.
70. Sedlacek M, Dimaano F, Uribarri J. Relationship between phosphorus and creatinine clearance in peritoneal dialysis: clinical
implications. Am J Kidney Dis. 2000;36(5):10201024.
71. Koolenga L. Phosphorus balance with daily dialysis. Semin
Dial. 2007;20(4):342345.
72. Wallot M, Klaus-Eugen B, Winter A, Georger B, Lettgen B,
Bald M. Calcium acetate versus calcium carbonate as oral
phosphate binder in pediatric and adolescent hemodialysis
patients. Pediatr Nephrol. 1996;10:625630.
73. Coburn JW, Koppel MH, Brickman AS, Massry SG. Study of
intestinal absorption of calcium in patients with renal failure.
Kidney Int. 1973;3:264272.
RENAL DISEASE
74. Kurz, P, Monier-Faugere MC, Bognar B, et al. Evidence for

abnormal calcium homeostasis in patients with adynamic
bone disease. Kidney Int. 1994;46:855561.
75. Pedrozzi NE, Truttman, AC, Faraone R, et al. Circulating
ionized and total magnesium in end-stage kidney disease.
Nephron. 2002;92(3):616621.
76. Skarupskiene, I, Kuzminskis V, Bumblyte IA, et al. Changes of
trace elements in blood of patients with chronic renal failure.
Dial Transplantation. 2005;34(12):870880.
77. Parekh RS, Carroll CE, Wolfe RA, Port FK. Cardiovascular
mortality in children and young adults with end-stage renal
disease. J Pediatr. 2002;141:191197.
78. Mitnefes MM. Cardiovascular complications of pediatric
chronic kidney disease. Pediatr Nephrol. 2008;23:2739.
79. Milliner DS, Morgenstern BZ, Murphy M, Gonyea J, Sterioff
S. Lipid levels following renal transplantation in pediatric
recipients. Transplant Proc. 1994;26:112114.
80. Stenvinkel P, Heimburger O, Paultre F, et al. Strong association between malnutrition, inflammation, and atherosclerosis
in chronic renal failure. Kidney Int. 1999;55:18991911.
81. Sylvestre LC, Fonseca KP, Stinghen AE, Pereira AM, Meneses
RP, Pecoits-Filho R. The malnutrition and inflammation axis
in pediatric patients with chronic kidney disease. Pediatr
Nephrol. 2007;22:864873.
82. Wong CS, Gipson DS, Gillen DL, et al. Anthropometric
measures and risk of death in children with end-stage renal
disease. Am J Kidney Dis. 2000;36:811819.
83. McPartland KJ, Pomposelli JJ. Update on immunosuppressive
drugs useds in solid-organ transplantation and their nutrition
implications. Nutr Clin Pract. 2007;22:467473.
84. Fine RN, Webber SA, Olthoff KM, Kelly DA, Harmon WE,
eds. Pediatric Solid Organ Transplantation. 2nd ed. Oxford
UK: Blackwell Publishing; 2007.
85. Salvatierra O Jr, Singh T, Shifrin R, et al. Successful transplantation of adult-sized kidneys into infants requires maintenance
of high aortic blood flow. Transplantation. 1998;66:819823.
86. Salvatierra O Jr, Millan M, Concepcion, W. Pediatric renal
transplantation with considerations for successful outcomes.
Semin Pediatr Surg. 2006;15:208217.
87. Andreoli SP. Acute renal failute. Pediatrics. 2002;14:183188.
88. Star RA. Treatment of acute renal failure. Kidney Int.
1998;54:18171831.
89. Symons JM, Brophy PD, et al. Continuous renal replacement therapy in children up to 10kg. Am J Kidney Dis.
2003;41(5):984989.
90. Lopez-Herce J, Sanchez C. Transpyloric enteral nutrition in
the critically ill child with renal failure. Intensive Care Med.
2006;32:15991605.
91. Maxvold NJ, Smoyer WE, Custer JR, Bunchman TE. Amino
acid loss and nitrogen balance in critically ill children with
acute renal failure: A prospective comparison between classic
hemofiltration and hemofiltration with dialysis. Crit Care
Med. 2000;28(4):11611165.
92. Scheinkestel F, Adams F, et al. Impact of increasing parenteral
protein loads on amino acid levels and balance in critically
ill anuric patients on continuous renal replacement therapy.
Nutrition. 2003;19:733740.
281
93. Zappitelli M, Goldstein SL, Symons JM, Somers MJ, et al.

Protein and calorie prescription for children and young
adults receiving continuous renal replacement therapy: A
report from the Prospective Pediatric Continuous Renal
Replacement Therapy Registry Group. Pediatr Crit Care Med.
2008;36:32393245.
94. Nakamura AT, Btaiche IF, Pasko DA, Jain JC, Mueller BA. In
vitro clearance of trace elements via continuous renal replacement therapy. J Ren Nutr. 2004;14(4):214219.
95. Berger, MM, Shenkin, A, et al. Copper, selenium, zinc, and
thiamine balances during continuous venovenous hemodiafiltration in critically ill patients. Am J Clin Nutr. 2004;80:410.
96. Chiolero, R. Berger M. Nutritional support during renal
replacement therapy. Acute Kidney Inj. 2007;156:267274.
97. Moghal NE, Embleton ND. Management of acute renal failure
in the newborn. Semin Fetal Neonatal Med. 2006;11:207213.
98. Abitbol CL, Bauer CR, Montane B, Chandar J, Duara S,
Zilleruelo G. Long-term follow-up of extremely low birth
weight infants with neonatal renal failure. Pediatr Nephrol.
2003;18:887893.
99. Spinozzi NS, Nelson P. Nutrition support in the newborn
intensive care unit. J Ren Nutr. 1996;6(4):188197.
100. Groh-Wargo S, Thompson M, Hovasi Cox J, eds. ADA Pocket
Guide to Neonatal Nutrition. Chicago, IL: American Dietetic
Association; 2009.
101. Ledermann SE, Spitz L, Moloney J, Rees L, Trompeter RS.
Gastrostomy feeding in infants and children on peritoneal
dialysis. Pediatr Nephrol. 2002;17:246250.
102. Coleman JE, Watson AR, Rance CH, Moore E. Gastrostomy
buttons for nutritional support on chronic dialysis. Nephrol
Dial Transplant. 1998;13:20412046.
103. Ellis EN, Yiu V, Harley F, et al. The impact of supplemental
feeding in young children on dialysis: A report of the North
American Pediatric Renal Transplant Cooperative Study.
104. Coleman JE, Norman LJ, Watson AR. Provision of dietetic
care in children on chronic peritoneal dialysis. J Ren Nutr.
1999;9(3):145148.
105. Hawkins NM, Coffey S, Lawson MS, Delves HT. Potential
aluminum toxicity in infants fed special infant formula. J
Pediatr Gastroenterol Nutr. 1994;19:377381.
106. Warady BA, Kriley M, Belden B, Hellerstein S, Alon U. Nutritional and behavioural aspects of nasogastric tube feeding in
infants receiving chronic peritoneal dialysis. Adv Perit Dial.
1990;6:265268.
107. Rodriguez-Soriano J, Arant BS, Brodehl J, Norman ME. Fluid
and electrolyte imbalances in children with chronic renal
failure. Am J Kidney Dis. 1986;7(4):268274.
108. Ruley EJ, Bock GH, Kerzner B, Abbott AW, Majd M, Chatoor
I. Feeding disorders and gastroesophageal reflux in infants
with chronic renal failure. Pediatr Nephrol. 1989;3:424429.
109. Bunchman TE, Wood EG, Schenck MH, Weaver KA, Klein
BL, Lynch RE. Pretreatment of formula with sodium polystyrene sulfonate to reduce dietary potassium intake. Pediatr
Nephrol. 1991;5:2932.
110. Council on Renal Nutrition of New England. Intradialytic
parenteral nutrition. In: Renal Nutrition Handbook for Renal
Dietitians. Massachusetts National Kidney Foundation;
1993:8698.
282
111. Cherry N, Shalansky K. Efficacy of intradialytic parenteral

nutrition in malnourished hemodialysis patients. Am J Health
Syst Pharm. 2002;15:17361741.
112. Chertow GM, Ling J, Lew NL, Lazaras JM, Lowrie EG. The
association of intradialytic parenteral nutrition administration with survival in hemodialysis patients. Am J Kidney Dis.
1994;24:912920.
113. Kopple JD, Foulks CJ, Piraino B, Beto JA, Goldstein J.
Proposed Health Care Financing Administration Guidelines
for Reimbursement of Enteral and Parenteral Nutrition. Am J
Kidney Dis. 1995;26:995997.
114. National Kidney Foundation. Childhood Nephrotic Syn
drome. http://www.kidney.org/atoz/atozItem.cfm. Accessed
November 6, 2008.
115. Ramello A, Vitale C, Marangella M. Epidemiology of nephrolithiasis. J Nephrol. 2000;13(3):S45S50.
116. VanDervoort K, Wiesen J, Frank R, et al. Urolithiasis in
pediatric patients: a single center study of incidence, clinical
presentation and outcome. J Urol. 2007;177:23002305.
117. Lande MB, Varade W, Erkan E, Niederbracht Y, Schwartz GJ.
Role of urinary supersaturation in the evaluation of children
with urolithiasis. Pediatr Nephrol. 2005;20:491494.
118. Meschi T, Maggiore U, Fiaccadori E, et al. The effect of fruits

and vegetables on urinary stone risk factors. Kidney Int.
2004;66:24022410.
119. Pak CYC. Medical management of urinary stone disease.
Nephron Clin Pract. 2004;98:4953.
120. Bataille P, Pruna A, Gregoire I, et al. Critical role of oxalate
restriction in association with calcium restriction to decrease
the probability of being a stone former: insufficient effect in
idiopathic hypercalciuria. Nephron. 1985;39:321324.
121. Knoll T, Zollner A, Wendt-Nordahl G, Michel MS, Alken
P. Cystinuria in childhood and adolescence: recommendations for diagnosis, treatment and follow-up. Pediatr Nephrol.
2005;20:1924.
122. Caldas A, Broyer M, Dechaux M, Kleinknecht C. Primary
distal tubular acidosis in childhood: clinical study and longterm follow-up of 28 patients. J Pediatr. 1992;121:233241.
123. NDI Foundation. Diagnosis and Treatment of NDI.
http://w w w.ndif.org/pages/6-Diagnosis_Treatment.
Gastrointestinal Disease
25
Donald George, MD and Elizabeth Bobo, MS, RD, LDN, CNSD
CONTENTS
Learning Objectives
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
Mechanisms of Nutrition Deficiency
Gastroesophageal Reflux. . . . . . . . . . . . . . . . . . . . . . . . . .
Celiac Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Inflammatory Bowel Disease. . . . . . . . . . . . . . . . . . . . . . .
Diarrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pancreatic Insufficiency . . . . . . . . . . . . . . . . . . . . . . . . . .
Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Disorders of Chyle Loss. . . . . . . . . . . . . . . . . . . . . . . . . . .
Functional Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
286
287
289
291
292
293
294
295
Gastroparesis
Constipation
Cyclic Vomiting Syndrome
Irritable Bowel Syndrome
Eosinophilic Conditions of the Gut. . . . . . . . . . . . . . . . . . 296

Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
1. Enumerate the mechanisms leading to nutrition deficiency in gastrointestinal diseases.

2. List several common gastrointestinal diseases in children and review the pathophysiology as it applies to
nutrition.
3. Describe the role of nutrition support as primary treatment of inflammatory bowel disease, celiac disease,
and functional gastrointestinal disorders.
Introduction
The tasks of ingesting, processing, digesting, and absorbing

nutrients are coordinated through a complex network of
neural and hormonal factors that help direct the function
of specialized gastrointestinal (GI) cells. GI diseases may
cause malnutrition by affecting nutrient intake, nutrient
absorption, or nutrient requirements. When dealing with a
patient who has a GI disease, the clinician must determine if
the patient is malnourished, whether nutrition deficiencies
are likely to occur, and whether the patient would benefit
from nutrition therapy.
Mechanisms of Nutrition Deficiency

Mechanisms responsible for nutrition deficiency are
summarized in Table 25-1. They include the following:
Disordered Ingestion
Disordered ingestion may result from refusal to feed, an
inadequate diet, or from difficulty swallowing. Difficulty
swallowing can be related to oral, neurological, or esophageal diseases. Inability to chew or produce saliva also
interferes with the ability to swallow. In addition, a number
of behavioral problems (eg, food aversion, depression, and
283
284
eating disorders) influence the ability to ingest nutrients.

Gastric inflammation or vomiting of any cause will limit
the ability to eat.
Failure of Digestion
Failure of digestion occurs in diseases that affect the production of digestive enzymes from the stomach (pepsin),
pancreas (pancreatic insufficiency), or the surface of the GI
tract (lactase deficiency or sucrase-isomaltase deficiency).
Bile acids are important in the solubilization of fat, and
patients with cholestasis of any cause will have impaired
digestion.
Failure of Absorption
Failure of absorption occurs if there is an inadequate
surface area available either due to mucosal injury or to
surgical foreshortening of the GI tract. There may be failure
of systems involved in particular nutrient absorption (eg,
pernicious anemia, glucose-galactose malabsorption). Lack
of luminal factors such as biliary secretions will impair
absorption, especially of lipids. Deficiency of luminal bile
salts occurs in liver disease, gallbladder disease, or disease
of the biliary ducts.
In rare instances, absorption may not occur despite
an adequate surface area. Congenital anomalies such as
microvillus inclusion disease preclude normal absorption
while motility problems such as pseudoobstruction may
interfere with absorption by inhibiting movement of the
food bolus.
Increased Needs
A hypermetabolic state resulting in increased energy needs
can occur in diseases with fever, increased work of breathing,
or because of medications needed.
Nutrition deficiency usually involves multiple mechanisms. For example, a patient with Crohns disease may have
a poor appetite or be unable to eat because of pain or oral
ulcers. In addition, there may be small bowel involvement or
intestinal resection that affects absorption (eg, vitamin B12
in the terminal ileum). Some patients with Crohns disease
will have lactase deficiency. Further, the presence of fever
or underlying inflammation may increase needs for energy
and protein.
Table 25-1 Mechanisms of Nutrition Deficiency

Mechanism
Examples
Disordered Ingestion
Anorexia
Dental disease
Dysphagia of any cause
Esophagitis
Foreign body
Inadequate access to food
Pancreatic enzyme deficiency
Sucrase-isomaltase deficiency
Cholestasis with failure of bile salt secretion
Short bowel syndrome due to surgery
Celiac disease
Liver disease
Movement disorders
Fever
Failure of Digestion
Failure of Absorption
Increased Needs
Nutrition assessment is an essential component of the
evaluation of all children. Monitoring of growth should be
part of the routine well-child examination. Assessment of
both linear and ponderal growth of the child or adolescent
is central to evaluation of nutrition status. Alterations in
patterns of linear growth and weight gain (both inadequate
as well as excessive weight gain) may be the earliest manifestation of disease. Malnutrition is commonly diagnosed
in hospitalized patients and is also a common comorbidity
in patients with GI disease.13 Malnutrition during illness
may complicate the response to therapies or impair recovery
(Table 25-2). Thus, nutrition assessment is an integral part
of both the initial and ongoing evaluation of all children
with acute and/or chronic disease and is of crucial importance in the evaluation of the child with GI disease.
The initial nutrition evaluation includes both subjective and objective assessment of the patients current
nutrition status and projected nutrition requirements. The
subjective assessment includes the presence and duration
of GI symptoms, fever, frequent infections, fatigue, food
aversion, allergies to particular foods, or feeding intolerance. Specific attention is paid to previous growth, detailed
diet history, changes in body weight and dietary intake, GI
symptoms (eg, abdominal pain, diarrhea, and vomiting),
and anorexia. The objective assessment should include
data from clinical, anthropometric, and laboratory evaluations (Table 25-3). Clinical data include the diagnosis,
current medical or surgical problems, allergies, and medications that may affect nutrition support options. Objective
measures of nutrition status include growth indices (both
previous and current), current weight, and Tanner stage.
GASTROINTESTINAL DISEASE
The determination of body mass index (BMI) for children

> 3 years of age provides important information regarding
the nutrition status. In children < 2 years of age, weight-forlength is used. In children between the ages of 2 and 3, BMI
is used when a standing height is obtained while weight-forlength is used when a recumbent length is obtained. Specific
normative data are available.
Table 25-2 GI Nutrient Deficiencies4,44,57
Nutrient
Signs/Symptoms of
Deficiency
Iron
Fatigue
Microcytic anemia
Folate
Megaloblastic anemia
Glossitis
Diarrhea
Forgetfulness
Megaloblastic anemia
Ataxia
Diarrhea
Mental status changes
Paresthesias
Glossitis
Osteopenia
Osteoporosis
Tetany
Bone pain
Muscle weakness
Tetany
Osteomalacia
Rickets
Night blindness
Decreased appetite
Decreased immune function
Hyperkeratosis
Bleeding
Bruising
Hemolytic anemia
Truncal ataxia
Hypo or areflexia
Vitamin B12
Calcium
Vitamin D
Vitamin A
Vitamin K
Vitamin E
Zinc
Magnesium
Diarrhea
Dry skin
Skin sloughing on palms
Mental status changes
Hair loss
Growth stunting
Anorexia
Muscle cramps
Bone pain
Nausea
Seizures
Laboratory Markers
hgb
hct
MCV
RDW
% TIBC
ferritin
serum iron
serum folate
red blood cell folate
MCV
MCV
hgb
serum vitamin B12
serum total calcium

serum ionized calcium
serum alk phos
25-hydroxyvitamin D
plasma vitamin A
PTT
serum creatinine
creatinuria
serum vitamin E:total
serum lipid ratio
serum alk phos
serum zinc*
urinary zinc**
serum magnesium
* Zinc binds to serum proteins, which can make levels appear low if
protein levels are depleted.
** Associated with disease status.
285
Table 25-3 Nutrition Assessment

History
Gastrointestinal Symptoms
(diarrhea, vomiting)
Feeding tolerance
Allergies/Aversion
Developmental feeding skills
Recent changes in growth or intake
Clinical Data
Diagnosis
Medications
Anthropometry (height, weight, Tanner stage)
Laboratory
Blood: Electrolytes, CRP, albumin, prealbumin, CBC,
vitamin levels, minerals (eg, iron and zinc)
Stool: pH and reducing substances (carbohydrate
malabsorption)
Quantitative fat
Body composition: DEXA, bioelectric impedance
Careful examination of the child is the initial step

in evaluation.4 Obesity and wasting are obvious. Edema,
dehydration, excess fat, or decreased muscle mass can be
appreciable. Anthropometric measurements, including
midarm circumference and skinfold thickness determinations, are useful. It is standard practice to measure these
parameters in patients at risk for chronic malnutrition such
as those with pancreatic insufficiency, inflammatory bowel
disease, celiac disease, or short bowel syndrome in which
maldigestion or malabsorption may be prominent. It is rare
to find many stigmata of severe malnutrition in children.
Most often wasting, sometimes accompanied by edema, is
seen. The clinician, however, should have special concern
for micronutrient deficiencies, especially in children with
inflammatory disorders or disorders of absorption.
Specific attention is paid to examination of the
abdomen. Abdominal tenderness, abdominal distention,
and the presence of bowel sounds not only provide helpful
clues to the nature of the disease process but also influence treatment decisions. There may be other findings
that suggest nutrient deficiency. Angular stomatitis and
dermatitis may suggest riboflavin deficiency. Dry cracked
skin in areas exposed to sunlight suggests niacin deficiency.
Dystrophic nails, spooning of the nails, or pallor of the
conjunctiva or skin may suggest iron deficiency. Peripheral
neuropathy can be seen with a number of vitamin deficiencies including thiamin, B6, B12 , and niacin. Zinc deficiency
is often manifested by alopecia and perioral or perianal
rash. Bowing of the legs, tetany, or rickets suggest vitamin
D deficiency. Petechiae, bruising of the skin, or bleeding
gums may indicate vitamin K deficiency as may be seen in
liver disease.
286
Gastroesophageal Reflux
Gastroesophageal reflux (GER) is the passage of gastric

contents into the esophagus with or without regurgitation.
It can occur several times a day in healthy infants, children,
and adults. 57 Regurgitation occurs daily in 40% of healthy
infants and usually resolves spontaneously by 12 to 24
months of age.810 However, regurgitation occurs at least
weekly in 12% to 15% of children ages 3 to 17 years 6 (Table
25-4). Gastroesophageal reflux disease (GERD) refers to
reflux-associated tissue damage (eg, esophagitis) or symptoms severe enough to impair quality of life.11
Table 25-4 Incidence of Regurgitation
Infancy (Daily GERD)
3 mo
6 mo
12 mo
Children (Weekly)
39 y
1017 y
40%
30%
15%
12%
15%
The genesis of reflux-related injury and reflux symptoms

is not the same. Each relates to a combination of factors that
lead to an excessive number of reflux events, impaired clearance of material from the esophagus, increased acidity, or
decreased buffering of the refluxed material or impaired
protection of the esophageal or supraesophageal mucosa.12
The most important mechanism causing GER is transient
lower esophageal sphincter (LES) relaxations.13 Delayed
gastric emptying, increased intra-abdominal pressure, and
chronically reduced LES resting pressure have also been
implicated.14 Studies of gastric emptying have shown it is
related to both the composition and caloric density of the
feedings. Higher fat diets or diets of higher caloric density
will slow the emptying and thereby promote reflux.
GER and GERD have a variety of presentations that
vary with age. Regurgitation associated with poor growth,
irritability, or airway compromise are common reasons for
evaluation in infancy. Heartburn and epigastric abdominal
pain are more common complaints in older children and
adolescents. Abnormal posturing (Sandifers syndrome)
and acute life-threatening events (ALTEs) are typical
manifestations in the infant with GERD but are rarely seen
in older children or adults (Table 25-5).
Regurgitation in infancy most often is nothing serious.
Most instances of infantile GER resolve spontaneously.
However, a minority of infants may have severe or prolonged
problems that lead to caloric insufficiency and malnutrition.
Some severe cases result in failure to thrive (FTT). FTT may
be due to persistent vomiting, difficulty feeding (coughing
or gagging), and feeding aversion with subsequent lack of
intake.15 In these cases specialized nutrition support may

be needed. This may be accomplished orally with the use of
specialized formulas or supplements. In some patients with
complicated GER or GERD, alternate enteral access may be
needed. Factors that influence this decision include aspiration risk, degree of malnutrition, the age of the child, and
associated anatomical or neurological problems.
Table 25-5 Common Presentation of GERD
Age
Examples
Infant
Regurgitation
Vomiting
Feeding difficulties (acute)
Unexplained crying
Failure to thrive
Posturing
Vomiting
Cough
Abdominal pain
Sore throat
Respiratory difficulties
Hoarseness
Regurgitation
Chest pain
Heartburn
Epigastric pain
Dysphagia
Child
Adolescent
Disordered ingestion or nutrient losses due to vomiting

or regurgitation dominate the clinical picture. In children
who have poor weight gain, or weight loss, attention is paid
to modalities to increase calories. Insufficient oral intake
can be related to pain associated with eating, food aversion
due to vomiting, or dysphagia associated with esophagitis.
Treatments to reduce emesis in infants with regurgitation include smaller feedings, thickening the formula with
cereal or a pre-thickened formula, and positioning. Smaller,
more frequent feeds are often suggested but are sometimes
impractical and poorly tolerated by babies and parents.
Thickening of feedings has been shown to reduce symptomatic GER. Agents commonly used to thicken formula
include rice cereal, guar gum, carob bean gum, locust bean
gum, pectin, pre-gelatinized waxy rice starch, and soy polysaccharides.15,16 Thickened formulas lessen the frequency
of emesis, but may contribute to some undesirable side
effects. Despite a significantly reduced number of episodes
of obvious reflux and emesis, pH probe studies do not indicate a reduction in exposure to acid in the esophagus.17,18
Further, studies found increased postprandial coughing
in infants fed thickened formula, suggesting continued

reflux despite improvement in emesis.19 Thickening infant
formulas is relatively free of major side effects; however,
complications such as increased cough and increased acid
exposure are documented.20,21
Also of concern is the effect of thickened formulas on
the macronutrient content of formula as well as micronutrient absorption. Thickening of formulas with rice cereal
alters the macronutrient composition of the formula by
providing additional calories and protein. Importantly,
indigestible carbohydrate thickening agents, such as locust
bean gum, have been linked with decreased bioavailability
of calcium, zinc, and iron. Conversely, digestible carbohydrate thickening agents, such as pre-gelatinized waxy
rice starch, have not been linked with decreased nutrient
absorption. 22 Due to lack of definite data regarding the
efficacy of thickened formulas it is recommended that they
only be used under medical supervision.16,20,23
In older children with GER, the nutrition therapy is
dependent on individual tolerance to various foods. There
is sparse evidence to support avoidance of caffeine, coffee
in particular, peppermint, chocolate, and spicy foods.2326
Obesity and exposure to alcohol and tobacco smoke may
worsen GER.23 Spearmint does not have an effect on esophageal reflux nor does the fat content of a meal except in
the absence of delayed gastric emptying.2628 Data suggest
that GER may be reduced in malnourished, neurologically hindered children when they have been nutritionally
repleted.29
Medications commonly used in the treatment of GER
include proton pump inhibitors (PPIs) and H2 histamine
receptor antagonists. These medications are associated with
various nutrition-related side effects (Table 25-6). Also
worthy of mention is the decreased absorption of supplemental iron associated with PPI usage. 30 There are concerns
as well about possible infection risk from long-term use of
PPIs. 31,32
Table 25-6 Potential Effects of Medications Used for GERD30
Side effect
Diarrhea
Constipation
Abdominal pain
Nausea/vomiting
Anorexia
Anemia
Weight gain/loss
Hepatotoxicity
Proton pump
inhibitor
H2 Histamine
receptor antagonist
X
X
X
X
X
X
X
X
X
X
X
287
Prokinetic medications are often suggested to improve

gastric emptying. Metoclopramide is often prescribed
although evidence supporting its effectiveness is scant. It
reduces symptoms, however it is associated with many side
effects that limit its use. 33 Erythromycin has prokinetic
activity and improves gastric emptying although it has not
been shown to improve GER symptoms. These medications
are most commonly used in patients with weight loss or
failure to gain related to GER.
Clinical outcome in GER can be measured in a variety
of ways. Symptom reduction can be monitored by recall
or the use of diaries with symptom severity and frequency
estimates. For GER causing poor weight gain, improvement
in weight gain over time is the accepted measure. Lower
esophageal pH recording is accepted as a valid measure of
GER, however serial recordings are rarely used in clinical
practice.
Celiac Disease
Celiac disease is a T-cell mediated autoimmune, chronic

inflammatory disorder. It is characterized by damage to the
small intestinal mucosa in genetically susceptible individuals and is due to abnormal reactions to the gliadin fraction
of wheat gluten and similar peptides present in barley and
rye. There is a specific peptide fragment of gliadin, made up
of 33 amino acids, that is resistant to degradation by pancreatic, gastric, or small intestinal conditions or enzymes, that
passes through the epithelial barrier and interacts with
immune cells of the intestine. Immune responses affecting
both the adaptive and innate immunity promote an inflammatory reaction in the lamina propria of the intestinal wall
leading to villus atrophy. The genetic factors are linked to
the human leukocyte antigen (HLA) system, which regulates the immune response.
The availability of serologic testing for celiac disease
has changed our understanding of both the prevalence and
presentation of the disease. Previously celiac disease was
diagnosed mainly in patients who had typical symptoms
(Table 25-7). Screening studies now suggest that celiac
disease occurs in roughly 1% of the population. There is
little difference in the rates in Europe compared to North
America, North Africa, or the Middle East. 34
The typical presentation of celiac disease usually occurs
in the first few years of life and manifests as diarrhea with
growth failure and anemia. It is now recognized that celiac
disease can present at any age following inclusion of gluten
in the diet and has a variety of manifestations, many of
which are extraintestinal in nature. Indeed, with the development and implementation of screening of patients at
288
risk (Table 25-8) it is clear that some patients with celiac

disease are asymptomatic despite significant intestinal
mucosal injury. Further, patients may have symptoms that
do not immediately call to mind intestinal disease. Older
children and adolescents may present with constitutional
symptoms such as fatigue or lassitude. GI symptoms may
be mild or even absent. Patients with celiac disease often
have derangements of bone and mineral metabolism and
idiopathic osteopenia may be the sole clinical feature. 35,36
Table 25-7 Presentation of Celiac Disease
Typical (Usually Young)
Weight loss
Failure to grow
Vomiting
Diarrhea
Bloating
Anorexia
Abdominal pain
Atypical (Adolescent
Constipation
Young Adult)
Short stature
Dermatitis Herpetiformis
Osteopenia
Elevated liver enzymes
Arthritis
Iron deficiency
Anemia
Dental enamel defects
Silent (Any age)
No obvious signs or symptoms; patient
identified when tested because of
risk factors and on biopsy has typical
enteropathy
Latent (Any age)
Mild or non-specific symptoms identified
by screening; positive serology but normal
biopsy. May develop typical disease at a
later time.
Table 25-8 Groups at Risk for Celiac Disease

Relative of Patient with Celiac Disease
Diabetes Mellitus (Type 1)
Down Syndrome
Thyroiditis
Turner Syndrome
William Syndrome
Other Autoimmune Diseases
The mainstay of diagnosis of celiac disease remains the

small intestinal biopsy with demonstration of the typical
features of enteropathy. Serologic tests are a valuable adjunct
in the diagnosis and are often the initial diagnostic tool in
patients with unexplained GI symptoms, anemia, or poor

growth. Further, they are used to screen high-risk groups,
and to aid in monitoring compliance with diet. Serologic
tests available include the tissue transglutaminase (tTG)
IgG and IgA and anti-endomysial (AEM) antibodies. Antireticulin antibodies are rarely used as the more sensitive and
specific tests are commonly available. Recently serology
using antibodies to deamidated gliadin have become available. These appear to have sensitivity and specificity similar
to those of the tTG antibodies.
The effects of celiac disease on nutrition status are
profound. A patient may have linear and/or ponderal growth
failure. Diarrhea and weight loss may also be present. In
addition vitamin and mineral deficiencies may be present
at the time of diagnosis. A thorough physical assessment
of the patient and assessment of laboratory values when
indicated are necessary to identify such deficiencies. Attention is paid to growth, bony abnormalities, and pigmentary
changes. Laboratory investigation, including serology, is
often revealing. In particular microcytic or macrocytic
anemia may be present due to impaired absorption of iron
or folic acid in the proximal intestine37,38or B12 in the distal
small bowel. Other nutrients of concern include, but are not
limited to, fat-soluble vitamins (A, D, E, and K), zinc, and
calcium. Special attention is paid to vitamin D. Calcium
supplementation may also be needed. Inadequate calcium
may be due to malabsorption or poor dietary intake. Lactose
intolerance is common in untreated patients due to damage
to the villi. Most often this improves with treatment;
however, adult-type lactase deficiency, not associated with
intestinal injury, may complicate the clinical picture.
The primary nutrition management of celiac disease
includes complete avoidance of all gluten and correction
of any vitamin/mineral deficiencies. The fundamental
basis of the gluten-free (GF) diet includes avoidance of
wheat, barley, and rye. Oats that are specifically labeled
gluten free may be consumed in the diet; however, general
commercial oats may not be consumed secondary to crosscontamination with wheat in processing. 39 Refer to Table
25-9 for a list of gluten-containing and gluten-free grains.
The diet is more cumbersome than simply avoiding the
grains listed as containing gluten as there may be secondary
hidden sources of gluten in processed foods in the form of
additives. Detailed patient instruction on label reading and
avoiding cross-contamination is crucial for proper adherence to the GF diet. When replenishing vitamin/mineral
stores with dietary supplements it is important to read the
label for the presence of gluten as many dietary supplements
are notGF.
Table 25-9 Grains and Gluten

Gluten Containing
Gluten Free
Barley
Bulgur
Couscous
Dinkle (spelt)
Durum
Einkorn
Emmer
Farina
Fu
Graham flour
Kamut
Seitan
Semolina
Rye
Wheat
Triticale
Amaranth
Arrowroot
Buckwheat
Corn
Flaxseed
Rice
Millet
Milo
Potato flour
Quinoa
Sorghum
Soy
Tapioca
Tef
Taro flour
Urd
Note: This is not an all-inclusive list.
Removal of gluten from the diet usually results in clinical and histological recovery. Specialized oral feedings or
enteral feedings are rarely necessary in a patient with celiac
disease. Parenteral feedings are not used unless there is
some other indication for that therapy.
When the diagnosis of celiac disease is confirmed,
routine nutrition follow-up of the child is necessary to
monitor growth parameters, promote adherence to the
diet, and to assure proper nutrition, particularly because
many of the gluten-free products are not fortified. Ongoing
monitoring of vitamins (especially A, D, B12 , and folate), as
well as assessment of anemia and markers of bone health, is
suggested.40 Fortunately, with proper nutrition and adherence to the GF diet, bone density in children returns to
normal 1 year post-initiation of the diet.41
Clinical outcome is measured by resumption of normal
growth and weight gain and by monitoring of serologic
markers, especially tTG and IgA. Failure of tTG IgG and
IgA levels to return to normal values after adherence to a
gluten-free diet for 6 to 12 months warrants further inspection of the childs diet for inadvertent gluten consumption.
Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) refers to chronic inflammation anywhere along the GI tract. The term includes
Crohns disease, ulcerative colitis, and indeterminate colitis
(ie, IBD with features that do not allow clear distinction
between Crohns disease and ulcerative colitis). These are
chronic conditions that affect children of any age although
they most commonly manifest in the second decade of life.
289
The most important risk factor for developing IBD is a positive family history.
The incidence of Crohns disease seems to be increasing
in childhood while the rates of ulcerative colitis are steady.
IBD may present at any age. Ulcerative colitis is more
common in younger children. Peak age of incidence of
Crohns disease is in the second decade of life.
Inflammation of the bowel leads to a number of
derangements that culminate in diarrhea, GI bleeding, and
abdominal pain. Other symptoms depend on the location
of inflammation within the GI tract. For example, vomiting
is more prominent in patients with gastric or small bowel
disease. The most common presentation is a patient with
abdominal pain and diarrhea. Stools may be bloody. Weight
loss is common, especially in patients with Crohns disease.
However, non-specific manifestations of the disease may
be the initial manifestations and failure to recognize their
importance may lead to delay in the diagnosis. Joint pain and
swelling, skin rashes, muscle pain, elevated liver enzymes,
or eye changes (uveitis, iritis, or episcleritis) may be present
prior to any specific GI manifestation. Oral ulcerations can
range from painless to severe pain with bleeding. It is well
recognized that deterioration of linear and ponderal growth
may precede the development of more specific symptoms
by months or in some cases even years.
The effect of IBD on nutrition status is multifaceted.
Growth, bone health, and macronutrient and micronutrient
stores are commonly affected and malnutrition is common.42
Weight loss is a common presenting symptom in all forms
of IBD. Linear growth failure can occur as well but is more
frequently associated with Crohns disease.
Nutrition assessment of children with IBD includes
measurements of weight, height, and calculation of body
mass index (BMI). These values should be plotted and
followed serially on appropriate Centers for Disease Control
and Prevention (CDC) growth charts.43 The importance
of tracking these measurements is emphasized by the fact
that upon diagnosis the majority of children with ulcerative colitis and especially Crohns disease will have growth
failure.44 In fact, reduced linear growth velocity may precede
GI manifestations of IBD by months or even years.4547
Criteria for defining growth failure include a height velocity
< 3rd percentile, a height < 3rd percentile, or a bone age less
than chronological age by 2 or more standard deviations.48
Males may be more susceptible to growth failure, but all
children with IBD are at risk.43,49 Factors affecting risk
include malnutrition, treatment modality, and intestinal
inflammation.
Malnutrition in IBD patients is multifactorial and
290
includes energy losses, increased requirements, malabsorption, and decreased energy intake due to diarrhea,
abdominal pain, and other disease-related side effects. 50
Further contributing to malnutrition is poor appetite
related cytokine activity in the inflammatory process. 51,52
Inflammatory cytokines have also been shown to reduce
insulin-like growth factor 1 (IGF-1). 5355 Children with
active Crohns disease often have lower levels of serum
IGF-1 levels than controls. In addition, chronic usage of
corticosteroids as treatment can suppress IGF-1 and also
decrease osteoblast activity.43,56 Limited data suggest that
nutrition therapy in comparison to corticosteroid usage
may be beneficial in the treatment of Crohns disease and
spare linear growth.48 More research is needed to substantiate these findings.48
Assessment of nutrition status includes sufficiency of
vitamin and mineral stores. Analyses of dietary records
and/or 24-hour food recall as well as laboratory values are
helpful in assessing micronutrient status. Commonly deficient nutrients include iron, folate, vitamin B12 , vitamin
D, calcium, zinc, and magnesium.43,57 Refer to Table 25-2
for information regarding deficiency signs/symptoms and
laboratory markers. Reduced iron stores are associated with
decreased intake, reduced absorption, and increased losses
(ie, blood loss). Often, iron supplementation is required
along with a diet rich in iron and vitamin C to correct
the deficiency. 57 Laboratory values to monitor iron status
include hemoglobin, reticulocyte count, mean corpuscular
volume red blood cell (RBC) distribution width, ferritin,
transferrin saturation, and iron. 50
Folate stores may be affected by insufficient intake,
because many good sources of folate (eg, leafy green
vegetables) are often not tolerated by the child with active
inflammation. In addition, medications used in disease
treatment such as methotrexate and sulphasalazine have
direct and deleterious effects on folate metabolism. Children on these medications need folate supplementation.43,57
Vitamin B12 deficiency may occur in children with
involvement of the stomach and terminal ileum and in
cases of bacterial overgrowth.44,57 Notably, deficiency may
be masked by supplementation of folate. Deficiency is
corrected by intramuscular injection, oral supplementation,
or nasalgel. 57
Maintenance of adequate calcium and vitamin D stores
is imperative in children with IBD, particularly in those
receiving steroid therapy due to the relationship of steroid
usage and decreased bone mineral density. Lactose intolerance often limits consumption of milk and dairy products,
rich in these nutrients. 57 Supplementation may be required
to obtain values within normal limits. Research suggests

that supplementation of vitamin D above the standard
recommendation may be necessary to achieve an appropriate 25-hydroxyvitamin D level. 58 Children with Crohns
disease of the upper intestine and children with darker
complexions may have an increased need for vitamin D
supplementation. 58,59 The winter season may also dictate
increased need. 58
Zinc and magnesium deficiencies are associated with
increased stool output and may require supplementation.
Treatment is usually given empirically as interpretation
of serum zinc levels is sometimes difficult. Oral magnesium supplementation is important, but can worsen
diarrhea if administered at increased doses over a short
timeframe.43,57
Energy and protein needs of the child with IBD are
based on collected anthropometric data as well as disease
status. In the adequately nourished child with IBD, resting
energy expenditure (REE) is no different than in healthy
children.43 However, in children with insufficient energy
stores and increased inflammation, energy needs may be
elevated 5% to 35% above estimated needs.43 There are
no guidelines for protein supplementation at this time.43
However, it may be prudent to increase protein delivery in
a child with inflammation, infection, or postoperatively. 57
Enteral nutrition (EN) is the recommended route of nutrition support in IBD when needs cannot be met through oral
intake alone. Parenteral nutrition (PN) may be indicated if
the enteral route is not feasible or insufficient to solely meet
nutrient needs.43 Furthermore, PN may be indicated preand/or postoperatively. Refer to the chapter on pediatric
surgery (Chapter 32) for more information regarding PN
and surgery.
There is evidence that nutrition therapy may be as effective in inducing disease remission as corticosteroid usage in
children with active Crohns disease. 6063 This method of
treatment may be particularly beneficial in children with
ileal or ileocolonic IBD. With EN as primary therapy the
child follows a supplement-only diet, either orally or with
tube feedings, for approximately 8 weeks. 53,62 There is no
significant difference in outcomes of patients receiving
a polymeric or elemental diet.64,65 After 8 weeks solids
are gradually reintroduced as the nutrition supplement
is concurrently reduced. 53,62 There may also be a role for
nutrition therapy in maintaining disease remission. 6668
However, in North America the primary mode of treatment for pediatric IBD patients is corticosteroids, in part
secondary to compliance issues with nutrition-based treatment regimens.43,69 Conversely, nutrition therapy is more
commonly employed in Western European countries.69

Decreased bone mineral density, as determined by
dual energy x-ray absorptiometry (DEXA) scan, is an
unfortunate side effect of IBD. Osteopenia may result from
malnutrition, inadequate calcium intake or malabsorption,
vitamin D deficiency, physical inactivity, or corticosteroid
use or may be related to cytokines released as part of the
inflammatory disease. Children receiving 7.5 mg/d of
steroids, a lifetime dose of 5 g, or 12 months of exposure
are particularly at increased risk and should be monitored
closely. 50
Diarrhea
Worldwide, diarrheal disease is a major cause of morbidity

and mortality in children. Despite improvements in sanitation, aggressive use of oral rehydration therapy and early
refeeding, diarrhea remains a significant cause of undernutrition and malnutrition in both developed and developing
countries.
Diarrhea is defined as the excessive loss of fluid and
electrolyte in the stool. This may also be associated with
nutrient loss. Acute diarrhea (ie, diarrhea of sudden onset) is
most often related to infection or specific food intolerance.
Chronic diarrhea (diarrhea that lasts more than 2 weeks
without obvious cause) has a number of possible etiologies.
It is beyond the scope of this chapter to discuss in detail the
many different causes of diarrhea. Emphasis here is on the
general principles guiding nutrition therapy in patents with
the symptoms.
The basis for diarrhea is impaired transport of intestinal
content including nutrients, electrolytes, and other solutes.
Water movement across the intestinal mucosa depends on
the active and passive fluxes of solute. Diarrhea encompasses 4 mechanisms that often overlap. Each mechanism
may present a unique nutrition challenge (Table 25-10). In
addition, patients with diarrhea often do not ingest adequate
amounts of nutrients.
Table 25-10 Pathophysiology of Diarrhea
Osmotic
Increased osmotic load due to failure to absorb
Secretory
Net intestinal secretion of fluid and electrolytes
Motility
Rapid transit with failure to dry
Inflammatory
Combination of the above with added exudative
loss of protein
Medication
Opioids
Calcium Channel Blockers
Anti-cholinergic
Osmotic diarrhea happens when a non-absorbed material, often carbohydrate, creates an osmotic load in the distal
291
bowel and produces increased fluid losses. This can be due to

either congenital or acquired disease. A common example is
diarrhea associated with lactose intolerance. Excessive sugar
intake by children, either juices or sodas, may contribute to
osmotic diarrhea. Ingestion of non-absorbable materials
such as sorbitol or xylitol, used in some candies, will cause
diarrhea as well. This type of diarrhea will stop with fasting
or the removal of the offending solute.
Secretory diarrhea occurs when the intestinal surface
cells secrete fluid into the lumen of the bowel. This may be
due to congenital disorders, such as congenital chloridorrhea, or acquired. Toxins may induce fluid and electrolyte
secretion. This is seen with cholera and some other infections. Also some tumors may produce hormones that induce
secretion. Secretory diarrhea does not stop with fasting.
Children with motility-type diarrhea often have normal
absorption and digestion; however, they have rapid transit
with resultant looseness and fluidity of stools. This mechanism predominates in toddlers diarrhea or irritable bowel
syndrome.
Intestinal inflammation is associated with diarrhea.
It often involves elements of the other 3 mechanisms. In
addition there may be increased loss of blood and protein.
Infectious enteritis, celiac disease, IBD, eosinophilic disease
of the GI tract, and certain medications can cause intestinal
inflammation.
Diarrhea can affect nutrition status in numerous
ways. Reduced and/or altered dietary intake, fecal loses
of macronutrients and micronutrients, fluid losses, and
malabsorption of ingested nutrients are all factors that can
compromise the child with diarrhea. Prolonged diarrhea
coupled with insufficient dietary intake may result in growth
failure.70,71 Interestingly, malnutrition is an independent
risk factor for development of diarrhea.70 Thus, correction
of diarrhea-associated malnutrition is not only crucial for
assuring proper growth of the child but also for prevention
of future diarrheal episodes.
Impaired absorption and/or increased losses of carbohydrates, particularly lactose, protein, fat, and fluids, are
associated with acute and chronic diarrhea episodes.70,7274
In cases of acute diarrhea the degree of malabsorption and/
or loss is dependent upon the type and severity of infection.73 A common occurrence during infectious diarrhea
is the development of dehydration. Subsequently, acidosis
secondary to high output of bicarbonate may occur. To
correct severe dehydration (> 10% loss in body weight)
100 mL/kg of sodium-containing fluid should be administered intravenously. The amount of sodium depends on
the type of dehydration. Within the first hour, half of the
292
dosage may be administered while the remaining fluids

may be given over a 3- to 6-hour period. Plasma expanders
may also be indicated. Following correction of dehydration,
maintenance fluids may be given. If dehydration is mild, oral
fluids may be given using an oral rehydrate solution (ORS)
containing sodium, chloride, bicarbonate, and potassium at
a dosage of 50 to 120 mL/kg over 4 to 6 hours, then followed
by maintenance fluids. Fluids with a high osmotic load, such
as sodas, should not be given as they may worsen the diarrhea.70 In the absence of vomiting, feeding of a regular diet
(ie, breast milk, infant formula, and/or solids) should begin
after rehydration commences to reduce or prevent malnutrition and subsequent growth stunting.70,71,74 Caloric intake
enhances recovery.74
The approach to management of chronic diarrhea is
dependent on the etiology of the condition. For example,
in cases of sucrase-isomaltase deficiency the management
strategy is avoidance of dietary sucrose due to the absence
of the sucrase-isomaltase enzyme on the intestinal surface.
This condition usually presents when juices, formula, or
solids containing sucrose are introduced to the infants
diet.75 Absence of the sucrase-isomaltase enzyme prevents
breakdown and absorption of the sucrose disaccharide,
which in turn results in osmotic diarrhea.76 Other symptoms include, but are not limited to, failure to thrive, colic,
abdominal distention, and gassiness.75,77 Similarly, individuals with chronic lactose intolerance also may present
with abdominal distention, gassiness, and diarrhea. Lactose
intolerance is a result of absence of the lactase enzyme to
break down the dairy carbohydrate lactose. Management
of this condition involves avoidance of lactose-containing
foods/beverages or supplementing with lactase pills prior to
ingestion of lactose-containing foods. Fructose is found in
the diet as the free sugar, as a component of the disaccharide
sucrose, and in a polymeric form (fructans). Free fructose
has limited absorption in the small intestine. Fructans are
neither digested nor absorbed. Fructose malabsorption
contributes to osmotic load. In addition, it provides substrate
for bacterial fermentation and may affect GI motility, all
leading to diarrhea. This malabsorption may contribute to
abdominal pain. Treatment is dietary restriction of fructose
and fructan intake.
In both acute and chronic diarrhea various micronutrients may be compromised either due to failure of absorption
or increased losses in the stool. Losses commonly associated with diarrhea include zinc, copper, folate, magnesium,
vitamin A, vitamin B12 , and trace elements, particularly
selenium.70,72,78,79 The clinician should be mindful of signs
of deficiency of these nutrients and conduct laboratory
screening as appropriate. Supplementation of probiotics,

particularly of Lactobacillus GG and Saccharomyces boulardii,
may be beneficial in the management of diarrhea.80,81
However, there are currently no standard guidelines for
using probiotics in the management of pediatric diarrhea.
Pancreatic Insufficiency
The pancreas is a small but metabolically active organ that

has both manufacturing (exocrine) and control (endocrine)
functions. Islet cells within the pancreas make insulin and
glucagon, central to glucose homeostasis. The exocrine
pancreas consists of cells organized into acini and the
duct system providing a pathway to the small intestine.
The pancreatic juice secreted by these cells contains bicarbonate as well as digestive enzymes. Some of these enzymes
(amylase, lipase, and phosphor lipase) are secreted in an
active form. Others (eg, trypsin, chymotrypsin) are secreted
in inactive forms (zymogens). Activation of the zymogens
occurs when pancreatic juice mixes with enterokinase in
the duodenum. Secretion of pancreatic juice in response to
a meal is controlled by many factors including the nervous
system and hormones such as pancreozymin and secretin
among others. This secretion of the digestive enzymes is a
tightly regulated feedback loop. If the amount of digestive enzyme delivered to the intestine is inadequate for the
digestion of the fat, carbohydrate, and protein in the meal,
pancreatic insufficiency exists.
Cystic fibrosis (Chapter 28) is the most common cause
of pancreatic insufficiency in childhood. Other causes
of pancreatic insufficiency in childhood are rarer (Table
25-11).
Table 25-11 Pancreatic Insufficiency Not CF
Congenital
Shwachman-Diamond syndrome
Pearson syndrome
Johanson-Blizzard syndrome
Specific enzyme defects
Acquired
Chronic pancreatitis
Common duct obstructions
Shwachman-Diamond syndrome is the second most

common cause of pancreatic insufficiency in children. It is
estimated to occur in 1 in 20,000 live births. It results from
the failure of normal development of pancreatic exocrine
tissue in utero. The normal tissue is replaced with fat. 82,83
The ductal tissue remains intact and over time there is
improvement in pancreatic function. 84 A specific gene
defect has been described.85 The presenting features include
pancreatic insufficiency, hematologic abnormalities (especially variable neutropenia), bone abnormalities (especially
metaphyseal dysostosis), and short stature. Steatorrhea is

most prominent early in life. Because of the neutropenia,
there is concern for infectious complications.
Johanson-Blizzard syndrome is a rare disorder and the
incidence and natural history are unknown. Patients have
pancreatic insufficiency with midline ectodermal defects
and hypoplasia of the alae nasae.86 Even more rare is Pearson
syndrome, which is exocrine pancreatic insufficiency associated with sideroblastic anemia.87 It results from defects in
mitochondrial DNA.88 Because it is a mitochondrial disease,
there can be multiorgan involvement.
In addition, isolated congenital deficiencies in lipase and
trypsinogen are described but are exceedingly rare. These
are treated with enzyme replacement therapy. Amylase
deficiency with associated starch intolerance is described in
infants but is typically developmental in nature and no cases
are described in adults. It can cause diarrhea but is rarely a
cause of poor growth and rarely requires treatment.
Failure to thrive, as indicated by growth failure and
malnutrition, is commonly associated with pancreatic
insufficiency. It is a result of maldigestion, malabsorption,
insufficient caloric intake, and increased caloric requirements. As a product of malabsorption, fat-soluble vitamin
deficiency may develop.89 Malabsorption, calorie loss,
and failure to thrive are treated with dietary intervention,
pancreatic enzyme replacement therapy, and supplementation of fat-soluble vitamins.
Nutrition management of diseases of pancreatic
insufficiency dictates a diet liberal in fats and calories
and supplemented with pancreatic enzyme replacement
therapy.89 Research indicates that pancreatic insufficient
individuals have a higher resting energy requirement
than pancreatic sufficient individuals.90 Thus, calories will
likely need to be provided in greater than 100% of estimated needs.89 Pancreatic enzyme replacement should be
conducted using proprietary preparations due to the lack
of data with the usage of generic enzyme preparations.91
Enzymes should be ingested prior to meals, snacks, and
consumption of milk products to aid in digestion of fat.
Enzyme dosage should not exceed 2500 lipase units/kg per
meal or 4000 lipase units/g fat per day to avoid fibrosing
colonopathy.92 For more detailed information pertaining
to pancreatic enzyme replacement therapy refer to the
chapter on pulmonary diseases (Chapter 28). Also in need
of supplementation may be the fat-soluble vitamins A, D,
E, and K. These vitamins should be supplemented with a
water miscible form. Refer to the chapter on pulmonary
diseases (Chapter 28) for a more detailed discussion of
these vitamins.
293
Pancreatitis
Pancreatitis is an inflammatory process of the pancreas

with variable involvement of other organs and tissues.
Exposure to a causal factor initiates a cascade of events in
which trypsinogen is converted to trypsin in quantities
that overwhelm the innate protective mechanisms. Causes
of pancreatitis include trauma, infection, drugs or toxins,
multisystem disease, and congenital abnormalities of the
pancreatic or biliary ductal system. Many cases do not have
a clear trigger identified. In children most cases are either
acute and isolated or recurrent acute attacks. Chronic
pancreatitis is seen more commonly in adults. In children it
is most often related to structural malformation or a specific
gene defect as seen in hereditary pancreatitis.
The incidence of acute pancreatitis in childhood is
uncertain. Though not rare, it accounts for a small proportion of pediatric admissions.93,94 Likewise, the incidence of
chronic pancreatitis is not clear.
Most of the pancreas is composed of acinar cells.
Ductules and ducts connect the acini to the duodenum.
The islet cells (which secrete insulin and glucagon) function independently of the acinar cells. The acinar cells
synthesize and store digestive enzymes. All enzymes except
amylase and lipase are stored as inactive proenzymes that
require activation by the action of trypsin. Trypsinogen
(the inactive form of trypsin) is activated in the lumen of
the bowel by the mucosal enzyme enterokinase. In some
instances, trypsinogen may auto-activate. This premature
activation of trypsin with subsequent activation of other
proteases leads to digestion of the pancreas itself. There are
a number of mechanisms for protection of acinar cells from
this auto-activation including presence of trypsin inhibitors
that block the action of trypsin; also, trypsin can inactivate itself through autolysis. This inactivation reaction is
a calcium-dependent process and aberrations of calcium
concentration may trigger an episode of acute pancreatitis.
If any of these mechanisms are disturbed, pancreatic injury
will result.
Pancreatitis is diagnosed by the combination of abdominal pain with elevation of the levels of amylase and lipase
in the serum. The levels of the enzymes do not predict the
severity of pancreatitis. There are no scoring systems applicable to children as there are for adults. Clinical features
suggestive of more severe disease include hypotension,
renal failure, altered sensorium, and hemorrhage.
Initial management of children with acute pancreatitis
is analgesia and intravenous fluids. If vomiting is present,
a nasogastric tube is used to decompress the stomach. In
patients with mild disease, enteral feedings are withheld for
294
a short period. Re-initiation of feedings is based on resolution of abdominal pain and ileus and vomiting. Most patients
with mild disease recover quickly without complications.
Patients with severe pancreatitis often show signs of
hemodynamic instability and are at risk for multiple complications including severe nutrition depletion. Nutrition
support is important in these patients and is considered an
active therapeutic intervention.95 Patients can be fed enterally by nasogastric (NG) or nasojejunal (NJ) tube or by the
intravenous route. Although there are a number of studies
in adults, data concerning nutrition support in pediatric
patients with pancreatitis are scarce. Adult studies suggest
a trend to fewer adverse outcomes in patients who receive
enteral as opposed to parenteral feedings, however the
effect on outcome is not clear.96 There does not seem to be a
difference in feedings of polymeric versus semi-elemental or
immune-enhancing formulas.97 A study in children with
severe acute pancreatitis found little difference between EN
and PN in length of stay, infection, mortality, or need for
surgery.98
Chronic pancreatitis is a condition where continued
inflammation of the pancreas produces irreversible changes
in the gland. In some cases it is related to continued recurrent injury from acute attacks. Often the etiology is not
clear even when risk factors are present. In adults, repeated
exposure to toxins (eg, alcohol) is often implicated. In children, hereditary factors such as mutation of the trypsinogen
molecule, or mutations of the cystic fibrosis transmembrane
regulator (CFTR) gene or trypsin inhibitor genes are often
sought. Autoimmune disorders, both isolated autoimmune
pancreatitis as well as systemic autoimmune diseases, are
seen. Patients with recurrent acute pancreatitis are at risk
for developing chronic pancreatitis.99
Treatment of chronic pancreatitis revolves around
several concerns: chronic pain, development of diabetes
due to islet cell destruction, and pancreatic insufficiency
due to acinar cell destruction. Pain impacts ability to ingest
nutrients, and the treatment of chronic pain is beyond the
scope of this chapter. In addition the treatment of diabetes
mellitus is discussed elsewhere (Chapter 21). Digestive
enzyme insufficiency is a late complication of chronic
pancreatitis. The treatment for pancreatic digestive enzyme
insufficiency is enzyme replacement. The goal is to provide
enzyme supplements enough to restore digestive function.
The dose of pancreatic enzyme is calculated according to
the lipase content. A usual dose of enzyme is 1000 to 2500
units of lipase per kilogram of body weight per meal. This is
often altered based on the estimated fat content of the meal.
This is discussed in more detail in the chapter on cystic
fibrosis (Chapter 28). Both polymeric as well as elemental

dietary supplements have been used for nutrition support,
and there are scant data evaluating the effectiveness in children. It deserves to be restated that a major goal of nutrition
support in these patients is maintenance of normal growth.
Disorders of Chyle Loss
Chyle is a creamy fluid consisting of fat, protein, electrolytes, and lymphocytes and is an important aspect of the
metabolism of fat. Triglycerides are broken down in the
intestinal lumen to fatty acids and mono-acyl glycerols.
They are absorbed into the intestinal epithelial cells. This
process is aided by the action of bile salts mixing with the
fatty acids forming micelles that enhance the transport of
the molecules. Within the enterocytes, the absorbed fatty
acids are re-esterified to glycerol and the resultant lipid
is complexed with proteins (forming chylomicrons) and
transported through the lymphatic system of the GI tract
and abdomen ultimately into the thoracic duct and then
into the blood stream. Disorders of chyle loss are rare with
the most common disorders being chylothorax or chylous
ascites. Chylothorax is defined by pooling of lymphatic
fluid, chyle, in mediastinal or pleural cavities. Chylous
ascites occurs when there is lymphatic disruption in the
abdominal cavity with resultant pooling of chyle in the
abdomen. This condition is usually seen as a complication
of surgery100 although congenital defects of lymph flow are
also described. For more detailed information refer to the
chapter on cardiac disease (Chapter 23). A less common
disorder of chyle is that of intestinal lymphangiectasia. This
condition results from failure of lymph flow often related
to inflammation, causing enlargement of intestinal lymph
vessels, which causes breakage of the lacteals and spillage
of chyle into the intestinal lumen.101 As a result protein
losing enteropathy, hypoalbuminemia, and edema may
result. Hypogammaglobulinemia is often present. Edema
of the intestinal mucosa causes malabsorption. Steatorrhea is typically seen.102 Even more rare are the disorders
of chylomicron formation such as abetalipoproteinemia in
which there is a defect in the ability to complex the lipids
with carrier proteins and therefore the lipid is not carried
into the lymphatic system.
Regardless of the specific disorder of chyle processing,
the nutrition approach is similar. The initial treatment is
restriction of dietary fat. A low-fat, high-protein diet is
recommended because there is usually associated protein
loss in the GI tract. Because medium-chain length fatty
acids and triglycerides can be metabolized without entry
into the lymphatic system, dietary fats should be primarily
from medium-chain triglycerides (MCTs), often by using a

specialized high MCT, low long-chain triglyceride (LCT)
formula.101 The rationale of this diet is twofold. One,
the decreased amount of fat lowers the amount of circulating chyle. This reduction lowers the risk of lacteal cells
becoming dilated and releasing chyle. Two, MCTs are
directly transported via the portal system, which reduces
lymphatic circulation.101,102 Most often, this diet is needed
for 4 to 8 weeks.100 One should be cautious to supply sufficient amounts of essential fatty acids, linoleic and linolenic
acids, to prevent deficiency. The American Academy of
Pediatrics recommends that a minimum of 3% of calories
should come from these essential fatty acids.100 PN may
be initiated in instances when EN is not adequate to meet
nutrient needs or not indicated for other reasons. Lipids in
PN are not absorbed via the lymphatic system and have no
affect on the condition.
Functional Disorders
The functional disorders are a diverse group of conditions

in which symptoms persist for a prolonged period and there
is no specific tissue change associated with the symptom.
These include recurrent and/or chronic abdominal pain,
chronic non-specific diarrhea, gastroparesis, cyclic vomiting
syndrome, and constipation. Because the underlying
pathophysiology is unclear, both the evaluation and treatment is related to the predominant symptom. Malnutrition
is rare in this group of patients and, if present, suggests an
alternative diagnosis. Frequently, dietary interventions are
suggested for symptom control. These include increasing
fiber, reducing fermentable carbohydrate, and altering the
fat content of the diet. These interventions are often recommended and frequently reported to be helpful though data
documenting effectiveness are lacking.
Chronic abdominal pain is a common symptom in children and adolescents and it is estimated to affect 10% to 15%
of the population at some time.103 The etiology and pathogenesis are unknown and there are no specific diagnostic
markers to help in diagnosis. The clinical presentation and
careful history and physical examination will often suggest
that the diagnosis is functional abdominal pain. A few laboratory or x-ray studies may assist in the evaluation and are
remarkable for their normality.
The role of dietary modifications in the management of
the functional abdominal pain disorders is not established.
If symptoms are mainly post-prandial or include the sensation of bloating, a low-fat diet is sometimes recommended.
If diarrhea or constipation is prominently associated with
the pain, an increase in the amount of fiber in the diet is
295
considered. Poor absorption of ingested carbohydrate may

trigger symptoms in susceptible individuals. Therefore,
restrictions of lactose (milk), fructose (carbonated beverages and certain fruits), or dietary starches (corn, wheat, oat,
and potato) are sometimes tried. Restriction of non-absorbable sugar alcohols, often used as artificial sweeteners (eg,
sorbitol, xylitol), is advised. It is important to avoid multiply
restrictive diets as they may lead to nutrition insufficiency.
Gastroparesis
Gastroparesis is the delay of emptying of the stomach in
the absence of a mechanical obstruction. There are multiple
causes (Table 25-12). Disorders of the intestinal musculature (myopathic) and the intestinal nervous system
(neuropathic), both congenital and acquired, are described.
Common causes are immaturity (especially in premature
infants), viral infections, systemic diseases, and drugs.
Gastroparesis often complicates the management of type 1
diabetes mellitus. Evaluation should include assessment of
gastric anatomy and function (eg, upper GI series x-ray or
gastric emptying study) but also the search for and treatment of any underlying condition and bacterial overgrowth.
Importantly, malnutrition may be both a cause as well as a
result of gastroparesis.
Table 25-12 Conditions Associated with Gastroparesis
Infection
Postviral illness (eg, rotovirus)
Neurological Disease
Mitochondrial disorders
Familial dysautonomia
Systemic Disease
Diabetes
Malnutrition
Connective tissue disorders
There are many symptoms of gastroparesis including

nausea, vomiting, bloating, upper abdominal discomfort,
early satiety, heartburn, esophageal reflux, and decreased
appetite.104106 These symptoms may lead to malnutrition
and the need for nutrition support. Initial treatment of
gastroparesis should include maximizing the therapy of
treatable systemic illness (eg, optimizing glycemic control
in the diabetic patient) and eliminating causes such as
medications.
The nutrition assessment of a child with gastroparesis
should include a dietary recall and/or dietary record, evaluation of changes in weight over time, laboratory studies,
description of symptoms, and listing of medications as
well as nutrition supplements.107 The dietary recall and
or/record provides important information regarding both
symptoms and feeding. Factors to consider are meal volume
296
tolerance, preference of liquids over solids, and fiber and

fat tolerance.107 Because early satiety is commonly seen in
gastroparesis, small frequent meals may be better tolerated
than 3 large meals.104,107 Liquids are often better tolerated
than solids. Thus, a diet of liquids and/or purees may be
more effective in delivering ample nutrition than a conventional solid-based diet.104,106,107 Avoidance of a high-fiber and
high-fat diet, with the exception of fat in liquid nutrition, is
also often beneficial in delivering nutrition as both of these
nutrients delay gastric emptying.107 Dietary osmolality is
less an issue in managing gastroparesis.107
Laboratory markers include ferritin, glucose, and
hemoglobin A1C. Iron deficiency anemia is common in this
cohort of patients, in part due to symptom management.
Usage of acid-reducing medications to manage reflux and
heartburn decreases gastric acid, needed to convert dietary
iron to its more absorbable form. Further, usage of jejunal
tube feeds to control vomiting and promote weight gain can
increase the risk of iron deficiency anemia as the duodenum
is the main area of iron absorption.107 Ferritin is a more
appropriate marker to screen for iron deficiency anemia
than hemoglobin and hematocrit. However, it is important
to remember that ferritin is an acute phase respondent and
will not be accurate during acute inflammation.107,108
Constipation
Constipation is a common symptom among humans of all
ages and is often especially troubling in infants and young
children. It is most often both self-limited and short lived.
However, a substantial number of patients have symptoms
that persist for 6 months or more. Constipation may be
related to inadequate intake of fluid or fiber, side effects of
medication, inactivity, or disordered bowel motility. Most
cases are idiopathic and fulfill the definitions of functional
constipation. Although most recognize a role for diet in
both the etiology and the treatment of constipation, there
are little data to allow identification of specific foods as
either causal or beneficial.
The role of cows milk in constipation has been recognized for some time, although the mechanism is unclear.109
There is increasing evidence to suggest a role of cows milk
protein sensitivity in constipation.110,111 In addition, it is
known that the fat content of milk may also be associated
with harder or more difficult-to-pass stools.
Historically, a high-fiber diet has been recommended
for children with constipation. However, few studies document benefit.112,113 There is also no conclusive evidence that
fiber supplements or a lactose-free diet is beneficial in alleviating recurrent abdominal pain in children.114 However,
in some children it may be beneficial to undergo a trial of a

high-fiber (0.75 g soluble fiber per year of age), lactose-free,
and low-fructose diet for symptom management.115
Cyclic Vomiting Syndrome

Although increasingly recognized in children, the pathogenesis of cyclic vomiting syndrome remains unknown. The
clinical features overlap with those of abdominal migraine.
The distinguishing characteristic is a repeated pattern of
stereotypical episodes of severe vomiting often associated
with pallor, lethargy, and abdominal pain. The episodes
are similar in onset and usually duration. There is often a
prodrome of variable duration. An important feature is that
the children return to baseline health in between episodes.
In cyclic vomiting syndrome the primary nutrition concern is management of any fluid and electrolyte
disturbances that may arise as there is no known dietary
intervention to prevent onset or reduce duration of the
condition.103
Irritable Bowel Syndrome

In irritable bowel syndrome (IBS) there is no significant
evidence to support that diet causes or can treat the condition. It may be prudent to undergo an elimination trial
of lactose-, fructose-, and/or sorbitol-containing foods
as intolerance to these foods manifests as abdominal
pain.116118 The role of dietary fiber, particularly that of
soluble fiber, in symptom management, especially of
constipation, is debatable. Soluble fiber is found in fruits,
vegetables, and whole grains. When ingested, fiber helps
to give the stool a gel-like consistency and serves as a fuel
source for colonic bacteria. The end result is a reduction in
gut transit time and, subsequently, a reduction in constipation and intracolonic pressure.119,120 To date, there are
no definitive conclusions as to the benefit of fiber in IBS
symptom management.121 Nutrition counseling should
be individualized based on the patients reported foodsymptom correlations secondary to limited pediatric data
on the topic.122 The suspected offending food should be
removed from the diet for 2 to 3 weeks. If no relief in symptoms is observed, the food may be added back to the diet.
Eosinophilic Conditions of the Gut
Eosinophilic gastroenteritis is a condition characterized by

either patchy or diffuse infiltration of eosinophils anywhere
in the GI tract. Damage to the GI tract is due to both the
infiltration and degranulation of eosinophils. The triggering process is not clear. Both IgE and non-IgE mediated
sensitivities are described. Many patients (especially older
patients) have conditions such as a high eosinophil count,

asthma, allergic rhinitis, or eczema suggesting underlying
atopy. Allergies to food or inhalants are sometimes implicated. In addition there is often a family history of atopy. It
may affect children of any age.
The signs and symptoms are non-specific and the
presentation varies by location, depth and extent of the
eosinophilic infiltration (Table 25-13). There may be
involvement of the mucosal, muscular, or serosal layers.
Mucosal disease presents as nausea and vomiting, diarrhea
(often bloody), malabsorption, and weight loss. When the
muscular layers are involved, there are signs and symptoms
of obstruction. If there is serosal involvement there may be
ascites. The most common symptom is colicky abdominal
pain.
Table 25-13 Presentation Characteristics of Eosinophilic Gastroenteritis
by Tissue
TISSUE
PRESENTATION CHARACTERISTICS
Mucosal
Diarrhea
GI bleeding
Vomiting
Abdominal pain
Muscular
Vomiting
Colicky
Abdominal pain
Serosal
Ascites
Abdominal pain
The most frequently seen form of eosinophilic gastroenteritis is proctitis in infants. The disorder is characterized
by the bloody diarrhea in an infant less than 2 months of
age.
Cases of food-induced eosinophilic proctocolitis are
reported regardless of being breastfed or formula fed.
Infants presenting with this condition usually have normal
linear and ponderal growth. The infants will have diarrhea,
usually accompanied by mucous and/or blood, and often
with pain or straining at the time of bowel motion. Biopsy of
the rectal mucosa will show eosinophilic infiltration of the
mucosa. Frequently the diagnosis is made on clinical presentation alone. The dietary management of this condition
involves elimination of the offending protein until approximately 9 to 12 months of age. If an infant is breastfed then
the offending protein should be removed from the mothers
diet. Earlier introduction of the protein will usually result in
bleeding.123
In older children with eosinophilic conditions of the
gut symptoms include, but are not limited to, vomiting,
297
abdominal pain, diarrhea, hematochezia, poor growth/

weight gain, and iron deficiency anemia.124 The recommended dietary treatment is avoidance of the offending
allergens. Particular attention should be paid to the quality
of the diet as malnutrition may develop if numerous foods
are eliminated.123 For some children usage of an amino acid
based formula may be appropriate.124
Summary
Because of the central role of the digestive system in maintaining normal nutrition, disease of the GI tract, liver, or
pancreas has a profound influence on growth and development of children. Provision of adequate nutrition support
can not only improve nutrition parameters and growth but
also in many cases can treat the underlying disease. Careful
evaluation of the child with assessment of nutrition needs is
the initial step in effective management. The clinical examination and judiciously applied laboratory investigation will
identify nutrition deficiencies. With understanding of the
underlying disease process, appropriate nutrition management can improve growth, quality of life, and outcomes of
these patients.
A 15 year old boy is admitted to the hospital because of diarrhea and abdominal pain. He has had unintentional weight
loss of 15 pounds in the last 3 months. Laboratory evaluation reveals:
Albumin 3.1
Total Protein 6.2
Hemoglobin/hematocrit 9.3/27
MCV 71 (nl >79)
WBC 11,500
Radiology studies demonstrated inflammation of the ileum
and cecum.
1. Diet therapy should include:
A. A polymeric defined formula diet
B. A semi-elemental defined formula diet
C. An elemental defined formula diet
D. Any of A, B, or C
E. A clear liquid diet
2. His medical therapy includes methotrexate and
sulphasalazine. Supplementation should include:
A. Folate, B12, and iron
B. Pyridoxine, thiamin, and magnesium
C. B12, vitamin C, and manganese
D. Folate, vitamin C, and copper
298
3. In a patient with celiac disease, a gluten-free diet should

be maintained:
A. Until diarrhea subsides
B. Until normal linear growth is established
C. Until new and as yet undiscovered treatments are
available
D. Until bone mineral density has returned to normal
E. A gluten-free diet is not necessary
4. Enterokinase is synthesized by:
A. Pancreatic acinar cells
B. Intestinal mucosal cells
C. Liver cells
D. Neutrophils
5. Enterokinase is an enzyme that:
A. Digests fat
B. Activates eosinophil degranulation
C. Transports glucose into the cell
D. Activates trypsinogen to trypsin
References
1. Gibbons T, Fuchs GJ. Malnutrition: a hidden problem in

hospitalized children. Clin Pediatr. 2009;48:356361.
2. Naber TH, Schermer T, de Bree A, Nusteling K, et al. Prevalence of malnutrition in nonsurgical hospitalized patients and
its association with disease complications. Am J Clin Nutr.
1997;66:12321239.
3. Motil KJ, Phillips SM, Conkin CA. Nutritional assessment.
In: Wyllie R, Hyams JS, Kay M, eds. Pediatric Gastrointestinal
and Liver Disease. Pathophysiology, Diagnosis, Management. 3rd
ed. London: Saunders Elsevier; 2006:10951111.
4. Baker SS, Baker RD, Davis AM. Pediatric Nutrition Support.
Sudbury, MA: Jones and Bartlett Publishers; 2007:459475.
5. Shay S, Tutian R, Sifrim D, et al. Twenty-four hour ambulatory
simultaneous impedance and pH monitoring: a multicenter
report of normal values from 60 healthy volunteers. Am J
Gastroenterol. 2004;99:10371043.
6. Nelson SP, Chen EH, Syniar GM, et al. Prevalence of
symptoms of gastroesophageal reflux during childhood: a
pediatric practice-based survey. Arch Pediatric Adol Med.
2000;154:150154.
7. Vandenplas Y, Goyvaerts H, Helven R, Sacre L. Gastroesophageal reflux, as measured by 24-hour pH monitoring, in
509 healthy infants screened for risk of sudden infant death
syndrome. Pediatrics. 1991;88:834890.
8. Martin AJ, Pratt N, Kennedy JD, et al. Natural history and
familial relationships of infant spilling to 9 years of age. Pediatrics. 2002;109:10611067.
9. Nelson SP, Chen EH, Syniar GM, et al. Prevalence of
symptoms of gastroesophageal reflux during infancy: A
pediatric practice-based survey. Arch Pediatr Adolesc Med.
1997;151;569572.
10. Nelson SP, Chen EH, Syniar GM, Christoffel KK. One year
follow up of symptoms of gastroesophageal reflux during
infancy. Pediatric Practice Research Group. Pediatrics.
1998;102:e67.
11. Vandenplas Y. Gastroesophageal reflux. In: Wyllie R, Hyams
JS, Kay M, eds. Pediatric Gastrointestinal and Liver Disease.
Pathophysiology, Diagnosis, Management. 3rd ed. London:
Saunders Elsevier; 2006:305325.
12. Pandolfino JE, Kwiatek MA, Kahrilas PJ.
The pathophysiologic basis for epidemiologic trends in gastroesophageal reflux
disease. Gastroenterol Clin North Am. 2008;37:827843.
13. Vandenplas Y, Hassall E. Mechanics of gastroesophageal
reflux and gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2002;35:119136.
14. Kawahara H, Dent J, Davidson G. Mechanics responsible
for gastroesophageal reflux in children. Gastroenterology.
1997;113:399408.
15. Vanderhoof JA, Moran JR, Harris CL, Merkel KL, Orenstein
SR. Efficacy of a pre-thickened infant formula: a multicenter,
double-blind, randomized, placebo-controlled parallel group
trial in 104 infants with symptomatic gastroesophageal reflux.
Clin Pediatr. 2003;42:483495.
16. Aggett PJ, Agostoni C, Axelsson I, et al. Anti-reflux or antiregurgitation milk products for infants and young children: a
commentary by the ESPGHAN Committee on Nutrition. J
17. Vandenplas Y, De Wolf D, Sacre L. Influence of xanthines on
gastroesophageal reflux in infants at risk for sudden infant
death syndrome. Pediatrics. 1986;77:807810.
18. Wenzl TG, Schneider S, Scheele F, Silny J, Heimann G,
Skopnik H. Effects of thickened feeding on gastroesophageal
reflux in infants: a placebo-controlled crossover study using
intraluminal impedance. Pediatrics. 2003;111(4 Pt 1):e355e359.
19. Orenstein SR, Shalaby TM, Putnam PE. Thickened feedings
as a cause of increased coughing when used as therapy for
gastroesophageal reflux in infants. J Pediatr. 1992;121:913915.
20. Huang R-C, Forbes DA, Davies MW. Feed thickener
for newborn infants with gastro-oesophageal reflux.
Cochrane Database of Syst Rev. 2002;(3):CD003211.
doi:10.1002/14651858.CD003211.
21. Craig WR, Hanlon-Dearman A, Sinclair C, Taback SP,
Moffatt M. Metoclopramide, thickened feedings and positioning for gastro oesophageal reflux in children under two
years. Cochran Database Syst Rev. 2009;(3):CD003502.
doi:10.1002/14651858.CD003502 pub 2.
22. Bosscher D, Van Caillie-Bertrand M, Van Dyck K, Robberecht
H, Van Cauwenbergh R, Deelstra H. Thickening infant
formula with digestible and indigestible carbohydrate: availability of calcium, iron, and zinc in vitro. J Pediatr Gastroenterol
Nutr. 2000;30:373378.
23. Rudolph CD, Mazur LJ, Liptak GS, et al.; North American
Society for Pediatric Gastroenterology and Nutrition. Guidelines for evaluation and treatment of gastroesophageal reflux
in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J
Pediatr Gastroenterol Nutr. 2001;32:Supp 2:S131.
24. Hills JM, Aaronson PI. The mechanism of action of peppermint oil on gastrointestinal smooth muscle. Gastroenterology.
1991;101:5565.
25. Wendl B, Pfeiffer A, Pehl C, Schmidt T, Kaess H. Effect of
decaffeination of coffee or tea on gastro-oesophageal reflux.
Aliment Pharmacol Ther. 1994;8:283287.
26. Pehl C, Pfeiffer A, Wendl B, Kaess H. The effect of decaffeination of coffee on gastroesophageal reflux in patients with reflux
disease. Aliment Pharmacol Ther. 1997;11:483486.
27. Bulat R, Fachnie E, Chauhan U, Chen Y, Tougas G. Lack of
effect of spearmint on lower esophageal sphincter function
and acid reflux in healthy volunteers. Aliment Pharmacol Ther.
1999;13:805812.
28. Penagini R, Mangano M, Bianchi PA. Effect of increasing the
fat content but not the energy load of a meal on gastro-oesophageal reflux and lower oesophageal sphincter motor function.
Gut. 1998;42:330333.
29. Lewis D, Khoshoo V, Pencharz PB, Golladay ES. Impact of
nutritional rehabilitation on gastroesophageal reflux in neurologically impaired children. J Pediatr Surg. 1994;29:167169.
30. Skidmore-Roth L. Mosbys Drug Guide for Nurses. 4th ed. St.
Louis, MO: Mosby; 2001.
31. Herzig SJ, Howell MD, Ngo LH, Marcantonio GR. Acidsuppressive medication use and the risk for hospital-acquired
pneumonia. JAMA. 2009;301(20):21202188.
32. Canani RB, Cirillo P, Roggero P, Romano C, Malamisura B,
et al. Therapy with gastric acid inhibitors increases the risk of
acute gastroenteritis and community-acquired pneumonia in
children. Pediatrics. 2006;117(5):e817e820.
33. Craig WR, Hanlon-Dearman A, Sinclair C, Taback SP,
Moffatt M. Metoclopramide, thickened feedings and positioning for gastro oesophageal reflux in children under two
years. Cochrane Database of Syst Rev. 2004;(3):CD003502.
doi:10.1002/14651858.CD003211.
34. Green PHR, Collier C. Celiac disease. N Engl J Med. 2007;
357:17311743.
35. DAmico MA, Holmes J, Stavropoulos SN, et al. Presenta
tion of celiac disease in the United States: prominent effect of
breast feeding. Clin Pediatr (Phila). 2005;44:249258.
36. Rampertab SD, Poorfan N, Baur P, Singh P, et al. Trends in
the presentation of celiac disease. Am J Med. 2006;119(4):
355.e9355.e14.
37. Haapalahti M, Kulmala P, Karttunen TJ, et al. Nutritional
status in adolescents and young adults with screen-detected
celiac disease. J Pediatr Gastroenterol Nutr. 2005;40:566570.
38. Fasano A, Catassi C. Current approaches to diagnosis and
treatment of celiac disease: an evolving spectrum. Gastroenterology. 2001;120:636651.
39. See J, Murray JA. Gluten-free diet: The medical and nutrition
management of celiac disease. Nutr Clin Pract. 2006;21:115.
40. Hallert C, Grant C, Grehn S, et al. Evidence of poor vitamin
status in celiac patients on a gluten-free diet for 10 Years.
Aliment Pharmacol Ther. 2002;16:13331339.
41. Mora S, Barera G, Beccio S, et al. A prospective, longitudinal
study of the long-term effect of treatment on bone density in
children with celiac disease. J Pediatr. 2001;139(4):473475.
42. Shamir R. Nutritional aspects in inflammatory bowel disease.
J Pediatr Gastroenterol Nutr. 2009;48:586588.
299
43. Kleinman RE, Baldassano RN, Caplan A, et al. Nutrition

support for pediatric patients with inflammatory bowel
disease: a clinical report of the North American Society for
Pediatric Gastroenterology, Hepatology and Nutrition. J
44. Seidman E, LeLeiko N, Ament M, et al. Nutritional issues in
pediatric inflammatory bowel disease. J Pediatr Gastroenterol
Nutr. 1991;12:424438.
45. Kanof ME, Lake AM, Bayless TM. Decreased height velocity
in children and adolescents before the diagnosis of Crohns
disease. Gastroenterology. 1988;95:15231527.
46. Saha MT, Ruuska T, Laippala P, Lenko HL. Growth of prepubertal children with inflammatory bowel disease. J Pediatr
47. Markowitz J, Grancher K, Rosa J, Aiges H, Daum F. Growth
failure in pediatric inflammatory bowel disease. J Pediatr
48. Newby EA, Sawczenko A, Thomas AG, et al. Interventions for
growth failure in childhood Crohns disease. Cochrane Database of Syst Rev. 2005;(3):CD003873. doi:10.1002/14651858.
CD003873.pub2.
49. Sentongo TA, Semeao EJ, Piccoli DA, Stallings VA, Zemel BS.
Growth, body composition and nutritional status in children
and adolescents with Crohns disease. J Pediatr Gastroenterol
Nutr. 2000;31:3340.
50. Mamula P, Markowitz JE, Baldassano RN. Inflammatory
bowel disease in early childhood and adolescence: special
considerations. Gastroenterol Clin N Am. 2003;32:967995.
51. Bodnar RJ, Pasternak GW, Mann PE, Paul D, Warren R,
Donner DB. Mediation of anorexia by human recombinant
tumor necrosis factor through a peripheral action in the rat.
Cancer Research. 1989;49:62806282.
52. Hellerstein MK, Meydani SN, Meydani M, et al. Interleukin-1
induced anorexia in the rat. J Clin Invest. 1989;84:228235.
53. Wiskin AE, Wootton SA, Beattie RM. Nutrition issues in
pediatric Crohns disease. Nutr Clin Pract. 2007;22:214222.
54. Motil KJ, Grand RJ, Davis-Kraft L, Ferlic LL, OBrian Smith E.
Growth failure in children with inflammatory bowel disease:
a prospective study. Gastroenterology. 1993;105:681691.
55. Ballinger AB, Azooz O, El-Haj T, Poole S, Farthing MJG.
Growth failure occurs through a decrease in insulin-like
growth factor 1 which is independent of undernutrition in a
rat model of colitis. Gut. 2000;46:694700.
56. Navarro FA, Hanauer SB, Kirschner BS. Effect of long-term
low-dose prednisone on height velocity and disease activity in
pediatric and adolescent patients with Crohn disease. J Pediatr
57. Eiden KA. Nutritional considerations in inflammatory bowel
disease. Practical Gastroenterol. 2003;27:3354.
58. Sentongo TA, Semaeo EJ, Stettler N, Piccoli DA, Stallings
VA, Zemel BS. Vitamin D status in children, adolescents
and young adults with Crohn disease. Am J Clin Nutr.
2002;76:10771081.
59. Pappa HM, Gordon CM, Saslowsky TM, et al. Vitamin D
status in children and young adults with inflammatory bowel
disease. Pediatrics. 2006;118:19501961.
300
60. Sanderson IR, Udeen S, Davies PS, Savage MO, Walker-Smith

JA. Remission induced by an elemental diet in small bowel
Crohns disease. Arch Dis Child. 1987;61:123127.
61. Borrelli O, Cordischi L, Cirulli M, et al. Polymeric diet alone
versus corticosteroids in the treatment of active pediatric
Crohns disease: a randomized controlled open-label trial.
Clin Gastroenterol Hepatol. 2006;4:744753.
62. Canani RB, Terrin G, Borrelli O, et al. Short- and long-term
therapeutic efficacy of nutritional therapy and corticosteroids
in pediatric Crohns disease. Dig Liver Dis. 2006;38:381387.
63. Lochs H, Dejong C, Hammarqvist F, et al. ESPEN Guidelines on Enteral Nutrition: Gastroenterology. Clin Nutr.
2006;25:260274.
64. Zachos M, Tondeur M, Griffiths AM. Enteral nutritional
therapy for induction of remission in Crohns disease.
doi:10.1002/14651858.CD000542.pub2.
65. Griffiths AM, Ohlsson A, Sherman PM, Sutherland LR. Metaanalysis of enteral nutrition as a primary treatment of active
Crohns disease. Gastroenterology. 1995;108:10561067.
66. Akobeng AK, Thomas, AG. Enteral nutrition for maintenance
of remission in Crohns disease. Cochrane Database of Syst Rev.
2007;(3):CD005984.doi:10.1002/14651858.CD005984.pub2.
67. Takagi S, Utsunomiya K, Kuriyama S, et al. Effectiveness of
an half elemental diet as maintenance therapy for Crohns
disease: a randomized-controlled trial. Aliment Pharmacol
Ther. 2006;24:13331340.
68. Wilschanski M, Sherman P, Pencharz P, Davis L, Corey M,
Griffiths A. Supplementary enteral nutrition maintains remission in pediatric Crohns disease. Gut. 1996;38:543548.
69. Levine A, Milo T, Buller H, Markowitz J. Consensus
and controversy in the management of pediatric Crohns
disease: an international survey. J Pediatr Gastroenterol Nutr.
2003;36:464469.
70. Gracey M. Nutritional effects and management of diarrhea in
infancy. Acta Paediatr Suppl. 1999;430:110126.
71. Lutter CK, Habicht JP, Rivera JA, Martorell R. The relationship
between energy intake and diarrhoeal disease in their effects
on child growth: biological model, evidence, and implications
for public health policy. Food Nutr Bull. 1992;14:3642.
72. Rosenberg IH, Solomons NW, Schneider RE. Malabsorption
associated with diarrhea and intestinal infections. Am J Clin
Nutr. 1977;30:12481253.
73. Molla A, Molla AM, Rahim A. Intake and absorption of nutrients in children with cholera and rotavirus infection during
acute diarrhea and after recovery. Nutr Res. 1982;2:233242.
74. Islam M, Roy SK, Begum M, Chisti MJ. Dietary intake and
clinical response of hospitalized patients with acute diarrhea.
Food Nutr Bull. 2008;29:2531.
75. Treem WR. Congenital sucrase-isomaltase deficiency. J
Pediatr Gastroenterol Nutr. 1995; 21:114.
76. Belmont JW, Reid B, Taylor W, et al. Congenital sucraseisomaltase deficiency presenting with failure to thrive,
hypercalcemia and nephrocalcinosis. BMC Pediatrics.
2002;2:4.
77. Treem WR, McAdams L, Stanford L, Kastoff G, Justinich

C, Hyams J. Sacrosidase therapy for congenital sucraseisomaltase deficiency. J Pediatr Gastroenterol Nutr.
1999;28:137142.
78. Castillo-Duran C, Vial P, Uauy R. Trace mineral balance
during acute diarrhea in infants. J Pediatr. 1988;113:452457.
79. Matoth Y, Zamir R, Bar-Shani S, Grossowicz N. Studies in
folic acid in infancy. II. folic and folinic acid blood levels in
infants with diarrhea, malnutrition, and infection. Pediatrics.
1964;33:694699.
80. Guandalini S. Probiotics for children with diarrhea. J Clin
Gasteroenterol. 2008;42:S5357.
81. Wallace B. Clinical use of probiotics in the pediatric population. Nutr Clin Pract. 2009;24:5059.
82. Bodian M, Sheldon W. Lightwood R. Congenital hypoplasia
of the exocrine pancreas. Acta Pediatric. 1964;53:282293.
83. Shwachman H, Diamond LK, Oski FA, Khan KT. The
syndrome of pancreatic insufficiency and bone marrow
dysfunction. J Pediatr. 1964; 65:645663.
84. Mack DR, Forstner GG, Wilschanski M, Freedman MH,
Durie PR. Shwachman syndrome: exocrine pancreatic
dysfunction and variable phenotypic expression. Gastroenterology. 1996;111:15931602.
85. Boocock GR, Morrison JA, Popovic M, et al. Mutations in
SBDS are associated with Shwachman-Diamond syndrome.
Nat Genetics. 2003;33:97101.
86. Johanson AJ, Blizzard RM. A syndrome of congenital
hypoplasia of the alae nasi, deafness, hypothyroidism,
dwarfism, absent permanent teeth and malabsorption. J
Pediatr. 1971;79:982987.
87. Pearson HA, Lobel JS, Kochshis SA, et al. A new syndrome of
refractory sideroblastic anemia with vacuolization of marrow
precursors and exocrine pancreatic dysfunction. J Pediatr.
1979;95:976984.
88. Rotig A, Cormier V, Knoll F, et al. Site-specific deletions of
the mitochondrial genome in the Pearson marrow-pancreas
syndrome. Genomics. 1991;10:502504.
89. Lerner A, Branski D, Lebenthal E. Pancreatic diseases in children. Pediatr Clin North Am. 1996;43:125156.
90. Moudiou T, Galli-Tsinopoulou A, Nousia-Arvanitakis S. Effect
of exocrine pancreatic function on resting energy expenditure
in cystic fibrosis. Acta Paediatrica .2007;96:15211525.
91. Stallings VA, Stark LJ, Robinson KA, Feranchak AP, Quinton,
H. Evidence-based practice recommendations for nutritionrelated management of children and adults with cystic fibrosis
and pancreatic insufficiency: results of a systematic review. J
Am Diet Assoc. 2008;108:832839.
92. Borowitz D, Baker RD, Stallings V. Consensus report on
nutrition for pediatric patients with cystic fibrosis. J Pediatr
93. Lopez MJ. The changing incidence of acute pancreatitis
in children: a single institution perspective. J Pediatr.
2002;140:622624.
94. Park A, Latif SU, Shah AU, et. al. Changing referral trends of
acute pancreatitis in children: a 12year single center analysis.
95. March PC. What is the best way to feed patients with pancreatitis. Curr Opin Crit Care. 2009;15:131138.
96. Al-Omran M, Groof A, Wilke D. Enteral versus parenteral
nutrition for acute pancreatitis. Cochrane Database of Syst Rev.
2003;(1):CD002837. doi:10.1002/14651858.CD002837
97. Petrov MS, Loveday BP, Pylypchuk RD, McIlroy K, Phillips AR, Winsdor JA. Systematic review and meta-analysis of
enteral nutrition formulations in acute pancreatitis. 2009; Br
J Surg. 96:12431252.
98. Doley RP, Yadav TD, Wig JD, et al. Enteral nutrition in severe
acute pancreatitis. J Pancreas (Online). 2009;9:157162.
99. Werlin SL, Kugathasan S, Frautschy BC. Pancreatitis in children. J Pediatr Gastroenterol Nutr. 2003;12:4752.
100. Suddaby EC, Schiller S. Management of chylothorax in children. Pediatr Nurs. 2004;30:290295.
101. McDonald KQ , Bears CM. A preterm infant with intestinal
lymphangiectasia: a diagnostic dilemma. Neonatal Network.
2009;28:2936.
102. Bliss CM, Schroy PC. Primary intestinal lymphangiectasia.
Curr Treat Options Gastroenterol. 2004;7:36.
103. Hyams J, Colletti R, Faure C, et al. Functional gastrointestinal
disorders: Working Group Report of the First World Congress
of Pediatric Gastroenterology, Hepatology and Nutrition. J
Pediatr Gastroenterol Nutr. 2002;35:S110117.
104. Feigenbaum K. Treating gastroparesis. Diabetes Self Manag.
2006;23(5):24.26, 2830, 32.
105. Kim CH, Nelson DK. Venting percutaneous gastrostomy in
the treatment of refractory idiopathic gastroparesis. Gastrointest Endosc. 1998;47(1):6770.
106. Parkman HP, Hasler WL, Fisher RD. American Gastroenterological Association technical review on the
diagnosis and treatment of gastroparesis. Gastroenterology.
2004;127:15921622.
107. Parrish CR, Yoshida CM. Nutrition intervention for the
patient with gastroparesis: an update. Pract Gastroenterol.
2005;30:2966.
108. Gabay C, Kushner I. Acute-phase proteins and other
systemic responses to inflammation. New Engl J Med.
1999;320:448454.
109. Clein NW. Cows milk allergy in infants. Pediatr Clin North
Am. 1954;25:949962.
110. Iacono G, Cavataio F, Montalto G, et al. Intolerance of cows
milk and chronic constipation in children. N Engl J Med.
1998;339:11001104.
111. Dahr S, Tahan S, Sole D, et al. Cows milk protein intolerance
and chronic constipation in children. Pediatr Allergy Immunol.
2001;12:339342.
301
112. Guimres EV, Goulart EM, Penna FJ. Dietary fiber intake,
stool frequency and colonic transit time in chronic functional constipation in children. Braz J Med Biol Res.
2001;34:11471153.
113. Pijpers, MA, Tabbers MM, Benninga MA, et al. Currently
recommended treatments of childhood constipation are not
evidence based: a systematic literature review on the effect
of laxative treatment and dietary measures. Arch Dis Child.
2009;94:117131.
114. Huertas-Ceballos AA, Logan S, Bennett C, Macarthur C.
Dietary interventions for recurrent abdominal pain (RAP) and
irritable bowel syndrome (IBS) in childhood. Cochrane Database of Syst Rev. 2009;(1)CD003019. doi:10.1002/14651858.
CD003019.pub3.
115. Whitfield KL, Shulman RJ. Treatment options for functional
gastrointestinal disorders: from empiric to complementary
approaches. Pediatr Ann. 2009;38:288294.
116. Sood MR. Treatment approaches to irritable bowel syndrome.
Pediatr Ann. 2009;38:272276.
117. Goldstein R, Braverman D, Stankiewicz H. Carbohydrate
malabsorption and the effect of dietary restriction on symptoms of irritable bowel syndrome and functional bowel
complaints. Israel Med Assoc J. 2000;2:583587.
118. Fernndez-Baares F, Esteve-Pardo M, de Leon R, et al. Sugar
malabsorption in functional bowel disease: clinical implications. Am J Gastroenterol. 1993;88:20442050.
119. Shen YA, Nahas R. Complementary and alternative medicine
for treatment of irritable bowel syndrome. Can Fam Physician.
2009;55:143148.
120. Bijkerk CJ, Muris JWM, Knottnerus JA, Hoes AW, de Wit
NJ. Systematic review: the role of different types of fibre in
the treatment of irritable bowel syndrome. Aliment Pharmacol
Ther. 2004;19:245251.
121. Quartero AO, Meiniche-Schmidt V, Muris J, Rubin G, de
Wit N. Bulking agents, antispasmodic and antidepressant
medication for the treatment of irritable bowel syndrome.
doi:10.1002/14651858.CD003460.pub2.
122. Torii A, Toda G. Management of irritable bowel syndrome.
Intern Med. 2004;43:353358.
123. Talley NJ. Gut eosinophilia in food allergy and systemic
and autoimmune diseases. Gastroenterol Clin N Am.
2008;37:307332.
124. Salvatore S, Hauser B, Devreker T, Arrigo S, Vandenplas Y.
Chronic enteropathy and feeding in children: an update.
Nutrition. 2008;24:12051216.
26
Hepatic Disease
Samuel A. Kocoshis, MD and Renee A. Wieman, RD, CSP, LD, CNSD
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
Malnutrition in Liver Diseases . . . . . . . . . . . . . . . . . . . . . 303
Inadequate Intake
Iatrogenic Factors
Malabsorption
Hypermetabolism
Specific Pediatric Liver Disorders. . . . . . . . . . . . . . . . . . . 305

Neonatal Cholestasis
Non-Cholestatic Liver Disease
Nutrition as Primary Therapy for SelectLiverDisorders. 306

Glycogen Storage Disease
Wilsons Disease
Nonalcoholic Fatty Liver Disease (NAFLD)
Assessment of Nutrition State . . . . . . . . . . . . . . . . . . . . . 307

Specific Nutrient Requirements . . . . . . . . . . . . . . . . . . . . 307
Energy
Protein
Lipids and Fat-Soluble Vitamins
Fluids
Other Vitamins and Minerals
Enteral Nutrition Support . . . . . . . . . . . . . . . . . . . . . . . . . 308

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308
302
Learning Objectives
1. Recognize the energy and protein requirements of children with chronic liver disease.
2. Describe nutrition support modalities for children with
chronic liver disease.
3. Understand the diagnosis and management of metabolic liver diseases such as glycogenoses and Wilsons
disease.
4. Comprehend the factors causing malabsorption in
pediatric liver disease.
Introduction
Children with liver disease face an important nutrition

impediment because the liver is so crucial for maintaining
homeostasis. The liver is responsible for synthesis, storage,
and metabolism of carbohydrate, protein, and fat. Additionally, major growth factors such as insulin-like growth
factor-1 (IGF-1) and its binding proteins are directly
synthesized by the liver. Under conditions of severe liver
dysfunction, pediatric patients become growth-hormone
resistant.1 In addition to growth hormone resistance,
the pediatric patient suffering from chronic liver disease
is prone to hypoglycemia because the liver is the major
storage organ for glycogen, and a malfunctioning liver has
reduced glycogen stores. Protein synthesis may be directly
impaired and amino acid utilization for energy may also be
accelerated in the face of reduced glycogen stores. 2 Furthermore, detoxification of ammonia and synthesis of clotting
proteins may also be impaired. Finally, the synthesis of
cholesterol and high-density lipoproteins may be impaired
as can uptake, hydrolysis, and transport of triglycerides. 3
These changes can result in hypertriglyceridemia and
concomitant hypocholesterolemia under conditions of
severe hepatic dysfunction.
HEPATIC DISEASE
Nutrition management of infants and children with liver

disease is a critical component of the overall care required
for optimal interventions and metabolic control of these
patients. It is best accomplished via a team approach with
the team being composed of multiple medical disciplines
including hepatologists, nurses, dietitians, pharmacists,
social workers, speech therapists, occupational therapists,
and physical therapists.
Nutrition requirements are dependent on the disease
being treated, the anticipated disease course, and the likelihood that liver transplantation will be necessary. Acute
diseases such as viral or toxin-induced hepatitis typically
require no supportive therapy alone, whereas nutrition
therapy is the definitive therapy for some metabolic
disorders.
Malnutrition in Liver Diseases
Malnutrition is common in pediatric liver disease and adversely affects survival prior to and following liver transplantation. Beyond the impaired intermediate metabol ism
of carbohydrate, protein, and fat, a variety of factors ac
counts for malnutrition in the context of primary hepatic
disease. Most studies exploring mechanisms of malnutrition in liver disease have been performed in adults, but it
is known that malnutrition can occur both prior to and
after liver transplantation in children. Even though those
mechanisms may not have been fully investigated in pediatric patients, it is quite likely that they contribute to pediatric as well as adult malnutrition among patients with
liverdisease.
Inadequate Intake
A foremost concern among adult and pediatric liver patients
is inadequate dietary intake. A simple reason that intake
might be inadequate is that these patients are frequently
offered low-protein, low-sodium diets that are unappetizing and unappealing. This practice may not only result
in suboptimal oral intake but also provide a diet of poor
caloric quality. Secondly, many forms of liver disease result
in anorexia. One potential mechanism is elevation of serum
and tissue leptin levels.4 Leptin, an appetite-suppressing
hormone, is probably cleared via the liver, and serum levels
are elevated in patients with hepatic fibrosis as well as
other forms of liver disease. The role of leptin in producing
anorexia among patients with liver disease remains controversial, specifically because leptin levels are consistently
normal in some forms of liver disease such as primary
biliary cirrhosis and consistently elevated in other forms
such as Laennecs cirrhosis.4 A third factor accounting for
303
anorexia is hepatic encephalopathy. Anorexia has long been

recognized as a major symptom of encephalopathy, and it
is remarkably difficult to treat without successfully treating
the underlying cause of liver disease. Among children with
inflammatory hepatitides, pro-inflammatory cytokines
are released. The relationship between these cytokines
and anorexia is very well established. While the phenomenon of hyperinsulinemia and insulin resistance has not
been established in children with chronic liver disease,
it has been established in adults, and may also contribute
to their anorexia. 5 Yet another factor potentially contributing to anorexia is zinc deficiency, which is known to be
quite common among patients with chronic liver disease. 6
Finally, the gastric capacity of children with either massive
hepatosplenomegaly or ascites may be so restricted due to
gastric compression by viscera or ascitic fluid that adequate
oral intake becomes impossible.
Iatrogenic Factors
The effect of iatrogenic factors upon the nutrition state of
pediatric liver patients should not be minimized. Excessive
restriction of sodium in the absence of fluid overload will
result in a salt depletion syndrome, and may actually induce
a secondary hyperaldosteronism that would not have been
present otherwise. This factor can lead to both malnutrition and growth failure. Unwarranted protein restriction
can also result in deficiencies of both somatic and visceral
proteins with subsequent malnutrition. Therefore, clinicians caring for children with liver dysfunction should
refrain from restricting either salt or protein in the absence
of ascites or encephalopathy refractory to pharmacotherapy.
Known to be relatively safe, large-volume paracentesis has
been a popular therapy for adults with ascites, but it has
been relatively unpopular in the pediatric setting because
of concerns about the large, rapid fluid shifts that might be
induced.6 This potential complication notwithstanding,
the practice now has advocates within the pediatric hepatology community. If large-volume paracentesis is used
in pediatric patients, the loss of plasma proteins can be
prodigious, rendering the patient deficient in both visceral
and somatic proteins. Hence, for patients undergoing paracentesis, adequate protein intake should be maintained in
the absence of overt encephalopathy. Many of the medications administered to children with hepatic disease may
negatively impact upon their nutrition state. Diuretics, if
administered overzealously, may salt-deplete them. Broadspectrum systemic or enteral antibiotics may eliminate
vitamin K-synthesizing enteric flora, resulting in vitamin
K deficiency among cholestatic patients. Additionally,
304
neomycin, commonly administered for hepatic encephalopathy, is believed to produce villous atrophy, to reduce
intestinal surface area, and to result in malabsorption of
multiple nutrients. Administration of lactulose for encephalopathy may speed intestinal transit enough to result in
malabsorption as well. Finally, cholestyramine, an anion
exchange resin used to treat the pruritis of cholestasis by
binding bile acids, may be so efficient that the intraluminal
bile acid concentration may fall below the critical micellar
concentration, resulting in fat and fat-soluble vitamin
malabsorption.7 Because cholestyramine exchanges organic
anions for chloride, hyperchloremic metabolic acidosis
with resultant growth failure and malnutrition may occur
in children on this medication.
Malabsorption
Pediatric patients with liver disease are more likely to have
cholestatic disease than their adult counterparts. In cholestatic patients, bile acids are retained within the liver, and
excreted very poorly into bile. Therefore, intraduodenal
primary bile acid concentrations customarily fall below
the critical micellar concentration necessary for efficient
solubilization and transport of fat and fat-soluble vitamins across the unstirred water layer into the enterocyte.
Thus malabsorption is very common and requires enteral
administration of large quantities of fat-soluble vitamins
as well as an enteral cocktail of medium-chain triglycerides (MCTs) and long-chain triglycerides (LCTs) in food
or formula. Patients must receive enough long-chain fat
to prevent essential fatty acid deficiency (EFAD) and they
must receive enough medium-chain fat to optimize their
enteric fat balance. Linoleic and linolenic acids, which are
essential fatty acids (EFAs), are long-chain fats that can
only be derived via dietary LCTs. MCT formulas that were
designed during the late 1960s for cholestatic patients were
deficient in LCTs, commonly resulting in EFAD among this
population.8
Malabsorption may occur in select cases of pediatric
cholestasis from not only intraluminal bile acid deficiency
but also from exocrine pancreatic insufficiency. Both cystic
fibrosis and Shwachman-Diamond syndrome, systemic
disorders characterized by exocrine pancreatic insufficiency,
may present during the neonatal period with cholestasis.
Exocrine pancreatic insufficiency is a less-recognized
feature of two childhood disorders characterized by severe
cholestasis: progressive familial intrahepatic cholestasis,
type 1 (PFIC1) and Alagille syndrome. PFIC1, previously
known as Byler disease, is due to a mutation in the ATP8B1
gene, previously known as the FIC1 gene. ATP8B1 mutations
result in reduced activity of the FXR nuclear receptor, which

maintains intra-hepatocyte bile acid homeostasis along
with moduating the activity of the cystic fibrosis transporter (CFTR). As a result, patients with PFIC1 frequently
experience diarrhea, malabsorption, recurrent pancreatitis,
and pancreatic fibrosis which results in exocrine pancreatic
insufficiency.9 Patients with Alagille syndrome also experience exocrine pancreatic insufficiency. Alagille syndrome
arises due to mutations in the Jagged 1 gene that participates
in the notch signaling pathway.10 These mutations result in
bile duct malformations leading to intrahepatic bile duct
paucity. Children with Alagille syndrome frequently have
steatorrhea disproportionate in magnitude to their degree
of cholestasis. Studies have documented pancreatic insufficiency in Alagille syndrome patients which is due to
pancreatic ductal and acinar malformations. Similar pancreatic histology is seen in Jagged 1 knock-out animals whose
pancreatic ductules and acini are malformed in a fashion
similar to bile ductules.11 It is notable that any form of
chronic liver disease, whether cholestatic or noncholestatic,
may be associated with exocrine pancreatic insufficiency.
Longstanding cirrhosis and portal hypertension occasionally result in exocrine pancreatic insufficiency due to either
pancreatic fibrosis on the basis of venous congestion or due
to the absence of hepatic regulatory mechanisms for satisfactory pancreatic enzyme secretion in response to a dietary
stimulus.12
Intestinal function itself may become impaired among
children with chronic liver disease. Portal hypertension
with or without cholestasis may be so severe as to result in
protein-losing enteropathy. In addition, the elevated serum
bile acid concentrations observed in cholestasis may have a
deleterious effect upon small intestinal function. In studies
performed among dogs with surgically created Thirry-Vella
loops, exposure of the mesenteric artery to bile acids at
concentrations of 8 to 22 mol results in impaired transport
of water and electrolytes.13
Hypermetabolism
The prevalence of hypermetabolism is unknown in children with liver disease, but at least 30% of cirrhotic adults
are hypermetabolic.2 Even though some cirrhotic adults
are normometabolic and a few are hypometabolic, those
who are hypermetabolic display measured resting energy
expenditure (REE) 20% or more above predicted energy
expenditure. Hypermetabolism in cirrhotic adults is closely
associated with suboptimal total body mass and total body
protein. One documented mechanism for this phenomenon
is increased adrenal tone presumably because of reduced
HEPATIC DISEASE
hepatic catecholamine metabolism. Those patients with

documented hypermetabolism express a starvation pattern
when their respiratory quotient is measured. They have
respiratory quotients approaching 0.6, documenting that
they begin utilizing fat for energy quite early after a fast
suggesting reduction in glycogen stores. Under these conditions, gluconeogenesis is increased and protein catabolism
is accelerated. Thus hypermetabolic patients with cirrhosis
are best served by taking 4 or 5 meals per day and receiving
adequate dietary protein even in the face of encephalopathy.
For this reason, pharmacologic management of encephalopathy should be attempted prior to reduction of protein in
cirrhotic patients.
Specific Pediatric Liver Disorders

Neonatal Cholestasis
Infantile liver disease is quite commonly cholestatic in
nature.14 Extrahepatic biliary atresia is responsible for
approximately 50% of cases among infants with cholestasis.
Others suffer from a wide variety of infectious and metabolic disorders. As molecular medicine has advanced,
disorders previously lumped within the wastebasket
diagnosis of neonatal hepatitis are now being recognized
as discrete entities. Infantile cholestatic disorders such as
Alagille syndrome, neonatal iron storage disease, PFIC1,
PFIC2, PFIC3, citrin deficiency, Niemann-Pick type C,
type I tyrosinemia, galactosemia, hereditary fructose intolerance, and type IV glycogenosis are but a few of the myriad
infantile disorders characterized by cholestasis at the time
of presentation. Cholestasis, while not universally present,
may also be the dominant symptom for selected patients
with -1-antitrypsin deficiency or cystic fibrosis.
Nutrition strategies may be the definitive therapy for
some of these disorders. For example, elimination of dietary
galactose for galactosemia and fructose for hereditary fructose intolerance are curative. For other disorders, such as
tyrosinemia, reduction of dietary tyrosine is helpful, but not
curative. Because the block in tyrosine metabolism results
in the overabundance of toxic intermediates such as succinylacetone, succinylacetoacetate, fumarylacetoacetate,
and maleylacetoacetate, upstream inhibition of tyrosine
metabolism with 2-(2-nitro-4-trifluoromethylbenzoyl)1,3-cyclohexanedione (NTBC) has been life saving insofar
as metabolism is shunted to nontoxic intermediates such as
parahydroxy-phenylpyruvate.15 The etiology for neonatal
iron storage disease is uncertain, but evidence is accumulating that it is an alloimmune disorder with maternal
antibodies affecting the fetal liver.16 Iron storage may thus
305
be secondary rather than primary. Unlike the therapy of

adult-onset hemochromatosis associated with mutations
in the HFE gene, therapy of neonatal iron storage probably should not include chelation, which can theoretically
render infants susceptible to bloodstream infections with
siderophagic bacteria.
Whatever the cause of neonatal cholestasis, the basic
nutrition strategy should be to provide ample quantities
of fat-soluble vitamins (A, D, K, and E) and to monitor
vitamin levels and/or coagulation studies frequently to
prevent fat-soluble vitamin deficiency. Because some
element of fat malabsorption nearly always occurs during
cholestatic periods a substantial percentage of fat calories
should be given in the form of MCTs, which do not require
micellar solubilization prior to absorption into the portal
circulation. However, infants should not be overloaded
with MCTs insofar as they cannot be stored and must be
immediately oxidized, rendering infants at risk for metabolic acidosis from the short-chain fatty acid oxidation
products.17 Furthermore, MCTs are less calorically dense
than LCTs because of the reduced number of carbon atoms
in their skeleton. Finally, in the 1980s, overenthusiastic
efforts to provide MCTs to cholestatic infants resulted in
providing diets inadequate in EFAs thereby producing
EFAD. At worst, with complete biliary diversion, about
50% of long-chain fats can be absorbed without full solubilization. Therefore, infants with cholestasis should receive
a mixture of MCTs and LCTs. 8 Formulas with a 1:1 mix of
the two types of fat tend to result in optimal fat balance for
cholestatic infants.
Non-Cholestatic Liver Disease

Some pediatric liver disorders result in cholestasis only
intermittently. Among these disorders are the viral hepatitides, autoimmune hepatitis, -1-antitrypsin deficiency,
the glycogenoses, mitochondrial hepatopathies, Wilsons
disease, and nonalcoholic steatohepatitis. When the patient
is not cholestatic, absorption is customarily normal and
specialized formulas may be unnecessary, but it is imperative to provide adequate caloric and protein intake. It is also
important to recognize the underlying metabolic abnormalities that impede adequate assimilation of calories and
to design nutrition regimens that maximize energy availability. The provision of 150% of the estimated caloric and
protein requirement to cirrhotic patients is quite reasonable
based upon adult data suggesting hypermetabolism. 2 Additionally, patients with primary mitochondrial disorders or
glycogenoses should be advised to avoid prolonged fasting.
The incomplete beta oxidation in mitochondrial disease
306
and absent glycogenolysis will result in hypoglycemia and/

or the production of other toxins.
Nutrition as Primary Therapy for

SelectLiverDisorders
Glycogen Storage Disease
The glycogen storage diseases (GSDs), also known as
glycogenoses, are a group of disorders whereby enzyme
defects adversely affect glycogen degradation or glycogen
synthesis. There are at least 10 of these disorders of which
some affect liver, some affect muscle, and some affect both.
Dietary therapy is variably effective for these disorders18
(eg, the only effective therapy for type IV GSD is liver
transplantation). Among those for which dietary therapy
is beneficial, types II and VI have shown only modest
responses to high-protein diets with the only definitive
therapy for type II being enzyme replacement. The greatest
dietary advances have been made for type I. This disorder,
caused by impaired movement of glucose-6-phosphatase
into or out of the endoplasmic reticulum, is characterized
by fasting hypoglycemia, hyperuricemia, lactic acidosis,
and hyperlipidemia. Type IB is also characterized by
neutrophil dysfunction and frequently inflammatory bowel
disease. Late complications include hepatic adenomas,
pulmonary hypertension, and renal hyperfiltration. Initial
trials of continuous enteral glucose or polycose infusions
instituted during the 1980s in order to prevent hypoglycemia had the unexpected benefit of totally or partially
reversing lactic acidosis, hyperuricemia, and hyperlipidemia. Glucose infusion rates of 8 mg/kg/min for infants,
6 mg/kg/min for children, and 4 mg/kg/min for adults
were empirically noted to be beneficial. More recently, raw
cornstarch has been utilized in preference to glucose polymers because of its longer duration of action obviating the
need for a nasogastric tube or gastrostomy tube feedings.
It is important that the cornstarch be uncooked, because
cooking partially hydrolyzes it and produces a glucose
tolerance curve similar to that of glucose. A dose of 1.75 to
2.75 g/kg will deliver about 5 to 7mg/kg/min of glucose
for approximately 6 hours.18
Wilsons Disease
Wilsons disease is due to a mutation in a p-type ATPase
responsible for transporting copper across membranes to
permit formation of metallothionein and to permit biliary
excretion of copper.19 Defective copper excretion results in
excessive hepatic copper stores leading to hepatic dysfunction. Excessive brain and renal copper stores are responsible
for central nervous system and renal manifestations.

Wilsons disease, if diagnosed early, can be treated with
copper chelators. The hepatic manifestations vary from
mild transaminase elevation to fulminant hepatic failure.
Customarily when the total body copper level is elevated,
there is a reciprocal deficiency in zinc which is a cofactor
for alkaline phosphatase synthesis. Therefore, in Wilsons
disease, the alkaline phosphatase level is disproportionally
low in the presence of severe liver dysfunction. Chelation
is employed to increase copper excretion or to decrease
copper absorption. D-penicillamine has been used for
years, but trientene is just as effective with a lower risk of
complications. Zinc can be used to prevent copper absorption by competitive inhibition of intestinal transporters. A
newer agent, tetrahydromolybdenate, shows great promise
insofar as it complexes with copper in the intestinal lumen
rendering copper unabsorbable, and it is absorbed itself,
complexing with serum copper and albumin, thereby
preventing cellular uptake of copper. Beyond chelation,
dietary therapy is important, especially in the early phases of
treatment. High-copper foods such as shellfish, nuts, gelatin,
mushrooms, liver, and soy products should be avoided. In
addition, the copper content of the patients major water
supply should be analyzed if well water is consumed.
Nonalcoholic Fatty Liver Disease (NAFLD)

It is ironic that overnutrition should be the etiology of a liver
disease that is seen in pandemic proportions throughout
the world. Approximately 20% of the population of the
United States is obese, and 75% of obese individuals have
some degree of fatty liver. NAFLD may range in severity
from simple fatty infiltrate on one end of the spectrum to
nonalcoholic steatohepatitis (NASH) on the other end. 20 By
definition, NASH is characterized by both fat and inflammation, and its prognosis is far worse than that of fatty
liver alone. Natural progression or a second hepatic insult
of any sort may result in fibrosis and eventually cirrhosis.
The factors governing the progression of NAFLD to NASH
are not fully understood, but oxidative stress seems to
play a role in the process. Therapy should target comorbid
conditions such as type 2 diabetes mellitus and hypertri
glyceridemia as well as emphasizing weight reduction. In
addition, treatment with betaine, n-acetylcysteine, vitamin
E, or ursodeoxycholic acid may lower liver enzyme levels.
Oral hypoglycemics such as gemfibril or metformin may
decrease hepatic steatosis and improve liver enzyme levels
whereas clofibrate seems to be ineffective. Ultimately, the
most reliable therapy is a sensible weight loss regimen. The
optimal rate of loss should be < 0.9 kg/wk because too rapid
HEPATIC DISEASE
307
a rate may result in excessive lipid peroxidation and more

rapid progression to fibrosis.20
Specific Nutrient Requirements
Assessment of Nutrition State
Increased energy needs have been shown in some pediatric

clients with liver disease with elevated REEs up to 127% to
140% of the predicted REE values. 25 Energy requirements
vary as well, based on age, activity level, degree of malnutrition, and malabsorption. These infants and children can
require up to 130% to 150% of the recommended daily allowance (RDA) for energy based on ideal weight for length.
Infants with cholestatic liver disease generally require 120
to 150 kcal/kg/d based on estimated dry weight rather than
measured weight in the presence of ascites. 25
A subjective global assessment is one of the most reliable

and acceptable standards of assessment when compared
with other objective measures. Based on this assessment,
patients can be evaluated and grouped into those who
require immediate and aggressive nutrition interventions,
those at risk of developing malnutrition, and those who will
do well without nutrition interventions. 21,22
A comprehensive nutrition assessment is imperative
in infants and children with liver disease. Reassessments
should be done periodically (~monthly) to evaluate lean
body mass changes and the complicating side effects that
lead to changes in intake (ie, anorexia, early satiety, nausea),
in addition to diarrhea and the use of diuretics which leads to
increased losses. Continual nutrition evaluations are imperative to determine the degree of malnutrition and execute
individualized nutrition care plans adapted to preserve
somatic and adipose body reserves while curtailing the
metabolic instability universal with progressive disease.
The assessment should begin with a complete and
meticulous review of medical, laboratory, and physical information focusing on nutrition-related problems. A detailed
diet history of usual dietary intake of calories, protein, and
fat sources; weight changes; and medication intake should
also be evaluated. This information will assist in tailoring an
attainable and realistic plan for maximal nutrition preservation. The usual anthropometric markers of nutrition status
are not reliable in patients with advanced liver disease. Body
weight can be dramatically elevated from ascites, edema,
and hepatosplenomegaly, masking weight loss. 23
Malnutrition is best appraised through serial upper
extremity measurement of mid-arm muscle circumferences
(MAMCs) and triceps skinfolds (TSFs). The upper extremities are less subject to fluid accumulation and provide
insight into body mass stores.23 These anthropometric
measures are easily performed, inexpensive, non-invasive,
and can provide key information for detecting nutrition
decline, mandating urgent restoration of these stores with
aggressive nutrition interventions.
Plasma protein levels of albumin, prealbumin, and
retinol-binding protein, which are synthesized in the liver,
are more a marker of the severity of the liver disease than
the visceral protein status.24
Energy
Protein
Goals for age are generally provided unless encephalopathy
with fulminant hepatic failure and an elevated ammonia
level are observed. Enough protein must be provided to
preserve lean body mass and prevent catabolism with the
breakdown of endogenous protein stores, but not contribute
to hyperammonemia and encephalopathy. Infants generally
require 3 to 4 g/kg/d.24 The use of branched-chain amino
acid (BCAA) formulas or supplements in infants and children, though improving nitrogen balance, 26 has fallen out of
favor because the cost/benefit ratio remains low.
Lipids and Fat-Soluble Vitamins

There is no rationale for restricting lipids and fats in children with liver disease insofar as they are the main source
of calories during infancy and early childhood. Increased
dietary fat intake may augment the amount of steatorrhea
observed, but potentially increases the overall amount
of calories absorbed. Formulas that contain ~50% of the
fat as MCT oil are recommended for infants and children
with cholestatic liver disease, but the clinician should make
certain that proper intake of long-chain fatty acids (~10%
of calories) is maintained to prevent EFAD. MCT oil can
affect the palatability and acceptance of oral formula so
choosing a formula with a lower concentration of MCT oil
may be required to achieve sufficient intake.24
Fat-soluble vitamin (A, D, E, and K) supplementation is standard in infants and children with cholestatic
liver disease and customary doses are listed in Table 26-1.
Vitamin K deficiency has dire consequences because of the
risk of fatal hemorrhagic disease, and prophylactic supplementation is indicated. Vitamin D deficiency may take
longer to develop, but becomes evident in children during
periods of rapid bone growth. Children with liver disease
can easily develop rickets and osteoporosis, and pathologic
308
fractures may result. Vitamin E deficiency can lead to

neuromuscular abnormalities, which are reversible when
adequate vitamin E supplementation is initiated. Vitamin
A deficiency is rarely seen in these children because it is
the least sensitive to malabsorption. These vitamin levels
should be evaluated at least every 3 months and aggressive
supplementation initiated to normalize plasma level. 27
TABLE 26-1 Fat-Soluble Vitamin Recommendations
Vitamin
Amount Given
Vitamin A (aqueous)
25-OH vitamin D
Vitamin E
Vitamin K
1000 IU/kg/d up to 25000 IU

35 mcg/kg/d
2025 IU/kg/d as TPGS
2.55 mg/d 3 times per week
Fluids
Management of fluid homeostasis, ascites, and sodium
balance mandate maintaining a delicate balance for pediatric patients with liver disease. The decision to diurese a
patient with hyponatremia generally depends upon a global
assessment of fluid status. A patient with signs of dehydration should be given salt when hyponatremic whereas a
patient appearing overhydrated may actually be suffering
from dilutional hyponatremia and require diuresis with
fluid and salt restriction. Only non-nutritive fluids should
be limited when fluid restriction is initiated. 28 Salt restriction should not be excessive, because salt elimination is
much more benignly accomplished via loop diuretics.
Other Vitamins and Minerals

The incidence of water-soluble vitamin deficiency in children with liver disease has not been comprehensively
studied, and clinical manifestations are rare given that
infant and pediatric formulas that are supplemented with
these vitamins are required in large volumes in order to
increase caloric intake.
Iron supplementation may be required if recurrent
mucosal hemorrhage from varices or gastropathy takes
place.
Urinary excretion of zinc is increased in chronic
cholestatic liver disease, but the cause and associated consequences are unknown based on the current literature.29
Enteral Nutrition Support
Caloric intake can be improved via the use of supplemental

nasoenteric tube feedings with high-calorie formulas when
oral intake is inadequate to achieve goals. Increased caloric
intake can first be achieved through increasing formula
concentration and adding modular additives such as glucose
polymers and medium-chain fats. By not concentrating the

formula base alone, protein concentrations can be maintained within appropriate ranges for age and weight. Free
water should be sufficiently provided to keep osmolality of
the formula low. A 30 cal/oz MCT-containing formula is
ideal for infants. Formula selections should contain at least
50% of the fat as MCT oil for maximized enteral absorption
of fat calories. Several palatable infant and pediatric enteral
formulas containing at least 50% of the fat as MCT oil are
currently marketed.
Patients with arm muscle circumferences below the
5th percentile should receive supplemental nutrition
prior to transplantation. 30 When infants and children are
unable to consume adequate calories to maintain their lean
body mass, supplemental enteral tube feeding should be
initiated. Nasogastric tubes are preferred if patients can
tolerate adequate formula volume to achieve goals because
they are easily placed and replaced if removed. However, in
many instances nasojejunal feeding tubes must be utilized
because of emesis and volume intolerance secondary to
poor gastric emptying. Gastrostomy tubes are generally
not placed in the face of ascites, and organomegaly may
preclude their placement percutaneously. Nocturnal drip
feedings are frequently used so that normal oral feeding
during the day can be maintained. This feeding schedule
may also be beneficial for patients with progressive liver
disease or infants with small body mass who are unable
to maintain normal glucose levels overnight. Progression to 24-hour continuous tube feeding infusions may
be required to provide the increased calories required for
proper nutrition.
Parenteral nutrition (PN) should be considered only when

enteral supplementation fails or cannot be utilized (ie,
during periods of gastrointestinal hemorrhage). In some
cases it may be required in addition to enteral support when
lean body mass cannot be maintained. If possible, some
enteral alimentation should be given if only to maintain gut
integrity.
When long-term PN is required, careful monitoring
of copper levels is mandatory to prevent either toxicity or
deficiency. Most centers employ standard amino acids,
dextrose, lipids, electrolytes, and minerals in quantities
meeting nutrition needs while minimizing metabolic
complications. Even though enrichment in BCAAs may
improve nitrogen balance marginally, adequate protein
nutriture may be attained by providing standard amino
acids. 30
HEPATIC DISEASE
Conclusion
The goals of nutrition for pediatric patients with liver disease

are to optimize their potential for normal growth and development, prevent further liver injury, prevent worsening of
the patients nutrition status, minimize the risk of infection, avoid vitamin and mineral deficiency, and improve the
patients quality of life. This requires detailed attention to
all of the components of nutrition support by caregivers, by
the patient, and by the patients family working as a team to
provide optimal care.
1. What is the best serial marker of nutrition status in

pediatric patients with liver disease?
A. Fat-soluble vitamin levels
B. Upper extremity anthropometric measurements
C. Prealbumin
D. Weight/length or BMI
E. A & D
2. Which of the following liver disorders is most likely to
be associated with exocrine pancreatic insufficiency?
A. Hepatitis C
B. Alagille syndrome
C. Autoimmune hepatitis
D. Extrahepatic biliary atresia
3. In the nutrition therapy of Wilsons disease which
should be avoided?
A. Grapefruit
B. Red meat
C. Endive
D. Lobster
4. Which of the following have been utilized for the nutrition therapy of glycogen storage disease, type I?
A. Subcutaneous octreotide
B. Glucagon infusions
C. Cooked cornstarch
D. Metformin
E. Raw cornstarch
References
1. Bucuvalas JC, Horn JA, Chernausek SD. Resistance to growth

hormone in children with chronic liver disease. Pediatric
Transplantation. 1997;1:7379.
2. Merli O, Riggio M, Leonetti F, et al. Impaired nonoxidative
glucose metabolism in patients with liver cirrhosis: effects of
two insulin doses. Metabolism. 1997;46:840843.
3. Muller P, Felin R, Lambrecht J, et al. Hypertriglyceridaemia
secondary to liver disease. Eur J Clin Invest. 1974;4:419428.
309
4. Ben-Ari Z, Schafer Z, Sulkes J, et al. Alterations in serum

leptin in chronic liver disease. Dig Dis Sci. 2002;47:183189.
5. Selberg O, Burchert W, Van Der Hoff J. Insulin resistance
in liver cirrhosis. Positron-emission tomography scan
analysis of skeletal muscle glucose metabolism. J Clin Invest.
1993;91:18971903.
6. Gines P, Arroyo V. Is there still a need for albumin infusions to
treat patients with liver disease? Gut. 2000;46:588590.
7. West RJ, Lloyd JK. The effect of cholestyramine on intestinal
absorption. Gut. 1975;16:9398.
8. Pettei MJ, Daftary S, Levine JJ. Essential fatty acid deficiency
associated with the use of a medium-chain-triglyceride infant
formula in pediatric hepatobiliary disease. Am J Clin Nutr.
1991;53(5):12171221.
9. Knisely AS. Progressive familial intrahepatic cholestasis: a
personal perspective. Pediatr Dev Pathol. 2000;3:113125.
10. Piccoli DA, Spinner NB. Alagille syndrome and the Jagged1
gene. Semin Liver Dis. 2001;21:525534.
11. Golson ML, Loomes KM, Oakey R, et al. Ductal malformation and pancreatitis in mice caused by conditional Jag1
deletion. Gastroenterology. 2009;136:17611771.e1.
12. Lee SP, Lai KS. Exocrine pancreatic function in hepatic
cirrhosis. Am J Gastroenterol. 1976;65(3):244248.
13. Berant M, Diamond E, Alon U, et al. Effect of infusion of bile
salts into the mesenteric artery in situ on jejunal mucosal
transport function in dogs. J Pediatr Gastroenterol Nutr.
1988;7:588593.
14. Bezerra JA, Balistreri WF. Cholestatic syndromes of infancy
and childhood. Semin Gastrointest Dis. 2001;12:5465.
15. Masurel-Paulet A, Poggi-Bach J, Rolland MO, et al. NTBC
treatment in long-term tyrosinaemia type I outcome in French
patients. J Inherit Metab Dis. 2008;31:8187.
16. Rand EB, Karpen SJ, Kelly S, et al. Treatment of neonatal
hemochromatosis with exchange transfusion and intravenous
immunoglobulin. J Pediatr. 2009;155:566571.
17. Wanten GJ, Naber AH. Cellular and physiological effects
of medium-chain triglycerides. Mini Rev Med Chem.
2004;4:847857.
18. Heller S, Worona L, Consuelo A. Nutritional therapy for
glycogen storage diseases. J Pediatr Gastroenterol Nutr.
2008;47(Suppl 1):S15S21.
19. Pfeil S, Lynn DJ. Wilsons disease: copper unfettered. J Clin
Gastroenterol. 1999;29:2231.
20. McCullough AJ. Update on nonalcoholic fatty liver disease. J
Clin Gastroenterol. 2002;34:255262.
21. Merli M, Romiti A, Riggio O, et al. Optimal nutritional indexes
in chronic liver disease. J Parenter Enteral Nutr. 1987;11(Suppl
5):S130S134.
22. Hasse J, Strong S, Gorman MA, Liepa G. Subjective global
assessment: alternative nutrition assessment technique for
liver transplant candidates. Nutrition. 1993;339343.
23. Sokol RJ, Stall C. Anthropometric evaluation of children with
chronic liver disease. Am J Clin Nutr. 1990;52:203208.
24. Protheroe SM. Feeding the child with chronic liver disease.
Nutrition. 1998;14:796800.
25. Pierro A, Koletzko B, Carnelli V, et al. Resting energy expenditure is increased in infants with extra hepatic biliary atresia
and cirrhosis. J Pediatric Surg. 1989;24:534538.
310
26. Sokal E, Baudoux MC, Collette E, et al. Branched chain

amino acids improve body composition and nitrogen balance
in a rat model of extra hepatic biliary atresia. Pediatr Res.
1996;40:6671.
27. Sokol RJ, Butler-Simon N, Conner C, et al. Multicenter trial
of d-alpha-tocopheryl polyethylene glycol 1000 succinate for
the treatment of vitamin E deficiency in children with chronic
cholestasis. Gastroenterology. 1993;104:17271735.
28. Gines P, Guevara M. Hyponatremia in cirrhosis: pathogenesis, clinical significance, and management. Hepatology.
2008;48:10021010.
29. Saner G, Solu D, Yiitba M, Skc S, Elkabes B. Zinc

nutrition in children with chronic liver disease. J Trace
Elements in Exp Med. 2000;13:271276.
30. Goulet OJ, de Ville de Goyet, Otte JB, Ricour C. Preoperative
nutritional evaluation and support of liver transplantation in
children. Transplant Proc. 1987;19:32493255.
27
Intestinal Failure
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Definition of Intestinal Failure . . . . . . . . . . . . . . . . . . . . . 312
Scope of the Problem
Etiology of Intestinal Failure. . . . . . . . . . . . . . . . . . . . . . . 313

Intestinal Adaptation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313
Enteral Nutrition
Fluid Management
Medications
Non-Transplant Surgery
General Principles
Complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
Nutrition Deficiencies
Functional and Metabolic Complications
Liver Disease
Central Line Complications
Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
Quality of Life
Intestinal Transplant
Learning Objectives
1. Understand that while intestinal length is important, it

is not the only factor that determines a childs ability to
reach enteral autonomy.
2. Understand that the intestinal adaptive process takes
months and even years before enteral autonomy can, if
ever, be achieved.
3. Describe why enteral nutrition is necessary for intestinal adaptation to occur.
4. Explain how lipid-lowering strategies for soy-based
lipid preparations or substitution with a fish-oil based
lipid can improve serum aminotransferase levels and
reduce serum bilirubin.
Introduction
Intestinal failure (IF) in infants and children is a devastating condition that can be broadly defined as the inability
of the intestinal tract to sustain life without supplemental
parenteral nutrition (PN).1,2 Prior to PN, many infants died
as a consequence of insufficient bowel length or function.
Infants found to have an abdominal catastrophe at laparotomy for conditions such as necrotizing enterocolitis
(NEC), volvulus, or gastroschisis were simply closed and
made comfortable to await the natural course of their tragic
circumstance. However, with the development of safe PN,
central line placement and care, improved medical and
surgical management, including intestinal transplantation, these infants now have an opportunity to survive with
a satisfactory or even excellent quality of life. The clinical
course for the child can be challenging and frustrating
to the family as well as those who provide medical care
and support. Intestinal adaptation, if it occurs at all, can
require months or years before the intestine can adequately
311
312
accommodate the growing child independent from PN.

Along the way, the child is at risk for episodes of dehydration, electrolyte imbalance, and macro- and micronutrient
deficiencies. More importantly, life-threatening complications such as sepsis, end-stage liver disease, and vascular
thrombosis may occur.
Management of children with IF is best provided by an
experienced multidisciplinary team that includes experts
in pediatric gastroenterology, surgery, nutrition, nursing,
social work, and feeding techniques. Most management
strategies have not been rigorously investigated, leaving
much to experience, tradition, trial and error, or art as
most would prefer. The great majority of studies of children
with IF are single-site experiences, with small numbers of
patients collected over many decades. 36 The goals of this
brief chapter are to review the topic of intestinal failure and
outline some strategies that might be useful in the care and
management of infants and children with intestinal failure.
Definition of Intestinal Failure
The small intestine almost doubles in length during the

last trimester with the normal full-term infant having 210
to 350 cm at birth.7 This fact makes defining residual bowel
length problematic when the resection and residual length
measurements occur early in the third trimester. While the
literature attempts to define short bowel syndrome (SBS) as
the remnant intestine measuring less than 75 cm, a better
approach was put forward by Teitelbaum and colleagues. 6
They propose incorporating gestational age into the assessment and suggest that infants with less than 10% of their
estimated bowel length are at increased risk of death than
those with a longer residual bowel length.
Intestinal failure is a functional description independent of bowel length and better reflects the nature of the
clinical condition encountered in practice. It identifies
a child whose loss of intestinal length or competence is
below the minimal amount necessary to maintain normal
digestion and absorption of nutrients and fluids for weight
gain and growth in children independent of PN. Such a
definition acknowledges children with conditions such as
immune-mediated enteropathy, enteric myopathy, mitochondrial disorders, intestinal pseudoobstruction, tufting
enteropathy, and microvillus inclusion disease who have
a normal length of intestine but inadequate function to
sustain life without PN.
Scope of the Problem

Surprisingly, neither the incidence nor prevalence of IF/SBS
in the United States is well known.8 In 1992, Wallander et al
estimated the incidence of extreme SBS to be between 3 to

5 per 100,000 births per year.9 However, improvements in
neonatal intensive care, anesthesia, and surgical techniques
have improved survival of children who would have previously died, thus it is likely that the incidence and prevalence
has increased in recent years.10 Other estimates suggest
that at least 16,000 children are on home PN (HPN) in the
United States, but the precise number on PN for management of IF/SBS is unknown.11 More importantly, we have
no estimate of the number of children with SBS who have
been weaned from PN but remain at risk for various nutritional and growth abnormalities as a consequence of their
altered intestinal anatomy. The annual costs for managing a
PN-dependent patient with IF/SBS are estimated to range
between $100,000 and $150,000 with a mortality rate
of approximately 30% at 5 years for those who cannot be
weaned from PN.10
Table 27-1 Causes of Intestinal Failure in Children
Prenatal
Gastroschisis/Omphalocele
Intestinal atresia
Total intestinal or very long-segment Hirschsprungs
disease
Constitutive enterocyte disorders
Tufting enteropathy
Microvillus inclusion disease
Megacystis microcolon hypoperistalsis syndrome
Malrotation/Volvulus
Bladder extrophy
Neonatal
Necrotizing enterocolitis
Vascular thrombosis
Desquamative enteropathy (Intracellular 4
integrinmutation)
Malrotation/Volvulus
Postnatal
Complicated intussusception
Trauma
Seat belt injury
Suction evisceration (eg, swimming pool drain)
Riding lawn mower injury
Extensive vascular anomaly
Autoimmune/immune mediated enteropathy
Tumor
Fibroma
Desmoid
Sclerosing encapsulating peritonitis (abdominal cocoon)
Munchausen Syndrome by Proxy
Protracted diarrhea of infancy
Intestinal motility disorders
Mitochondrial defects/mutations
Intestinal pseudoobstruction
INTESTINAL FAILURE
Etiology of Intestinal Failure
Conditions associated with IF in infants and children are

generally due to surgical short bowel syndrome (SBS),
motility disorders, or enterocyte abnormalities (Table
27-1).1 SBS is the underlying cause in the majority of these
patients, the etiology of which may be congenital abnormalities such as gastroschisis, intestinal atresia, malrotation with
volvulus, or acquired causes such as necrotizing enterocolitis
(NEC), vascular thrombosis, or trauma. Less commonly
seen are motility disorders such as total aganglionosis and
chronic intestinal pseudoobstruction or enterocyte abnormalities such as microvillus inclusion disease and tufting
enteropathy.
Intestinal Adaptation
Intestinal adaptation is a complex and incompletely understood process that ensues following significant bowel
resection to compensate for the loss of intestinal surface
area. It is characterized by both functional and morphologic
changes in the remnant bowel.12,13 Enteral nutrition (EN) is
necessary for adaptation. Clinical features associated with
patients who are eventually weaned from PN include the
absence of jaundice or cholestasis, a shorter duration of PN,
the presence of the ileal-cecal valve, an intact colon, small
bowel length greater than 15 cm, and placement of the small
intestine in continuity with the colon. 5 The underlying
physiologic mechanisms by which these clinical factors
might directly impact the adaptive process in the human
is incompletely understood. For instance, it is not clear
whether the ileal-cecal valve must be physically present or
whether its presence merely serves as a marker for a long
colon segment. Over time, the residual bowel lengthens and
dilates and is thought to be a positive sign of adaptation.
However, this anatomical change may be associated with
complications such as altered intestinal motility that can
result in stasis of luminal contents and bacterial overgrowth
which can negatively impact adaptation. Surgical techniques
aimed to improve intestinal function by increasing bowel
length and reducing bowel diameter include the Bianchi
procedure and Serial Transverse Enteroplasty (STEP).14,15
The adaptive process occurs over many months or
years. 5,16 Increased enteral intake, or hyperphagia, is associated with intestinal adaptation in adults.17 The impact of
luminal nutrients upon intestinal adaptation is complex,
but likely involves a direct trophic effect on intestinal
epithelium, as well as stimulation of trophic hormones
and pancreaticobiliary secretions.18 In animal models, it
appears that a more complex nutrient enhances adaptation better than one that is simple or more processed.
313
For example, disaccharides enhance adaptation more

effectively than monosaccharides,19 and whole proteins
are more adaptogenic than protein hydrolysates. 20 Testing
these findings in the human have not been undertaken in
a rigorous fashion. Hormones and growth factors such
as growth hormone, glucagon-like peptide 2, glutamine,
cholecystokinin, gastrin, insulin, peptide YY, and entero
glucagon, as well as dietary fiber and short-chain fatty acids
have been shown to be involved in the adaptive process,
but their clinical significance in humans remains unclear.18
The functional capabilities of the remnant intestine also
impacts adaptation. For instance, complete absence of
the ileum precludes absorption of bile acids and vitamin
B12 . The absence of the ileal-cecal valve appears to have a
negative impact on intestinal adaptation for some, but not
all patients. 35,21,22 However, it is possible that the presence
of a sufficient length of colon may be just as, if not more,
important than the presence or absence of the ileal-cecal
valve.23,24 A biomarker for intestinal adaptation, such as
citrulline,25 would ideally reflect the quality and quantity of
intestinal function, but its clinical usefulness is uncertain.
Markers of hepatic function in patients with IF have not
been evaluated. Valid biomarkers are urgently needed so
that successful rehabilitation regimens can be objectively
identified, and adaptation failure can be recognized earlier.
Translational studies to identify potential genetic susceptibilities that would favor or impede intestinal adaptation
have not been performed.26
Management
Enteral Nutrition
Enteral feeding is essential if intestinal adaptation is to
occur. The 2 initial considerations are the type of formula
used and the manner in which it is provided. Breast milk
is preferred and its use has been associated with decreased
duration of PN. 3 The beneficial effects of breast milk are
attributable to its immunoprotective properties, effect on
postnatal development of intestinal flora, and its nutrient
composition that includes long-chain triglycerides (LCTs),
free amino acids, nucleotides, and growth factors as well
as complex protein and fat. 27 When breast milk is unavailable, however, formula choice is complicated by a variety of
options that reflect differences in the desired complexity of
protein, fat, and carbohydrate. Complex nutrients, such as
polysaccharides and whole protein, increase the functional
workload of the intestine, and as result, may stimulate adaptation.28 Unfortunately, studies to identify the ideal enteral
protein 2931 and lipid32 have been plagued by insufficient
314
numbers of patients or have been extrapolated from animal

models.
A variety of methods are used to deliver enteral feedings to the intestinal lumen and include oral, gastric as
bolus or continuous, or jejunal which can only be given
as a continuous feeding. Advantages of early oral feeding
include stimulation of oral digestive enzymes and maintenance of oral feeding skills to prevent oral aversion. 33 If the
patient is capable of oral feeding, but is incapable of taking
sufficient calories, supplemental direct enteral feeding is
possible via a nasogastric tube, gastrostomy, or direct jejunal
feeding. Continuous enteral infusion was found to be more
beneficial in very low birth weight infants, 34 but studies in
piglets suggest that bolus feedings are more advantageous. 35
Continuous versus bolus feedings have not been thoroughly
studied in older infants and children.
Clinical decisions to adjust the enteral feeding regimen
are determined by a number of factors, primarily stool or
ostomy output, evidence of malabsorption, and other less
objective symptoms such as abdominal fullness, irritability,
and regurgitation. Currently, decisions related to advancing
enteral feeding, weaning PN, and long-term monitoring
of patients at risk for growth failure are based almost
completely upon experience, tradition, and art rather than
evidence-based algorithms. However, the understanding of
the relative importance of these factors, how they are incorporated into the daily management, and how they impact
adaptation in patients with IF/SBS is critical if management
of infants with IF/SBS is to move beyond art and tradition
and into an evidence-based practice of medicine.
Parenteral nutrition (PN), first introduced in the late 1960s,
is now an established life-saving treatment for children with
IF/SBS. 3638 Components of PN include glucose, amino
acids, lipids, electrolytes, vitamins, minerals, trace elements,
and water. Glucose is the primary source of energy in PN,
but glucose oxidation varies depending upon age and diagnosis. 39,40 Glucose infusion rates that are in excess of the
patients oxidative capacity will promote fat deposition.41
While glucose infusion rates vary, an intake greater than
10 mg/kg/min may result in the conversion of glucose to
fat.42 An amino acid solution, ranging from > 2.5 g/kg/d for
preterm infants to 0.75 g/kg/d for adolescents, is administered to support protein metabolism.43 Amino acids are best
utilized when balanced with a proper proportion of nonnitrogen calories. The ideal ratio of nitrogen:non-nitrogen
calories is estimated to be between 1:150 to 1:400.44 The
lipid source currently available in the United States is soy
based. It is administered to prevent essential fatty acid

deficiency and to provide an efficient, high-density caloric
source. An estimated 0.5 g/kg/d of intravenous lipid is the
minimal requirement to prevent deficiency.45 An intravenous lipid preparation containing omega-3 fatty acids was
recently reported to reduce the incidence of PN-related
cholestasis,46 but it has not been rigorously studied in
children. Similar reductions in serum bilirubin have been
achieved by limiting soy-derived lipid to 1 g/kg/d or less.
Serum electrolytes are monitored on a regular basis and
adjustments in electrolyte concentration are based on individual needs of the patient. Guidelines for pediatric vitamin,
mineral, and trace element supplementation are available,
but they are supported by a paucity of data. 37 While PN is
life saving in children with IF/SBS, long-term use of PN
is often complicated by sepsis and liver disease which can
become life threatening.
Given the host of potential complications associated
with PN and IF/SBS, careful longitudinal monitoring
should be implemented to reduce complications and
improve outcome. The frequency of monitoring will depend
upon patient age, duration of PN, and acute changes in the
clinical condition. Growth parameters (eg, height or length,
weight, head circumference) should be checked at each
clinical visit. For infants and young children, monthly visits
are typical. For older children, on stable PN, visit frequency
can be extended to every 3 to 4 months. Please see chapter
on evaluation and monitoring (Chapter 36).
Fluid Management
In addition to PN, children may also require supplemental
fluid management. This is particularly important for children with an ileostomy or those who are in continuity, but
with a short length of colon. These children are at increased
risk of developing salt and water depletion and should be
monitored carefully.47 Unless the childs fluid and electrolyte requirements are very consistent day to day and week to
week, supplemental fluids should be calculated and administered separate from PN as this allows for more rapid,
and less expensive, adjustments in fluid and electrolyte
administration.
Medications
A variety of medications are used to manage symptoms and
complications associated with IF/SBS. It is important to
know that not one of them has been studied in a randomized fashion in an adequately powered study.
Intestinal dysmotility is common in children with IF/
SBS. Anti-motility agents (eg, loperamide) are used in an
INTESTINAL FAILURE
attempt to delay intestinal transit in hopes to provide a

longer duration of contact between the intestinal mucosa
and luminal nutrients. Children with gastroschisis are
more likely to have problems with delayed gastric emptying
and non-propulsive intestinal motility. In this setting,
pro-motility agents (eg, metoclopramide, erythromycin,
or amoxicillin-clavulanic acid) have been used to improve
intestinal motility. Cisapride was removed from the market
in the United States due to its association with cardiac
arrhythmias.
Anti-secretory agents are used to reduce fluid secretion
and stool output. Histamine-2 blockers and proton pump
inhibitors might be useful during the early months following
massive intestinal resection. However, continued use, in
the absence of clear benefit, may place the child at increased
risk for bacterial overgrowth or Candida esophagitis as
gastric acid serves a useful function in limiting fungal and
bacterial growth.
Bile acid binding resins (eg, cholestyramine) have been
tried in patients with little or no ileum when increased stool
output is thought to be related to bile acid malabsorption.
These agents are not easily administered, have little or no
palatability, and their efficacy in this clinical setting has not
been tested.
Non-Transplant Surgery
Half of children with SBS will have more than one abdominal operation.48 Following the initial surgical intervention,
subsequent surgeries often address complications such
as stricture, intestinal dilation, and placement of invasive
feeding devices which are all considered standard of care.49
Longitudinal intestinal lengthening and tailoring
(LILT) and STEP represent advanced techniques that
both taper dilated segments of bowel and increase intestinal length. Digestive function may improve not only
because aboral flow is facilitated by a normalized luminal
caliber, but also because subsequent adaptation may
lead to increased intestinal surface area. LILT was first
described in 1980 by Bianchi,15 and has since been used
at many centers.1 Criteria for using LILT vary, but generally require greater than 20 cm of symmetrically dilated
intestine in the context of residual intestine > 40 cm.1
Standardized indications, contraindications, and surgical
guidelines have not been developed, which may explain
inconsistent results reported in literature. 50 STEP involves
the application of a stapling device incompletely across
a dilated loop of intestine in serial fashion to create a
zig-zag pattern that results in a lumen both narrower and
longer. Since its description by Kim et al 51 in 2003, it has
315
become an accepted technique at many intestinal failure

centers. 52
While there is a growing literature describing individual experiences with non-transplant surgery for children
with IF/SBS, the relatively small numbers of patients, retrospective nature of data collection spanning many years, and
heterogeneous definitions and patient characteristics have
limited the ability to promulgate data-driven indications
and timing for these techniques.
General Principles
With the understanding that management of IF is highly
individualized and that evidence-based practice supported
by randomized, controlled trials is lacking, the following
outline might serve as a principled guide to the management of intestinal failure in children:
1. TPN
a. Glucose infusion rate: < 15 mg/kg/min for the duration
of infusion.
b. Protein: < 3 g/kg/d, closer to 3 for infants, lower for older
children.
c. Fat: In the first month, may need 12 g/kg/d; but after
that, with an eye on the degree of cholestasis and total
caloric needs, would consider different strategies.
i. 1 g/kg/d given every other day; or MWF or M/Th.
ii. Lipid reduction presumes that some enteral feeding
is possible.
iii. Follow essential fatty acids every 3 months.
d. Fluid: Based on needs, it is hard to provide sufficient calories with less than 125 cc/kg/d; may need additional salt
and water to support losses.
2. Enteral feeds
a. Use oral feeds if at all possible to maintain oral skills and
stimulate EGF, even if the child has a G-tube. 35 cc/feed
and then gradually increase as one can.
b. Breast milk is preferred and a casein hydrolysate/MCTcontaining formula is the authors fallback, assuming that
intestinal adaptation is favored by a more complex enteral
diet; use of an amino acid-containing formula can be
reserved for protein allergy.
c. J-tubes should be used rarely, as they further shorten the
length of useable bowel length.
3. Advancing feeds/reducing PN
a. The patient will tell you.
i. More concerned about the volume of stools than the
number (which can be confused with squirts); so,
for example, 10 stools per day may be okay if only
34 or so are big enough to leave the diaper; if the
bottom is not excoriated; if the family is comfortable; if
hydration is maintained.
316
ii. Aim for a rate of weight gain that follows the isopleth in
a box that surrounds the 5th percentile; adjust for SGA.
Not trying to achieve weight gain at the 50th percentile,
although if one can with minimal PN support, that is
fine. The goal is to find the minimal amount of PN to
support reasonable weight gain and growth.
b. Once on < 25% total calories from PN, and reasonable
stool output and satisfactory weight gain and growth
is established, one may consider a change from PN to
D10 LR observe for 23 months; then hold the fluids for
2months or so before pulling the line; unless the line is so
much trouble that keeping it in is too problematic.
4. Non-transplant surgery
a. When to consider in a child with short bowel syndrome
i. A sufficient length of small bowel is dilated and
1. Enteral feedings are not able to be advanced
2. The child is experiencing poor weight gain and/
or growth
b. What type of surgery?
i. May be surgeon specific; a learning curve is needed
for both the STEP and Bianchi, but more so for the
Bianchi
ii. You can STEP a STEP, and STEP a Bianchi, but you
cannot Bianchi a STEP
Complications
Nutrition Deficiencies
Deficiencies in vitamins, minerals, and trace elements
are associated with IF/SBS. Malabsorption of fat-soluble
vitamins A, D, E, and K may result from an insufficient
intraluminal concentration of bile acids secondary to
excess fecal loss. 53 Surgical resections of the duodenum or
ileum, which have unique absorptive functions, add to the
risk of developing nutrition deficiencies. The duodenum is
a primary site for iron and folate absorption and its resection can result in these micronutrient deficiencies. Absence
of the ileum, with its unique ability to absorb vitamin B12
and bile acids, places the patient at risk for fat-soluble
vitamin and vitamin B12 deficiency. Calcium and magnesium deficiencies can result from binding to intraluminal
long-chain fatty acid. 54,55 Deficiencies of other minerals and
trace elements such as zinc, riboflavin, thiamin, biotin, and
also selenium can occur. 56 In addition, nutrient deficiencies hinder intestinal adaptation further compounding the
clinical impact. 57
Functional and Metabolic Complications

Following massive bowel resection that alters normal intestinal physiology, a number of acute and chronic medical
complications develop that prompt an effort for medical
interventions. Unfortunately, many interventions and
treatments have not been adequately studied with sufficient
numbers of patients.
Hypergastinemia develops shortly after small bowel
resection and can reduce nutrient absorption by inactivating pancreatic enzymes, and precipitating bile salts,
thus leading to diarrhea as well as nausea and vomiting. 5860
Small case series have reported mixed benefits of acid
reduction to improve absorption. 6164 However, there are
no large trials demonstrating a benefit to the use of these
medications in children with IF/SBS. Indiscriminate use of
these medications may predispose patients to small bowel
bacterial overgrowth, calcium and iron malabsorption, or a
heightened risk of Candida esophagitis or sepsis.65 Bile acid
malabsorption as a consequence of ileal resection can result
in a secretory diarrhea that complicates fat and fat-soluble
vitamin absorption.66 Rapid intestinal transit occurs
following small bowel resection67,68 and is often managed
with the use of anti-motility agents such as loperamide
which have mixed effects on water and salt balance.69,70
Nephrolithiasis, when it occurs in the setting of IF/SBS, is
typically due to either uric acid or calcium oxalate stones.71
Alterations in gastrointestinal motility, along with
the use of acid blocking agents, may increase the bacterial content in the small intestine resulting in bacterial
overgrowth (BO). BO can deconjugate luminal bile acids
making them ineffective in micellar formation and can
be associated with mucosal inflammation, nutrient deficiencies (notably vitamin B12), D-lactic acidosis as well as
cramps, diarrhea, GI bleeding, and arthritis. The relationship between small bowel BO and systemic sepsis is not well
understood.7275 BO is most often treated empirically with
intermittent oral doses of broad-spectrum antibiotics, and
in some cases probiotics, but there are many varying practices for the frequency and duration of administration with
no data available to evaluate relative efficacies.
D-lactic acidosis is a unique feature of patients with
IF/SBS and was first described in children in 1983.76
The combination of a high anion gap acidosis and altered
mental status that develops after a high carbohydrate
enteral feeding should prompt the clinical suspicion of
D-lactic acidosis. Treatment involves discontinuation of
enteral feeding, selective bowel decontamination, and, if
needed, a surgical procedure aimed at decreasing intestinal
diameter and reducing bacterial overgrowth.77,78 Frequent
INTESTINAL FAILURE
antibiotic therapy may, paradoxically, place the patient at

risk for D-lactic acidosis by creating a selective advantage
for D-lactate producing bacteria.79
Liver Disease
Liver disease is the most frequent complication of long-term
PN with consequences that include cirrhosis, end-stage liver
disease, and even death.80 The incidence of IF/SBS-associated liver disease (IFALD) is as high as 50% in infants who
receive PN for 2 months with end-stage liver disease developing in 90% of premature infants on PN for more than
3 months.81 Elevated serum transaminase and bilirubin
levels are commonly observed in infants on PN, but these
levels can normalize and jaundice resolve with intestinal
adaptation and PN withdrawal. The long-term outcome
of IFALD in patients who adapt is unknown. The population currently thought to be at greatest risk for IFALD are
premature infants with a birth weight < 1 kg and those with
IF/SBS resulting from surgical resection.8284 The etiology of
IFALD remains unknown but is likely multi-factorial with
prematurity, multiple abdominal surgeries, lack of enterally
stimulated bile flow, bacterial sepsis, and components or
deficiencies of PN infusates all potential contributors.
Treatment of PN-associated liver disease is empiric and
imperfect. Current strategies to avert liver disease associated with long-term PN include employing a choleretic such
as ursodeoxycholic acid, 85 bowel decontamination to treat
bacterial overgrowth, 83,85 vigilant daily catheter care,86 and
modifying PN formulations. Infusing PN calories over less
than 24 hours, casually referred to as cycling PN, is thought
to improve cholestasis.87 The underlying mechanism for this
action and effect is not clearly understood, but may involve
providing a metabolic rest from the continuous infusion
of calories, protein, and/or carbohydrate. Administration of
pediatric formulations of PN that include specific targeted
amino acids including taurine88 and limiting the infusion
of dextrose so as to potentially decrease steatosis have also
been utilized.89 Decreasing the aluminum and manganese
content in PN may decrease hepatotoxicity.90,91 Decreasing
the amount or altering the type of lipids administered may
improve serum transaminase levels, reverse PN-associated
liver disease, or reduce lipid peroxidation.46,92,93 Recently,
use of a fish oil-based intravenous lipid source was found to
be associated with improvement of serum bilirubin in two
children,46 although its long-term use in an animal model
was associated with increased fibrosis.94 Unfortunately,
most of these interventions to reduce or prevent IFALD
are employed empirically and lack significant clinical
confirmation in large pediatric trials. Once end-stage liver
317
disease develops, portal hypertension, variceal and stomal

bleeding, infection, hypoglycemia, and hyperammonemia
occur, making a combined liver-intestinal transplant the
only remaining life-saving measure.
Central Line Complications

Maintaining central venous catheter (CVC) access is critical
in the long-term management of IF/SBS. Loss of vascular
access can be fatal in this population and is an indication for
intestinal transplantation. As a result, salvage of the CVC
line is a strategy employed to preserve vascular access. In
addition, the advancement of newer approaches such as
recanalization of a thrombosed vessel has been employed
in selected patients when vascular sites are limited.95,96 The
threshold for removing CVC lines and referral to centers that
perform recanalization is likely variable from both an institutional and physician standpoint. A greater understanding
of the source of this variability will allow standardization to
a best practice model and allow centers participating in
this collaborative to preserve access sites and better equip
patients for long-term survival.
Sepsis is an important cause of death in children with
IF/SBS. Accordingly, multiple factors contribute to the
management of suspected sepsis in the patient with IF/SBS
including age and presence of a CVC. Catheter-associated
bloodstream infections (CABSIs) are responsible for a
majority of the infectious morbidity. While the true incidence of CABSIs is unknown, IF/SBS patients constitute
a high-risk group within the CVC population. Potential
risk factors include the proximity of fecal material to line
entry sites and connections, frequent line access for laboratory tests, and intestinal bacterial translocation. While
translocation occurs in animal models, its proof in human
populations is elusive.97 At the same time, several lines of
evidence suggest a role for bacterial translocation in IF/
SBS. There is a greater incidence of enteric organisms
isolated in cultures from these patients compared to other
populations with CVC lines.98 Furthermore, a comparison
of CVC isolates with fecal flora and mesenteric lymph node
cultures were highly concordant.99 Finally, the incidence
of infection has been demonstrated to be increased while
advancing enteral feeds.100
While CABSIs are of the greatest concern, patients
with IF/SBS are also subject to numerous other central
line-related complications. Of these, thrombosis and line
breakage are the 2 most frequent. Fortunately, there is a
high salvage rate and treatment with thrombolytics or CVC
repair has been shown to result in a high CVC salvage rate.101
The development of consensus guidelines based upon the
318
accrual of data across the population of IF/SBS is predicted

to reduce CVC-associated complications as well as lengthen
the life-span of each individual catheter and preserve access
sites critical to survival and potential transplantation.
Outcomes
Infants and children must digest and absorb sufficient
calories, vitamins, minerals, and trace elements to gain
weight, grow, and develop. Children with IF/SBS are incapable of sustaining adequate growth and development
without supplemental PN. Successful intestinal adaptation
implies complete independence from PN while continuing
to demonstrate satisfactory growth and development.
However, there are no prospective studies available to
address long-term growth and development in children
with IF/SBS following PN withdrawal. A recent retrospective study of 87 children identified over a period of 16 years
provides some insight into the long-term problems that
children with IF/SBS may face.16 The authors found that in
those children who achieved enteral autonomy, maximum
weight gain and growth was achieved during the first 4 years
after weaning PN. However, between 4 and 8 years post-PN,
weight gain and growth, expressed as a z score, appeared
to decline with the weight z score 8 years post-PN almost
identical to the weight at the time of weaning and height z
score slightly lower than the score at the time of weaning.
Interestingly, 21 children were noted to enter puberty at an
age similar to their peers.
Quality of Life
Studies in adult patients have identified reduced quality of
life (QOL) scores in patients with SBS, which were further
reduced if the patient was on HPN. Interestingly, the presence of a stoma did not appear to influence their quality
of life.102 Similarly detailed studies that address QOL and
school performance have not been performed in children,
however, children on HPN appear to fare better than those
hospitalized for PN.103,104
Intestinal Transplant
Intestinal transplant is reserved as the final life-saving
procedure for patients with irreversible IF/SBS and lifethreatening complications of PN administration. In 1994,
very few intestinal transplants were performed in the pediatric population worldwide (approximately 25 according
to the Intestinal Transplant Registry), with unsatisfactory outcomes in these early years.1 With advances in
posttransplant care and immunosuppression protocols,

these outcomes have drastically improved. 2 More than
900 intestinal transplants have now been performed in all
age groups worldwide, with more than 500 in the pediatric
population.2,3 Five-year patient survival rates exceed 50%
worldwide.4 Unfortunately, the indications for intestinal
transplant are broad and subject to a significant degree of
interpretation. There is a need for evidence-based parameters
that would improve the selection of patients for intestinal
transplant and determine optimal timing for transplant to
maximize outcomes and minimize the need for combined
organ transplantation.
A subset of patients with IF/SBS and associated liver
disease may benefit from an isolated liver transplant.105107
It has been postulated that IFALD may hinder bowel
adaptation and delay progression toward enteral feeding
tolerance.8 In fact, various authors have reported remarkable bowel adaptation and feeding tolerance after isolated
liver transplant for severe IFALD.4,5,105
1. A 30-week infant with 35 cm of small bowel, an ilealcecal valve, and an intact colon has an advantage over a
full-term infant with the same anatomy because:
A. Etiologies for short bowel syndrome are different
between the two groups.
B. Premature infants who survive are constitutionally
stronger than full-term infants.
C. The small intestinal length doubles in the last
trimester.
D. Complications associated with PN are less frequent
in the premature infant.
2. A clinical feature associated with enteral autonomy is:
A. Being a female
B. Small intestine in continuity with the colon
C. Absent ileal-cecal valve
D. Having fewer than 10 stools per day
3. PN associated liver disease is caused by:
A. Intravenous lipid
B. Lack of enteral feeding
C. Recurrent infections
D. Multiple factors, including all of the above
4. The best method to provide enteral feeding for children
with intestinal failure is via:
A. Gastrostomy
B. Nasogastric tube
C. Jejunal feeding
D. Oral feeding
INTESTINAL FAILURE
References
1. Goulet O, Ruemmele F, Lacaille F, Colomb V. Irreversible intestinal failure. J Pediatr Gastroenterol Nutr.
2004;38(3):250269.
2. Kocoshis SA, Beath SV, Booth IW, et al. Intestinal failure
and small bowel transplantation, including clinical nutrition: Working Group Report of the Second World Congress
of Pediatric Gastroenterology, Hepatology, and Nutrition. J
Pediatr Gastroenterol Nutr. 2004;39(Suppl 2):S655S661.
3. Andorsky DJ, Lund DP, Lillehei CW, et al. Nutritional and
other postoperative management of neonates with short
bowel syndrome correlates with clinical outcomes. J Pediatr.
2001;139(1):2733.
4. Goulet OJ, Revillon Y, Jan D, et al. Neonatal short bowel
syndrome. J Pediatr. 1991;119(1 ( Pt 1)):1823.
5. Quios-Teijeira RE, Ament ME, Reyen L, et al. Long-term
parenteral nutritional support and intestinal adaptation in
children with short bowel syndrome: a 25-year experience. J
Pediatr. 2004;145(2):157163.
6. Spencer AU, Neaga A, West B, et al. Pediatric short bowel
syndrome: redefining predictors of success. Ann Surg.
2005;242(3):403409; discussion 409412.
7. Touloukian RJ, Smith GJ. Normal intestinal length in preterm
infants. J Pediatr Surg. 1983;18(6):720723.
8. DeLegge M, Alsolaiman MM, Barbour E, et al. Short bowel
syndrome: parenteral nutrition versus intestinal transplantation. Where are we today? Dig Dis Sci. 2007;52(4):876892.
9. Wallander J, Ewald U, Lackgren G, et al. Extreme short bowel
syndrome in neonates: an indication for small bowel transplantation? Transplant Proc. 1992;24(3):12301235.
10. Schalamon J, Mayr JM, Hollwarth ME. Mortality and
economics in short bowel syndrome. Best Pract Res Clin
Gastroenterol. 2003;17(6):931942.
11. Colomb V. Economic aspects of paediatric home
parenteral nutrition. Curr Opin Clin Nutr Metab Care.
2000;3(3):237239.
12. Tavakkolizadeh A, Whang EE. Understanding and augmenting human intestinal adaptation: a call for more clinical
research. J Parenter Enteral Nutr. 2002;26(4):251255.
13. Drozdowski L, Thomson AB. Intestinal mucosal adaptation .
World J Gastroenterol. 2006; 2(29):46144627.
14. Javid P, Kim H, Duggan C, Jaksic T. Serial transverse enteroplasty is associated with successful short-term outcomes
in infants with short bowel syndrome. J Pediatr Surg.
2005;40(6):10191023; discussion 10231024.
15. Bianchi A. Intestinal loop lengthening--a technique
for increasing small intestinal length. J Pediatr Surg.
1980;15(2):145151.
16. Goulet O, Gobet B, Talbotec C, et al. Outcome and longterm growth after extensive small bowel resection in the
neonatal period: a survey of 87 children. Eur J Pediatr Surg.
2005;15(2):95101.
17. Crenn P, Morin MC, Joly F, Penven S, Thuillier F, Messing B.
Net digestive absorption and adaptive hyperphagia in adult
short bowel patients. Gut. 2004;53(9):12791286.
18. DiBaise JK, Young RJ, Vanderhoof JA. Intestinal rehabilitation and the short bowel syndrome: part 1. Am J Gastroenterol.
2004;99(7):13861395.
319
19. Weser E, Babbitt J, Hoban M, Vandeventer A. Intestinal adaptation. Different growth responses to disaccharides compared
with monosaccharides in rat small bowel. Gastroenterology.
1986;91(6):15211527.
20. Vanderhoof JA, Grandjean CJ, Burkley KT et al. Effect of
casein versus casein hydrolysate on mucosal adaptation
following massive bowel resection in infant rats. J Pediatr
21. Wasa M, Takagi Y, Sando K, et al. Intestinal adaptation in
pediatric patients with short-bowel syndrome. Eur J Pediatr
Surg. 1999;9(4):207209.
22. Gambarara M, Ferretti F, Bagolan P. Ultra-short-bowel
syndrome is not an absolute indication to smallbowel transplantation in childhood. Eur J Pediatr Surg.
1999;9(4):267270.
23. Jeppesen PB, Mortensen PB. The influence of a preserved
colon on the absorption of medium chain fat in patients with
small bowel resection. Gut. 1998;43(4):478483.
24. Nightingale JM, Lennard-Jones JE, Gertner DJ, et al.
Colonic preservation reduces need for parenteral therapy,
increases incidence of renal stones, but does not change high
prevalence of gall stones in patients with a short bowel. Gut.
1992;33(11):14931497.
25. Luo M, Fernndez-Estvariz C, Manatunga AK, et al. Are
plasma citrulline and glutamine biomarkers of intestinal
absorptive function in patients with short bowel syndrome? J
26. Bernal NP, Stehr W, Zhang Y, Profitt S, Erwin CR, Warner
BW. Evidence for active Wnt signaling during postresection
intestinal adaptation. J Pediatr Surg. 2005;40(6):10251029;
discussion 1029.
27. Levy J. Immunonutrition: the pediatric experience. Nutrition.
1998;14(78):641647.
28. Vanderhoof JA, Langnas AN. Short-bowel syndrome in children and adults. Gastroenterology. 1997;113(5):17671778.
29. Ksiazyk J, Piena M, Kierkus J, Lyszkowska M. Hydrolyzed
versus nonhydrolyzed protein diet in short bowel syndrome in
children. J Pediatr Gastroenterol Nutr. 2002;35(5):615618.
30. Bines J, Francis D, Hill D. Reducing parenteral requirement
in children with short bowel syndrome: impact of an amino
acid-based complete infant formula. J Pediatr Gastroenterol
Nutr. 1998;26(2):123128.
31. Taylor S, Sondheimer J, Sokol R, Silverman A, Wilson H.
Noninfectious colitis associated with short gut syndrome in
infants. J Pediatr. 1991;119(1 ( Pt 1)):2428.
32. Vanderhoof JA, Grandjean CJ, Kaufman SS, Burkely KT,
Antonson DL. Effect of high percentage medium-chain triglyceride diet on mucosal adaptation following massive bowel
resection in rats. J Parenter Enteral Nutr. 1984;8(6):685689.
33. Blackman JA, Nelson CL. Reinstituting oral feedings in
children fed by gastrostomy tube. Clin Pediatr. (Phila)
1985;24(8):434438.
34. Dsilna A, Christensson K, Alfredsson L, et al. Continuous
feeding promotes gastrointestinal tolerance and growth in
very low birth weight infants. J Pediatr. 2005;147(1):4349.
35. Shulman RJ, Redel CA, Stathos TH. Bolus versus continuous feedings stimulate small-intestinal growth and
development in the newborn pig. J Pediatr Gastroenterol Nutr.
1994;18(3):350354.
320
36. Rhoads JE. The development of TPN: an interview with

pioneer surgical nutritionist Jonathan E. Rhoads, MD. [Interview by Carolyn T. Spencer and Charlene Compher]. J Am
Diet Assoc. 2001;101(7):747750.
37. Shulman RJ, Phillips S. Parenteral nutrition in infants and
38. Dudrick SJ, Wilmore DW, Vars HM, Rhoads JE. Long-term
total parenteral nutrition with growth, development, and
positive nitrogen balance. Surgery. 1968;64(1):134142.
39. Lafeber HN, Sulkers EJ, Chapman TE, et al. Glucose production and oxidation in preterm infants during total parenteral
nutrition. Pediatr Res. 1990;28(2):153157.
40. Sheridan RL, Yong-Ming Y, Prelack K, Young VR, Burke
JF, Tompkins RG. Maximal parenteral glucose oxidation
in hypermetabolic young children: a stable isotope study. J
41. Kalhan SC, Kilic I. Carbohydrate as nutrient in the infant
and child: range of acceptable intake. Eur J Clin Nutr.
1999;53(Suppl 1):S94S100.
42. Nose O, Tipton JR, Yabuuchi H. Effect of the energy source
on changes in energy expenditure, respiratory quotient, and
nitrogen balance during total parenteral nutrition in children.
Pediatr Res. 1987;21(6):538541.
43. Safe Practices for Parenteral Nutrition Formulations.
National Advisory Group on Standards and Practice
Guidelines for Parenteral Nutrition. J Parenter Enteral Nutr.
1998;22(2):4966.
44. Peters C, Fischer JE. Studies on calorie to nitrogen ratio for total
parenteral nutrition. Surg Gynecol Obstet. 1980;151(1):18.
45. Gutcher GR, Farrell PM. Intravenous infusion of lipid for
the prevention of essential fatty acid deficiency in premature
infants. Am J Clin Nutr. 1991;54(6):10241028.
46. Gura KM, Duggan CP, Collier SB, et al. Reversal of parenteral
nutrition-associated liver disease in two infants with short
bowel syndrome using parenteral fish oil: implications for
future management. Pediatrics. 2006;118(1):e197e201.
47. Schwarz K, Ternberg J, Bell M, Keating J. Sodium
needs of infants and children with ileostomy. J Pediatr.
1983;102(4);509513.
48. Thompson JS. Reoperation in patients with the short bowel
syndrome. Am J Surg. 1992;164(5):453456; discussion
456457.
49. Wales PW. Surgical therapy for short bowel syndrome. Pediatr
Surg Int. 2004;20(9):647657.
50. Bianchi A. From the cradle to enteral autonomy: the role of
autologous gastrointestinal reconstruction. Gastroenterology.
2006;130(2 Suppl 1):S138S146.
51. Kim HB, Fauza D, Garza J, Oh JT, Nurko S, Jaksic T. Serial
transverse enteroplasty (STEP): a novel bowel lengthening
procedure. J Pediatr Surg. 2003;38(3):425429.
52. Modi B, Javid P, Jaksic T, et al. First Report of the International Serial Transverse Enteroplasty Data Registry:
Indications, Efficacy, and Complications. J Am Coll Surg.
2007; 204(3):365371.
53. Ohkohchi N, Andoh T, Izumi U, Igarashi Y, Ohi R. Disorder of
bile acid metabolism in children with short bowel syndrome. J
Gastroenterol. 1997;32(4):472479.
54. Ament ME. Bone mineral content in patients with short

bowel syndrome: the impact of parenteral nutrition. J Pediatr.
1998;132(3 Pt 1):386388.
55. Fleming CR, George L, Stoner GL, et al. The importance of
urinary magnesium values in patients with gut failure. Mayo
Clin Proc. 1996;71(1):2124.
56. Buchman AL. Etiology and initial management of short bowel
syndrome. Gastroenterology. 2006;130(2 Suppl 1):S5S15.
57. Ziegler TR, Evans ME, Fernndez-Estvariz C, Jones DP.
Trophic and cytoprotective nutrition for intestinal adaptation, mucosal repair, and barrier function. Annu Rev Nutr.
2003;23:229261.
58. Buxton B. Small bowel resection and gastric acid hypersecretion. Gut. 1974;15(3):229238.
59. Go VL, Poley JR, Hofmann AF, Summerskill WH. Disturbances in fat digestion induced by acidic jejunal pH
due to gastric hypersecretion in man. Gastroenterology.
1970;58(5):638646.
60. Williams NS, Evans P, King RF. Gastric acid secretion
and gastrin production in the short bowel syndrome. Gut.
1985;26(9):914919.
61. Cortot A, Fleming CR, Malagelada JR. Improved nutrient
absorption after cimetidine in short-bowel syndrome with
gastric hypersecretion. N Engl J Med. 1979;300(2):7980.
62. Nightingale JM, Walker ER, Farthing MJ, Lennard-Jones JE.
Effect of omeprazole on intestinal output in the short bowel
syndrome. Aliment Pharmacol Ther. 1991;5(4):405412.
63. Tang SJ, Nieto J, Jenson DM, Ohning GV, Pisegna JR.
The novel use of an intravenous proton pump inhibitor in
a patient with short bowel syndrome. J Clin Gastroenterol.
2002;34(1):6263.
64. Malagelada JR. Pathophysiological responses to meals in the
Zollinger-Ellison syndrome: 2. Gastric emptying and its effect
on duodenal function. Gut. 1980;21(2):98104.
65. Chocarro MA, Galindo TF, Ruiz-Irastorza G, et al. Risk
factors for esophageal candidiasis. Eur J Clin Microbiol Infect
Dis. 2000;19(2):96100.
66. Westergaard H. Bile acid malabsorption . Curr Treat Options
Gastroenterol. 2007;10(1): 2833.
67. Nightingale JM, Kamm MA, van der Sijp JR, et al. Disturbed
gastric emptying in the short bowel syndrome. Evidence for a
colonic brake. Gut. 1993;34(9):11711176.
68. Reynell PC, Spray GH. Small intestinal function in the rat after
massive resections. Gastroenterology. 1956;31(4):361368.
69. Nightingale JM, Lennard-Jones JE, Walker ER. A patient
with jejunostomy liberated from home intravenous therapy
after 14 years; contribution of balance studies. Clin Nutr.
1992;11(2):101105.
70. Rodrigues CA, Lennard-Jones JE, Thompson DG, et al.
The effects of octreotide, soy polysaccharide, codeine and
loperamide on nutrient, fluid and electrolyte absorption
in the short-bowel syndrome. Aliment Pharmacol Ther.
1989;3(2):159169.
71. Nightingale JM. Hepatobiliary, renal and bone complications of intestinal failure. Best Pract Res Clin Gastroenterol.
2003;17(6):907929.
INTESTINAL FAILURE
72. Dibaise JK, Young RJ, Vanderhoof JA. Enteric microbial

flora, bacterial overgrowth, and short-bowel syndrome. Clin
Gastroenterol Hepatol. 2006;4(1):1120.
73. OKeefe SJ. Bacterial overgrowth and liver complications
in short bowel intestinal failure patients. Gastroenterology.
2006;130(2 Suppl 1):S67S69.
74. Puwanant ML, Mo-Suwan, Patrapinyokul S. Recurrent
D-lactic acidosis in a child with short bowel syndrome. Asia
Pac J Clin Nutr. 2005;14(2):195198.
75. Quigley EM, Quera R. Small intestinal bacterial overgrowth:
roles of antibiotics, prebiotics, and probiotics. Gastroenterology. 2006;130(2 Suppl 1):S78S90.
76. Perlmutter DH, Boyle JT, Campos JM, Egler JM, Watkins
JM. D-Lactic acidosis in children: an unusual metabolic
complication of small bowel resection. J Pediatr. 1983;
102(2):234238.
77. Mayne AJ, Handy DJ, Pierce MA, George RH, Booth IW.
Dietary management of D-lactic acidosis in short bowel
syndrome. Arch Dis Child. 1990;65(2):229231.
78. Hosie S, Loff S, Wirth H, Rapp HJ, von Buch C, Waag
KL. Experience of 49 longitudinal intestinal lengthening
procedures for short bowel syndrome. Eur J Pediatr Surg.
2006;16(3):171175.
79. Coronado BE, Opal SM, Yoburn DC. Antibiotic-induced
D-lactic acidosis. Ann Intern Med. 1995;122(11):839842.
80. Goulet O, Ruemmele F. Causes and management of intestinal failure in children. Gastroenterology. 2006;130(2 Suppl
1):S16S28.
81. Kelly DA. Liver complications of pediatric parenteral nutritionepidemiology. Nutrition. 1998;14(1):153157.
82. Teitelbaum DH. Parenteral nutrition-associated cholestasis.
Curr Opin Pediatr. 1997;9(3):270275.
83. Kelly DA. Intestinal failure-associated liver disease: what
do we know today? Gastroenterology. 2006;130(2 Suppl
1):S70S77.
84. Beale EF, Nelson RM, Bucciarelli RL, Donnelly WH, Eitzman
DV. Intrahepatic cholestasis associated with parenteral nutrition in premature infants. Pediatrics. 1979;64(3):342347.
85. Gnsar C, Melek M, Karaca I, et al. The biochemical and
histopathological effects of ursodeoxycholic acid and metronidazole on total parenteral nutrition-associated hepatic
dysfunction: an experimental study. Hepatogastroenterology.
2002;49(44):497500.
86. Colomb V, Fabeiro M, Dabbas M, Goulet O, Merckx J, Ricour
C. Central venous catheter-related infections in children
on long-term home parenteral nutrition: incidence and risk
factors. Clin Nutr. 2000;19(5):355359.
87. Burstyne M, Jensen GL. Abnormal liver functions as a result
of total parenteral nutrition in a patient with short-bowel
syndrome. Nutrition. 2000;16(1112):10901092.
88. Cooke RJ, Whitington PF, Kelts D. Effect of taurine supplementation on hepatic function during short-term parenteral
nutrition in the premature infant. J Pediatr Gastroenterol Nutr.
1984;3(2):234238.
89. Bresson JL, Narcy P, Putet G, Ricour C, Sachs C, Rey J.
Energy substrate utilization in infants receiving total parenteral nutrition with different glucose to fat ratios. Pediatr Res.
1989;25(6):645648.
321
90. Advenier E, Landry C, Colomb V, et al. Aluminum contamination of parenteral nutrition and aluminum loading in children
on long-term parenteral nutrition. J Pediatr Gastroenterol Nutr.
2003;36(4):448453.
91. Kafritsa Y, Fell J, Long S, Bynevelt M, Taylor W, Milla P.
Long-term outcome of brain manganese deposition in
patients on home parenteral nutrition. Arch Dis Child.
1998;79(3):263265.
92. Goulet O, de Potter S, Antbi H, et al. Long-term efficacy
and safety of a new olive oil-based intravenous fat emulsion
in pediatric patients: a double-blind randomized study. Am J
Clin Nutr. 1999;70(3):338345.
93. Cavicchi M, Crenn P, Beau P, Degott C, Boutron MC,
Messing B. Severe liver complications associated with longterm parenteral nutrition are dependent on lipid parenteral
input. Transplant Proc. 1998;30(6):2547.
94. Kohl M, Wedel T, Entenmann A, et al. Influence of
different intravenous lipid emulsions on hepatobiliary
dysfunction in a rabbit model. J Pediatr Gastroenterol Nutr.
2007;44(2):237244.
95. Rodrigues AF, Van Mourik IDM, Sharif K, et al. Management of end-stage central venous access in children referred
for possible small bowel transplantation. J Pediatr Gastroenterol Nutr. 2006;42(4):427433.
96. Lang EV, Reyes J, Faintuch S, Smith A, Abu-Elmagd K. Central
venous recanalization in patients with short gut syndrome:
restoration of candidacy for intestinal and multivisceral transplantation. J Vasc Interv Radiol. 2005;16(9):12031213.
97. Lichtman SN. Translocation of bacteria from gut lumen to
mesenteric lymph nodes--and beyond? J Pediatr Gastroenterol
Nutr. 1991;13(4):433434.
98. Piedra PA, Dryja DM, LaScolea LJ Jr. Incidence of catheterassociated gram-negative bacteremia in children with short
bowel syndrome. J Clin Microbiol. 1989;27(6):13171319.
99. Kurkchubasche AG, Smith SD, Rowe MI. Catheter sepsis in
short-bowel syndrome. Arch Surg. 1992;127(1):2124; discussion 2425.
100. Weber TR. Enteral feeding increases sepsis in infants with
short bowel syndrome. J Pediatr Surg. 1995;30(7):10861088;
discussion 10881089.
101. Moukarzel AA, Haddad I, Ament M, et al. 230 patient years of
experience with home long-term parenteral nutrition in childhood: natural history and life of central venous catheters. J
Pediatr Surg. 1994;29(10):13231327.
102. Carlsson E, Bosaeus I, Nordgren S. Quality of life and
concerns in patients with short bowel syndrome. Clin Nutr.
2003;22(5):445452.
103. Candusso M, Faraguna D, Sperli D, Dodaro N, et al. Outcome
and quality of life in paediatric home parenteral nutrition.
Curr Opin Clin Nutr Metab Care. 2002;5(3):309314.
104. Heine RG, Bines, JE. New approaches to parenteral nutrition in infants and children. J Paediatr Child Health.
2002;38(5):433437.
105. Botha JF, Grant WJ, Torres C, et al. Isolated liver transplantation in infants with end-stage liver disease due to short bowel
syndrome. Liver Transpl. 2006;12(7):10621066.
322
106. Diamond IR, Wales PW, Grant DR, Fecteau A. Isolated liver
transplantation in pediatric short bowel syndrome: is there a
role? J Pediatr Surg. 2006;41(5):955959.
107. Horslen SP, Sudan DL, Iyer KR et al. Isolated liver transplantation in infants with end-stage liver disease associated with
short bowel syndrome. Ann Surg. 2002;235(3):435439.
28
Pulmonary Disorders
Allison Mallowe, RD, LDN, Suzanne Michel, MPH, RD, LDN, and Maria Mascarenhas, MBBS
Learning Objectives
CONTENTS
Cystic Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
Pathophysiology
Nutrition Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325

Nutrition Recommendations . . . . . . . . . . . . . . . . . . . . . . . 325
Macronutrients
Micronutrients
Minerals
Nutrition Support. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pancreatic Enzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Eating Behaviors and CF. . . . . . . . . . . . . . . . . . . . . . . . . .
Nutrition-Related Cystic Fibrosis Complications. . . . . . .
329
330
330
331
Osteoporosis or Bone Disease

CF-Related Diabetes
Lung Transplantation
Gastrointestinal
Other Chronic Lung Diseases . . . . . . . . . . . . . . . . . . . . . . 332

Overview and Pathophysiology
Bronchopulmonary Dysplasia
Asthma
Technology Dependent
Nutrition Recommendations
Bone Health in Chronic Lung Disease
Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334
1. Understand the role of nutrition in lung disease.

2. Discuss nutrition as related to complications of cystic
fibrosis (CF).
3. List components of nutrition assessment for persons
with pulmonary disease.
4. Understand micronutrient abnormalities that can
occur in CF.
Cystic Fibrosis
Pathophysiology
Cystic fibrosis (CF) is a common autosomal recessive
genetic disorder that is most frequently seen in people of
northern European descent. In the United States CF occurs
in approximately 1 in 2,500 live births and affects approximately 30,000 Americans. The CF gene was isolated in
19891 and since then more than 1,500 mutations have been
identified. The gene, which is localized on the short arm of
chromosome 7, is called the cystic fibrosis transmembrane
regulator (CFTR) and controls the flow of sodium and
chloride ions across the cell membrane. Mutations in the
gene result in abnormal epithelial ion transport in multiple
organs in the body. Clinical outcomes have been related to
the type of mutation. With the advent of almost universal
newborn screening programs in the United States, it is estimated that the average life expectancy will increase from the
current median predicted life expectancy of 37.4 years. 2
Diagnosis during the newborn period by newborn
screening results in early nutrition intervention and
improved nutrition status, which may lead to better quality
of life and prolonged survival. (See Table 28-1 for clinical
features and diagnosis of CF.) Historically an abnormal
323
324
sweat test (chloride values > 60 mEq/L) was considered

diagnostic, but it is now recognized that this gold standard
may not always be abnormal. Based on the severity of the
mutation, the clinical picture is variable and gene analysis,
nasal potential differences, and sputum cultures may be
required for the diagnosis of CF. 3
Table 28-1 Clinical Features and Diagnosis of Cystic Fibrosis
Clinical Features Manifested
in Infants
Clinical Features Manifested

in the General CF Population
Meconium ileus
Meconium peritonitis
Intestinal atresia
Recurrent obstructive respiratory
disease/infections
Rectal prolapse
Failure to thrive
Obstructive jaundice
Hyponatremic dehydration
Malabsorption
Salty taste in sweat (when
kissed)
Zinc deficiency
Fat-soluble vitamin deficiency
Recurrent cough or wheeze

Clubbing of fingers and toes
Hyperinflation of chest
Cystic fibrosis-related diabetes
Chest wall deformities
Nasal polyps
Cirrhosis and portal hypertension
Recurrent pancreatitis
Gallbladder disease
Focal biliary cirrhosis
Zinc deficiency & EFAD dermatitis
Fat-soluble vitamin deficiencies
Hyponatremic deficiency without
renal disease
EFAD: essential fatty acid deficiency.

Adapted from Gottschlich MM. Pulmonary disease. In: Gottschlich MM.
The Science and Practice of Nutrition Support: A Core-Based Curriculum.
Dubuque, IA: Kendall/Hunt Publishing Co; 2001:501516.
Because the expression of the CF gene is limited to

epithelial cells, the organs affected are primarily mucusproducing organs such as lungs, gastrointestinal (GI) tract,
liver, pancreas, and sweat glands.4 The transport of sodium
and chloride across cell membranes is regulated by cyclic
adenosine monophosphate and calcium, both of which are
controlled by CFTR. 5 The respiratory epithelial cells are
impermeable to chloride ions which results in an increase
in airway sodium absorption. The movement of sodium
into the cells results in the movement of water into the cell,
leading to dehydration of the airway mucus and decreased
ciliary function. This results in viscous secretions in the
lung, liver, pancreas, and GI tract and in duct obstruction in
sweat glands and elevated sweat chloride levels.
Pulmonary involvement is initially associated with
infection with Staphylococcus aureus and later Pseudomonas
aeruginosa. Chronic pulmonary damage, bronchiectasis,
fibrosis, and decreasing lung function occur over time.
Impaired gas exchange occurs secondary to airflow
resistance, hyperinflation, and uneven distribution of ventilation. Bacterial adherence and colonization both result
in a sustained host inflammatory response. Stimulated

neutrophils release large amounts of oxidants and proteases
including elastase which leads to increased mucus production, bacterial trapping, and further lung damage.6 Clinical
symptoms include cough, production of mucus, air trapping, and ultimately end-stage lung disease requiring lung
transplantation.
In the pancreas there is accumulation of thick mucus
in the acinar glands leading to an obstruction of the ducts.
Damage occurs in the glands due to the release of lytic
enzymes resulting in chronic inflammation, fibrosis, fatty
infiltration of the pancreas, and pancreatic insufficiency
(PI). These changes can occur in utero in patients with
severe mutations. PI is seen in about 70% to 80% of patients
at diagnosis.7 Patients with adequate pancreatic function at
diagnosis who are pancreatic sufficient (PS) may go on to
develop PI over time, hence need to be monitored carefully.
Clinical symptoms of PI include malabsorption, diarrhea,
weight loss, poor growth, vitamin deficiencies, increased
gas, and abdominal pain. Some patients may have a voracious appetite in an effort to ingest sufficient calories to
compensate for energy loss in their bowel movement from
maldigestion and malabsorption. Approximately 5% to
15% of persons with CF will develop cystic fibrosis-related
diabetes (CFRD) and it is expected that this number will
increase as life expectancy increases. 8
Similar fluid and electrolyte disturbances occur in the
GI tract causing sticky mucus and stool accumulation which
can result in meconium ileus in the newborn and distal
intestinal obstruction syndrome (DIOS) in older children
and adults. Meconium ileus, or the build-up of meconium
in utero, is the earliest manifestation of CF. Infants can be
born with meconium plugs, intestinal obstruction, atresias,
volvulus, perforations, and meconium pseudocyst. DIOS is
the accumulation of sticky stool in the GI tract, primarily
in the terminal ileum and cecal area. It may occur in all
persons who have CF (PI and PS). Predisposing factors are
decreased fluid intake, decreased salt intake, malabsorption, and decreased motility. Other changes in the GI tract
include abnormal gastric and intestinal motility.
In the liver CFTR is expressed in the biliary epithelium, and similar abnormalities of ion transport occur. This
results in the decreased flow of bile with secondary hepatocyte damage, inflammation, fibrosis, and cirrhosis. In
males, obstruction of the vas deferens results in infertility
and in patients with mild mutations may be the presenting
feature that leads to the diagnosis of CF.
PULMONARY DISORDERS
There is a strong correlation between pulmonary function

and nutritional status. In children, a body mass index (BMI)
at or above the 50th percentile has been associated with
improved survival and optimal lung function. Associations
between deteriorating lung function and worsening nutrition status have been noted.4,9 Malnutrition results from:
increased needs (increased metabolic rate,10 infections,
work of breathing, cough); increased losses (malabsorption
due to pancreatic, liver, and intestinal disease; intestinal
resection; vomiting; and CFRD); and decreased nutrient
intake (anorexia, gastroesophageal reflux disease (GERD),
eating disorders, abdominal pain, constipation, malaise,
and medications). Aggressive nutrition intervention is often
required to improve nutrition status.
Nutrition assessment is an important component
in the care of persons who have CF. Factors that affect
nutrition status include maldigestion and malabsorption
of fat, protein, carbohydrates, and fat-soluble vitamins;
decreasing pulmonary function; chronic pulmonary infections and increased oxidative stress; decreased energy
intake; increased energy requirements; and CFRD. A
comprehensive nutrition assessment must be performed
at diagnosis and yearly. This consists of an assessment of
(1) growth including pattern of weight and height based
on the growth curve, head circumference (as appropriate),
and BMI percentile; (2) biochemical indicators such as
vitamin and mineral levels; (3) nutrient intake; (4) eating
behavior and family eating patterns; (5) pancreatic enzyme
replacement therapy (PERT) management; (6) physical
activity; (7) severity of lung disease; (8) presence of any
comorbidity such as CFRD, chronic infections, cirrhosis,
or bacterial overgrowth; and (9) factors which may impact
the patients ability to meet nutrition goals. Assessment of
bone health should be performed yearly and, as indicated,
growth parameters (height, weight, head circumference,
weight for length, or BMI percentile) should be assessed
and monitored at every visit. Arm anthropometrics can be
measured as well. Based on the above information caloric
requirements are calculated, vitamin and mineral prescription adjusted, and anthropometric goals calculated.
A nutrition screen must be performed at every visit so as
to identify inadequate weight gain, weight loss, and faltering
of linear growth. When these occur, a nutrition assessment
must be performed, causes identified, and appropriate interventions implemented (Table 28-2).
325
Table 28-2 Nutrition Assessment Parameters for Cystic Fibrosis

Frequency of Assessment
andReassessment
Parameter
Anthropometrics
Occipital-frontal head
circumference
Body weight, height, length,
head circumference
MAMC, TSF
Nutritional Intake
24-hour recall
3-day dietary fat balance
coefficient of
fat absorption < 93% or 85%
in infants
fecal elastase used to define
steatorhhea
Biochemical
CBC with differential
Iron studies
Fat-soluble vitamins
Alpha-tocopherol
Serum plasma retinol
25-OH vitamin D
PIVKA II
Essential Fatty Acid Deficiency
Ratio of triene to tetraene
25-OH vitamin D
Measured only up to age 2 years

Every 3 months
Annually
Routine care and diagnostic
Evaluate weight loss, growth,
diagnosis
Routine care and diagnosis

Diagnose iron deficiency anemia
Routine care and diagnosis
Diagnostic
Yearly
MAMC: mid-arm muscle circumference; TSF: triceps skinfold; CBC:

complete blood count.
Adapted from Gottschlich MM. Pulmonary disease. In: Gottschlich MM.
The Science and Practice of Nutrition Support: A Core-Based Curriculum.
Dubuque, IA: Kendall/Hunt Publishing Co; 2001:501516.
Macronutrients
Energy
As previously described, individuals who have CF have
increased energy needs. Exact caloric prescriptions and
formulas to calculate caloric need are difficult to provide
due to individual patient variation11 but improved weight
status has been found at intakes ranging from 110% to 200%
of energy needs for the healthy population.12 Energy needs
of each patient should be assessed on an individual basis and
reflect the pattern of weight gain and fat stores.13 An estimation of individual caloric need is based upon nutrition status,
growth pattern, fat stores, current dietary intake, degree of
fat malabsorption, clinical status (including pulmonary
326
function), level of activity, and incorporation of additional

requirements for nutrition repletion, weight gain, and/or
catch-up growth.14
Fat
The energy goal can be best achieved by consuming a diet that
contains 35% to 40% of calories as fat.13 Ongoing research
suggests that a diet containing sources of linolenic acid (LA),
such as flax seed, canola, and soy oils and cold-water marine
fish, may be beneficial for persons who have CF.15 Historically the amount but not type of fat has been emphasized.
Clinicians are encouraged to be aware of the symptoms of
essential fatty acid deficiency (EFAD). Most common symptoms of LA deficiency are poor growth and scaly skin lesions,
confirmed by an increase in triene-tetraene ratio of plasma
lipids.8 EFAD can occur not only in patients with severe
lung disease, significant malabsorption, and/or cirrhosis but
also in patients with normal nutrition status. It is not known
whether the deficiency is due to a primary metabolic disorder
or due to malabsorption and increased oxidative stress.15
Protein
Specific recommendations for protein intake in CF are
not available, although there is some evidence that protein
needs are met if a higher calorie diet is consumed14 and 15%
to 20% of total calories are from protein.16
Carbohydrate
The diet should contain sufficient carbohydrate to meet
energy needs. As with persons who do not have CF, it is best
if the source is from foods which contribute to the overall
nutrient intake, including fiber.
Infants
Infants require a diet that will promote optimal weight
gain, and, when indicated, catch-up growth. Human milk
or standard infant formula is recommended. When necessary, fortified human milk or calorically dense formula may
be used to promote and/or maintain weight gain.17 Infants
with CF have specific sodium requirements (see section on
Sodium Chloride). Infants may require 120 to 150 kcal/kg/d
to achieve catch-up growth.13 Hydrolyzed protein formulas
containing medium-chain triglycerides (MCTs) are not
indicated in the absence of a medical reason, such as bowel
surgery with significant bowel resection due to meconium
ileus or liver abnormalities. Solids are added to the diet of
infants who have CF on the same schedule used for nonaffected infants.8 Care must be taken when adding solids to
avoid replacing nutrient- and energy-rich infant milks with
low-calorie, low-nutrient foods. Adding oil to commercial

jarred infant foods will increase calories; up to 1 teaspoon
of oil to every 4 oz of baby food is suggested. Revised guidelines for infant feeding emphasize the safety and benefits
of earlier introduction of meat for the energy, protein, zinc,
and iron content for all infants.8 Parents who wish to prepare
homemade solids may require instruction. Positive feeding
behaviors should be encouraged throughout the feeding
experience.17
Micronutrients
All persons with CF, both PI and using PERT and PS,18
require supplementation with micronutrients. Deficiencies
of fat-soluble vitamins19 and zinc20 have been demonstrated
in infants diagnosed through newborn screening and do
not correct without appropriate supplementation and, if
indicated, PERT. Children and adolescents are at risk for
micronutrient deficiencies due to:14
Inadequate intake
Malabsorption possibly due to suboptimal PERT
Malabsorption due to residual or incomplete bile salt
absorption
Poor clinical status and poor lung function
Increased utilization and reduced bioavailability
Liver disease
Bowel resection
Late diagnosis of CF
Poor adherence to or inappropriate supplementation.
Multivitamins designed to meet the fat-soluble vitamin
needs of persons who have CF (CF-specific multivitamins)
are available in North America (Table 28-3). These vitamins
contain fat- and water-soluble vitamins and zinc. The content
reflects the recommendations provided in the U.S. Pediatric
Nutrition Consensus Report,13 the European Nutrition
Consensus Report,21 the U.S. Bone Consensus Report,22
and/or current research. Dosage and form of the CF-specific
multivitamin supplementation is dependent on results of
laboratory evaluation of vitamin levels and the patients age.
Patients may require additional single-nutrient supplements
(ie, vitamins A, E, D, K), if blood levels cannot be maintained on the CF-specific multivitamins. If the CF-specific
multivitamin is unavailable, single-vitamin supplements are
necessary to make up the difference in content of traditional
multivitamins compared to recommendations.
For additional information specific to vitamins and
CF the reader is referred to www.SourceCF.com for
newsletters.
PULMONARY DISORDERS
327
Table 28-3 Fat-Soluble Vitamins and Zinc Content of Multivitamins1

Age
CFF Consensus
Report 2
012 months
13 years
1,500
5,000
48 years
5,00010,000
918 years
10,000
> 18 years
8000
012 months
13
4050
80150
48
100200
918 years
200400
> 18 years
400
012 months
13
4004
8004
48 years
800
918 years
800
> 18 years
800
012 months
13
300500
300500
48 years
300500
918 years
300500
> 18 years
1,000
012 months
13 years
48 years
9 yearsAdult
SourceCF
Drops, Chewables,
Softgels
ADEK Chewables
AquADEKs
Drops, Softgels
Vitamin A (IU) Retinol and Beta-Carotene (BC)

4627 (1 mL) 75% BC
5,751 (1 mL) 87% BC
11,502 (2 mL) 87% BC
9254 (2 mL) 75% BC
16,000 / chewable 9,000 / chewable Ages 410 yrs 18,167
88% BC
60% BC
/ 1 softgel, 92% BC
18,000 / 2
Ages 10 and up
32,000 / 2 softgels
chewables
36,334 / 2 softgels,
88% BC
60% BC
92% BC
18,000 / 2
36,334 / 2 softgels
32,000 / 2 softgels
chewables
92% BC
88% BC
60% BC
Vitamin E (IU)
50 (1 mL)
50 (1 mL)3
100 (2 mL)
100 (2 mL)3
Ages 410 yrs: 150 /
200 / chewable
150 / chewable
1 softgel
Ages 10 and up: 300
400 / 2 softgels
300 / 2 chewables
/ 2 softgels
400 / 2 softgels
300 / 2 chewables
300 / 2 softgels
Vitamin D (IU)
500 (1 mL)
400 (1 mL)
1000 (2 mL)
800 (2 mL)
Ages 410 yrs: 800 /
1000 / chewable
400 / chewable
1 softgel
Ages 10 and up:
2000 / 2 softgels 800 / 2 chewables
1600 / 2 softgels
2000 / 2 softgels 800 / 2 chewables 1600 / 2 softgels
Vitamin K (mcg)
400 (1 mL)
400 (1 mL)
800 (2 mL)
800 (2 mL)
Ages 410 yrs: 700 /
800 / chewable
150 / chewable
1 softgel
Ages 10 and up:
1600 / 2 softgels 300 / 2 chewables
1400 / 2 softgels
1600 / 2 softgels 300 / 2 chewables 1400 / 2 softgels
Zinc (mg)
5 (1 mL)
5 (1 mL)
10 (2 mL)
10 (2 mL)
For 410 yrs:
7.5 / chewable
15 / chewable
10 / softgel
For Ages 10+:
30/ 2 softgels
15 / 2 chewables
20 / 2 softgels
Vitamax
Drops, Chewables
Poly-Vi-Sol Drops
Centrum
Chewable, Tablet
3,170 (1 mL) 0%BC 1,500 (1 mL) 0% BC

6,340 (2 mL) 0% BC 3,000 (2 mL) 0% BC
5,000 / chewable 3,500 / chewable
50% BC
29% BC
10,000 / 2
7,000 / 2 tablets
chewables
29% BC
50% BC
10,000 / 2
7,000 / 2 tablets
chewables
29% BC
50% BC
50 (1 mL)
100 (2 mL)
5 (1 mL)
10 (2 mL)
200 / chewable
30 / chewable
400 / 2 chewables
60 / 2 tablets
400 / 2 chewables
60 / 2 tablets
400 (1 mL)
800 (2 mL)
400 (1 mL)
800 (2 mL)
400 / chewable
400 / chewable
800 / 2 chewables
800 / 2 tablets
800 / 2 chewables
800 / 2 tablets
300 (1 mL)
600 (2 mL)
0
0
200 / chewable
10 / chewable
400 / 2 chewables
50 / 2 tablets
400 / 2 chewables
50 / 2 tablets
7.5 (1 mL)
15 (2 mL)
0
0
7.5 / chewable
15 / chewable
15 / 2 chewables
22 / 2 tablets
1. The content of this table is as of December 2008. Products also contain a full range of water-soluble vitamins. Information not included in this table.
Fora copy of the full table, go to: www.SourceCF.com.
2. Cystic Fibrosis Foundation. Pediatric Nutrition for Patients with Cystic Fibrosis Consensus Conference Report March 2001 (Table 7).
3. Also contains mixed tocopherols.
4. Based on Guidelines to Bone Health and Disease in Cystic Fibrosis Consensus Conference Report June 2002 (Figure 2).
5. ADEK is registered trademark of Axcan Pharma Inc., AquADEKs is a registered trademark of Yasoo Health Inc., Vitamax is a registered trademark of
Shear/Kershman Labs. Inc., Poly-Vi-Sol Drops is a registered trademark of Mead Johnson and Company, Centrum is a registered trademark of Wyeth
Consumer Care.
Table reproduced with permission of SourceCF Inc., a subsidiary of Eurand Pharmaceuticals, Inc.
328
Vitamin A
Vitamin A plays an important role in vision, immunity, lung

health, and overall health, yet excessive intake of retinol can
cause liver and/or bone complications. Retinol is an acute
phase reactant and best measured when the patient is not ill.
Liver disease or zinc deficiency can cause low serum retinol
levels. The total vitamin A content of CF-specific multivitamins is based on both retinol and beta-carotene. The risk
of toxicity is avoided with a higher concentration of betacarotene.
Vitamin E
Optimizing serum vitamin E will prevent the neurological

complications once seen in people who have CF. More
recently the role of vitamin E as an antioxidant in preserving
overall health in CF has been investigated.23 Vitamin E is
transported in the body with lipid, including cholesterol.
People who have CF often have low cholesterol levels, therefore serum levels should be assessed as a ratio of vitamin E24
to total lipid 25 or to total cholesterol.25 Liver disease can
cause low vitamin E levels.
Vitamin D
Persons who have CF are at risk for low serum vitamin D.

Current repletion recommendations22 do not correct serum
levels in the majority of patients.26 Patients with liver disease
may have low vitamin D levels. Serum 25-hydroxyvitamin
D [25(OH)D] should be assessed annually, preferably in the
late fall and, if necessary, treated daily with D3-cholecalciferol. The exact dose necessary for all patients is unknown at
this time; therefore dosage is based on individual need.
Vitamin K
Vitamin K is essential for normal blood clotting and bone

health. Persons who have CF are at risk for vitamin K deficiency due to fat malabsorption and routine use of antibiotics.
Additionally, any patient who has CF and liver disease is at
greater risk for vitamin K deficiency. Clotting time, or PT
(prothrombin time), has been the standard test for assessing
overall vitamin K nutrition, but a number of studies using
PIVKA II provided evidence that in CF, vitamin K deficiency
exists in patients with normal PT.2729 Over-the-counter
multivitamins contain insufficient vitamin K to meet the
needs of persons who have CF. The vitamin K content of
CF-specific multivitamins is sufficient for the majority of
patients, although some people may require additional
supplementation based on laboratory results.
Water-Soluble Vitamins
Deficiency of water-soluble vitamins in CF is rare, but
has been reported in patients not receiving multivitamins
and/or receiving medications interfering with B vitamins. 30 Over time, patients who have had a resection of the
terminal ileum will develop vitamin B12 deficiency requiring
supplementation.14
Minerals
Sodium Chloride
Persons who have CF lose excessive sodium in their sweat
and require supplementation throughout the year, especially
in the summer months. Inadequate salt intake can be life
threatening and/or result in poor appetite with subsequent
poor growth. All infants who have CF and an elevated sweat
test are to be supplemented with 12.6 mEq (1/8 teaspoon)
of salt daily from birth to 6 months of age at which time the
dose is increased to 25.2 mEq (1/4 teaspoon) daily.17 The
salt is added in small, frequent amounts to baby formula or
applesauce used to dose PERT until the daily dose is met.
Salt supplementation is continued until the child is eating
a diet rich in salt and added salt. Children and adolescents
are to be counseled to consume salt, over and above their
usual intake, when participating in physical activity. It may
be necessary to add salt to sports drinks to meet sodium
chloride needs (1/8 teaspoon to 12 oz). 31
Zinc
Pancreatic insufficient infants, prior to treatment with
PERT, lose excessive zinc in their stool. Acrodermatitis
enteropathica like rash, which resembles a severe rash in
the diaper area and the perioral area, is a clinical symptom
of zinc deficiency and is treated with PERT and zinc supplementation. More subtle symptoms of zinc deficiency which
can be seen at any age include lack of appetite, dysgeusia,
poor growth, and compromised immunity. Laboratory
studies to determine zinc status are generally uninformative.
When zinc deficiency is suspected the usual supplemental
dose is 1mg elemental zinc per kilogram daily for 6 months
in addition to that contained in the patients daily multivitamin. Over-the-counter infant vitamin drops do not contain
zinc. Over-the-counter childrens chewable vitamins and
adult formulations contain zinc as do all of the CF-specific
multivitamins. When choosing a zinc preparation, it is
important to note which zinc salt is in the chosen product so
that the correct dose can be determined. For example, zinc
sulfate is 23% elemental zinc but zinc gluconate is only 14%
elemental zinc.
PULMONARY DISORDERS
Iron
Iron status in the general population is affected by a
number of factors, including dietary intake, blood loss, and
medications. For persons with CF, all of these factors, plus
malabsorption, hemoptysis, short bowel syndrome, bacterial
overgrowth, liver and renal diseases, and chronic inflammation contribute to altered iron status. Patients can have iron
deficiency anemia, anemia of chronic disease or a combination of both. Prior to prescribing iron supplementation the
form of anemia must be defined. 32 Assessing iron status in
CF is complicated by chronic inflammation. Serum ferritin,
an acute-phase reactant, may be falsely elevated in CF, thus
masking iron deficiency anemia. Measurement of soluble
transferring receptor levels may be helpful in diagnosis.
Calcium
It is important to optimize the calcium intake of persons
who have CF. In lieu of specific calcium recommendations
for person who have CF, the RD should refer to those in the
DRI. The CFF Bone Consensus Report may be referred
to for more detail regarding bone health and CF. 22 At a
minimum, the adequate intake levels should be achieved in
all patients.
Magnesium
Patients receiving aminoglycosides may require supplemental magnesium. Blood levels should be monitored. 33
Fluoride
CF-specific vitamins do not contain fluoride; therefore the
patients primary care physician may need to prescribe a
supplement if local water is not fluoridated.
Assessment
Blood levels of fat-soluble vitamins should be measured at
diagnosis for patients diagnosed greater than 1 year of age
and annually thereafter.13 For newly diagnosed infants, it is
recommended that levels of vitamins E, A, and D be assessed
1 to 3 months after starting supplementation and annually
thereafter.17 Prothrombin time is insensitive to vitamin K
deficiency in CF.27 PIVKA II provides a better indicator of
vitamin K nutrition, but laboratory reference standards for
full-term infants are not available, and therefore checking
PIVKA II levels is not recommended in the newborn period.
Serum electrolytes and complete blood count is measured
at 2 to 3 months of age and annually or as indicated.17 For
children and adolescents assessment of fat-soluble vitamins, including PIVKA II and CBC with differential, is
done at diagnosis and annually, unless otherwise indicated.
329
Laboratory studies for individual micronutrients may be

necessary when modifying the treatment care plan, such as
starting tube feeding.
Nutrition Support
There is a positive correlation between pulmonary function and weight.12 The CF Foundation recommends the
following nutrition goals:
Infants: weight for length at the 50th percentile by 2
years of age
Children 2 to 20 years of age: BMI percentile at or
above the 50th percentile
Adults: BMI of 22 for women and 23 for men12
Additionally, children are expected to meet their
genetic potential for growth. Therefore, nutrition interventions to reach and maintain weight and growth goals are
often necessary. Behavioral interventions for parents, caregivers, and patients may also help improve caloric intake,
thus weight gain. 34 Weight percentiles are believed to be at
their lowest during the first 2 years of life and early adolescence therefore making aggressive nutrition intervention
important during these time periods. 35 For toddlers and
older children, initially using high-calorie oral supplements or additives may be indicated. Infant formula can
be concentrated or high-calorie modulars added to provide
adequate calories. However in some children this may not
be sufficient to sustain a desired weight and growth status
and enteral feeding may be indicated. There are no specific
guidelines regarding when to initiate enteral feeding in the
pediatric CF population. The CF Foundation Clinical Practice Guidelines Subcommittee on Growth and Nutrition
has determined that for children with growth deficits, oral
or enteral supplements should be used to improve the rate
of weight gain.12 Enteral tube feeding can be via nasogastric
tube, gastrostomy tube, or jejunostomy tube. The nasogastric tube can be inserted and removed daily for short-term
use. Adherence to this intervention may prove difficult. A
gastrostomy tube may be more appropriate and allow for
flexibility of feeding. Feeding via the gastrostomy tube can
be intermittent, bolus, or continuous feeds. Continuous
feeds generally occur nocturnally. Nighttime feedings
allow for regular meal and snack pattern during the day.
Enteral tube feeding may be complicated by early morning
fullness and vomiting, loss of appetite, and poor body image
and self-esteem concerns. The reader is directed to papers
related to these concerns. 3537 It is important to strike a
balance between initiation of enteral feeding and severity
of lung disease to optimize the benefit of the intervention.
Feeding via a jejunostomy tube is infrequent in patients
330
with CF and usually occurs in patients with significant

upper gastrointestinal dysmotility, failure of anti-reflux
procedures, intubated patients, and in some postoperative
patients. Parenteral nutrition (PN) is considered a more
aggressive intervention and not routinely used in the daily
management of CF.
Pancreatic Enzymes
Persons who are pancreatic insufficient require PERT.

Pancreatic damage and destruction occurs in utero or
after birth, resulting in the absence of bicarbonate rich and
enzyme-containing pancreatic juice in the duodenum to help
digest food. PERT has played a pivotal role in improving the
care and outcome of persons with CF. 38 There are a variety
of enzymes available with subtle differences among brands
and forms. As of this writing the most commonly used
enteric-coated enzymes in the United States are: Creon by
Solvay; Pancrecarb by Digestive Care; Zenpep by Eurand;
and Ultrase by Axcan, Inc. Due to changes in PERT content
mandated by the Food and Drug Administration and to be
put in place by April 2010 the reader is referred to the manufacturers Web site for details regarding enzyme content.

A non-enteric-coated form of enzyme, such as Viokase
by Axcan, is subject to destruction by the acidic gastric environment.8 Microspheres and microtablets are enteric-coated
to protect the enzyme from the acidic gastric milieu. The
enteric coating allows for activation to occur in the alkaline
pH of the duodenum, past the acidic gastric contents. If the
pancreas is unable to deliver bicarbonate pancreatic juice to
the duodenum, gastric acid from the stomach is not neutralized resulting in an acidic duodenal pH. Acidity in the
gastrointestinal tract may prevent or retard dissolution of
enteric-coated pancreatic enzymes. 39 If activation does not
take place in the small intestine, absorption of macro- and
micronutrients cannot occur. Additional medications which
reduce or block acid production and raise the duodenal pH
may be needed to enhance PERT effectiveness. Even so, all
nutrients may not be fully absorbed. If fat malabsorption
persists, consider lack of bile acids an etiology.
The pancreatic enzyme replacement products contain
lipase, protease, and amylase for digestion of fat, protein,
and carbohydrates, respectively. Enzyme activity or potency
is based on the amount of lipase per capsule or gel cap. For
example, for Creon 5 the 5 refers to 5,000 lipase units per
capsule. Creon 5 also contains 3,600 amylase units and
200 protease units.
PERT starting dose for infants of 2,000 to 4,000 units
of lipase per 120 mL of formula or breast milk is recommended. 39 Though dosing is best calculated using units of
lipase per gram of fat ingested, it is perhaps more practical

to use a dosing schedule with weight-adjusted guidelines. 39
For children less than 4 years of age the recommendation
is to began at 1,000 lipase units per kilogram per meal and
over 4 years of age 500 lipase units per kilogram per meal.
Dosing for snacks is routinely half of usual meal dose. The
recommendations are not to exceed a dose of 2,500 units of
lipase per kilogram body weight per meal or 10,000 lipase
units per kilogram per day and are based on a usual intake
of 3 meals plus 2 snacks per day. 39
Persons with CF should be viewed individually in
regards to dosing and response to PERT. Careful monitoring of growth, stool pattern, and the absence or presence
of gastrointestinal symptoms is necessary to determine the
adequacy of therapy. For infants and children unable to
swallow enzyme capsules, the enzyme beads are removed
from the capsule(s) and mixed with a small amount (1/8 to
1/2 teaspoon for infants, more for children) of applesauce
and given at the time of each feeding.8 PERT is given at the
beginning of the feeding or meal. If mealtime is more than
30 minutes, then it is recommended that the dose be split
and given at the beginning and halfway during the meal.
For infants, to avoid mucosal erosion, the mouth should be
checked for beads following each feeding. The infants perianal area may require protection against enzyme excreted
in the stool. Patients can be instructed to apply a thick layer
of barrier cream to protect the skin around the anus.
Persons with CF who receive nasogastric tube, gastrostomy tube, or jejunostomy tube feedings need PERT
supplementation. The amount and type of enzyme given
depends on the type of formula and the ability of the patient
to take enzymes orally. In general a meal dose of PERT is
given before and after night tube feeds when using an intact
formula.13 Some patients may benefit from an additional dose
midway during the feedings at night. During the day PERT
is best given before each bolus and this dose is dependent
on the amount and type of fat in the bolus. Enzymes can
be administered via the gastrostomy tube if the size of the
bead is small enough to go through the tube and not cause
clogging. PancrecarbFour by Digestive Care contains
microspheres/microtabs that fit through a gastrostomy tube.
The reader is referred to the manufacturers Web site for more
information.
Eating Behaviors and CF
The importance of nutrition in CF is recognized by the CF

Care Team and by parents of children who have CF. Pressure surrounding the importance of nutrition includes:
improving and maintaining weight and adherence to PERT
PULMONARY DISORDERS
and supplemental vitamins and/or minerals. As a result,

mealtimes can become challenging. Parents of children
with CF commonly report mealtime behavior problems
including: poor appetite, avoidance of eating by talking,
and spitting out food. 34 A negative correlation between the
childrens caloric intake and the number of problematic
mealtime behaviors has been identified.40
Young children appear to be particularly at risk for
behavioral difficulties at mealtime if their parents feel
unusually concerned about their childrens health and
caloric/food intake.40 For parents of infants with CF, the
transition from formula to solids may present a challenge
and parents may need guidance surrounding positive
eating behaviors and high-calorie solids. The toddler stage
is typically characterized by changing food interests and
neophobia (fear of new foods), which for children with CF
may complicate the selection of high-fat foods and food
additives. 34 Parents may benefit from guidance to prevent
and/or manage food refusal behaviors. Anticipatory guidance might include education centered on avoidance of
parental behaviors that may inadvertently reinforce noneating behaviors and advice directed toward reinforcement
of desired behaviors through praise and limit setting.40 As
children become adolescents, a struggle for control and
independence may ensue. In this period, the challenge may
be providing education and direction so that the child/
adolescent makes appropriate choices that improve or
maintain optimal nutrition status. Birch has stated that the
foundation for teen and adult eating styles is laid in childhood as the parent and child work through issues of control
regarding feeding andeating.41
Nutrition-Related Cystic Fibrosis

Complications
Osteoporosis or Bone Disease
Bone disease is increasingly recognized in persons who
have CF. Decreased bone density, fractures, and kyphosis
occur earlier in persons with CF than in healthy controls.42
The incidence of osteoporosis and fracture increases with
increasing age and are prevalent in adult patients and in
those with end-stage lung disease. Predisposing factors
include inflammatory cytokines, vitamin D deficiency,
inadequate calcium intake, use of corticosteroids, delayed
puberty, short bowel syndrome, and liver disease. It is
recommended that patients 8 years of age or older with
the following risk factors get a baseline dual energy X-ray
absorptiometry (DEXA) scan: small body size, low weight
for height, decreased physical activity, low vitamin D
331
levels, prolonged corticosteroid usage, delayed puberty,

low calcium intake, history of fractures, family history of
osteoporosis, significant lung disease, or liver disease. 22
Normative data are available for DEXA scans for children
above 3 years of age. Treatment includes optimizing nutrition (calcium, vitamins D and K, and nutrition status),
increasing physical activity, controlling underlying inflammation, decreasing use of corticosteroids as indicated, and
addressing any hormone deficiencies. In adults bisphosphonates have been used in patients with osteoporosis and
stress fractures, but in children there are limited data on
their safety.
CF-Related Diabetes
CF-related diabetes (CFRD) shares features of both type
1 and type 2 diabetes, but it is a distinct clinical entity.43
Diabetes occurs when people either are insulin deficient or
insulin resistant. Individuals with CFRD are insulin deficient as a result of destruction by fibrosis or scarring of beta
cells in the pancreas that produce insulin.44 Glucose metabolism is strongly influenced by factors unique to CF, including
undernutrition, chronic and acute infection, elevated energy
expenditure, glucagon deficiency, malabsorption, abnormal
intestinal transit time, and liver dysfunction. These factors
are not static and may fluctuate over time in CF.43
Retrospective studies have shown that pulmonary
decline and weight loss begin 2 to 4 years before diagnosis of CFRD.43 Symptoms of CFRD include polydipsia,
polyuria, weight loss or inability to gain weight despite
aggressive nutrition intervention, poor growth, and poor
progression of puberty or unexplained chronic decline in
pulmonary function.43 Any patient with these symptoms
should be screened for CFRD using the CF Foundation
recommendation.43
In the routine management of CF, casual glucose levels
are measured annually. If the person has a random blood
glucose level of 126 mg/dL, further workup for CFRD
should be conducted. Tests include fasting blood glucose or
2-hour oral glucose tolerance test (OGTT). The CF Foundation assembled a consensus conference on CFRD and
issued recommendations for monitoring glucose intolerance; refer to these recommendations for further screening
of CFRD.43
When discrepancies exist between the nutrition
recommendations of the 2 diseases, the CFRD recommendations supersede those for type 1 and type 2 diabetes.
The CF Foundation Consensus Statement on Diagnosis,
Screening, and Management of Cystic Fibrosis Related
Diabetes Mellitus43 currently promotes these 2 principles
332
for nutrition management of CFRD:

Achievement of optimal nutrition status through intake
of sufficient calories is critical for survival in persons
with CF.
Near-normalization of blood glucose levels is necessary
to ensure optimal nutritional and metabolic status
Diet guidelines for type 1 and type 2 diabetes are not
recommended for people who have CFRD.43 Ideally the
person with CFRD is to maintain/achieve a healthy body
weight and is encouraged to continue a high-calorie, highfat and high-sodium diet. Carbohydrate counting, meal
timing, and insulin therapy are significant interventions for
management of CFRD.16
Lung Transplantation
Lung transplantation remains the most aggressive therapy
for end-stage lung disease.45 Persons with CF are candidates
for lung transplantation when they exhibit severely reduced
lung function and progressive deterioration in their health
and quality of life.16 For children and adults, the largest
obstacle to long-term survival remains chronic allograft
rejection secondary to the development of bronchiolitis
obliterans. Common weight criteria for adults are 80% to
130% IBW or BMI of 18.5 to 30 kg/m. There is no pediatric
weight criterion. Further research in the area of weight and
nutrition status is needed in the pediatric lung transplant
population.
Gastrointestinal
Gastrointestinal (GI) manifestations are frequently seen
in persons with CF and involve all parts of the GI tract.46
Gastroesophageal reflux (GER) occurs at all ages and the
incidence varies between 25% and 100% depending on the
study. Complications of GER include feeding disorders,
decreased caloric intake, failure to thrive, apnea in infants,
vomiting, esophagitis, worsening of lung disease, esophageal strictures, and Barretts esophagus. Reflux can be a
significant problem in lung transplant recipients and is associated with rejection in the posttransplant period. Often a
fundoplication is recommended in the pretransplant period.
Gastroparesis and constipation can be seen in CF and the
latter may be 3 times more frequent than DIOS. Bacterial
overgrowth occurs in up to 60% of patients.47 Predisposing
factors include frequent antibiotic use, intestinal dysmotility, history of previous GI surgery, and sticky intestinal
secretions that trap bacteria. DIOS is seen in all persons with
CF, not just in those with PI. Dehydration of the intestinal
secretions, coupled with electrolyte imbalances and sticky
mucus, and poor motility lead to the accumulation of stool
in the ileocecal junction resulting in abdominal pain and

vomiting. Treatment/prophylaxis consists of optimizing
fluid and electrolyte intake, correction of any malabsorption
and the use of laxatives/stool softeners, such as polyethyleneglycol. Prevention is vital, and an attempt to find
the precipitating factor for every episode should be made.
Celiac disease, inflammatory bowel disease, eosinophilic
esophagitis, and GI malignancies may also occur in CF.
Patients with pancreatic sufficiency are at risk for recurrent bouts of pancreatitis. Over time some of these patients
may become PI. The most common liver lesion in patients
with CF is fatty liver. Also seen are hepatitis, fibrosis, and
cirrhosis with portal hypertension. Gallbladder dysfunction
is frequent and a non-functioning gallbladder or gallstones
can be seen on ultrasound examination. Biliary dyskinesia
can result in right upper quadrant abdominal pain. Some
patients with liver disease will progress to end-stage liver
disease and develop complications from cirrhosis (portal
encephalopathy and uncontrolled variceal bleeds) and
require liver transplantation.
Other Chronic Lung Diseases

Overview and Pathophysiology
Chronic lung disease (CLD) is seen in premature infants
who have significant respiratory disease, in infants and
children with congenital heart disease who need ventilator
support in the neonatal period, in patients with difficult-tomanage asthma or reactive airways disease (RAD), and in
patients with chronic respiratory insufficiency requiring
ventilator support.
Bronchopulmonary Dysplasia
Bronchopulmonary dysplasia (BPD) is a form of chronic
lung disease that develops in preterm infants given positive
pressure ventilation and oxygen. The pathophysiology is
complex and due to small airway damage, abnormal alveolar
development, and decreased surface area for gas exchange.48
Additionally there is damage to small blood vessels in the
lungs and secondary damage to the heart and brain. BPD is
most commonly seen in preterm infants with a birth weight
of more than 1250 g and 30 weeks gestational age. Males
tend to be more affected. Surfactant therapy is used soon
after birth to prevent lung damage. Energy requirements
are increased and are in the range of 125 to 150 kcal/kg/d.49
Vitamin A supplementation is important and often used in
the neonatal intensive care unit to prevent BPD. Vitamin E
supplementation is not helpful. These patients also have large
insensible water losses and need extra fluid which results in
PULMONARY DISORDERS
opening of the patent ductus arteriosus and further stress on

the lungs. Fluid restriction often results in inadequate nutrition intake. Calcium status is poor due to decreased intake
and increased losses from diuretics. Adequate intakes of
calcium and phosphorus, protein (33.5 g/kg/d), and antioxidants (copper, zinc, and manganese) are required and it
is important to avoid excessive carbohydrate intake because
it can impact on pulmonary function by altering the respiratory quotient. These patients often receive corticosteroids
and diuretics for treatment of the lung disease often with
significant consequences: increased sodium, potassium
and magnesium losses, kidney stones, gallstones, and bone
disease.
Infants with severe BPD are at high risk for the following
problems during the first 2 years of life: pulmonary infections, frequent hospitalizations, RAD, and more frequent
visits to the doctor. These patients also may have developmental delay, poor muscular development, poor feeding
skills, poor growth, and chronic lung disease. Infants with
BPD often have impaired weight for length and problems
with oxygen diffusion resulting in a chronic oxygen requirement. Caloric needs are high because catch-up growth is
often a goal. The co-existence of reflux and BPD can exacerbate poor oral motor function and can worsen feeding
problems in patients with developmental delay. Reflux can
also worsen lung disease. Supplemental feeds are often
required.
Asthma
Asthma or RAD is the most common cause of hospital
admissions in children. It is a chronic pediatric lung
disease where there is chronic inflammation of the
airways involving eosinophils, mast cells, T lymphocytes,
macrophages, neutrophils, and epithelial cells. Additionally
there is variable air flow obstruction and increased bronchial responsiveness to a variety of environmental stimuli.
The presence of airway edema and mucus contributes to the
obstruction and bronchial reactivity that is seen. 50 Environmental triggers affect the normal development of the
respiratory and immune systems in genetically predisposed
individuals. 51 Patients often require chronic inhaled or
pulses of systemic corticosteroids. Excessive oral cortico
steroid use over time can result in growth failure, fluid and
sodium retention, a voracious appetite, excessive weight
gain, hypertension, glucose intolerance, and obesity. There
appears to be considerable variation in the side effects of
inhaled corticosteroids. Growth, puberty and bone health
can be affected depending on the duration and dose. 52
Early data suggest the use of antioxidants, Lactobacillus,
333
and omega-3 fatty acids has been associated with a reduction in symptoms and reduced development of asthma in
those with atopy. 52 In children a linear association between
obesity (increased BMI) and asthma has been noted with a
6% increase in prevalence per unit increase of BMI. 53
Technology Dependent
Children with chronic respiratory failure may require
chronic ventilatory support. At-risk children include those
with: neuromuscular dystrophy, spinal muscular atrophy,
Duschennes muscular dystrophy, spinal cord injuries,
BPD, congenital diaphragmatic hernia, severe lung
malformations, congenital hypoventilation syndrome,
and myelomeningiocoele. From the above diagnoses, of
patients who require ventilator support, patients with
BPD and neuromuscular dystrophy are the most frequent.
Respiratory support can be non-invasive (BIPAP) or invasive (tracheostomy and ventilator). The pathophysiology
includes respiratory insufficiency (seen in BPD and pulmonary hypoplasia), secondary damage to the lungs from
severe cardiac disease resulting in decreased surface area,
decreased oxygen absorption, increased carbon dioxide
retention, poor lung development, small-volume lungs,
and insufficient vascular bed. There may also be decreased
central drive for respiration as seen in persons with congenital central hypoventilation syndrome. Since these patients
have decreased work of breathing, their energy requirements are subsequently decreased. If careful attention is
not paid to their nutrition regimens, they can have excessive weight gain which can further impact their respiration
status negatively. Often, in an attempt to decrease calories,
overall nutrient intake, especially protein and mineral
intake, suffers. These patients may also be at risk for bone
disease due to decreased weight bearing and micronutrient
deficiency (vitamin D and calcium).
For children with BPD and asthma it is best to monitor
growth on a regular basis. Anthropometrics provide critical
information regarding the growth of the infant or child. In
the infant with BPD, factors that may increase caloric requirements include increased basal metabolic rate, increased
work of breathing, chronic illness or infections, and respiratory distress or metabolic complications.54 The infant may
struggle with fluid sensitivity, which may limit the intake of
calories and nutrients. Infants may have interrupted feeding
skill development, therefore may be poor oral feeders.54
334
In critically ill infants with BPD, efforts are made to prolong
life. Caloric provision is often relegated to secondary
importance, compared to pulmonary edema, reduced
cardiac output, and electrolyte imbalance. 54 Please refer
to the section on nutrition in the neonatal intensive care
unit for more detailed information on caring for the critically ill infant. As the infants condition improves, concerns
regarding fluid overload and thermal losses remain.
Continued monitoring of intake, growth, and development
is essential. Individualizing macronutrient needs based on
the patients growth in relation to the goal is best. Specific
to the infant with BPD, calcium and phosphorous may be
further compromised by diuretic therapy, steroid therapy,
long-term use of parenteral nutrition, and feeding delays. 54
For further information on micronutrients, please refer to
the vitamin and mineral chapters (Chapters 6, 7, and 8).
A diet providing appropriate amounts of macro- and
micronutrients based on the U.S. Department of Agriculture dietary guidelines for age is recommended. Increased
appetite, abdominal fat accumulation, sodium and fluid
retention, and steroid-induced glucose intolerance are
common side effects of oral corticosteroid therapy. Monitoring weight and linear growth on a regular basis is
important. Nutrition support is discussed in Chapter 34.
Bone Health in Chronic Lung Disease

Pharmacologic therapy is an element in treating asthma.
The use of oral and high-dosed inhaled steroids has an effect
on nutrition status. Chronic corticosteroid use does induce
osteoporosis. 54 Therefore, adequate amounts of calcium and
vitamin D supplementation are vital. To assess adequacy of
calcium and vitamin D include diet assessment, vitamin
D level, and DEXA scan. Normative data are available for
DEXA scans for children above 3 years of age.
Summary
Nutrition is an important part of the management of the

child who has chronic lung disease. In general the goal is
normal growth and development and correction of nutrition abnormalities that result from the underlying medical
condition and the therapies used to treat the disease. Good
nutrition status has been associated with improved lung
function and outcomes in patients with cystic fibrosis.
1. Pancreatic enzymes are available in non-enteric-coated

and enteric-coated form. How does the enteric coating
help with nutrient absorption?
A. Enteric coating is subject to destruction by the
harsh acid-peptic gastric environment
B. Allows the enzymes to get through the build-up of
thick mucus in the pancreatic ducts
C. Allows for the activation to occur in the alkaline pH
of the duodenum, past the gastric contents of the
stomach
2. Which fat-soluble vitamin blood levels should be
checked in persons with CF and why?
A. Vitamins A, D, K, and E and zinc. These are insensitive markers in CF.
B. Vitamins A, D, E, and PIVKA II, to assure
adequacy.
C. Vitamins A, D, E, and PIVKA II. These are insensitive markers in laboratory tests.
3. A baseline DEXA scan is recommended at the age of 8
years, especially if risk factors are present. Which of the
following set of risk factors are necessary to be aware of?
A. Small body size, low weight for height, decreased
physical activity, low vitamin D levels, cortico
steroid usage, delayed puberty, low calcium intake,
history of fractures, family history of osteoporosis,
significant lung disease or liver disease
B. Increasing physical activity, large body frame,
asthma, low calcium intake
C. Increasing physical activity, large body frame, low
weight for height, history of fractures, cortico
steroid use, delayed puberty, liver disease
4. In BPD, energy requirements are elevated. What other
nutrition treatments might be beneficial?
A. Optimize vitamin E in nutrition intake
B. Supplement vitamin A; provide appropriate fluid
intake and adequate amounts of calcium, phosphorous, protein, and antioxidants; and avoid excessive
intake of carbohydrates
C. Provide high levels of carbohydrates and fluids
References
1. Riordan J, Rommens J, Kerem B, et al. Identification of the

cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989;245(4922):10661073.
2. Cystic Fibrosis Foundation Patient Registry. 2007 Annual
data report to the center directors, Bethesda, MD.
PULMONARY DISORDERS
3. Farrell PM, Rosenstein BJ, White TB, et al. Guidelines for

diagnosis of cystic fibrosis in newborns through older adults:
Cystic Fibrosis Foundation Consensus Report. J Pediatr.
2008;153(2):S4S14.
4. Amin R, Ratjen F. Cystic fibrosis: a review of pulmonary and
nutritional therapies. Adv Pediatr. 2008;55:99121.
5. Walker WA, Watkins JB, Duggan, C. Nutrition in Pediatrics:
Basic Science and Clinical Applications. 3rd ed. Hamilton,
London: BC Decker Inc; 2003:672.
6. Tiddens H, Rosenfeld M. Respiratory manifestations of cystic
fibrosis. In: Taussig LM, Landau LI, eds. Pediatric Respiratory
Medicine. 2nd ed. Mosby Elsevier; 2008;871887.
7. Gaskin K, Allen J. Exocrine pancreatic disease including
cystic fibrosis. In: Walker WA, Watkins JB, Duggan C, eds.
Nutrition in Pediatrics. Hamilton, London: BC Decker Inc;
2003:671685.
Grove Village, IL: The American Academy of Pediatrics;
2009.
9. Konstan MW, Butler SM, Wohl MEB, et al. Growth and
nutritional indexes in early life predict pulmonary function in
cystic fibrosis. J Pediatr. 2003;142:624630.
10. Stallings VA, Tomezsko JL, Schall JI, et al. Adolescent development and energy expenditure in females with CF. Clin Nutr.
2005;24:737745.
11. Trabulsi J, Ittenbach RF, Schall JI, et al. Evaluation of formulas
for calculating total energy requirements of preadolescent children with cystic fibrosis. Am J Clin Nutr. 2007;85:144151.
12. Stallings VA, Stark LJ, Robinson KA, Feranchk AP, Quinton
H; Clinical Practice Guidelines in Growth and Nutrition
Subcommittee (Ad Hoc Working Group). Evidence-based
practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic
insufficiency: results of a systematic review. J Am Diet Assoc.
2008;108:832839.
13. Borowitz D, Baker RD, Stallings V. Consensus report on
14. Australasian Clinical Practice Guidelines for Nutrition and
Cystic Fibrosis, 2005. www.cysticfibrosis.org.au/pdf/CF_
Nutrition_Guidelines.pdf. Accessed December 2008.
15. Maqbool A, Schall JI, Garcia-Espana JF, et al. Serum linoleic
acid status as a clinical indicator of essential fatty acid status
in children with cystic fibrosis. J Pediatr Gastroenterol Nutr.
2008;47(5):635644.
16. Gottschlich MM. Pulmonary disease. In: Gottschlich MM.
The Science and Practice of Nutrition Support: A Core-Based
Curriculum. Dubuque, IA: Kendall/Hunt Publishing Co:
2001:501516.
17. Borowitz D, Robinson KA, Rosenfeld M, et al. Management of
infants diagnosed with cystic fibrosis: A Cystic Fibrosis Foundation workshop report. J Pediatr. Accepted for publication.
18. Lancellotti L, DOrazio C, Mastella G, Lippi U. Deficiency of
vitamins E and A in cystic fibrosis is independent of pancreatic
function and current enzyme and vitamin supplementation.
Eur J Pediatr. 1996;155:281285.
335
19. Feranchak AP, Sontag MK, Wagerner JS, Hammond KB,

Accurso FJ, Sokol RJ. Prospective, long-term study of fatsoluble vitamin status in children with cystic fibrosis identified
by newborn screen. J Pediatr. 1999;135(5):601610.
20. Krebs NF, Sontag M, Accurso FJ, Hambidge KM. Low plasma
zinc concentrations in young infants with cystic fibrosis. J
Pediatr. 1998;133(6):761764.
21. Sinaasappel M, Stern M, Littlewood J, Wolfe S, Steinkamp G,
Heijerman HGM. Nutrition in patients with cystic fibrosis: a
European consensus. J Cyst Fibros. 2002;1:5175.
22. Aris RM, Merkel PA, Bachrach LK, et al. Consensus Statement: Guide to bone health and disease in cystic fibrosis. J
Clin Endocrinol Metab. 2005;90:18881896.
23. Wood LG, Fitzgerald DA, Lee AK, et al. Improved antioxidant
and fatty acid status of patients with cystic fibrosis after antioxidant supplementation is linked to improved lung function.
Am J Clin Nutr. 2003;77:150159.
24. Horwitt MK, Harvey CC, Dahm CH Jr, Searcy MT. Relationship between tocopherol and serum lipid levels for
determination of nutritional adequacy. Ann NY Acd Sci.
1972;203:223236.
25. Huang SH, Schall JI, Zemel BS, Stallings VA. Vitamin E status
in children with cystic fibrosis and pancreatic insufficiency. J
Pediatr. 2006;148:556559.
26. Green D, Carson K, Leonard A, et al. Current treatment
recommendations for correcting vitamin D deficiency in
pediatric patients with cystic fibrosis are inadequate. J Pediatr.
2008;153:554559.
27. Beker LT, Ahrens RA, Fink RD, et al. Effect of vitamin K1
supplementation on vitamin K status in cystic fibrosis patients.
28. Wilson DC, Rashid M, Durie PR, et al. Treatment of vitamin K
deficiency in cystic fibrosis: effectiveness of a daily fat-soluble
vitamin combination. J Pediatr. 2001;138:851.
29. Conway SP, Wolfe SP, Brownlee KG, et al. Vitamin K
status among children with cystic fibrosis and its relationship to bone mineral density and bone turnover. Pediatrics.
2005;115:13251331.
30. McCabe H. Riboflavin deficiency in cystic fibrosis: three case
reports. J Hum Nutr Dietet. 2001;14:365370.
31. Kriemler S, Wilk B, Schurer W, Wilson W, Bar-Or O.
Preventing dehydration in children with cystic fibrosis who
exercise in the heat. Med Sci Sports Exerc. 1993;31:774779.
32. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J
Med. 2005; 352:10111023.
33. vonVigier RO, Truttmann AC, Zindler-Schmocker K, et
al. Aminoglycosides and renal magnesium homeostasis in
humans. Nephrol Dial Transplan. 2000;15:822826.
34. Powers SW, Byars KC, Mitchell MJ, Patton SR, Schindler T,
Zeller MH. A randomized pilot study of behavioral treatment
to increase caloric intake in toddlers with cystic fibrosis. Childrens Health Care. 2003;32(4):297311.
35. Erksine JM, Lingard C, Sontag M. Update on enteral nutrition
support for cystic fibrosis. Nutr Clin Pract. 2007;22:223232.
36. Abbott J, Conway S, Etherington C, et al. Perceived body
image and eating behavior in young adults with cystic fibrosis
and their healthy peers. J Behav Med. 2000;23:501517.
336
37. Gilchrist FJ, Lenney W. Distorted body image and anorexia

complicating cystic fibrosis in an adolescent. J Cystic Fibros.
2008;7(5):437439.
38. Littlewood JM. The historical development of nutritional and
dietetic management of cystic fibrosis. Based on a paper delivered at the XIIIth International Cystic Fibrosis Congress.
Stockholm, Sweden; June 2000. Available from http://www.
cysticfibrosismedicine.com.
39. Borowitz DS, Grand RJ, Drurie PR, et al. Use of pancreatic
enzyme supplements for patients with cystic fibrosis in the
context of fibrosing colonopathy. J Pediatr. 1995;127(68):14.
40. Crist W, McDonnell P, Beck M, Gillespie CT, Barrett P,
Mathews J. Behavior at mealtimes and the young child with
cystic fibrosis. J Dev Behav Pediatr. 1994;15(3):157161.
41. Birch LL, Fischer JA. Appetite and eating behavior in children.
Pediatr Clin North Am. 1995;42(4):931953.
42. Henderson RC, Spector BB. Kyphosis and fractures in
children and young adults in cystic fibrosis. J Pediatr.
1994;25(2):208212.
43. Moran A, Hardin D, Rodman D, et al. Diagnosis, screening
and management of cystic fibrosis related diabetes mellitus:
a consensus conference report. Diabetes Res Clinical Practice.
1999;45:6173.
44. ORiordan S, Robinson P, Donaghue KC, Moran A. Management of cystic fibrosis-related diabetes. Pediatr Diabetes.
2008;9(part I):338344.
45. Thiou TG, Cahill BC. Pediatric lung transplantation for cystic
fibrosis. Transplantation. 2008;86(5):636637.
46. Mascarenhas MR. Treatment of gastrointestinal problems in cystic fibrosis. Curr Trea Options Gastroenterol.
2003;6(5):427441.
47. Fridge JL, Conrad C, Gerson L, Cox K. Risk factors for small
bowel bacterial overgrowth in cystic fibrosis. J Pediatr Gastroenterol Nutr. 2007;44(2):212218.
48. Rajiah P. Bronchopulmonary dysplasia [emedicine website].
June 9, 2006. Available at http://emedicine.medscape.com/
article/406564. Accessed December 2008.
49. Cox JH. Bronchopulmonary dysplasia. In: Groh-Wargo S,
Thompson M, Cox JH, eds. Nutritional Care for High-Risk
Newborns. Chicago, IL: Precept Press Inc; 2000.
50. Morris MJ. Asthma [emedicine website]. July 10, 2008. Available at http://emedicine.medscape.com/article/29630.
Accessed December 2008.
51. Sly PD. Asthma: Disease mechanisms and cell biology. In:
Taussig LM, Landau LI, eds. Pediatric Respiratory Medicine.
2nd ed. Mosby Elsevier; 2008;791804.
52. Landau LI, Martinez FD. Asthma: Treatment. In Pediatric Respiratory Medicine. 2nd ed. Mosby Elsevier;
2008:829844.
53. Sithole F, Douwes J, Burstyn I, et al. Body mass index in childhood: a linear association. Asthma. 2008;45(6):473477.
54. Queen Samour P, King K. Pulmonary diseases. In: Queen
Samour P, King K. Handbook of Pediatric Nutrition. 3rd ed.
Sudbury, MA: Jones and Bartlett Publication;2005:307349.
Organ Transplantation
29
Anita Nucci, PhD, RD, LD, Sharon Strohm, MBA, RD, LDN, Neelam Katyal, MS, RD, LDN, and Beth Lytle, RD, LDN
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
Indications for Organ Transplantation . . . . . . . . . . . . . . . 338
Nutrition Assessment Before Transplant . . . . . . . . . . . . . 339
Anthropometric Assessment
Biochemical Tests
Macro- and Micronutrient Requirements
Feeding History
Nutrition Management After Transplantation . . . . . . . . . 340

Intestine
Liver
Kidney
Heart
Lung
Food Safety. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345

Current Status of Organ Transplantation inChildren . . . 346
Learning Objectives
1. Describe the indications for pediatric intestine, liver,

kidney, heart, and lung transplantation.
2. Describe the key nutrition factors that should be examined prior to solid organ transplantation in children.
3. Explain the posttransplant nutrition management
issues related to each of the following solid organs:
intestine, liver, kidney, heart, and lung.
4. State the current outcomes, including morbidity and
mortality, of childhood organ transplantation.
Introduction
Transplantation of organs such as the liver, kidney, and

heart has been performed successfully in children for
several decades and comprises 30%, 45%, and 16% of all
pediatric transplants, respectively.1 The number of intestinal
transplants performed annually has increased considerably
over the last 20 years and reductions in both morbidity
and mortality have been observed. However, neither the
number of children receiving a lung transplant (~2% of
all transplants in children) nor the survival rate after lung
transplantation has changed in the last decade.1
Despite differences between children and adults in the
causes of organ failure that result in organ transplantation,
and response to and complications associated with immunosuppression, graft survival rates are similar.1 Advances
in surgical techniques and the emergence of tacrolimus
as the primary therapeutic immunosuppressive agent in
organ transplantation has improved survival.13 Even with
these improvements, postoperative nutrition management
remains challenging for some organ transplant recipients
as complications may result in the need for modifications
in nutrition therapy. Coordinated interdisciplinary team
337
338
management of the pediatric transplant patient is necessary

to address the many issues that may arise, including compliance with medication and nutrition regimens. Long-term
outcomes such as adequate growth and development and
improved quality of life are still being examined.
Indications for Organ Transplantation
The diagnoses that lead to the majority of intestine, liver,

kidney, heart, and lung transplants in children are shown
in Table 29-1.1 Children with irreversible intestinal failure
may be considered as candidates for intestinal transplantation. Patients are considered to have intestinal failure when
fluid, electrolyte, and nutrition status cannot be maintained
without parenteral nutrition (PN) and this dependence on
PN has led to complications that include catheter infections,
sepsis, loss of venous access, cholestatic liver disease, and
in some instances, liver failure.4,5 The initial evaluation of
potential transplant candidates includes determination of
venous access, functional status of the intestine (including
motility studies), length of the intestine, degree of liver
damage from PN, and the involvement of other organs
in the disease. This information helps the medical team
to identify which type of allograft the patient will need.
Allograft options include an isolated small intestine, liver/
small intestine, or a multivisceral graft (liver, stomach,
duodenum-pancreas, and small bowel).
Table 29-1 Diagnoses That Lead to the Majority of Intestine, Liver, Kidney,
Heart, and Lung Transplants in Children
Organ
Diagnoses
Intestine
Gastroschisis
Midgut volvulus
Necrotizing enterocolitis
Biliary atresia
Acute hepatic necrosis
Metabolic disease
Aplasia/hypoplasia/dysplasia
Obstructive uropathy
Focal segmental glomerular sclerosis
Congenital disease
Cardiomyopathies
Cystic fibrosis
Congenital heart disease (primarily those < 1 year of age)
Primary pulmonary hypertension
Liver
Kidney
Heart
Lung
Liver transplantation is the only therapy available for

children with end-stage liver disease. Complications while
awaiting liver transplantation may include gastrointestinal bleeding and encephalopathy, jaundice, pruritus, and
ascites. Growth failure is also common.1 Approximately half

of pediatric liver transplant recipients receive a standard
orthotopic liver transplant with a whole organ. Younger
children more often receive a split-liver transplant from a
deceased donor or a reduced size graft from a deceased or
living donor.
Kidney transplant is the most common of solid organ
transplants. It is a reasonably safe and cost-effective treatment for end-stage renal disease (ESRD). Optimal nutrition
status prior to transplant correlates favorably with posttransplant outcomes. ESRD in infants and young children is most
commonly due to congenital anomalies. Forty-five percent
is related to renal hypoplasia or dysplasia, obstructive or
reflux uropathy due to posterior urethral valves, agenesis
or abdominal muscular defects (prune belly syndrome), or
pyelonephritis. Renal failure in older children is generally
caused by acquired renal disease, known as glomerulonephritis. In infants with ESRD, early transplantation should
be considered to avoid risks that can develop from chronic
uremia and dialysis.6 In patients who are awaiting a renal
transplant, there is a higher mortality rate for those who are
on chronic dialysis than those who are not. Children with
renal disease may receive a kidney transplant prior to the
time when the disease becomes end-stage. Complications
from chronic renal insufficiency include failure to thrive,
delayed psychomotor development, hypervolemia, hyperkalemia, and metabolic bone disease. Children who have
received a kidney transplant have improved survival as well
as improved rehabilitation compared to children on chronic
dialysis.7
The majority of children undergoing orthotopic heart
transplantation have congenital heart disease. While
end-stage cardiomyopathy and congenital heart disease
with ventricular failure are the primary reasons for transplantation,1 a subset of children are transplanted due to
protein-losing enteropathy (PLE) after a Fontan procedure.
PLE eventually results in low serum blood protein with
subsequent ascites and edema as a result of the inability to
maintain fluid within the vascular space of the abdomen
and peripheral tissues, respectively. Other symptoms such
as diarrhea and malnutrition may also be present.
The primary reason for lung transplantation, particularly in children over the age of 1 year, is cystic fibrosis (CF)
followed by idiopathic pulmonary arterial hypertension.
Heart-lung transplantation has become less common in
recent years due in part to the decreased availability of both
organs with the increased use of isolated heart transplants.
Additional reasons include improved surgical technique
for isolated lung transplantation and the recognition that
ORGAN TRANSPLANTATION
heart-lung transplants are not necessary for children with

these disorders. It is, however, indicated in situations where
end-stage lung disease is coupled with severe dysfunction of
the left ventricle.8
Nutrition Assessment Before Transplant

A thorough nutrition assessment pretransplant is critical
to help maximize a childs nutrition status and increase the
chance of a successful outcome after transplant. Anthropometric measurement in children is a valuable tool because it
is easily obtained and age-specific standards are available.
Growth measures should be plotted and followed over time
for all transplant candidates. These include weight, length
or height, weight for length or height, and occipital head
circumference (if < 3 years of age). If the patient is > 2 years
of age, body mass index (BMI) should also be calculated and
monitored. Adjustments in energy intake should be made to
maintain growth velocity, unless contraindicated due to the
childs condition. Measurement of triceps skinfold thickness and mid-arm circumference may also be followed.
However, it is important to use appropriate instruments,
the same observer, and serial measurements to interpret
these results.
339
Along with anthropometric measurement, a child should
also be given a physical examination. This preliminary look
may then lead to more detailed evaluation, if necessary. Hair
that is sparse or easily breakable may indicate malnutrition.
Dry skin may be a sign of vitamin A or folic acid deficiency
and skeletal changes may point to problems with vitamin D
or calcium metabolism.
Biochemical Tests
Monitoring of laboratory tests helps the clinician to adjust
the provision of nutrients and electrolytes in the diet,
enteral feedings, intravenous replacement fluids, and/or PN
both pre- and posttransplant. Table 29-2 shows the basic
biochemical tests that are often monitored before transplant
by type of solid organ.913
Macro- and Micronutrient Requirements

Calorie requirements for children on oral or enteral nutrition (EN) are usually assessed based on the dietary reference
intakes (DRIs) for age with modifications made to maintain
or accelerate growth and development.14 Indirect calorimetry remains the best and most accurate way to assess basal
metabolic requirements. However, this option is often not
practical to perform, or it may produce unreliable results
Table 29-2 Biochemical Tests Monitored Before Transplant by Type of Solid Organ913
Biochemical Tests
CBC with platelets

PT/PTT
Electrolytes
CO2
BUN and creatinine
Calcium, phosphorous,
magnesium
Glucose
Liver function tests
Alkaline phosphatase
Amylase, lipase
Albumin
Triglyceride
Vitamins
Minerals
Other
Intestine
Liver
Kidney
X
X
X
X
X
X
X
X
Heart
Lung
X
X
X
X
X
X
X
X
X
X
X
X
X
X
A
E
D (25 and 1,25 OH)
B12
RBC folate
Zn
Cu
Se
Mn
Carnitine
X
X
X
X
X
X
X
X
A
E
D (25-OH) if no renal impairment
D (1,25 OH) if renal impairment
PTH
X
X
A
E
D (25-OH)
Glycosylated hemoglobin
340
if a child is mechanically ventilated and there are multiple

air leaks. For children on both EN and PN, calorie requirements are usually estimated at 5% to 10% less than the
estimate for oral/enteral intake alone. Calorie requirements
in those dependent on PN may be even lower. Overfeeding,
particularly for those receiving PN, may enhance the
onset of cholestatic liver disease in children with intestinal
failure.15 Malnutrition, if present, should be corrected if
possible prior to transplant as it places the recipient at an
increased risk of infection, impaired wound healing, and
extended rehabilitation after transplant. Assessment of
macro- and micronutrient intake is needed to determine
need for supplementation or need to obtain nutrition lab
values. Stool or ostomy output should be assessed to determine if stool studies are warranted or further nutrition lab
studies are needed or if medications should be considered.
Protein requirements are generally estimated based
on the DRI for age.16 Adjustments are made based on the
childs liver and renal function.
Feeding History
A complete nutrition assessment should also include a
history of enteral feeding tolerance and current eating
habits. Children with chronic diseases have often tried
many different types of infant and enteral formulas before
choosing the most tolerated option. It is important to note
the type of formula and route and the percentage of calories
that are contributing to the childs total calorie intake when
providing both EN and PN.
Infants and children who receive long-term enteral
feedings are also at risk for oral aversion due to the absence
of oral feeding.9 Normal feeding and swallowing development may have been missed. For children who can swallow,
oral feeding of small amounts of varied food tastes and
textures is encouraged. Maintenance of oral stimulation
may help in the posttransplant period when the patient is
transitioning from enteral to oral feedings. Children with
oral aversion or other feeding issues should be referred to a
feeding clinic as soon as possible.17 A Video Feeding Study
may be needed to evaluate the safety of the child to take oral
fluids and solids.
Nutrition Management After Transplantation

Intestine
Protein and calorie requirements of the post-intestinal pediatric transplant patient will vary based on the childs age,
weight, and growth status as well as pretransplant nutrition

state, ventilation status, wound healing, and the presence
or absence of sepsis and rejection. Caloric requirements
may range from 70% to 120% of estimated requirements.
Protein is generally provided at 150% of the estimated nutrition need and may be adjusted if renal or liver dysfunction
occurs.18 Additional zinc may be required in addition to any
other micronutrient that was previously deficient.18
Initial Enteral/Parenteral Nutrition Support
A continuous PN solution should be initiated in the early
postoperative period. The length of time that the initial
nutrition support will need to be provided, or subsequently
resumed after discontinuation, depends upon the childs
ability to tolerate enteral feedings as well as the development
of complications (eg, rejection, sepsis, and pancreatitis). The
volume and nutrient content of the solution should be determined by the childs renal and cardiopulmonary function
and biochemical indices. Measures such as serum electrolytes, glucose, blood urea nitrogen (BUN), creatinine,
triglyceride, albumin, prothrombin time (PT) and partial
thromboplastin time (PTT), platelets, and liver function
tests should be monitored regularly to assess organ function and the need to modify the PN or intravenous (IV)
fluid solutions. An IV fluid solution of normal saline or
Lactated Ringers is provided immediately posttransplant
to maintain fluid and electrolyte balance as well as replace
ileostomy and gastric fluid losses.
Upon the presence of ileostomy output or other evidence
of bowel function, enteral feedings should be started
(generally on postoperative day 3 or 4). Feedings should
be initiated continuously at a small volume and advanced
by small increments depending upon stoma output and
abdominal status. The choice of a starting feeding formula
as well as the route of administration (gastrostomy versus
jejunostomy) varies from center to center. If stoma output
increases, formula advancement should be paused and fiber
supplements and/or antidiarrheal agents may be provided.
In addition, formula volume may also need to be reduced
and fluid replacement increased. If a surgical jejunostomy
is placed during surgery then feedings should be transitioned from a jejunostomy to gastrostomy tube once the
goal volume is reached.18
An oral diet of clear liquids may be initiated once
the child has been extubated and enteral tube feedings
have been initiated and tolerated. The oral diet should be
advanced as tolerated but exclude foods high in simple
carbohydrates to control osmotic diarrhea. Some children
may also be sensitive to lactose-containing or high-fat
foods. As oral intake and absorption improves, continuous

enteral feedings should be cycled to overnight feedings in
an attempt to improve daytime oral intake. Children who
are orally aversive from years of dependency on PN may
require outpatient feeding therapy or an inpatient feeding
program.
Advancement of Enteral/Oral Feeding and
WeaningofParenteral Nutrition
PN weaning should begin when the child is medically stable.
PN should be gradually reduced by 2- to 4-hour increments
with a goal of a 12-hour infusion. Glucose levels should be
monitored regularly during the weaning process.
Nutrition Management of Complications
Immunosuppressive therapy posttransplant may result in
complications including hyperglycemia, hyperkalemia,
hypertension, hypomagnesemia, and hyperlipidemia,
all of which may require changes in nutrition therapy.
Tacrolimus has been shown to cause hyperkalemia and
hypomagnesemia.19 Potassium intake must be carefully
monitored, and many patients require magnesium supplementation. Corticosteroids are now reserved primarily
for rejection episodes but when used can cause hyperglycemia. Insulin therapy may be necessary in the short term
to control blood glucose levels. Corticosteroids and other
immunosuppressive drugs may also place patients at risk for
hyperlipidemia.
Chylous ascites can be a complication post-intestinal
transplant due to lymphatic ducts being severed. Giving
formula containing medium-chain triglyceride (MCT)
oil, which is water soluble and does not rely on this source
of transportation, will assist in the prevention of chylous
ascites. Should it occur, PN may be the primary or single
source of nutrition until resolved. EN and an oral diet
containing long-chain triglycerides (LCTs) can be slowly
reintroduced as tolerated.
Food allergies are not uncommon in children post-intestinal transplant. Symptoms include increased stool output,
abdominal distention or pain, abdominal cramping, weight
loss, and failure to thrive.18 Milk-protein, wheat, peanuts,
and egg allergies are the most commonly reported.20 Diagnosis may be made by tissue eosinophilia on gastrointestinal
biopsy, a serum radioallergosorbent test (RAST), or serum
IgE. Generally, foods reported as a Class 3 or 4 allergen after
a RAST should be restricted from the childs diet.18 Some
intestinal transplant patients also experience fat malabsorption. Symptoms include an increased stool output, oily
stool, weight loss, or abdominal cramping. Diagnosis may
341
be made with a fecal fat test. Pancreatic enzyme therapy

may be of benefit in patients with a quantitative fecal fat
>20%.21
Growth and development should be monitored closely
after transplant. Studies have shown improved growth
velocity in recent years.22,23 Caloric requirements should be
based on growth as well as activity and absorption levels.
Factors that may affect growth include episodes of rejection that necessitate corticosteroid usage and sepsis events
that result in reduction or discontinuation of enteral/oral
feedings.
Liver
Postoperative nutrition requirements for liver transplant
recipients should be designed to provide sufficient calories to minimize catabolism and prevent complications
from pretransplant nutrition issues. Biochemical parameters should be monitored and nutrition therapy adjusted
as needed.24 A postoperative liver transplant patient may
require PN if he or she is malnourished, has had complications, or if a lengthy recuperation is expected. During the
immediate postoperative period, PN should be infused
continuously.14 Guidelines for initiating postoperative PN
are shown in Table 29-3.18,24,25
A tube feeding may provide total enteral nutrition or be
used in conjunction with the oral route if intake is suboptimal. Breast milk is always preferred, if available. An intact
protein, age-appropriate formula should be used to start,
with a change to a hydrolyzed protein or a free amino-acid
hypoallergenic formula if an intolerance should occur. The
caloric density of formulas may need to be manipulated
depending upon fluid restrictions and caloric requirements. Initially the tube feeding should run continuously
until the oral diet is advanced. As the oral diet is advancing,
nocturnal enteral feedings or daytime bolus feedings may
need to be considered to support nutrition requirements. In
addition, a daily multivitamin supplement for age should be
provided.24 The posttransplant oral diet may be described
as a healthy diet for age with careful consideration of the
current Food Pyramid as well as the 2005 Dietary Guidelines
for Americans.26,27 The protein, fat, and carbohydrate content
of the diet should follow these guidelines with additional
consideration given for complications such as renal impairment, hypertension, hyperkalemia, and diabetes mellitus.
Calcium should be supplemented if intake is insufficient.
342
Table 29-3 Guidelines for Initiating Parenteral Nutrition after Liver Transplant18,24,25
Nutrient
Guidelines
Calories
Avoid overfeeding
Initially provide 120%130% of resting energy expenditure to meet postoperative transplant needs
Pre-existing nutrition needs, surgical complications, wound healing, sepsis, and rejection may further necessitate additional calories
Provide 15%20% of total calories as protein
Infants: 33.5 g/kg dry body weight
12 years: 2.53 g/kg dry body weight
313 years: 1.52.5 g/kg dry body weight
Adolescents: 11.5 g/kg dry body weight
Additional consideration should be given to renal function and wound healing
Trophamine (B. Braun, Irvine, CA) is the preferred amino acid source due to its branched chain amino acid content and lower pH
for maximum solubility of calcium and phosphorus (cysteine is added only for children < 1 year of age)
Provide 30% of total calories as fat
20% intravenous fat is preferred for its caloric density
Provide 50%55% of total calories as carbohydrate
Begin at same concentration as the initial intravenous fluid and advance glucose as tolerated to a maximum of:
Term Infants: 14 mg/kg/min
110 years: 11 mg/kg/min
1118 years: 8.5 mg/kg/min
Provide standard intravenous multivitamin for age
Provide parenteral trace mineral solution based on weight
Provide full amount of trace minerals in patients without liver dysfunction
Provide dose trace minerals + full amount of zinc with liver dysfunction secondary to cholestasis
Zinc should be supplemented at 1 times the DRI for age if wound healing is an issue
Based on weight, renal and cardiopulmonary function
Maintenance fluids:
110 kg dry body weight: 100 mL/kg/d
1020 kg dry body weight: 1000 mL + 50 mL/kg for each kg over 10
2030 kg dry body weight: 1500 mL + 20 mL for each kg over 20
Protein
Fat
Carbohydrate
Multivitamins
Trace Minerals
Fluid
Feeding Disorders
Advancement of the oral diet may be challenging in some
patients postoperatively. Oral aversion may occur in those
who required long-term PN, EN, and mechanical ventilation. These patients may require consultation from
an occupational and/or speech therapist. Patients who
required special diet restrictions before transplant (eg,
protein restriction) may continue to prefer the taste of their
restricted diet. Temporarily, these patients may continue
their pretransplant medical nutrition enteral formulas until
they readily incorporate a variety of foods in their diet.
Long-term goals for patients after liver transplant include
nutrition and life-style factors. Optimization of linear
growth and physical development as well as socialization
and participation in daily activities are desired. Calorie
requirements will vary with age, activity, and growth rate.
Children who exhibit linear growth impairment will need
calorie goals based on the DRI for height age.9 Those without
growth delay may initially consume calories based on the
DRI for age. Growth delay is common after liver transplant
due to the nutrition impact of the original disease and use
of corticosteroids. Catch-up growth for weight occurs more
rapidly than height.1,28,29 Linear growth and weight should
be monitored at primary care physician visits, and transplant centers alerted for any change in growth velocity. 30
Kidney
The nutrition recommendations for kidney transplant
patients immediately and later after transplant are shown in
Table 29-4. An age-appropriate oral diet can be started once
bowel function has resumed. An enteral tube feeding is
rarely needed after kidney transplant. However, for patients
who were fed via gastrostomy tube prior to transplant, it
may be necessary to continue tube feedings and gradually
343
Table 29-4 Nutrition Recommendations for Pediatric Kidney Transplant Recipients

Nutrient
Immediately Posttransplant
Later After Transplant
Calories
DRI for height-age. May need additional calories if patient is

underweight prior to transplant
125%150% DRI for age
Avoid simple sugars
30%40% of total calories
May need higher intakes, provide supplements as necessary
Unrestricted
Unrestricted unless necessary
Mildly restricted
Supplement as indicated by serum values
Unrestricted
DRI. Supplementation usually not necessary unless severely
malnourished prior to transplant, Vitamin D if indicated
DRI for height-age
Protein
Carbohydrates
Fat
Phosphorus
Calcium
Potassium
Sodium
Iron
Fluids
Vitamins
to transition over to oral feeds. Gastrostomy tubes should

only be removed after fluid and caloric needs are met
orally. 31 PN is also rarely needed after kidney transplant
unless the patient has acute tubular necrosis, intractable
diarrhea, non-functional gastrointestinal tract, or small
bowel obstruction. Volume and nutrients are adjusted
based on urinary output and graft function. Long-term
nutrition goals after kidney transplant include promoting
wound healing, promoting anabolism, preventing infection, promoting adequate growth, minimizing side effects
of medications, maintaining serum mineral and electrolyte
levels within normal limits, and maintaining blood pressure
within appropriate limits for age.
Hypertension can be caused by fluid overload, immunosuppressive agents, obesity, and/or a pre-existing condition of
hypertension. Therapy may include a sodium-restricted
diet, diuretics, or hypertensive drugs. Hyperglycemia may
be caused by corticosteroid use. Simple sugars should be
eliminated from the diet until glucose levels return to
normal. The development of new onset insulin-dependent
diabetes has been reported in a small percentage of recipients. 32 Hyperlipidemia resulting from the use of medications
(eg, corticosteroids, calcineurin inhibitors, and sirolimus)
as well as malnutrition and obesity should be evaluated and
treated as it can hasten the progression of renal disease. 33
Lipid profiles should be monitored and patients placed on
a moderate-fat diet with emphasis on healthy fats such as
olive oil, fish, and nuts. Anemia is a complication of renal
failure but does not always resolve after transplantation.
The presence of iron deficiency and dosage of immunosuppressant have been identified as causative factors associated
DRI for age

Unrestricted unless obesity is present
30%40% of total calories
May need higher intakes, provide supplements as necessary
Unrestricted
Unrestricted
Unrestricted unless hypertension or edema is present
Supplement as indicated by serum values
Unrestricted
DRI. Supplementation usually not necessary unless severely
malnourished prior to transplant, Vitamin D if indicated
with anemia after transplant. 34

Excessive weight gain may result from an increased
calorie intake secondary to steroid therapy, fewer dietary
restrictions, and improved feeling of well being as well as a
lack of exercise. Presence of bone disease may limit physical
activity and decrease energy expenditure. Early counseling
with a dietitian and repeated nutrition interventions are
needed to promote a healthy lifestyle and initiate a regular
exercise regimen. Steroid dosage should be decreased to
the lowest amount possible without loss of graft function.
Decreased bone mass, fragility, and fractures are a known
complication after transplant in adults. Alterations in bone
mass have been found in children and adolescents as well
with the greatest decrease in bone mineral density observed
during the first 6 months after transplant. 35 Bone mineral
density studies should be performed on a regular basis for
all children after transplant. Calcium, phosphorous, and
vitamin D supplements are prescribed based on the patients
intake and serum levels.
Adequate growth rate is directly related to age of
onset of disease and duration of disease and is assessed by
standard deviation scores or height deficit score (z score).
Height potential is greatly reduced in children with chronic
kidney disease before age 2 because one-third of growth
occurs during the first 2 years of life. Additional factors
include metabolic acidosis, renal osteodystrophy, and
catabolic states associated with infection, corticosteroid
dosage, and renal function after transplant. 36 Newer induction protocols may allow steroid-free immunosuppressive
regimens that in turn may prevent obesity, hypertension,
stunted growth, and non-compliance. 37 Use of recombinant growth hormones during puberty has been found to
be effective in increasing height. 38 Physical adverse effects
344
such as cushingoid appearance, short stature, scars, obesity,

hirsutism, and gum hyperplasia can cause lower self-esteem
and increased stress in adolescents. This may lead to noncompliance with medication therapy and an increased risk
of graft rejection. A social worker and child life specialist
can provide valuable insight and support in such situations.
Heart
The nutrition goals for posttransplant pediatric heart transplant recipients include achieving and maintaining ideal
body weight, limiting sweets and foods high in concentrated sugar, reducing foods high in fat and cholesterol, and
limiting salt.12 Most pediatric heart transplant recipients
progress to a full oral diet within 4 days of transplant. 3942
The exception are those orally aversive infants and children
who were dependent on EN and/or total parenteral nutrition pretransplant. These patients may require additional
nutrition support while receiving intensive oral rehabilitation therapy.
Dietary Modification
Alterations in diet may be necessary due to side effects of
medications and immunosuppression therapy. Hypertension, hyperglycemia, and weight gain are common in
posttransplant pediatric heart recipients.12 Lipid abnormalities have been reported at 1 year posttransplant.43
Calcineurin inhibitors may create these elevated serum
lipid levels, and a heart-healthy, low-cholesterol, low-saturated fat diet is recommended. 39
Osteoporosis is universal among pediatric posttransplant recipients. 39 The combined effects of nutrition status
before transplant along with calcineurin inhibitors and
steroids result in decreased calcium absorption and bone
formation. Supplemental vitamin D (400800 International
Units) and calcium (12001500 mg) are recommended. 39
In addition, an annual dual-energy x-ray absorptiometry
(DEXA) scan may be warranted in some cases. There
are little data on the use of biphosphates, calcitonin, and
hormone replacement therapy in the pediatric posttransplant population.
Pretransplant growth parameters will impact the
amount of catch-up growth needed posttransplant.4445
Infants and children have demonstrated appropriate growth
velocity and weight gain posttransplant. Weight gain with
lack of linear catch-up growth is characteristic of the adolescent heart transplant population. 39
Lung
The post-lung transplant nutrition goals are to provide
energy to prevent weight loss, promote healing, and prevent
infection while minimizing gastrointestinal complications
and avoiding drug-nutrient interactions. Calorie needs are
increased due to the bodys effort to fight infection and
promote wound healing. In contrast, the body uses less
energy due to the decreased work of breathing and limited
activity level immediately posttransplant. Considering this
combined effect, calorie requirements are typically 100% to
120% of the DRI for age.14 Protein needs are elevated due
to the healing process after surgery and are two times the
DRI.16
Enteral/Oral Supplementation
After transplant, the patient should be advanced to a regular
diet as soon as tolerated. Oral nutrition supplements may
be encouraged to maximize energy intake. Initially the
patient may not be able to meet calorie needs from oral
intake because of side effects (ie, nausea and vomiting)
from immunosuppressive medications. If the patient loses
10% of his or her admission weight and is not able to meet
caloric needs orally then supplemental tube feeds should be
recommended. Tube feedings have been shown to be more
effective than oral intake for weight gain after transplant.46
The patient often eats orally throughout the day and receives
nocturnal tube feeds. For patients with CF and pancreatic
insufficiency, semi-elemental formula may be necessary. If
calorie and protein needs are not met by oral diet and/or EN
then PN should be initiated.
Pancreatic Enzyme Supplements/Vitamin-Mineral
Supplementation
Patients with CF and pancreatic insufficiency will continue
to have pancreatic disease posttransplant. Pancreatic
enzyme therapy should resume with all meals and snacks.
Previous vitamin and mineral supplementation should
continue. Patients with CF are at risk of developing high
vitamin A and vitamin E serum levels after transplant.
These levels should be monitored because adjustments are
frequently required.47 Magnesium levels tend to be low after
transplant and supplementation may be necessary.
Common complications after lung transplant that require
nutrition intervention include infection and rejection, diabetes, osteoporosis, renal complications, and
gastrointestinal complications. Infection and rejection are

significant obstacles that occur after lung transplantation.
Both problems are related to the immune system. Infection can be a complication from oversuppression while
rejection is a result of too little suppression. Immunosuppressant drugs are medications given to prevent rejection
of the transplanted organ and it is a difficult balancing act
to determine the correct amount of immunosuppression
required for each patient.48 Common immunosuppressive
medications include tacrolimus, cyclosporin, prednisone,
mycophenolate, rapamycin, and azathioprine. Medication
doses are measured in the blood and adjustments are determined from these levels. Food can alter the absorption of
these drugs so it is important that patients take these medications either fasting or with meals on a consistent basis. It is
important to note any vomiting or diarrhea because this can
also influence the drug level. Other medications including
antacids, antibiotics, and antifungals can interfere with
immunosuppressant levels. Grapefruit, grapefruit juice, or
juice that contains grapefruit juice is discouraged because it
has also been shown to alter levels.
Impaired glucose tolerance and diabetes is relatively
common after lung transplantation, especially in patients
with CF. Hyperglycemia is due to the use of high-dose prednisone posttransplant and has also been associated with
the use of tacrolimus and cyclosporine. It is important to
monitor metered blood glucose levels several times per day
and periodically check glycosylated hemoglobin levels. The
recommended treatment consists of diet modification and
insulin therapy.49
Bone disease or osteoporosis is a problem generally
seen in patients with various types of respiratory diseases
both before and after transplant. 50 Exposure to medications
used after surgery, which includes long-term use of prednisone, cyclosporine, and tacrolimus, have all been associated
with bone loss. DEXA scans should be monitored annually
posttransplant to examine changes in bone density over
time. Recommendations for management of bone health
include maintaining a normal weight, calcium and vitamin
D supplementation, and routine exercise. 51
Renal function should be monitored closely after transplant because immunosuppressant drugs used to prevent
rejection can cause renal impairment. Patients with CF are
at greater risk for renal insufficiency as compared to patients
with other respiratory diseases. 52 Adequate amounts of
fluids should be encouraged with alterations in electrolyte
imbalances. It is especially important to increase oral fluids
when gastrostomy feeds are being decreased to make up the
difference of fluid loss from the tube feeds. Alterations in
345
diet may be necessary based on abnormalities indicated in

blood work.
Distal intestinal obstruction syndrome (DIOS) is a
common complication in CF transplant patients, with
an estimate of 20% incidence in the early posttransplant
period. 53 The combination of narcotics for pain management, inadequate intake food and fluid intake, and bed
rest put these patients at extremely high risk of developing
problems. Symptoms are characterized by abdominal pain,
abdominal distention, and vomiting. Some transplant
centers give polyethylene glycol lavage solution as routine
care to prevent DIOS after surgery. 53 Recommendations
for prevention of DIOS are to monitor bowel movements,
resume previous pancreatic enzyme regimen, encourage
adequate fluid intake, and use stool softeners as needed.
Lung transplantation is an accepted treatment option
for patients with various types of end-stage lung diseases.
There is currently a lack of research in the area of post-lung
transplant nutrition. Close monitoring of nutrition status is
essential to improve patient survival. As the success rates
improve, so will our understanding of both medical and
nutrition aspects of lung transplantation.
Food Safety
Because most transplant recipients are receiving immunosuppressive medications, they are particularly susceptible to
developing a foodborne illness caused by bacteria and other
pathogens that can contaminate food. The major pathogens
that can cause foodborne illness and the most common
sources of contamination associated with these pathogens
are shown in Table 29-5. 54 The United States Department
of Agriculture, Food Safety and Inspection Service recommends the following 4 basic steps to food safety: (1) clean
hands and surfaces often as bacteria can be spread from
surfaces to food; (2) separate meat, poultry, seafood, and
eggs from ready-to-eat foods to avoid cross-contamination;
(3) cook foods to proper temperatures; and (4) chill foods
promptly. In addition, it is important to adhere to the manufacturer Sell-by and Use-by dates when purchasing and
consuming perishable foods. When eating out, transplant
recipients should avoid any food that contains uncooked
ingredients and speak to the food preparer to ensure that
foods have been cooked to a proper minimum internal
temperature. In general, buffets should be avoided. When
traveling, gel packs should be used to keep food cold (40oF
or below) as well as insulated containers to keep cooked
food hot (140oF or above). 54
346
Table 29-5 Major Foodborne Pathogens and Common Sources

Pathogen
Bacteria
Campylobacter
Escherichia coli
Listeria monocytogenes
Salmonella
Vibrio vulnificus
Viruses
Norovirus
Protozoa
Cryptosporidium
Toxoplasma gondii
Sources
Raw and uncooked meat, poultry, milk,

and untreated water
Undercooked or raw beef, contaminated
produce, raw milk, unpasteurized juices
and ciders
Unpasteurized dairy products, sliced deli
meats, deli-style prepared egg, ham,
seafood, and chicken salads
Raw and undercooked eggs, undercooked
poultry and meat, unpasteurized dairy
products or juice, contaminated produce
Raw or undercooked fish or shellfish
Any food or water contaminated by
someone who is infected with the virus
Uncooked or contaminated food or water
Raw or undercooked meat or foods;
objects contaminated with cat feces
Current Status of Organ Transplantation

inChildren
Survival rates have continued to improve for both patients

and organ grafts.1 The 1- and 5-year survival rates for liver
and heart transplant recipients are approximately 90% and
85%, respectively.1,55 The 5-year survival rate for children
who have received a kidney transplant has been reported
at 95%.1,56 A recent report on the current status of pediatric intestinal transplantation noted that the 1- and 5-year
patient survival rate at centers of excellence has reached
95% and 77%, respectively. 57 Patient survival for children
who have received a lung transplant has remained relatively constant over the past decade with 5-year survival
at 50%. 58 Non-compliance with immunosuppressive treatment regimens remains a problem, particularly in the
adolescent transplant population, and is one factor related
to graft failure.1
Improvements with immunosuppressant treatment
therapies and increases in survival rates have enlarged
the population of pediatric transplant recipients. Interdisciplinary team management of the pediatric transplant
recipient is essential to assist with the complex medical and
psychological issues that can result from chronic disease
and the complications that can result from immunosuppressant therapy after transplant. In addition to medical issues,
patients and families also need to adjust to the new life that
transplantation has provided. In recent years, reported
outcomes after transplant have included not only survival
statistics but also discussions related to the achievement of

or return to physical, emotional, and social quality of life. 59
Growth and development are important determinants
of quality of life. Impaired growth and development is a
complication often experienced by pediatric transplant
patients. The presence or absence of impaired growth is
affected by the length of illness and graft function, the use
of corticosteroids, and development of infectious complications. 59 Quality of life after transplant often depends upon
the type of organ or organs received. Differences may also
exist in perceived quality of life between the transplant
recipient and his or her caregivers. Perceived physical and
social function after pediatric intestinal transplant was
reported by recipients to be similar to other school children.
However, their parents felt that their health and physical
abilities were less than normal.60 Children and adolescents
who have had a kidney transplant have reported improved
quality of life in terms of physical and social well-being
compared to children on dialysis.61 An early study on the
effect of heart or heart-lung transplantation on quality
of life in children showed improvement of quality of life
within the early post-operative period.62 In another quality
of life study completed with heart transplant recipients,
adolescents perceived their quality of life and well-being
as excellent compared to healthy controls.63 Finally, while
greater quality of life has been reported after pediatric lung
transplantation, the development of complications such
as infection is more common in children than adults and
results in reduced perception of quality of life.64 While it
is difficult to measure quality of life in the pediatric population, interest in the data is rising as life expectancy is
increasing. 59
1. Which of the following biochemical complications

may occur shortly after intestinal transplantation and
require changes in nutrition therapy?
A. Hyperkalemia, hypermagnesemia, hyperglycemia,
and hyperlipidemia
B. Hyperkalemia, hypomagnesemia, hypoglycemia,
and hyperlipidemia
C. Hyperkalemia, hypomagnesemia, hyperglycemia,
and hyperlipidemia
D. Hyperkalemia and hypermagnesemia
2. Common nutrition-related complications after kidney
transplant include:
A. Hyperlipidemia
B. Obesity
C. Hyperglycemia
D. All of the above
3. Which of the following supplements are not recommended for children with cystic fibrosis and pancreatic
insufficiency after lung transplantation?
A. Pancreatic enzymes
B. Standard enteral formula
C. Parenteral nutrition
D. Vitamins and minerals
References
1. Sudan D, Bacha EA, John E, Bartholomew A. Childhood

organ transplantation. Pediatr Rev. 2007;28(12):439452.
2. Todo S, Tzakis A, Abu-Elmagd K, et al. Cadaveric small bowel
and small bowel-liver transplantation in humans. Transplantation. 1992;53(2):369376.
3. Grant D, Abu-Elmagd K, Reyes J, et al. 2003 report of the
Intestine Transplant Registry: a new era has dawned. Ann
Surg. 2005;241:607613.
4. Nucci A, Barksdale E, Beserock N, et al. Long-term nutritional
outcome after pediatric intestinal transplantation. J Pediatr
Surg. 2002;37(3):460463.
5. Kowalski L, Nucci A, Reyes J. Intestinal transplantation. In:
Rolandelli RH, Bankhead R, Boullata JI, Compher CW, eds.
Clinical Nutrition Enteral and Tube Feeding. 4th ed. Philadelphia, PA: Elsevier Saunders; 2005:523529.
6. Khwaja K, Humar A, Najarian J. Kidney transplants for children under one year of age A single center experience. Pediatr
Transplant. 2003;7(3):163167.
7. Bartosh SM. Recipient characteristics: ESRD, chronic renal
failure, glomerulonephritis. In: Fine RN, Webber S, Kelly
D, Harmon W, Olthoff K, eds. Pediatric Solid Organ Transplantation. 2nd ed. Malden, MA: Blackwell Publishing;
2007:146152.
8. MacLaughlin EF. Recipient characteristics: Lung transplantation, heart-lung transplantation, cystic fibrosis. In: Fine
RN, Webber S, Kelly D, Harmon W, Olthoff K, eds. Pediatric
Solid Organ Transplantation. 2nd ed. Malden, MA: Blackwell
Publishing; 2007:314335.
9. Strohm S, Reyes J, Koehler A. Pediatric small bowel transplantation. In: Hasse JM, Blue LS, eds. Comprehensive Guide
to Transplant Nutrition. Chicago, IL: American Dietetic Association; 2002:216225.
10. Sutton MM. Pediatric liver transplantation. In: Hasse JM,
Blue LS, eds. Comprehensive Guide to Transplant Nutrition.
Chicago, IL: American Dietetic Association; 2002:182215.
11. Miller D, MacDonald D. Management of pediatric
patients with chronic kidney disease. Nephrol Nurs J.
2006;33(4):415429.
12. Heart Transplant Team, Childrens Hospital of Boston. Pediatric heart transplantation: a practical parent guide. http://
www.experiencejournal.com/cardiac/clinic/htbook.shtml.
13. Fulton JA, McKenna A. Pediatric lung transplantation. In:
Hasse JM, Blue LS, eds. Comprehensive Guide to Transplant
Nutrition. Chicago, IL: American Dietetic Association;
2002:153171.
347
14. Food and Nutrition Board, Institute of Medicine. Energy. In:

Otten JJ, Pitzi Hellwig J, Meyers LD, eds. Dietary Reference
Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: National Academy Press; 2006:625651.
15. Jeejeebhoy KN. Management of PN-induced cholestasis.
Pract Gastroenterol. 2005;24:6268.
16. Food and Nutrition Board, Institute of Medicine. Protein
and amino acids. In: Otten JJ, Pitzi Hellwig J, Meyers LD,
eds. Dietary Reference Intakes: The Essential Guide to Nutrient
Requirements. Washington, DC: National Academy Press;
2006:740772.
17. Byars KC, Burklow KA, Ferguson K, et al. A multicomponent
behavioral program for oral aversion in children dependent on gastrostomy feedings. J Pediatr Gastroenterol Nutr.
2003;37(4):473480.
18. Phillips SK, McGhee B, Reyes J. Pediatric Liver, Intestine, and
Multivisceral Transplantation: A Manual of Management and
Patient Care. Hudson, OH: Lexi-Comp, Inc; 2003.
19. Fung J, Allessiani M, Abu-Elmagd K, et al. Adverse
effects associated with the use of FK506. Transplant Proc.
1991;23:31053108.
20. Koehler A, Yaworski J, Gardner M, et al. Coordinated interdisciplinary management of pediatric intestinal failure: a 2-year
review. J Pediatr Surg. 2000;35(2):380385.
21. Strohm S, Koehler A, Mazariegos G. Nutrition management in pediatric small bowel transplant. Nutr Clin Prac.
1999;14:5863.
22. Kowalski L, Nucci A, Perez G, Mazariegos G, Sindhi R. Nutritional outcomes after elimination of routine steroid therapy in
pediatric intestinal transplantation [abstract]. World Transplant Congress; 2006.
23. Lacaille F, Vass N, Sauvat F. Long-term outcome, growth and
digestive function in children 2 to 18 years after intestinal
transplantation. Gut. 2008;57:455461.
24. Sutton MM. Pediatric liver transplantation. In: Hasse JM,
Blue LS, eds. Comprehensive Guide to Transplant Nutrition.
Chicago, IL: American Dietetic Association; 2002:182215.
25. The Nutrition Support Committee. In: Barksdale EM, Nucci
A, Yaworski JA. Parenteral Nutrition Manual. 5th ed. Pittsburgh, PA: Childrens Hospital of Pittsburgh; 2003.
26. Department of Health and Human Services. My Pyramid Food
Guidance System. Washington, DC: United States Department
of Agriculture; 2005.
27. Department of Health and Human Services. Dietary Guidelines for Americans 2005. Washington, DC: United States
Department of Agriculture; 2005.
28. Alonso E. Growth and developmental considerations
in pediatric liver transplantation. Liver Transplant.
2008;14:585591.
29. Burra P, De Bona M. Quality of life following organ transplantation. Transpl Int. 2007;20:397409.
30. Balistreri W, Welch T, Daniels S. Care of children with solidorgan transplants. In: McMillan J, Geigin RD, DeAngelis C,
Jones D. Oskis Pediatrics. 4th ed. New York, NY: Lippincott
Williams & Wilkins; 2006:26062608.
31. Wong H, Mylrea K, Manion CA, Bass MI, Feber J, Filler G.
Caregivers attitudes towards gastrostomy removal after renal
transplantation. Pediatr Transpl. 2005:9;574578.
348
32. Furth S, Neu A, Colombian P, Plotwick L, Turner ME,

Flvush B. Diabetes as a complication of Tacrolimus (FK506)
in pediatric renal transplant patients. Pediatr Nephrol.
1996;10:6466.
33. Saland JM, Ginsberg H, Fisher EA. Dyslipidemia in pediatric
renal disease: epidemiology, pathophysiology and management. Curr Opin Pediatr. 2002:14(2);197204.
34. Kausman JY, Powell HR, Jones CL. Anemia in pediatric renal
transplant recipients. Pediatr Nephrol. 2004:19;526530.
35. Feber J, Cochat P, Braillon P. Bone mineral density in
children after renal transplantation. Pediatr Nephrol.
2000;14:654657.
36. Fine RN. Management of growth retardation in pediatric recipients of renal allografts. Nat Clin Pract Nephrol.
2007;3:318324.
37. Ellis D, Shapiro R, Moritz M, et al. Renal transplantation
children managed with lymphocyte depleting agents and lowdose maintenance tacrolimus monotherapy. Transplantation.
2007:83(12);15631570.
38. Hokken-Koelega AC, Stijnen T, de Ridder MA, et al. Growth
hormone treatment in growth-retarded adolescents after renal
transplantation. Lancet. 1994;343:13131317.
39. Blume E. Current status of heart transplantation in children:
Update 2003. Pediatr Clin North Am. 2003;50:1384.
40. Wagner K, Webber SA, Kurland G, et al. New onset diabetes
mellitus in pediatric thoracic organ recipients under
tacrolimus based immunosuppression. J Heart Lung Transplant. 1997;16:275282.
41. Chin D, Rosenthal D, Bernstein D. Lipoprotein abnormalities
are highly prevalent in pediatric heart transplant recipients.
Pediatr Transpl. 2000;4:193199.
42. Penson MG, Winter WE, Fricker FJ, et al. Tacrolimus-based
triple drug immunosuppression minimizes serum lipid elevations in pediatric cardiac transplant recipients. J Heart Lung
Transplant. 1999;18:707713.
43. Pahl E. Heart transplantation: Literature review 2005-2006.
Pediatr Transpl. 2007;11:709715.
44. Canter C, Shaddy R, Bernstein D, et al. Indications for
heart transplantation in pediatric heart disease. Circulation.
2007;115:666667.
45. Cohen A, Addonizio LF, Softness B, et al. Growth and skeletal maturation after pediatric heart transplantation. Pediatr
Transpl. 2004;8:126135.
46. Fulton JA, Orenstein DM, Koehler AN, Kurland G. Nutrition
in pediatric double lung transplant patient with cystic fibrosis.
NCP. 1995;10:6772.
47. Robert R, Durie P, Verjee Z, Chaparro C, Corey M, Tullis
E. Increased vitamin A and E levels in adult cystic fibrosis
patients after lung transplantation. Transplantation.
2005;79(5):613615.
48. Visner GA, Goldfarb SB. Posttransplant monitoring of
pediatric lung transplant recipients. Curr Opin Pediatr.
2007;19:321326.
49. Moran A, Hardin D, Rodman D; and the Consensus

Committee. Consensus Document Diagnosis, Screening, and
Management of Cystic Fibrosis Related Diabetes Mellitus.
Bethesda, MD: Cystic Fibrosis Foundation. 1999.
50. Shane E, Papadopoulos A, Staron RB, et al. Bone loss
and fracture after lung transplantation. Transplantation.
1999;68(2):220227.
51. Dosanijh A. A review of nutritional problems and the
cystic fibrosis lung transplant patient. Pediatr Transpl.
2002;6:388391.
52. Schindler R, Radke C, Paul K, Frei U. Renal problems after
transplantation in renal patients. Nephrol Dial Transplant.
2001;16(7):13241328.
53. Gilljam M, Tullis E, Keshavjee S, Hutcheon M. GI complications after lung transplantation in patients with cystic fibrosis.
Chest. 2003;123:3741.
54. Food Safety and Inspection Service. Food Safety for Transplant
Recipients: A Need-to-Know Guide for Bone Marrow and Solid
Organ Transplant Recipients. Washington, DC: United States
Department of Agriculture. 2006.
55. North American Pediatric Renal Transplant Cooperative Study
(NAPRTCS) 2006 Annual Report. Rockville, MD; 2006.
56. Fricker FJ, Addonizio L, Bernstein D, et al. Heart transplantation in children: indications. Report of the Ad Hoc
Sub-committee of the Pediatric Committee of the American Society of Transplantation (AST). Pediatr Transplant.
1999;3:333342.
57. Mazariegos GV, Squires RH, Sindhi RK. Current perspectives
on pediatric intestinal transplantation. Curr Gastroenterol Rep.
2009;11:226233.
58. Marshall HI, Aurora P, Christie JD, et al. Registry of the International Society of Heart and Lung Transplantation. J Heart
Lung Transplant. 2008;27(9):937983.
59. Burra P, De Bona M. Quality of life following organ transplantation. Transpl Int. 2007;20:397409.
60. Sudan D, Horslen S, Botha J, et al. Quality of life after pediatric intestinal transplantation: the perception of pediatric
recipients and their parents. Am J Transplant. 2004;4:407.
61. Rubik J, Grenda R, Jakubowska-Winecka A, Dabrowska A.
Quality of life in children and adolescents with end-stage
renal disease treated with dialysis and kidney transplantation.
Pol Merkuriusz Lek. 2000;8:280.
62. Wray J, Radley-Smith R, Yacoub M. Effect of cardiac or heartlung transplantation on the quality of life of the paediatric
patient. Qual Life Res. 1992;1:4146.
63. Pollock-BarZiv SM, Anthony SJ, Niedra R, Dipchand AI,
West LJ. Quality of life and function following cardiac transplantation in adolescents. Transplant Proc. 2003;35:2468.
64. Mallory GB, Spray TL. Pediatric lung transplantation. Eur
Respir J. 2004;24:839.
30
Oncology, Hematopoietic Transplant,

andSurvivorship
Nancy Sacks, MS, RD, LDN, Elizabeth Wallace, RD, CNSC, LDN, Seema Desai, MS, RD, LDN, CNSD, Vinod K. Prasad, MD, MRCP
(London), David Henry, MS, BCOP, Virginia Guzikowski, MSN, CRNP, Liesje Nieman Carney, RD, CNSD, LDN, Beth Bogucki Wright, MS,
RD, CSP, LDN, and Susan Rheingold, MD
CONTENTS
General Oncology Overview. . . . . . . . . . . . . . . . . . . . . . . .
Hematopoietic Transplant. . . . . . . . . . . . . . . . . . . . . . . . .
Late Effects of Treatment for
Survivors of Childhood Cancer . . . . . . . . . . . . . . . . . . . . .
Appendix 30-1: Algorithm For Nutritional
Intervention In The Pediatric Oncology Patient. . . . . . . .
Appendix 30-2: Algorithm for Nutritional Intervention
and Categories of Nutritional Status in the Pediatric
Oncology Patient References and Resources . . . . . . .
Appendix 30-3: Categories of Nutritional Status
for the Pediatric Oncology Patient. . . . . . . . . . . . . . . . . .
Appendix 30-4: Gastrointestinal Supportive
Care Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Learning Objectives
349
354
362
365
366
367
368
1. Evaluate the nutrition status of the pediatric oncology

patient and determine the caloric, macronutrient, and
micronutrient needs of the patient.
2. Identify the common nutrition issues for children
undergoing hematopoietic stem cell transplantation.
3. Choose the most effective mode of nutrition support
and monitor its tolerance in the pediatric oncology
population.
4. Identify the nutrition and activity goals for survivors of
childhood cancer.
5. Become more knowledgeable regarding types of medication used to alleviate gastrointestinal problems.
General Oncology Overview
Pediatric cancer is the leading cause of death by disease in

children under the age of 15 years. It is estimated that 1 in
475 children will develop cancer by age 15 years, accounting
for more than 13,000 new cases of pediatric cancer a year
in the United States (ages 019 years). As a result of multimodal therapy, the 5-year survival has improved from less
than 50% in the 1970s to almost 80% today. Although the
cure rate varies, it is estimated that by the year 2010 that
1 out of 250 young adults will be a survivor of childhood
cancer.1 The type of cancer and treatments utilized adversely
impact nutrition status of the child with cancer during and
following therapy; therefore, it is essential to maximize
nutrition status at diagnosis, throughout therapy, and after.
Nutrition Aspects: Diagnoses and Malnutrition

The risk of malnutrition is a significant concern during
pediatric cancer treatment. Due to the increased nutrition
needs for growth and development during childhood, and
349
350
the metabolic stress of cancer, malnutrition is a frequent

treatment complication. Between 6% and 50% of children
will present with acute malnutrition at diagnosis.25 Higher
incidence of malnutrition may be related to delay in diagnosis, extent of disease, and location of the tumor. During
the course of therapy, malnutrition is observed in 8% to
32% of children.6 Higher incidences of malnutrition have a
direct correlation with more intensive courses of treatment,
often including transplant. Younger children may be at
particularly higher risk of acute malnutrition due to limited
nutrient stores and increased demand for growth.
Nutrient needs may not be met due to increased metabolic demands, depleted stores, or inadequate intake.7,8
Inadequate nutritional intake is common during therapy,
which can result in acute and long-term malnutrition.
Nutrition status should not be assessed by weight or appearance alone as large tumor burdens may disguise the loss of
adipose and lean muscle mass, thereby making it difficult to
assess nutrition status at diagnosis.
Certain diagnoses are more likely to result in nutrition problems due to altered metabolism, physiological
changes, and effects of antineoplastic therapy.9 Children
with sarcomas, neuroblastoma, and brain tumors typically
present at diagnosis with protein depletion and weight
loss.10,11 Other diagnoses that are at high risk for nutrition
complications include advanced stage Wilms tumor and
acute myelogenous leukemia (AML).
Multimodal Treatment and the Effects on Nutrition

Surgery
Surgical intervention is necessary for most solid tumors.
Nausea, vomiting, fatigue, altered bowel motility, and
decreased appetite pre- and postoperative are complications
that can impact the ability to meet nutrient requirements.
Solid tumors involving the gastrointestinal (GI) tract can
cause changes in absorption and nutrient delivery, and
affect digestion and absorption prior to surgical resection.12
Postoperative complications from GI tract or intraperitoneal organ surgery can include impaired swallow function,
decreased gastric capacity or emptying, ileus of the small
bowel, and altered bowel length and integrity. Children
malnourished at the time of surgery have been found to
have compromised wound healing and an increased risk of
morbidity and mortality, whereas well-nourished patients
have fewer surgical complications.13
Radiation Therapy
Radiation therapy is a treatment used independently or in
conjunction with surgery and chemotherapy. Radiation
destroys the genetic material within the cell, thereby killing
the malignant cell.14 Complications arise from radiation
therapy because healthy cells in the radiation field are inevitably damaged during treatment. The area most susceptible
to nutrition effects of radiation is the GI tract.15 Mucosa
from the mouth to the anus can be damaged causing malabsorption of nutrients, diarrhea, and severe pain both with
and without oral intake. In adults, the effect on appetite is
dependent on the involved radiation field, total dose of radiation, and number of fractions received.16 Acute side effects
of radiation may begin as early as 1 week from the initiation of radiotherapy, and last several weeks after the final
fraction. Patients receiving cranial radiation can develop
postradiation somnolence syndrome 6 to 8 weeks after
completion of radiation, causing severe lethargy and flu-like
symptoms. Expected side effects based upon the location of
the radiation field are found in Table 30-1.
Table 30-1 Nutrition-Related Side Effects of Radiation Therapy
Location
Adverse Reaction
Central Nervous System

Brain and Spinal Cord
Nausea/Vomiting
Fatigue
Loss of Appetite
Alterations in Pituitary Functions
Growth Failure
Xerostomia
Sore Mouth/Throat
Dysphagia
Mucositis
Altered Taste and Smell
Fatigue
Loss of Appetite
Nausea/Vomiting
Diarrhea
Abdominal Cramping
Bloating
Gas
Enteritis and Colitis
Lactose Intolerance
Fatigue
Loss of Appetite
Head and Neck

Tongue, Larynx, Pharynx
Oropharynx, Tonsils,
Salivary Glands
Abdomen and Pelvis

GI Tract, Reproductive Organs,
Rectum, Colon, Testicles
Chemotherapy
Classic cytotoxic chemotherapy works by inhibiting the
division of rapidly dividing cells.17 Although cancer cells
are the main target, rapidly dividing normal cells including
those of the GI tract, taste buds, hair, and bone marrow are
equally affected. The effect of chemotherapy on the patients
nutrition status is associated with the exact medication used,
dose, route of administration, and length of treatment.
ONCOLOGY, HEMATOPOIETIC TRANSPLANT, ANDSURVIVORSHIP
The most common nutrition-related side effect of

cytotoxic drugs is nausea and vomiting, but with modern
anti-emetics the degree of emesis is much less severe. Loss
of taste buds can make familiar foods unpalatable and cause
decreased appetite. All of these, along with anticipatory
effects, lead to anorexia. Some chemotherapy agents have
the side effects of diarrhea, others constipation, and many
lead to mild-to-severe mucositis due to slow replacement
growth of the mucosa. These all can significantly alter the
digestion and absorption of nutrients.17,18 Narcotic pain
medication and anti-emetics can cause drowsiness and
increase sleep time, leading to a secondary anorexia.
Nutrition Aspects of Cancer

Metabolic
Cancer cachexia is defined as a state of malnutrition characterized by anorexia, weight loss, muscle wasting, asthenia,
depression, chronic nausea, and anemia and results in
physiological distress, changes in body composition and
alterations in carbohydrate, lipid, and protein metabolism.19,20 These metabolic alterations result in weight loss
from muscle and adipose tissue, which compounds the
effects of inadequate intake and anorexia. Cytokines are
substances made by the cells of the immune system that
mediate cell and tissue function and assist in regulating
satiety signals and gastric emptying.21,22 Elevated cytokine
levels are found in patients with cancer, likely contributing
to the complex metabolic response of cancer cachexia. 23,24
Table 30-2 outlines the role of selected cytokines in nutrition and cachexia. Research has demonstrated that changes
in glucose, protein, and lipid metabolism in cancer patients
cause weight loss even before the patient experiences
decreased appetite and oral intake.2426
Energy utilization in the body can range from hypo- to
hypermetabolism.29 Tumor cells use glucose as their main
energy source, as well as anaerobic metabolism and amino
acids for tumor cell growth.26,30 Inefficient energy utilization by the tumor causes increased activity of the Cori cycle
to produce lactic acid to be converted to glucose. Gluconeogenesis, the production of glucose from the breakdown of
fat and protein stores, aids in glucose homeostasis. 31 Despite
the increased demand for glucose, patients frequently
exhibit relative glucose intolerance and insulin resistance. 32
An increase in lipolysis and decrease in lipogenesis allows
for large losses in fat mass in oncology patients. Muscle
protein synthesis is reduced, and acute phase protein
production in the liver is increased, leading to the risk of
muscle catabolism.
351
Table 30-2 Role of Cytokines and Hormones in Cancer Cachexia

Cytokine
Effect on nutrition
Tumor Necrosis Factor (TNF)
Suppresses lipoprotein lipase20

Increases cortocotropin-releasing
hormone which suppresses food
intake27
Blocks neuropeptide Y induced
feeding; increases corticotropinreleasing hormone27
Induces cachexia and acute
phase proteins in animal
models20,28
Induces cachexia; INF-g
antibodies reversed wasting27
Levels increased with greater
disease burden; inverse
correlation with BMI24
Low values associated with
greater disease burden24
Interleukin-1 (IL-1)
Interleukin-6 (IL-6)
Interferon (INF)-g
Peptide YY (PYY)
Ghrelin
Physiological
The toxicity of chemotherapy can cause changes in organ
function resulting in altered nutrient metabolism and excretion. Cisplatin and cyclophosphamide can cause electrolyte
wasting by the kidneys that can last for weeks after the
agent is given. Mild to moderate transaminitis and hyperbilirubinemia are common side effects of chemotherapy,
demonstrating direct effects on hepatic function. Tumors
of the nasopharynx, neck, mediastinum, and GI tract and
organs can cause direct obstruction and lead to decreased
oral intake. Other side effects of therapy leading to suboptimal intake are described in detail above.
Psychological
Emotional well-being is essential to achieving and maintaining physical health, including an optimal nutrition
status. Depression and anxiety affects up to 20% of all
patients diagnosed with cancer and one study in children
with cancer found that 59% had mild psychological problems. 33 While anxiety appears to affect younger children,
and depression older, both can lead to inactivity, loss of
appetite, self-criticism, and hopelessness. Self-image and
self-esteem, including perception of weight status and physical appearance, are important to monitor in the pre-teen
and teenage population. Learned food aversions due to fear
from eating and vomiting seem to affect toddlers and young
children. A specialized feeding program may be necessary
to help overcome food aversions and resume normal oral
intake and eating patterns during or after completion of
treatment.
352
Evaluation of Nutrition Status and Determination

ofNutrient Requirements
Energy and Protein
Determining nutrition status at diagnosis and potential
for malnutrition is necessary for good supportive care.19
Although no specific nutrition protocols exist for pediatric
oncology, it is recommended that a patients nutrition status
be categorized using guidelines developed by The Childrens Oncology Group (COG), Cancer Control Nutrition
Sub-Committee (Appendix 30-1). The American Dietetic
Association (ADA) has developed adult nutrition protocols
for medical, surgical, and radiation oncology patients that
may serve as a resource for the pediatric population, and for
the adolescents and young adults frequently treated in pediatric oncology centers. 34,35 Table 30-3 contains accepted
subjective and objective measures commonly used to evaluate pediatric nutrition status.
Caloric and protein needs are difficult to assess in the
pediatric oncology population, and are affected by current
nutrition status, disease state, and therapy protocols.
Appendix 30-2 contains formulas to assist in estimation
of caloric and protein needs. An activity/stress factor may
need to be utilized with these formulas; however, recent
literature reports that weight loss may be better correlated
to decreased oral intake and not increased energy expenditure. 36 Serum albumin and prealbumin values may indicate
depleted protein stores, although these values can be influenced by hydration status, stress, and liver function and
should be interpreted based on clinical status. 37
The goal of nutrition intervention for the child with cancer
is to provide adequate nutrients for growth and development, and reverse protein-calorie malnutrition. Optimal
growth and weight gain in pediatric patients is essential for
maximizing physical tolerance to treatment and decreasing
the amount of treatment delays. 8,38,39 Strategies for nutrition
intervention for specific symptoms should be implemented
in all patients. Table 30-4 provides general recommendations for nutrition intervention during therapy.40
Nutrition support should be individualized for each
child, with the development of a nutrition plan based upon
the patients nutrition assessment, disease type and stage,
treatment, and quality of life considerations. Studies show
that pediatric patients who receive intervention from a
registered dietitian during active treatment have improved
weight status through therapy.40 Guidelines for nutrition
intervention for pediatric cancer patients have been devel 2010 A.S.P.E.N. www.nutritioncare.org
oped by the American Academy of Pediatrics (AAP) and

modified by Andrassy and Chwals4,41 as well as the Cancer
Control Nutrition Sub-Committee of The Childrens
Oncology Group (Appendix 30-2).
Outcomes Measures
Biochemical Evaluation
Laboratory tests should be closely monitored from initial
nutrition assessment through repletion. One should assess
basic electrolytes (sodium, potassium, chloride, bicarbonate), glucose, renal function (creatinine, blood urea
nitrogen), minerals (calcium, phosphorus, magnesium),
liver function tests (alkaline phosphatase, serum aminotransferases, gamma glutamyl transferase (GGT), total
bilirubin), triglycerides, and cholesterol. Serum albumin
and prealbumin values may reflect protein stores.
Table 30-3 Components of Nutrition Assessment
Medical History
Diagnosis stage and date
Past medical history
Medication history
Anticipated therapy protocol
Anthropometics*
Weight history
BMI/Weight-for-age
Height-for-age
Recent growth trends
% Ideal body weight
% Usual body weight
% Diagnosis weight
Mid-arm circumference
Triceps skinfold
Dietary Intake
Current intake (amounts, stage, feeding times)
Evaluation
Usual intake
Feeding behavior
Modified oral intake
Tube feeds
Parenteral nutrition
Vitamin/Mineral supplementation
Gastrointestinal
Nausea
Symptoms/Side
Vomiting
Effects
Constipation
Diarrhea
Dry mouth
Taste changes
Mouth sores
Difficulty swallowing
Early satiety
Laboratory
Electrolytes
Assessment
Blood glucose
Serum proteins
Absolute neutrophil count
Complete blood count
Liver function tests
Quality of Life
Activity level
Family support system
Depression/Anxiety
Pain
Treatment plan
Resources
* Refer to Appendix 30-1, Algorithm for Nutritional Intervention and Appendix
30-2, Categories of Nutritional Status in the Pediatric Oncology Patient.
Table 30-4 Nutrition Strategies for Symptom Management

Symptom
Dietary Intervention Strategies
Nausea/Vomiting
Small frequent meals, high carbohydrate content,

non-acidic beverages, cold clear foods and
beverages, avoid extreme temperatures and highly
seasoned items, avoid high-fat content items
Small frequent meals, nutrient-dense foods and
supplements, carbohydrate and protein modulars,
create a pleasant atmosphere, dine with the child,
vary colors/flavors/textures of foods
Low fat, cold, or room temperature foods, avoid
caffeine, encourage adequate fluid intake
Herbs, spices, and marinades, cold non-odorous
foods, fruit-flavored beverages, good oral hygiene,
mint mouthwashes, lemon-flavored beverages
and sour candies
Soft diet, smooth bland moist foods, frozen
slushes/ices/ice cream, high-calorie liquid
beverages
Moist foods, encourage liquids with meals, add
sauces/gravy/butter/broth, add vinegar and
lemons to stimulate saliva, good oral hygiene
Anorexia
Diarrhea
Dysgeusia
Mucositis
Xerostomia
353
adolescents with leukemia. Suboptimal nutrition prior to or

while receiving therapy for acute lymphoblastic leukemia
(ALL) resulted in longer duration of treatment, prolonged
hospitalization, higher infection rate, increased mortality
during the first 2 phases of treatment, and lower rate of
5-year survival.4648
Tolerance to Treatment
Tolerance to treatment and delays in treatment are associated with nutrition status and disease. Patients treated for
stage IV neuroblastoma who were malnourished at diagnosis or who had weight loss early in treatment had increased
delays in therapy. 38,44 Malnourished patients with ALL or
Wilms tumor were more likely to require a reduction in
drug therapy relative to their better-nourished peers. 8,39,49
Patients who developed anthracycline-associated cardiomyopathy were more likely to be malnourished at initiation
of therapy. 50
Selection of Nutrition Support Route

Anthropometric
Physical examination is an important piece of the nutrition
evaluation. Promoting consistent growth along chart curve
percentiles is essential for long-term assessment. Growth
should be plotted and monitored for each patient monthly
on weight-for-age, length/height-for-age, body mass index
(BMI)-for-age (> 2 years), weight-for-length (< 2 years),
and head circumference (< 3 years of age). Measurement of
triceps skinfold thickness and mid-arm circumference for
assessment of fat and muscle stores may be beneficial when
unable to obtain accurate weights (eg, critically ill patients,
fluid retention).42
Disease Outcome
Though it cannot be used as an independent marker of
mortality, more severe malnutrition is frequently related to
a worse prognosis. 39,43,44 Several studies in pediatric solid
tumors have shown a correlation between outcome and
nutrition status. 39,43,44 There is a direct correlation between
outcome and nutrition status in localized solid tumors, but
not in patients with metastatic disease. 2 Decreased relapse
rates have been correlated with improved nutrition status
in children with localized solid tumors and lymphomas, but
not with advanced disease at diagnosis.2 Children with stage
IV neuroblastoma who were malnourished at diagnosis had
a significantly higher incidence of disease recurrence and
death 1 year into treatment.45
Similar results have been published associating poor
survival outcomes in malnourished and obese children and
Oral Nutrition
Oral nutrition is important to continue to promote normalized and developmentally appropriate feeding for children
and should be encouraged as much as is medically reasonable. Patients and families should be educated on the
appropriate strategies to alter nutrient intake using modulars
and supplements. Unfortunately many pediatric patients
on oral diet alone have significant weight loss and muscle
wasting51,52 and need to be supported by other means.
Enteral tube feeding (TF) may significantly enhance a
childs nutrition status during cancer therapy. 5254 Selection
of the correct formula must be determined in order to maximize nutrient intake. Though no large clinical trials have
been conducted, research suggests that a calorie concentrated formula may be more beneficial to malnourished
patients receiving TF. 53 Preliminary evidence regarding
the use of TF as supplementation or full calories, prior to
developing weight loss, shows an overall improvement in
the patients nutrition status at the end of therapy. 55 Tube
feedings can be provided enterally via nasogastric (NG),
nasojejunal (NJ), or a percutaneous endoscopy gastrotomy
(PEG) tube. Benefits of a PEG tube include a one-time
placement in a location that is not apparent, especially in
an appearance-conscious adolescent. It also bypasses the
issue of tube displacement with emesis and traumatic tube
replacement during periods of mucositis. The placement of
354
a prophylactic PEG tube prior to the initiation of radiation

for head and neck cancers in adults has resulted in decreased
incidence of morbidity related to weight loss. 5 This practice
should be considered for pediatric patients as many radiation side effects that affect adults also affect children. The
disadvantage of a PEG tube is the requirement for surgical
placement and a risk of cellulitis at the incision site.
Parenteral nutrition (PN) support has been documented
to increase a patients overall nutrition status, weight, and
anthropometric measurements, but has not improved
clinical outcomes.45,56 Though PN can provide shortterm improvement, the effects often subside when the PN
is discontinued. 57 Appendix 30-1 outlines intervention
considerations for oral, enteral, and parenteral nutrition.
Complementary and Alternative Medicine

Patients and families with chronic diseases often look to
resources outside of conventional medicine for treatment.
Complementary medicine is used in conjunction with
conventional medicine, while alternative medicine replaces
the westernized approach. An increasing number of patients
are using complementary and alternative medicine (CAM).
The use of CAM in pediatrics has been reported in up to
84% of patients in recent years. 58 The AAP has developed a
task force to review issues and develop resources for patients
and health care practitioners. 59
Limited clinical trials exist on the use of CAM in the
pediatric oncology population. Children should not be
placed on adult dosages of nutrition-related supplements
due to differences in metabolism and concerns of drug
interactions and toxicity. Further evaluation and clinical
trials need to be conducted before CAM can be routinely
recommended to patients.
Complications of Cancer Treatment

Anorexia or loss of appetite is a common side effect of cytotoxic therapy. Though typically seen as an independent
symptom, there are many variables that can cause anorexia.
Weight loss, cachexia, dehydration, persistent vomiting, and
early satiety can all cause anorexia in children. Anorexia may
be perpetuated by continuous cycles of chemotherapy and
other treatments.
Children receiving chemotherapy are at an increased
risk of developing infections. Per data in adults, it is understood that malnutrition can increase that risk by 15% to 20%,
and it likely translates to pediatrics.22 Energy requirements
may increase by 30% in patients fighting viral or bacterial
infections.23,60 Infections also induce a release of cytokines

IL-1, IL-6, and TNF, further compounding the cancer
cachexia phenomenon.61 Nutrient metabolism and absorption can also be altered during an infection due to increased
production of catecholamines, cortisol, glucagons, and
growth hormone.
Mucositis, the inflammation of mucosal membranes
lining the digestive tract, is a side effect of many chemotherapy agents and radiation. Mucositis can range in severity
from mild erythema to extensive mucosal sloughing at any
location in the GI tract. Oral mucositis can severely impact
oral intake and limit the placement of NG tubes secondary to
pain. Some research suggests that supplementing the patient
with oral glutamine may help to prevent and decrease the
severity of mucositis.62
Diarrhea causes a loss of fluids and electrolytes, as well
as nutrient malabsorption, and can be linked directly to
specific chemotherapies, radiation to the abdominal and
pelvic areas, and abdominal surgery. Other potential causes
for diarrhea during therapy include primary and secondary
infections, antibiotics, adverse drug effects, and stress.
Malabsorption complicates the use of some nutrition
interventions such as oral and TF. When combined with
limited nutrient intake, malabsorption can contribute to
severe weight loss in a short period of time. Surgery may
cause altered nutrient transit time, limiting the ability for
intestinal absorption. Chemotherapy induces vomiting,
diarrhea, mucositis, and enteritis, and radiation can cause
malabsorption throughout the entire GI tract. A decreased
production in saliva during and postradiation to the head
and neck causes a decrease in oral enzymes, while abdominal and pelvic radiation can cause enteritis and diarrhea.
Late effects of radiation may include mucosal inflammation
and intestinal fibrosis after an extended period posttherapy
which may not be reversible.15
Additional complications including dysgeusia, anosmia, and xerostomia can significantly alter oral intake
because of decreased palatability or decreased tolerance
of certain textures. Though these complications generally
subside, they can create long-standing food aversions.
Hematopoietic Transplant
Hematopoietic stem cell transplantation (HSCT) is performed to replace diseased and defective bone marrow and
restore hematopoietic and immunologic function. It is a
broad category and encompasses bone marrow transplantation (BMT), peripheral blood stem cell transplantation
(PBSCT), and umbilical cord blood transplantation
(UCBT) depending on the source of hematopoietic stem
cells. HSCT is a treatment option for children with a variety

of potentially fatal diseases including malignancies, immunodeficiency syndromes, severe aplastic anemia, Fanconis
anemia, and inherited metabolic disorders like Krabbes disease and Hurler syndrome. Pediatric malignancies treated
with HSCT include acute myeloid and lymphoblastic leukemia, Hodgkins disease and non-Hodgkins lymphoma,
myelodysplastic syndrome, and some solid tumors (eg,
high-risk neuroblastoma). HSCT offers the only curative
option for many of these children.
HSCT can be autologous (the patient receives his or her
own stem cells); allogeneic (the patient receives cells from
another person who may be a sibling, or parent (haplo) or
an unrelated donor); or syngeneic (when an identical twin
is the cell donor). Donors are selected on the basis of many
factors including the level of human leukocyte antigen
(HLA) matching. HLAs are genetically defined proteins or
antigens that are highly polymorphic and are encoded by
the major histocompatibility complex (MHC). Class I HLA
(-A, -B, and -C) antigens are expressed on almost all nucleated cells of the body. Class II proteins (-DR, -DQ , and
-DP) are mainly expressed on hematopoietic cells (B cells,
dendritic cells, and monocytes). Currently HLA typing
is performed by DNA-based methods. While full HLA
matching is preferred, mismatched donors are appropriate
in certain situations, especially if the graft source is a cord
blood unit. Donor availability and clinical requirements
determine the source of the stem cells. The donors may be
related or unrelated to the patient.
2.
3.
4.
Transplantation Process
1. Conditioning. The purpose of the conditioning regimen
is to destroy the defective or diseased marrow, kill
cancerous cells, create space for donor cells, and prevent
rejection of donor cells by neutralizing the patients
immune system. Conditioning therapy (also known
as cytoreduction or preparative regimen) consists of a
combination of chemotherapy drugs with or without
radiation and is given over a number of days prior to
transplant. There are 2 types of conditioning regimen:
(1) myeloablative and (2) non-myeloablative. Myeloablative, also known as conventional conditioning
regimen, uses high-dose chemotherapy and/or total
body irradiation that destroys or myeloablates the
bone marrow. The high-dose chemotherapy and radiation causes acute and long-term toxicities including
severe mucositis, myelosuppression, nausea, vomiting,
liver function abnormalities, and cardiotoxicity. The
non-myeloablative conditioning uses a milder form of
5.
6.
355
chemotherapy and/or radiation and therefore causes

less toxicity and can be used in patients with comorbidities. These transplants are also called mini or reduced
intensity transplants. However, risk of relapse is higher
following non-myeloablative transplants.
Infusion. After the completion of conditioning and
usually a day or 2 of rest, the stem cells are infused
via an intravenous catheter. It can take 30 minutes to
4 hours to infuse the cells depending on the type of
donor source and whether the product required any
manipulation (eg, volume depletion, red blood cell
(RBC) depletion, or T-cell depletion).
Pancytopenia. The conditioning regimen leads to
suppression or ablation of the bone marrow causing
a decrease in white blood cells (WBCs), platelets,
and RBCs. This period usually lasts for 2 to 4 weeks
depending on the donor source, cell dose, and many
other factors. During this period of pancytopenia,
patients have no white cell count and are at increased
risk of infections. Antimicrobial prophylaxis is
commonly used in this period. The patients also
require blood and platelet transfusions.
Engraftment. Engraftment is confirmed when absolute
neutrophil count (ANC) is > 500 per cubic mm for 3
consecutive days. Sometimes, it may take many weeks
for cells to engraft. During this process, some patients
may develop hyperacute graft versus host disease
(GVHD) which is also called engraftment syndrome
and is characterized by fever, rash, weight gain, and
in some cases severe capillary leak and pulmonary
edema.
Post-engraftment. In this period of continuing recovery
patients are vulnerable to many complications like
acute GVHD, graft failure, organ toxicity, drug-related
adverse reactions, and infections.
Long term. While most patients recover very well
without major complications, they are at risk for a
number of long-term problems including delayed and
slow growth and development, organ dysfunction,
neurocognitive issues, endocrine problems, chronic
GVHD, avascular necrosis, secondary malignancy,
and others.
Nutrition Evaluation and Nutrient Requirements

Children undergoing HSCT are at increased risk of malnutrition and it is critical to assess their needs, anticipate
problems, and institute appropriate preventive nutrition
support in a timely manner. The toxicity of conditioning
regimen affects the integrity of the GI tract causing
356
mucositis, nausea, vomiting, and diarrhea. These symptoms

may be further exacerbated by posttransplant complications like GVHD, infections, use of multiple antibiotics,
and immunosuppressive medications. These and other
complexities of HSCT are important to understand. The
nutrition status in some patients may be suboptimal due to
previous treatments, prolonged hospitalizations, and other
problems that have affected their ability to eat or drink well.
Certain diagnoses are more likely to be associated with
malnutrition at the time of diagnosis and during therapy (eg,
acute myelogenous leukemia and high-risk neuroblastoma)
which require much more intense initial chemotherapy
before they are even referred for HSCT. Fifty-four percent
of pediatric patients undergoing HSCT were reported to
have suboptimal nutrition status pretransplant.42 Impaired
pretransplant nutrition status was found to be a negative
prognostic factor leading to delayed engraftment.42 Prevention of malnutrition and preservation of nutrition status is
vital for better transplant outcomes. A complete nutrition
assessment should be performed at the time of hospital
admission. Nutrition status and nutrient needs continue
to change throughout the transplant process, therefore
continued assessment and evaluation is important during
the transplant process (refer to Table 30-3 for components
of nutrition assessment). Physiological and psychological
complications affecting nutrition status during therapy are
discussed in depth in the General Oncology section of this
chapter and thus will not be addressed here.
Height, weight, and BMI are good indicators of nutrition status. These should be measured at the time of
admission and throughout the recovery process. Serial
anthropometric measurements over a period of time are a
good measure of long-term nutrition status. Growth charts
should be maintained to help assess the growth velocity.
However, during early posttransplant stage, one should be
careful about using weight and BMI as the sole criteria to
assess changes in nutrition status. Body weight and BMI
are affected by hydration. Cheney et al observed fluid shifts
during the first 4 weeks after transplant and concluded that
the change in body weight did not correlate with the body
cell mass or fluid volume changes.63 Importantly, calculated
arm muscle area correlated well (p < 0.05) with changes in
body cell mass and is a better reflection of nutrition status.
BMI has been reported to be a poor predictor of nutrition status when compared with body cell mass.42 Despite
these limitations, serial height, weight, and BMI measurements combined with assessment of caloric and protein
intake and fluid balance are critically important and useful.

Weekly measurement of mid-arm circumference should be
considered.
Energy and Protein Needs
Patients undergoing HSCT show changes in energy requirements throughout the process.6466 During this period,
patients are in a hypermetabolic state with increased catabolism due to mucositis, fever, tissue repair, and marrow
regeneration. Increase in the metabolic rate can also be
caused by the conditioning regimen, fevers, and posttransplant complications.64 As a result, the caloric needs of the
HSCT patient have been reported to be as high as 150% of
the basal metabolic rate (BMR) of non-stressed well-nourished patients and 180% to 200% of BMR of malnourished
patients.6769 On the other hand, Duro et al observed
significant decreases in resting energy expenditure (REE)
following allogeneic stem cell transplant in patients with
leukemias and aplastic anemia, with return of energy
expenditure to pretransplant levels after engraftment. REE
decreased by 4% to 7% per week posttransplant as measured
by indirect calorimeter.66 Duggan et al also reported significant decline in REE after HSCT in pediatric patients. Some
of the decrease in REE is being attributed to decrease in
lean body mass.65 Studies assessing energy requirements
in HSCT are limited and equivocal. Further studies are
needed to better determine the caloric needs of pediatric
patients during transplant and posttransplant. Based on
current literature, indirect calorimetry for assessing caloric
requirement is the gold standard. In absence of indirect
calorimetry one should use clinical judgment while using
the calorie calculation formula and continue to assess for
potential overfeeding/underfeeding. Protein requirements are increased to minimize loss of lean body mass
and promote tissue repair. Table 30-5 provides caloric and
protein requirements of HSCT pediatric patients.
Table 30-5 Caloric and Protein Requirements of Pediatric HSCT
Patients67,69,71
Age
Calories
Protein (g/kg/d)
012 mo
BMR* x 1.61.8
3
BMR x 1.61.8
2.53
16 y
710 y
BMR x 1.41.6
2.4
1114 y
BMR x 1.41.6
2
BMR x 1.51.6
1.8
1518 y
> 19 y
BEE**x 1.5
1.5
*For BMR equation, refer to Appendix 30-2.
**BEE equations:
Male: 66 + (13.7 x wt in kg) + (5 x ht) (6.8 x age)
Female: 665 + (9.6 x wt in kg) + (1.7 x ht) (4.7 x age)
Fluid Needs
In general, daily fluid needs can be assessed using the
Holliday-Segar method.70 However, one must take into
consideration the various factors that impact daily fluid
balance. For example, fluid need is increased with fever, GI
losses (eg, vomiting, diarrhea), mucositis, open skin wounds,
and other factors.67 Liver and kidney dysfunction may lead
to fluid retention and may require fluid restriction. In addition to the total parenteral nutrition, and oral or enteral
intake, patients receive additional fluid with medications
and blood products and these must be taken into account.
Therefore, close monitoring of fluid status is important.
Vitamin and Mineral Needs
Vitamin and mineral requirements for patients undergoing
HSCT have not been determined. The nutrition support
regimen should meet 100% of the dietary reference intake
(DRI) of vitamins and minerals. If oral intake or enteral
nutrition support does not meet the vitamin and mineral
needs, then an iron-free multivitamin and mineral supplement should be provided. Generally, iron supplementation
is not required in HSCT patients because they receive
frequent blood transfusions and supplemental iron can
result in iron overload. The risk of vitamin and mineral
deficiency is particularly higher if the patient has diarrhea,
vomiting, and malabsorption. Thiamin, vitamin K, vitamin
D, calcium, or zinc deficiencies have been seen in some
patients. Vitamin K deficiency as determined by PIVKAII level was seen in 31% of pediatric patients undergoing
HCST and was attributed to use of phenytoin, inadequate
intake, or malabsorption. 54 The investigators did not find a
direct correlation between prothrombin time and vitamin
K status. However, in clinical practice prothrombin time
is a good indicator of significant vitamin K deficiency
and can guide vitamin K therapy. Antibiotic use has been
shown to decrease the production of vitamin K in the body.
HSCT patients receive multiple antibiotic treatments posttransplant; therefore, vitamin K supplementation of 1 mg/
kg should be provided weekly.67,71 In patients with severe
chronic diarrhea, zinc losses may be significant and supplementation may be necessary.
Patients undergoing HSCT often receive multiple
agents that alter bone metabolism as part of their treatment.
These include methotrexate, steroids, cyclosporine, and
total body irradiation. For many patients, physical activity
and exposure to sun is limited and can lead to additional
nutrition problems like osteopenia, vitamin D deficiency,
and eventually poor bone health. Therefore, serum
vitamin D and calcium should be routinely monitored and
357
supplemented. For further information on bone health, see

Late Effects of Treatment in Survivorship in this chapter.
Provision of Nutrition Support

Oral Route
High-dose chemotherapy and posttransplant complications
lead to anorexia, mucositis, nausea, vomiting, and diarrhea,
causing poor oral intake and malabsorption. Chemotherapy
drugs like busulfan, melphalan, cyclophosphamide, methotrexate, carboplatin, and most others can cause taste changes.
The etiology of taste changes in HSCT may be multifactorial including mucositis, hyposalivation, and side effects of
medications like antibiotics, antihypertensives, and antidepressants.72 About a third of patients receiving chemotherapy
and/or radiation demonstrate food aversion. Patients learn
to avoid foods that remind them of uncomfortable feelings
of nausea and vomiting.73 Oral intake and appetite in HSCT
patients does not return to a normal state until they are 4
to 6 weeks posttransplant.74 Severity of oral mucositis and
GVHD are the most significant factors affecting return
of oral intake.68 Appetite stimulants may be useful to help
stimulate appetite in patients who have engrafted and
do not have GVHD. Sometimes, even after return of oral
intake and absence of GVHD, oral feeding may be difficult
due to malabsorption. At this time a complete GI workup
to rule out fat and carbohydrate malabsorption, pancreatic
insufficiency, and bacterial overgrowth may be warranted.
In infants and toddlers with food aversion, feeding therapy
with the help of speech and occupational therapy should be
considered. Refeeding a child after HSCT is a slow process
and needs careful monitoring of symptoms and frequent
assessment.
Diet Restrictions
Most institutions prescribe a neutropenic or low bacteria
diet in the posttransplant period. In addition, a low-lactose
diet may also be recommended. The goal of a neutropenic
diet is to restrict foods that are believed to contain large
amounts of potentially pathogenic bacteria, which can
cause infections in the immuno-compromised patient.
Such food items include non-pasteurized dairy products;
aged cheeses; fresh fruits and vegetables; deli meats and
cheeses; deli-type salads (eg, potato salad, egg salad, tuna
salad, and pasta salads); undercooked meat, poultry, egg,
fish, and seafood; food with visible mold; salad dressings
made with egg and moldy cheeses; and bakery food products.69 Listeria monocytogenes, Escherichia coli, Salmonella,
Cryptosporidium parvum, and Campylobacter are the most
358
common pathogens that cause food-borne illness. Signs

and symptoms of a food-borne illness include stomach
ache, abdominal pain, diarrhea, nausea, vomiting, headache, fever, and chills.75 Studies have shown inconsistent
results regarding the effect of dietary modification on the
incidence of food-borne illness.76,77 Current A.S.P.E.N.
guidelines for HSCT adult patients state that until further
research is available it seems prudent to restrict high-risk
foods, as described above, during neutropenia.78 It is important to encourage patients and caretakers to practice safe
food handling.
Enteral Nutrition
Benefits of enteral nutrition (EN) in protecting the gut
integrity, preventing bacterial translocation, and being
cost-effective are well known. However, enteral feeding
has not been the norm for most pediatric HSCT patients
mainly because of risk of bleeding with tube placement
in the presence of pancytopenia and mucositis and due to
concerns about delayed gastric emptying and malabsorption of nutrients.68,79 In 2 small studies involving a total
of 49 patients, enteral feeding was found not only to be
feasible and cost-effective but also to be as successful as PN
in preserving the nutrition status of children undergoing
allogeneic HSCT.80,81 In an earlier study, Papadopoulo et al
reported that EN, when tolerated, is beneficial and prevents
the deterioration of nutrition status of pediatric patients
undergoing HSCT.82 EN may be attempted if there is no
active pathology in the GI tract and continued if the patient
is able to tolerate it. In case of intolerance, it may be possible
to modify the formula and tube placement. For example,
nasoduodenal (ND) or nasojejunal (NJ) tubes may have a
lower risk of causing vomiting and aspiration. 83 Refer to the
Algorithm (Appendix 30-1) in making decisions regarding
type of tube, delivery system, and formula selection.
In the setting of severe regimen-related GI toxicities leading
to poor oral intake and intolerance to EN, PN has been
historically used to support patients after HSCT. There are
mixed studies regarding the benefits and indications of PN
use in HSCT patients. In 1987, Weisdorf and colleagues84
demonstrated that prophylactic use of PN in previously
well-nourished HSCT patients was associated with positive
outcomes. In 1997, Charuhas et al71 reported that patients
who were randomized to PN resumed PO intake 6 days
later than an intravenous (IV) hydration group, and even
though the IV hydration group experienced 1.14% weight
loss there was no difference seen in re-admission, relapse,
or survival rates. However Roberts et al74 in 2005 reported

no difference in length of stay, engraftment time, days to
resume oral intake, and rate of infection in patients who
received PN versus patients on oral diet. They concluded
that prophylactic use of PN results in improved nutrition
status and does not affect the time to resume oral intake.
Reported benefits of PN include reversal of protein
energy malnutrition, restoration of immune-competence,
and enhanced tolerance to anti-neoplastic therapy. 69
However, use of PN is associated with increased risk for
several complications including line infections, hyper
glycemia, hypertriglyceridemia, and cholestasis.67 Patients
who present with compromised nutrition status prior to
transplant are at risk of refeeding syndrome (Chapter 19).
If a patient is at high risk for refeeding syndrome, nutrition
support should be slowly advanced to meet goal energy
requirements.85,86 As with any patient receiving PN, the
patient should be monitored closely and the nutrition
support regimen adjusted accordingly. Since most studies
are done on heterogeneous patient populations with regards
to type of transplant, diagnosis, kind of conditioning, age,
and pretransplant nutrition status and the small sample
size, there are no established criteria as to when PN should
be initiated. Based on our clinical experience PN should be
initiated after transplant for pediatric patients who receive
myeloablative conditioning regimen, who are expected to
have severe mucositis, or patients with poor nutrition status
prior to transplant. However patients with non-myeloablative conditioning regimen, with minimal or no mucositis,
and adequate nutrition status prior to transplant may be
placed on oral or enteral nutrition. Clinical judgment about
the type of nutrition support should not only include the
specifics of patient population but also the risk and benefits
of PN.
Nutrition Monitoring During HSCT

Monitoring and evaluating the efficacy of nutrition support
in patients undergoing HSCT is very important and a
complex process. However, there is a paucity of data to
support the use of a single specific test or a battery of tests
that could be used broadly in most clinical situations. This
section will examine the published data on various measures
of nutrition assessment.
Fluid and Electrolyte
Multiple factors, including the type and quantity of feeding,
impact fluid and electrolyte status. Decisions about the
volume and composition of total parenteral nutrition as
well as of the type and amount of enteral formula must be
359
Table 30-6 Side Effects of Some of the Drugs Commonly Used During HSCT
Drug
Usage
Side effect
Steroids
Immunosuppressive
Hyperglycemia, weight gain, osteoporosis, fluid and sodium retention, cardiomyopathy,

hypercholesterolemia, hypertriglyceridemia, gut infection
Methotrexate
Immunosuppressive
Mucositis, nausea, vomiting, diarrhea, hepatic and renal toxicities
Cyclosporine
Immunosuppressive
Hypertension, nephrotoxicity, significant hyperkalemia, hypomagnesemia, hepatotoxicity,

hyperglycemia, hyperlipidemia, hypercholesterolemia, nausea, vomiting
Tacrolimus
Immunosuppressive
Hypertension, nephrotoxicity, hyperkalemia, hypomagnesemia, hyperbilirubinemia, hypercalcemia,

hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperphosphatemia, hypocalcemia,
hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, elevated hepatic enzymes,
nausea/vomiting, anorexia, diarrhea
Sirolimus
Immunosuppressive
Edema, hyperlipidemia, hypercholesterolemia
Cellcept
Immunosuppressive
Nausea, vomiting, diarrhea, anorexia, renal impairment, neutropenia
Antithymoocyte
globulin (ATG)
Immunosuppressive
Infusion reactions, increased infection risk, hypotension, nausea, vomiting
Acyclovir
Antiviral
Nephrotoxicity, anorexia, nausea, vomiting, diarrhea, elevated hepatic enzymes, hyperbilirubinemia
Cefepime
Antibiotic
Nausea, vomiting, diarrhea
Amikacin
Antibiotic
Nephrotoxicity
Gentamicin
Antibiotic
Nephrotoxicity
Voriconazole
Antifungal
Hepatotoxic, skin rash, visual problems
Amphotericin
Antifungal
Nephrotoxicity
Micafungin
Antifungal
Hepatotoxic
Source: Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc; 2009. http://www.clinicalpharmacology.com. Accessed December 2009.
based on the state of fluid and electrolyte balance which

must be monitored daily and carefully. Mucositis, diarrhea, vomiting, excessive salivation, fever, and other factors
increase fluid losses. However, fluid retention is commonly
seen at the time of engraftment. Other problems including
sinusoidal obstruction syndrome (SOS) (formerly known
as veno-occlusive disease (VOD)) and renal insufficiency
may also cause fluid retention. In addition, they lead to
electrolyte problems. Severe inflammatory reaction in the
posttransplant period may lead to capillary leak and thirdspacing of fluids. In such a situation the weight may be high
but the intravascular compartment is depleted. Many drugs
like tacrolimus, cyclosporine, amphotericin, vancomycin,
and ifosfamide can cause increased urinary losses of electrolytes requiring increased supplementation. Table 30-6
shows side effects of some of the drugs commonly used
in HSCT. In general one should monitor basic biochemical indices like sodium, potassium, chloride, blood urea
nitrogen, creatinine, glucose, calcium, phosphorus, and
magnesium. See Table 30-7 for a suggested schedule for
monitoring of biochemical indices.
Table 30-7 Suggested Schedule for Monitoring Blood Biochemical and

Other Indices During Early Stages of HSCT
Lab
Frequency
Sodium, potassium, chloride,

carbonate, BUN, creatinine,
calcium, magnesium
Every day until stable on total

parenteral nutrition (TPN), then
3 times per week while on longterm TPN
3 times per week until stable on
TPN, then weekly
With consistent low-serum
calcium
3 times per week until Day +30,
then weekly while on TPN
Weekly while on multiple
antibiotics
Pretransplant; then every 3
months until 1 year
When increased losses suspected
Monthly when on long-term TPN
(46 weeks)
Weekly while on intravenous lipid
emulsion
Daily while inpatient, then with
every outpatient visit
Daily while inpatient
Phosphorus
Ionized calcium
LFTs, albumin, total bilirubin
Prothrombin time
Vitamin D (25 OH D2+D3)
Zinc
Manganese, copper, selenium
Triglycerides
Weights
Input/output
360
Triglycerides and Liver Function Tests

Fasting triglyceride levels should be obtained prior to
administration of intravenous fat emulsion (IVFE), and then
weekly for the duration of the IVFE therapy. Cyclosporine,
corticosteroids, tacrolimus, and sirolimus can all result in
elevated triglyceride levels. Serum triglyceride levels should
be monitored weekly if a patient is receiving any of the medications listed.67,71,79 During the first 4 weeks posttransplant,
patients are at risk for SOS. Liver function tests (LFTs)
should be monitored at least 3 times a week. If increasing
levels are noted, more frequent LFTs may be necessary.
Micronutrients
Copper, selenium, and manganese levels should be monitored monthly if a patient has been receiving PN for more
than 1 month, or in the presence of hyperbilirubinemia.67,71,87
If zinc supplementation is implemented, zinc levels (ie,
serum or plasma zinc) should be monitored. However, zinc
levels in blood are adversely affected by inflammation or
infection so this should be taken into account when interpreting results. Clinical discretion should be used when
evaluating zinc levels, keeping in mind that zinc levels in
blood do not reflect tissue stores.
Other Biochemical Indices
Low serum albumin is predictive of an increase in mortality,
poor outcome, complication rate, and length of stay and may
be low in severe and chronic malnutrition, but it is not a good
marker of acute nutrition status. 37 Nitrogen balance may be
useful to assess protein status but the accuracy of the calculation is compromised in patients with vomiting, diarrhea,
and renal insufficiency. Also, a 24-hour urine collection
in pediatric patients may be difficult. Serum transferrin,
prealbumin, and retinol binding protein are also not good
indicators of nutrition status. 37 During inflammatory states,
their hepatic synthesis is decreased by as much as 25% and
their intravascular concentration is reduced due to capillary
leak.88 Other factors like hydration, infection, and liver and
renal insufficiency also affect their levels.
Growth
Weight trends should be monitored daily, as well as intake
and output, throughout the entire transplant period.67
Length should be monitored monthly but one should be
mindful that critically ill transplant patients will likely
not attain age-expected linear velocity, despite provision
of optimal nutrition support. Although weight fluctuates
with fluid shifts, one study revealed that weight decreased
overall and height increased slowly (1.7 cm/mo) 4 months
posttransplant.89 The same study showed that triceps skinfold (TSF) measurements and midarm circumference
also decreased. Therefore, TSF measurements should be
obtained and monitored. Fluid shifts will not affect skinfold measurement.89 Bone growth can be monitored by
obtaining a dual-energy x-ray absorptiometry (DEXA) scan
bi-annually.90
HSCT Complications Impacting Nutrition

Pediatric patients undergoing HSCT are at significant risk
for developing many complications that may have direct and
indirect impact on the nutrition status. The most important
are described below.
Mucositis
Mucositis, or inflammation and breakdown of the mucosal
lining of the mouth and gut, may occur in up to 100% of
patients undergoing HSCT with high-dose chemotherapy.91
Severity depends on many factors including the dose intensity of chemotherapy and use of concomitant radiation.
Moderate to severe mucositis often requires IV narcotics.
In the presence of moderate and severe mucositis oral
intake is nearly impossible and PN is the only option. Severe
mucositis also predisposes to infections.92
Graft versus Host Disease

GVHD is caused by an immunologic reaction in which
donor-derived T-cells recognize the host cells as foreign
and attack them. Generally, acute GVHD occurs before
100 days posttransplant and chronic GVHD develops after
more than 100 days from transplant. This definition/classification is being replaced with the new classification by
the National Institutes of Health that includes late-onset
acute GVHD (after day 100) and an overlap syndrome with
features of both acute and chronic GVHD.93,94 Immunosuppressive drug combinations are used to prevent GVHD.
Calcineurin inhibitors, cyclosporine, and tacrolimus are
generally used with methotrexate, mycophenolate, steroids,
or sirolimus. High-dose steroids are used to treat acute
GVHD.95 For treating chronic GVHD, steroids with or
without calcineurin inhibitors are used.96
Acute GVHD
The organs most commonly affected in acute GVHD are the
skin (81%), gut (54%), and liver (50%).97 Skin is usually the
first organ to be involved. Symptoms of acute gut GVHD
include nausea, vomiting, loss of appetite, abdominal pain,
and diarrhea, which is secretory in nature and is voluminous
(> 2 L/d in severe cases).98 Gut GVHD most commonly
361
Table 30-8 Staging and Grading of Acute GVHD

Stage
Skin*
Liver bilirubin
Gut^#
+
Maculopapular rash < 25% body surface
23 mg/dL
Diarrhea, 5001000 mL/d or persistent nausea
++
Maculopapular rash 2550% body surface
36 mg/dL
Diarrhea, 10001500 mL/d
+++
Generalized erythroderma
615 mg/dL
Diarrhea, > 1500mL/d
++++
Desquamation and bullae
> 15 mg/dL
Abdominal pain with or without ileus
*Use rule of nines or burn chart to determine extent of rash.
^ Diarrhea volumes apply to adults.
# Persistent nausea requires endoscopic biopsy evidence of GVHD histology in the stomach or duodenum.
Overall Grade
0 (none)
I (mild)
II (moderate)
III (severe)
IV (Life threatening)
Skin
0
+ to ++
+ to +++
++ to +++
+ to ++++
Liver
0
0
+
++ to +++
++ to ++++
Gut
0
0
+
++ to +++
++ to ++++
Functional Impairment
0
0
+
++
+++
Reprinted with permission from Sullivan KM. Graft-vs-host disease. In: Blume KG, Forman SJ, Appelbaum F, eds. Thomas Hematopoietic Cell
Transplantation. 3rd ed. Oxford: Blackwell Publishing; 2004:635664.
affects the lower GI tract causing severe, high-output diarrhea associated with bleeding and cramping abdominal
pain.99 GVHD of the upper GI tract causes decreased appetite, nausea, and vomiting.79 Active GVHD leads to mucosal
degeneration, malabsorption, and protein loss. Liver GVHD
is characterized by cholestatic hyperbilirubinemia, however
it can be difficult to differentiate other causes of liver function impairment; the differential diagnosis includes SOS,
infection, sepsis, drug effects, iron overload, or PN-induced
cholestasis.98 Acute GVHD is graded based on the extent of
skin, liver, and gut involvement (see Table 30-8 for staging
and grading). Long-term survival (5 years) for grade III
is 25% and grade IV is 5%.100 Prevalence of acute GVHD
varies from 35% to 45% in full matched sibling donors to
60% to 80% in patients with 1 antigen HLA mismatched
transplant.101 With the same degree of HLA mismatch,
patients receiving umbilical cord blood transplant have
lower frequency of acute GVHD (35% to 65% compared to
60% to 80% in patients receiving unrelated donor graft).102
Chronic GVHD
Chronic GVHD involves skin, gut, liver, lungs, eyes, mouth,
and bone marrow. Risk factors for development of chronic
GVHD include the age of the patient and history of acute
GVHD. About 22% to 29% of pediatric patients undergoing
HSCT will develop chronic GVHD.103 In adult patients,
chronic GVHD ranges from 30% to 50% in HLA-matched
sibling transplant.104
A low-fiber, low-lactose, low-fat, bland diet may be
necessary during periods of acute GVHD, but use of this
dietary modification is not the norm.69 PN is warranted when
diarrheal output worsens with ingestion of food and EN.

Pancreatic Insufficiency
If diarrhea continues in absence of GVHD, patients should
be evaluated for pancreatic insufficiency.105 Of pediatric
patients undergoing HSCT, 4.9% were found to have acute
pancreatitis.102
Bacterial Overgrowth
Bacterial overgrowth has not been well studied and defined
in this group of patients. However, based on clinical reports,
if diarrhea continues after GVHD and infection and pancreatic insufficiency is ruled out, patients should be worked up
for bacterial overgrowth. Long-term use of antibiotics and
patients inability to take oral diets for prolonged periods
after HSCT can alter the type and quantity of bacterial flora
similar to short gut.
Infection
The immuno-suppressed patient is highly susceptible to
bacterial, viral, and fungal infections. C. difficile infection is
one of the common infections identified in the transplant
population.106 Some of the viral infections known to cause
diarrhea in HSCT patients are adenovirus, cytomegalovirus, astrovirus, and rotavirus.107 Infections affecting
the GI tract can lead to intolerance of oral intake and EN.
Antiviral, antifungal, and antibiotic medications can cause
loss of appetite, nausea, vomiting, diarrhea, and malabsorption. Antibiotic medications may also decrease the amount
of lactase enzyme in the intestine; if symptomatic, these
patients may benefit from a low-lactose diet.108,109
362
Hemorrhagic Cystitis
High-dose cyclophosphamide can lead to hemorrhagic
cystitis, a complication characterized by bloody urine.
Fluid intake may need to be twice the maintenance needs in
order to irrigate the blood clots in the bladder. Viral infections unique to the immuno-compromised patient, which
include adenovirus and BK virus, can also lead to hemorrhagic cystitis.67,87,108
Sinusoidal Obstruction Syndrome
SOS is usually seen between 1 to 4 weeks posttransplant
and reflects regimen-related toxicity.110 Injury to the
endothelial cells of the sinusoids, thickening of the hepatic
venules due to edema, and deposition of fibrin, factor VII,
and blood cell fragments leads to narrowing and increased
resistance to the blood flow through the venules. This causes
hepatic congestion and portal hypertension.111 Weight gain,
hyperbilirubinemia, ascites, right upper-quadrant pain,
and hepatomegaly are the clinical symptoms associated
with SOS. Severe SOS can lead to liver failure, hepatorenal
syndrome, portal hypertension, and multiorgan failure.
Pre-existing liver dysfunction, previous transplantation,
abdominal irradiation, conditioning regimen, adrenoleukodystrophy, and neuroblastoma are some of the risk factors
for SOS.112 The incidence of SOS in children after HSCT
ranges from 5% to 40%,112 and the mortality rate in severe
SOS has been reported to be as high as 47%.113
Conclusion
Nutrition assessment, support, and monitoring during
the transplant process are critical parts of patient management. These measures are even more important in pediatric
patients because of small size, need for continuing growth
and development, and the potential for rapid deterioration.
Comprehensive assessment may include information about
anthropometrics, food intake, appetite, presence of infection, organ dysfunction, wounds, nausea, vomiting, diarrhea,
and mucositis amongst others. Good clinical judgment is
critical and decision making should be individualized in an
effort to provide optimal nutrition management.
Late Effects of Treatment for Survivors of

Childhood Cancer
The 5-year survival rate for pediatric cancer has improved

and is about 80% for some diagnoses, although many patients
experience late effects or long-term health-related outcomes
that can result in organ dysfunction, second malignant
neoplasms, and adverse psychological sequelae.114
Risk factors for late effects can be due to tumor, from

direct tissue effects, tumor-induced organ dysfunction, and
mechanical effects. The multimodal treatment used during
treatment can also be responsible for many late effects. The
Childrens Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young
Adult Cancers (COG-LTFU Guidelines)115 extensively
review late effects of treatment used. Genetic predisposition, capacity for normal tissue repair, organ function not
affected by treatment, developmental status, and pre-morbid
state can influence development of late effects.114,116
Long-Term Follow-Up Guidelines

The COG-LTFU Guidelines115 are clinical practice guidelines used in screening and management of late effects that
can result from therapy used during treatment for pediatric
malignancies. The guidelines are evidence-based (utilizing
established associations between therapeutic exposures and
late effects to identify high-risk categories) and grounded in
the collective clinical experience of experts (matching the
magnitude of the risk with the intensity of the screening
recommendations). These guidelines are appropriate for
survivors of childhood, adolescent, or young adult cancers
2 or more years following the completion of cancer therapy.
Given the wide age range, some guidelines may not be applicable (ie, limiting alcohol intake in a 10-year-old); therefore,
clinicians must be guided by the age of the patient and the
relevance of the guidelines. References related to each late
effect and patient education materials on a variety of topics
are also included in the guidelines.115
When determining guidelines for cancer survivors it is
important to use traditional assessment/recommendations
taking into account the age of the survivor and his or her
pertinent clinical history. Suggestions are geared toward
leading a healthy lifestyle and include nutrition and activity
guidelines. The recommendations for cancer survivors is
that they adopt the prevention guidelines.
Gastrointestinal (GI) Problems in Survivors117

Treatment for childhood cancer can result in chronic problems of the intestine or other parts of the GI system including
bowel obstruction, gallstones, esophageal stricture, hepatic
fibrosis, colorectal cancer, and chronic enterocolitis.
Treatments that increase risk for having GI problems
include:
Radiation doses of 30 Gy (3000 cGy/rads) or higher
to the chest, neck, pelvis, or abdomen
Surgery in the pelvis or abdomen
Other risk factors include a family history of gallstones,

colorectal or esophageal cancer, patient history of bowel
adhesions (scarring) or bowel obstruction (blockage),
use of tobacco, or chronic GVHD
Possible symptoms of GI problems can include chronic
nausea, vomiting, acid reflux, constipation or diarrhea, pain
(with swallowing or abdominal), change in appetite, weight
loss, black tarry stools or blood in stool, abdominal distention, and jaundice. Suggestions for managing GI problems
include118:
1. Eat 5 or more servings of fruits and vegetables daily.
2. Choose a variety of foods from all food groups.
3. Include high-fiber foods in diet (eg, whole grain breads,
cereal).
4. Avoid foods high in sugar (eg, candy, soda).
5. Choose low-fat milk and dairy products.
6. When eating meats, choose leaner cuts and broil or boil
when preparing.
7. Decrease high-fat foods (potato chips, french fries).
8. Limit the use of alcohol.
9. Do not smoke or use tobacco and avoid second-hand
smoke.
Bone Health115
Bone is a living growing tissue (206 bones in the body) made
up of calcium, phosphorus, magnesium, vitamin D, and
fluoride. All of these nutrients are important in the development and maintenance of bone and other calcified tissues. A
consequence of childhood cancer treatment is a decrease in
peak bone mass from normal levels and an increased loss of
calcium from the bones. Survivors are at increased risk for
osteoporosis, a result of poor bone formation or too much
bone loss; therefore fractures may occur as bones become
weaker. Osteoporosis is diagnosed by an X-ray technique,
known as DEXA, which measures bone density or bone
mass and takes less than 20 minutes to complete.
Risk factors for osteoporosis are as follows:
1. General risk factors include female, family history of
osteoporosis, Caucasian or Asian, older age, small/thin
frame, smoking, diet low in calcium, increased amounts
of alcohol, caffeine or soda, lack of weight-bearing exercise and diet that is high in salt.
2. Risk factors in survivors of childhood cancer include
anti-cancer treatment utilizing methotrexate or corticosteroids as well as radiation to weight-bearing bones.
Other medical treatments such as anticonvulsants
and medication used to treat early puberty and endometriosis (Lupron) can affect bones. Drugs including
aluminum-containing antacids (Maalox), cholesterol-
363
lowering medication (cholestyramine) and high-dose

heparin for prolonged periods are risk factors.
3. Suggestions for decreasing risk of osteoporosis include
activity with weight-bearing (walking, dancing) and
resistance (light weight lifting) exercises.
General guidelines for calcium requirements are 1000 to
1500 mg/d (elemental calcium), but may vary based on age,
clinical history, and results of DEXA scan. Food sources
include dairy products (milk, cheese, yogurt) and non-dairy
sources (ie, salmon, collards, broccoli, white beans, fortified
foods such as orange juice and some cereals).
Calcium is found in supplements as a salt and is bound
to carbonate, gluconate, citrate, or lactate. The recommendations are based on elemental calcium. Calcium
carbonate is the most prevalent form of calcium supplement on the market and should be taken after meals as it
requires stomach acid for better absorption. It provides
more elemental calcium (40% elemental) than calcium
citrate; therefore, not as many tablets are required.
Calcium citrate is the best absorbed supplemental form of
calcium. It does not require extra stomach acid for absorption; therefore, it may be taken any time during the day,
even on an empty stomach.
Some brands list total weight of calcium salt, not the
amount of elemental calcium. Generic brands are less expensive, but they may not meet United States Pharmacopeia
(USP) standards for quality and purity. It is best to avoid
oyster shell, bone meal, or dolomite as they may contain
lead, mercury, or arsenic. The Nutrition Facts Label should
state the Percent Daily Value (%DV) based on 1000 mg of
elemental calcium. It is necessary to individualize calcium
requirements based on age and clinical history.
Vitamin D is needed to absorb calcium and is generally
found in dairy products that are fortified. It is recommended
that supplementation not exceed 800 International Units
per day, but should be based on age and clinical history.
Although we are able to make Vitamin D through sun exposure, it is felt that most people do not make enough due to
the use of sunscreens and limited sun exposure.
Heart Health after Treatment for Childhood Cancer119

Cancer treatments that can cause heart problems include
chemotherapy (anthracyclines) and radiation to the heart
or surrounding tissues. Types of heart problems that can
occur after treatment include left ventricular dysfunction,
cardiomyopathy, arrhythmias, valvular stenosis or insufficiency, pericardial fibrosis, and coronary artery disease.
Risk factors for developing heart problems can be due to
other medical conditions (obesity, high blood pressure,
364
diabetes, elevated cholesterol or triglycerides). Aerobic

exercise is generally safe and healthy for the heart, but some
forms of exercise can be stressful to the heart (eg, wrestling
and heavy weight lifting). Survivors who might be at risk for
having heart problems should check with their health care
provider before starting an exercise program.
Tests that are done to monitor heart function include
electrocardiogram (ECG), echocardiogram, or MUGA
scan and should be recommended by a health care provider
if appropriate. In order to prevent problems with the heart it
is best to stay at a healthy body weight, limit fat intake to no
more than 30% of calories, exercise moderately for at least
30 minutes on most days, and avoid smoking.
Diet and Physical Activity for Survivors119

American Institute for Cancer Research Recommendations
for Cancer Prevention118 include the following:
1. Be as lean as possible (not underweight).
2. Be physically active (30 minutes on most days).
3. Avoid sugary drinks. Limit intake of processed foods
high in fat and/or added sugar, or low in fiber.
4. Eat a variety of vegetables, fruits, whole grains, and
legumes (beans).
5. Limit consumption of red meat (beef, pork, lamb).
Avoid processed meats.
6. If consumed, limit alcoholic drinks to 2 for men and 1
for women per day.
7. Limit consumption of salty foods and foods processed
with salt (sodium).
8. Do not use supplements to protect against cancer.
9. Do not smoke or chew tobacco.

10. Handle food safely (immune system may be affected in
survivors risk for food-borne illness).
11. Rethink the pattern of eating with two-thirds of a meal
comprising vegetables, fruits, whole grains, and beans
and one-third coming from cheese or animal foods.
Maximize the variety of vegetables and fruits eaten
as they contain phytochemicals (plant compounds
that have been shown to act as antioxidants, boost the
immune system, have anti-inflammatory, antiviral, and
antibacterial effects, and aid in cellular repair).
Nutrients should be provided in the diet from a variety
of sources. Protein is needed for growth, repair of body
tissue, and assistance with maintaining immune function.
Carbohydrates and fats are the bodys major energy (calorie)
sources. Vitamins and minerals are essential for proper
growth and development and are needed to utilize the
energy in food. Water is important to prevent dehydration,
which may cause a person to feel listless or dizzy. Benefits
of regular exercise and good nutrition for childhood cancer
survivors include promoting healing of tissues/organs
damaged by cancer and treatment, building strength and
endurance, reducing risk of certain types of adult cancers
and diseases (eg, diabetes, heart disease), decreasing stress,
and providing a feeling of well-being.
Although late effects can occur in survivors of pediatric
cancer, a healthy lifestyle including proper diet and physical activity are important to maximize quality of life and
prevent the incidence of certain chronic diseases.
365
Appendix 30-1: Algorithm For Nutritional Intervention In The Pediatric Oncology Patient
Identify appropriate category: Age > 2 years choose either BMI (Body Mass Index) or IBW (Ideal Body Weight)

Age < 2 years choose WT/LT (Weight for Length) or IBW (Ideal Body Weight)
Categories for Nutritional Status

Underweight
Normal
BMI
< 5th % ile
5-85th % ile
WT/LT
< 10th % ile
10-90th % ile
< 70% Severe

> 70-80% Moderate
> 80-90% Mild
> 90-110 %
IBW
Risk of Overweight / Overweight*

> 85-95th % ile
> 95th % ile

> 90th % ile
> 110-120%
> 120%
*Evaluate for weight gain or loss
> 5 % wt loss from Usual Body Weight (UBW) or during therapy

or
Crossing > 2 percentile channels
NO
Meeting > 80 % estimated nutritional needs through
oral intake (food and supplements)
YES
YES
NO
NO
Encourage oral intake/supplements and monitor

weight/adequacy of diet once a month.
Will impending treatment adversely affect nutritional status

and ability to meet needs orally?
YES
NO
Oncologic prognosis warrants TPN (Total Parenteral Nutrition) or TF (Tube Feeding)

YES
Can patient safely tolerate/absorb nutrients via GI tract?
NO
YES
Is expected need for nutritional

support > 5 days?
Is patient a candidate
for tube feeding?
NO
YES
NO
Can intolerance be alleviated by changing formula or

using antiemetics/motility agents
TPN until GI tract can be

safely used
NO
Monitor and intervene as needed
TPN
YES
YES
High risk of pulmonary aspiration or excessive emesis
YES
NO
NO
Tube feedng required for > 3 months
Can tolerance be alleviated by changing formula, method

of administration or adding medication?
Provide tube feedings as tolerated and wean when

oral consumption is > 50% estimated needs
YES
NO
YES
Implement necessary changes
Post-pyloric feeds
Gastric feeds
NO
YES
Nasoenteric tube feeding

Nasogastric (NG)
Nasoduodenal (ND)
Nasojejunal (NJ)
Enterostomy tube feeding (PEG vs.G-Tube)

Gastrostomy (GT)
Jejunostomy (JT)
Gastro-Jejunostomy (G-JT)
Can patient tolerate feedings in strength and

amounts necessary to meet estimated needs?
Childrens Oncology Group, Cancer Control Nutrition Sub-Committee 10/04. Reprinted with permission.
366
Appendix 30-2: Algorithm for Nutritional Intervention and Categories of Nutritional Status in
the Pediatric Oncology Patient References and Resources
367
Appendix 30-2, continued
Appendix 30-3: Categories of Nutritional Status for the Pediatric Oncology Patient
Identify appropriate category: Age > 2 years choose either BMI1 (Body Mass Index) or IBW2 (Ideal Body Weight)

Age < 2 years choose WT/LT3 (Weight for Length) or IBW2 (Ideal Body Weight)
Weight loss/gain may or may not be present
Underweight
Normal
BMI
< 5th % ile
5-85th % ile
WT/LT
< 10th % ile
10-90th % ile
IBW
< 70% Severe70-80% Moderate

> 80-90% Mild
> 90-110 %
Risk of Overweight / Overweight*

> 85-95th % ile
> 95th % ile

> 90th % ile
> 110-120%
> 120%
BMI - Body Mass Index (percentile)

Hammer LD, Kraemer HC, Wilson DM, Ritter PL, Dornbusch SM. Standardized percentile curves of body-mass index for children
and adolescents. American Journal of Disease of Child. 145:259263, 1991.
Pietrobelli A, Faith MS, Allison DB, Gallagher D, Chiumello G, Heymsfield, SB. Body mass index as a measure of adiposity
among children and adolescents: A validation study. Journal of Pediatrics. 132:204210, 1998.
2
IBW - Ideal Body Weight for height or length (percentage)
Waterlow JC. Classification and definition of protein-calorie malnutrition. British Medical Journal 3: 566-569, 1972.
3
WT/LT - Weight for Length (percentile)
Motil KJ. Sensititve measures of nutritional status in children in hospital and in the field. International Journal ofCancer:
Suppl. 11: 2-9, 1998.
1
368
Appendix 30-4: Gastrointestinal Supportive

Care Medications
Nutrition support efforts in pediatric and adult cancer

patients are often complicated by problems with gut motility,
hyperacidity, nausea and vomiting, loss of appetite, and
treatment-induced mucositis. This appendix discusses some
of the medications available to help treat these conditions.
Motility Agents (Metoclopramide,

Erythromycin)
These agents have numerous uses, including to aid nasogastric intubations, and for gastroparesis, gastroesophageal
reflux, and intolerance to feedings.
Metoclopramide/Reglan
This drug blocks dopamine and at higher doses, 5 HT3
(serotonin) receptors. Its effects on motility may involve
increased release of acetylcholine in the gut. The effect on
the gut is increased forward peristalsis in the stomach and
duodenum. Metoclopramide has been used for the indications listed above as well as for chemotherapy-induced
nausea and vomiting. The latter use typically requires higher
doses. Data confirming the clinical utility vary with the indication. For chemotherapy-induced nausea and vomiting,
combinations of high-dose metoclopramide with dexamethasone and either diphenhydramine or lorazepam were
demonstrated to be effective in the 1980s, but serotonin
receptor antagonists such as ondansetron have been shown
to be superior. Metoclopramide is typically effective in
aiding intubations for patients with slow gastric motility and
for gastroparesis. Data proving utility in pediatric patients
with gastroesophageal reflux or feeding intolerance are
harder to find.120 Children are more sensitive to extrapyramidal side effects of dopamine blockers. Diphenhydramine
(Benadryl) is effective at preventing or treating dystonias,
while lorazepam is often more effective at reducing akathisias.121 While akathisias and dystonias are generally easily
reversed, there are a few reports of tardive dyskinesias
causing long-term movement disorders.120 In February 2009,
the Food and Drug Administration (FDA) announced it was
requiring a boxed warning in the labeling regarding the
risk of tardive dyskinesia with higher doses or longer-term
use of metoclopramide. Manufacturers must implement a
risk evaluation and mitigation strategy to ensure patients
receive a medication guide discussing the risk.122 The major
drug interactions involving metoclopramide relate to its
ability to speed transit through the gut. Drugs that are
designed for sustained release or that have slow dissolution
and absorption may have reduced absorption while a patient
is on metoclopramide. Other drugs such as tacrolimus and

cyclosporine may have increased absorption when a patient
is on metoclopramide.123 Doses of metoclopramide should
be reduced in patients with renal dysfunction.
Erythromycin
This drug is a macrolide antibiotic, but it also is a motilin
receptor agonist that increases proximal gut motility.120,124
Prokinetic effects are evident at doses as low as 4 to 12
mg/kg/d as compared to the 30 to 50 mg/kg/d used for
antimicrobial effects. Numerous studies suggest activity
of erythromycin for improving feeding tolerance in children.120,124 Typical problems with antimicrobial doses of
erythromycin include gastrointestinal upset, diarrhea, and
inhibition of P450 1A2 and 3A4 enzymes causing drug
interactions. These effects are less likely at the lower doses
used for motility. Although rare, there are some concerns
about adverse effects such as hepatotoxicity, ototoxicity,
cardiac arrhythmias, and pyloric stenosis.124 The latter has
been reported mostly in infants less than 2 weeks old. A
theoretical concern is the potential for low-dose antibiotics
to stimulate resistance among bacteria. This has not been
documented with the use of erythromycin for motility and
thus is an unknown. Caution should be used in patients with
hepatic impairment, largely due to the potential of erythromycin to cause hepatotoxicity.
Acid-Blocker Medications
H2 receptor antagonists and proton pump inhibitors have

been used mostly for ulcers or gastroesophageal reflux
disease in adults. They may be useful in children in situations
where blocking acid secretion is helpful. Although antacids
or sucralfate may be reasonable for short-term use in pediatrics, the aluminum that can be absorbed from sucralfate and
some antacids contraindicates any longer term use.
H2 Receptor Antagonists (Famotidine/Pepcid,

Ranitidine/Zantac, Nizatidine/Axid, Cimetidine/
Tagamet)
These drugs block histamine-induced acid secretion.
Higher doses of H2 receptor antagonists block acid secretion better than lower doses, although proton pump
inhibitors block acid secretion better than high doses of
H2 receptor antagonists.125127 Some data support the use
of H2 receptor antagonists for gastroesophageal reflux
disease in infants and young children, although a potential
limitation to chronic use is the development of tolerance to
the acid neutralization.128 Adverse effects are uncommon
but include headaches, sedation, and gastrointestinal side
effects. Cimetidine may inhibit the metabolism of some

drugs, but other H2 receptor antagonists are not likely to
affect drug metabolism. Any of these drugs may alter the
absorption of other drugs that are sensitive to higher gastric
pH (eg, ketoconazole, itraconazole, ampicillin, iron). All
4 of these drugs require reduced doses in patients with
renal impairment. H2 receptor antagonists are available in
nonprescription formulations.
Proton Pump Inhibitors (Omeprazole/Prilosec,

Lansoprazole/Prevacid, Pantoprazole/Protonix,
Esomeprazole/Nexium, Rabeprazole/Aciphex)
These drugs block hydrogen/potassium ATPase (the
proton pump), effectively blocking acid secretion induced
by virtually all stimuli. Proton pump inhibitors have shown
good activity in adults with GERD and hypersecretory
syndromes, and there is some evidence for efficacy in children with gastroesophageal reflux disease.128 As with H-2
receptor antagonists, adverse effects are rare but include
headaches and gastrointestinal effects such as abdominal
pain, constipation, or diarrhea. Altered absorption of other
drugs can occur due to elevated gastric pH, and omeprazole may inhibit some hepatic P450 enzymes, reducing
metabolism of some drugs such as warfarin.128 Proton
pump inhibitors work best when administered 15 to 30
minutes before a meal.129 Administration of lansoprazole
or omeprazole through an NG tube is best accomplished by
either using the lansoprazole Oral Disintegrating Tablet, or
mixing the enteric coated granules from the lansoprazole
or omeprazole capsule or packet for suspension in 8.4%
sodium bicarbonate solution (1 mEq/mL parenteral solutions are generally used for this).130,131 These formulations
are less viscous and appear to go through tubes better. An
alternative is mixing the contents with an acidic fruit juice,
which preserves the enteric coating until the granules
reach the alkaline contents of the small intestine. Another
alternative may be the intravenous formulations available
for pantoprazole and lansoprazole. Mixing enteric-coated
granules in water for administration results in a more
viscous solution that does not go through enteric tubes as
well. Dosaging guidelines are not available, but doses may
need to be reduced in patients with significant hepatic
impairment. Omeprazole is available as a nonprescription
drug.
Antiemetics
Antiemetics in pediatric hematology/oncology patients

are used primarily for nausea and vomiting due to chemotherapy, radiation, and surgery. Serotonin receptor
369
antagonists and dopamine blockers are generally useful for

all 3 causes. Other drugs discussed here are mostly used
for chemotherapy-induced nausea and vomiting. The most
recent American Society of Clinical Oncology antiemetic
guidelines include suggestions regarding radiation-induced
emesis.121 The National Comprehensive Cancer Network
publishes emesis guidelines (updated annually) on its Web
site, and the Multinational Association of Supportive Care
in Cancer also has published guidelines on the Internet.
All of these guidelines currently divide chemotherapy
drugs into classes that are high, moderate, low, or minimal
likelihood of causing emesis. Combinations of a serotonin
receptor antagonist with a steroid and aprepitant (Emend)
are recommended for highly emetogenic chemotherapy
regimens by all guidelines. Combinations of a serotonin
receptor antagonist and a steroid are generally recommended for moderately emetic regimens, a single agent
(often steroids) for low emetogenicity, and antiemetics only
as needed for minimally emetic regimens.
Serotonin Receptor (5HT3 or 5-hydroxytryptamine-3)

Antagonists (Ondansetron/Zofran, Granisetron/
Kytril, Dolasetron/Anzemet, Palonosetron/Aloxi)
These drugs block the effects of serotonin at the 5HT3
receptors in the gut and the chemotherapy receptor trigger
zone. They are generally better at reducing vomiting than at
reducing nausea.132 Used in equivalent doses, there are few
differences between these agents, although palonosetron
has a longer duration of activity, apparently due to its tighter
binding to receptors and longer half-life. Palonosetron may
be better at preventing delayed nausea and vomiting due
to this activity, although most studies have compared it to
a single dose of the shorter acting agents, which are more
likely to be used daily. In this class of drugs, the oral route of
administration is equally effective as intravenous, as long as
the patient is not actively vomiting. Recently, all antiemetic
guidelines have dropped serotonin receptor antagonists
from their recommended drugs to treat delayed nausea and
vomiting (more than 24 hours after chemotherapy) due to the
minimal evidence for their efficacy.133 The most likely adverse
effects with serotonin receptor antagonists are headaches,
and constipation with multiple-day use.132 Prolongation of
the QTc interval has been reported with this class of drugs,
although it is generally not thought to be clinically significant. However, the dolasetron package insert does contain a
warning regarding use in patients at increased risk of arrhythmias, and dolasetron is not approved for use in children
in Canada due to reports of cardiovascular adverse effects
(arrhythmias, cardiovascular arrest).134 Patients who have
370
received therapy with anthracyclines (doxorubicin, daunorubicin, idarubicin, epirubicin, mitoxantrone, cisplatin, or
ifosfamide) are at the greatest risk for cardiovascular side
effects. The latter 2 can cause electrolyte abnormalities due
to renal tubular losses of calcium, magnesium, potassium,
phosphate, and bicarbonate. These losses may require supplementation, and oral supplementation generally tastes bad and
is poorly absorbed. Anthracyclines and mitoxantrone cause
damage to cardiac myofibrils that may result in heart failure
for some patients. This is most common when young children
receive the drug, and at lifetime doses above 300 mg/m2 for
younger children and 450 to 550 mg/m2 for older children
and adults. Ondansetron has a prolonged half-life in patients
with severe liver impairment and doses should be reduced.
Palonosetron, dolasetron, and granisetron do not need dose
adjustments in renal or hepatic dysfunction.134
Aprepitant (Emend and Fosaprepitant,

theIntravenous Emend)
This drug is a neurokinin-1 receptor antagonist (its ligand is
Substance P) that has been found to produce a small reduction in acute nausea and vomiting, but a larger reduction in
delayed nausea and vomiting. The FDA-approved dosing is
for the first 3 days of the chemotherapy regimen, combined
with a serotonin receptor antagonist and a steroid, but not
as a single agent. Until 2008, only the oral formulation was
available and therefore there was not an easy way to administer this drug to most children. Although adolescents are
often large enough to be dosed as adults, children have generally not been treated with aprepitant. A potential problem
with aprepitant is its ability to inhibit P450 microsomal
enzymes and reduce metabolism of other drugs. Dexa
methasone doses of approximately 12 mg with aprepitant
are equivalent to 20 mg without aprepitant. Warfarin doses
will generally require reduction also. There is concern that
some chemotherapy drugs may have reduced clearance
when patients take aprepitant, but currently there are little
data suggesting clinical problems with this potential interaction. Regardless, it is important to only use aprepitant
for highly emetic regimens as indicated in current practice
guidelines, and to use caution when concomitant chemotherapy agents are known to be metabolized by hepatic
P450 enzymes.
Glucocorticoids (Dexamethasone/Decadron,
Methylprednisolone Sodium Succinate/Medrol)
These drugs have been used as antiemetics since the early
1980s, but it is still not clear how they work. They are used
mostly in combinations with a serotonin receptor antagonist
or metoclopramide, but can be used as single agents for mildly

emetic regimens. Glucocorticoids have a long list of adverse
effects, but the ones most commonly seen with short-term
use are hyperglycemia, gastrointestinal upset, hypertension,
and mental or behavioral changes. Doses should be reduced
when used with aprepitant, as mentioned above.
Phenothiazines (Prochlorperazine/Compazine,
Promethazine/ Phenergan, Chlorpromazine/
Thorazine) and Butyrophenones (Haloperidol/
Haldol, Droperidol/Inapsine)
These drugs block dopamine receptors in the vomiting
center and chemotherapy-receptor trigger-zone. These
agents are currently recommended mostly for acute nausea
and vomiting from mildly to moderately emetic chemotherapy regimens, or for breakthrough nausea and vomiting.
Prochlorperazine and promethazine have been used for
delayed nausea and vomiting with some success. Potential
side effects include sedation, anticholinergic effects such
as urinary retention or constipation, and alpha-adrenergic
blockade effects such as hypotension. However the major
adverse effects are extrapyramidal effects: akathisias
(restlessness) and dystonias (muscle contraction) such as
trismus and torticollis. These effects occur more frequently
in children and many pediatric practitioners limit the use
of dopamine blockers due to these side effects. Diphenhydramine (Benadryl) will generally reverse extrapyramidal
effects within 30 to 60 minutes, and has often been used
prophylactically to reduce the risk of extrapyramidal reactions. Also of note are specific issues with 2 of these drugs.
First, droperidol is either not used or dose-limited in many
institutions due to its ability to lengthen the QTc interval
and cause arrhythmias. Second, IV promethazine can be
very irritating on injection, and if injected into an artery
can cause significant tissue damage. Many institutions are
limiting its use to low doses or oral administration. Risk
may be minimal if central lines are available for administration, which is commonly the situation in children with
cancer. Additionally, promethazine has a boxed warning
in the package insert against using it in patients less than 2
years old, due to reports of fatal respiratory depression.
Cannabinoids (Dronabinol/Marinol, Nabilone/

Cesamet)
These drugs have been used mostly for patients who have
not responded well to more typical antiemetics. These drugs
are synthetic versions of THC (tetrahydrocannabinol),
the psychoactive component of marijuana. Early studies
suggested these agents were most effective in younger adult
patients, patients who had smoked marijuana, and patients

who developed euphoria while taking them. While many
pediatric institutions have some experience using these
agents in children, there are little data published on use in
children, and most of those data are with nabilone. Recommended doses of dronabinol are very high; some patients
tolerate the drug better when lower doses are used and
started prior to the chemotherapy. Adverse effects are the
same as for marijuana, including euphoria or dysphoria,
hypotension, tachycardia, increased appetite, dry mouth,
and occasionally hallucinations.
Atypical Antipsychotics (Olanzapine/Zyprexa)

These drugs are similar to the dopamine blockers discussed
above, but are less likely to cause extrapyramidal side
effects. Very few studies have been published, but there are
several case reports and small studies showing efficacy of
olanzapine in adult patients who have not responded well
to more standard antiemetics.132 Adult recommended doses
are 5 to 10 mg per day, with 2.5 to 5 mg per day being used
in case reports in children. Other than sedation, few side
effects have been reported with short-term use.
Antihistamines (Diphenhydramine/Benadryl) and

Benzodiazepines (Lorazepam/Ativan)
These drugs have been used as adjunctive agents for chemotherapy-induced nausea and vomiting. Neither has
good activity on its own as an antiemetic for chemotherapy,
although the sedation they cause may help the patient sleep
and have less nausea and vomiting. Diphenhydramine has
good anticholinergic activity in the brain, and is therefore
able to reduce and/or treat extrapyramidal reactions from
dopamine blockers. Likewise, lorazepam is beneficial in
reducing or treating akathisias caused by dopamine blockers. Lorazepams activity as an antianxiety medication and
its ability to cause anterograde amnesia in some patients may
help reduce anticipatory nausea and vomiting. Some pediatric patients develop paradoxical reactions to these agents,
becoming agitated instead of sedated. This appears to be
more common in younger patients and with higher doses.
Additionally, some pediatric patients become weepy or have
hallucinations, limiting the usefulness oflorazepam.
Appetite Stimulants
Weight loss in cancer patients may be due to numerous

factors, as described in detail in the prior sections. Appetite
stimulants have been used in attempts to counter weight
loss in cancer patients, but studies have had mixed results.
A review of adult studies by Yavuzsen135 suggests that of all
371
the drugs tried, only progestins and glucocorticoids showed

a benefit in cancer-induced anorexia and weight loss. There
are doubts about even these drugs, as the weight gain from
progestins such as megestrol may consist more of fat and
water than lean body mass136 and glucocorticoids have
negative anabolic effects that result in muscle weakness
over time.
Studies have shown at least some increased appetite and
weight gain benefit from methylprednisolone (Medrol),
dexamethasone (Decadron), and prednisone. In addition
to the short-term side effects discussed above in the antiemetic section, glucocorticoids have numerous long-term
side effects that include osteoporosis, aseptic necrosis, cataracts, easy tearing of the skin, and loss of muscle strength.
Perhaps the best use of these agents for increasing appetite
is in hospice patients where the longer term adverse effects
are of less consequence.
Megestrol/Megace and Medroxyprogesterone/

Provera
These drugs are progestins that have an effect of increasing
appetite and causing weight gain. Most studies of megestrol
have involved only adults, but one pediatric study used
megestrol in a few patients for whom cyproheptadine (see
below) did not work. Five of 7 children responded with
weight gain.137 As noted above, there is some doubt about the
nature of the weight gained (fluid retention or fat versus lean
body weight), but there are numerous studies documenting
the weight gain.135 Potential adverse effects of significance
include thrombophlebitis, photosensitivity, impotence in
men, and Cushings syndrome with adrenocortical suppression and the potential for Addisonian crisis.134,138
Dronabinol/Marinol (But Not Nabilone)

This drug has been studied for weight gain in adults, and
is FDA approved for treating anorexia in AIDS patients.
Little data are available on use in cancer patients with
anorexia or in pediatrics. While it does stimulate appetite
for periods of at least 5 months, there is minimal evidence
for efficacy in causing weight gain or reducing weight loss in
cancer patients.134,135,138,139 As noted above in the antiemetic
section, there are many potential adverse effects associated
with dronabinol, however the doses used for appetite stimulation are lower (2.5 mg twice daily) than those used for
antiemesis, so there may be fewer adverse effects.
Cyproheptadine/Periactin
This drug is a serotonin antagonist and antihistamine that
has been studied as an appetite stimulant in cancer patients.
372
An earlier study in adults showed increased appetite

but no less weight loss than with a placebo in adults with
advanced malignancies.140 A recent study in children with
cancer found that many did respond with weight gain, with
drowsiness as the only common side effect.137 Studies with
this agent are ongoing in children. Doses may need to be
reduced in patients with hepatic impairment.
to maintain oral intake. Opioids can be very helpful, but

frequently subject the patient to constipation and sometimes to nausea and vomiting, itching, or when dosed
excessively, respiratory depression. A number of drugs have
been used in attempts to reduce the frequency and severity
of mucositis (prevention).
Medications for Mucositis
Chlorhexidine/Peridex has antiseptic-type effects, and

since mucositis can result from fungal or viral mouth infections, this product might help. However there is minimal
evidence for benefits in preventing or treating mucositis
with chlorhexidine. Recent guidelines from the Multinational Association of Supportive Care in Cancer (MASCC)
do not recommend its use for either prophylaxis or treatment.141 Since most chlorhexidine-containing products also
contain alcohol, they may elicit pain in patients who already
have mucositis.
Mucositis consists of inflammatory ulcerations in the mouth

and gut that usually result from chemotherapy, radiation,
or the conditioning regimens for HSCT. Mucositis occurs
inconsistently after chemotherapy regimens outside of the
transplant setting, and the time course after chemotherapy
generally parallels that of neutropenia. These features make
it difficult to study since it occurs erratically and resolves
with or without therapy. Medications used for mucositis fit
into two categories: prevention or treatment. Treatments
treat symptoms, having little if any effect on the healing
rate of the mucositis. When mucositis is seen in the mouth,
presumably it is occurring throughout the gut, including
the stomach. Administration of acid-blocking drugs is
commonly thought to help, although data on the value of
this treatment are scarce. Medications used to treat symptoms of mucositis include drugs such as Magic Mouthwash
combinations, Gelclair, and opioids.
Magic Mouthwash
This usually contains viscous lidocaine, diphenhydramine,
and an antacid or nystatin. Lidocaine is a strong local anesthetic, diphenhydramine is a weak local anesthetic, and the
antacid may help neutralize acid in the stomach, although
the dose is probably too low to effectively raise gastric pH.
Nystatin is in combinations at some institutions because
mucositis may cause or be caused by Candida infections
(thrush). There are little if any published data on the efficacy of these combinations, but they relieve symptoms in
some patients. Combinations containing viscous lidocaine
have been reported to cause systemic lidocaine toxicity if
used in relatively high or frequent doses, especially in small
children or infants. Doses should be limited if the medication is to be swallowed. This is not a problem if it is swished
and spit out. Gelclair is a polymer-type combination of
polyvinylpyrrolidone, hyaluronic acid, and glycyrrhetinic
acid. It coats the mucosa of the mouth, protecting it from
air and irritants that elicit pain. It is suggested not to eat or
drink for an hour or more after using the Gelclair. Some
patients seem to benefit from this product. Opioids are used
when less potent treatments fail, and may allow the patient
Chlorhexidine/Peridex
Glutamine
Glutamine is an amino acid that is thought to be especially important to cells of the gut. Studies in the past have
suggested that it might help maintain the integrity of the gut
in patients receiving long-term total parenteral nutrition, or
may help prevent chemotherapy-induced mucositis. Studies
have suggested reductions in mucositis for autologous stem
cell transplant patients, but there also has been a suggestion
of increased relapses.141143 The most recent MASCC guidelines do not recommend the use of glutamine, but there is
enough interest that studies of specialized formulations of
glutamine are in clinical trials.
Palifermin/Kepivance
Palifermin/Kepivance is a recombinant human keratinocyte growth factor. It is approved and used for reducing
mucositis in patients with hematologic malignancies
receiving hematopoietic stem cell transplants. Use in solid
tumors is considered contraindicated by many practitioners due to the potential for stimulating epithelial cells (and
perhaps the cancers); however, studies in solid tumors in
patients receiving standard chemotherapy are in progress.
Palifermin is expensive and does cause some side effects
such as thick tongue, altered taste, and rashes. Palifermin
has been demonstrated to reduce the duration and severity
of oral mucositis as well as the use of opioids in patients
receiving autologous HSCT for hematologic malignancies.
There are less data for allogeneic transplants.
The MASCC guidelines mention numerous other
products (favorably or unfavorably), most of which are
not currently used in pediatrics. Slurries or suspensions of

sucralfate (Carafate) have been used in children with oral
mucositis, but there is a lack of efficacy data in general, plus
several negative studies in adults with radiation-induced
oral mucositis.141 Another product that is being studied
currently in children is Traumeel S. It is a homeopathic
mixture of approximately a dozen herbals or supplements
that is not thought to have side effects, although allergies
to ingredients would be a possibility. One study in children
and young adults receiving stem cell transplants showed
favorable results and further studies are ongoing.144
1. Mucositis is one of the complications affecting the

nutrition status of the pediatric oncology patient.
Which chemotherapy agent is most likely to lead to the
development of mucositis?
A. Methotrexate
B. Cyclophosphamide
C. Cytarabine
D. Carboplatin
2. One of the leading causes of death within the first 2
months post-hematopoietic transplant is sinusoidal
obstruction syndrome. Which of the following are
symptoms associated with the development of SOS?
A. Nausea, vomiting, bloody urine
B. Weight gain, ascites, hyperbilirubinemia, hepatomegaly
C. Pruritic rash, diarrhea, protein losing enteropathy
D. Dysgeusia, mouth sores, nausea
3. The use of EN in hematopoietic transplant is commonly
discouraged because of:
A. The need of frequent tube replacement
B. Risk of excessive bleeding with tube placement due
to mucositis
C. Dislodgement of the feeding tube
D. All of the above
4. Which is TRUE regarding agents used to enhance gut
motility?
A. Use of erythromycin to enhance gut motility
increases resistance among susceptible bacteria.
B. Children are more susceptible to the extrapyramidal side effects of both metoclopramide and
erythromycin than are adults.
C. Case reports of tardive dyskinesias with the use of
metoclopramide are too infrequent to be considered clinically important.
D. Motility-enhancing agents may increase or decrease
the absorption of other drugs.
373
5. Survivors of childhood cancer can be at greater risk for

osteoporosis due to:
A. History of corticosteroid use
B. Methotrexate containing regimen
C. Use of anticonvulsants
D. All of the above
References
1. National Cancer Institute, Surveillance Epidemiology and

End Results. SEER Cancer Statistics Review, 1975-2006.
http://seer.cancer.gov/csr/1975_2006. Accessed December
3, 2009.
2. Donaldson SS, Wesley MN, DeWys WD, Suskind RM, Jaffe
N, van Eys J. A study of the nutritional status of pediatric
cancer patients. Am J Dis Child. 1981;135:11071112.
3. Coates TD, Rickard KA, Grosfeld JL, Weetman RM. Nutrition support of children with neoplastic diseases. Surg Clin
North Am. 1986;66:11971212.
4. Mauer AM, Burgess JB, Donaldson SS, et al. Special nutritional needs of children with malignancies: a review. J Parenter
Enteral Nutr. 1990;14(3):315324.
5. Cady J. Nutritional support during radiotherapy for head and
neck cancer: the role of prophylactic feeding tube placement.
Clin J Oncol Nurs. 2007;11(6):875880.
6. Han-Markey T. Nutritional considerations in pediatric
oncology. Semin Oncol Nurs. 2000;16(2):146151.
7. Rickard KA, Gosfeld JL, Kirksey A, Ballantin TV, Baehner RL.
Reversal of protein-energy malnutrition during treatment of
advanced neoplastic disease. Ann Surg. 1979;190(6):771781.
8. Lahorra JM, Ginn-Pease ME, King DR. The prognostic signi
ficance of basic anthropometric data in children with advanced
solid tumors. Nutr Cancer. 1989;12(4):361369.
9. Cancer Therapy Evaluation Program. Common Toxicity
Criteria Document for Adverse Events, Version 3.0. DCTD,
NCI, NIH, DHHS. http://ctep.cancer.gov. Accessed
November 19, 2008.
10. Carter P, Carr D, van Eys J, Coody D. Nutritional parameters in
children with cancer. J Am Diet Assoc. 1983;82(6):616622.
11. Smith DE, Stevens MC, Booth IW. Malnutrition at diagnosis
of malignancy in childhood: common but mostly missed. Eur
J Pediatr. 1991;150(5):318322.
12. Donaldson SS, Wesley MN, Ghavii F, Shils ME, Suskind
RM, DeWys WD. A prospective randomized clinical trial of
total parenteral nutrition in children with cancer. Med Pediatr
Oncol. 1982;10(2):129139.
13. Barrera R. Nutrition support in cancer patients. J Parenter
Enteral Nutr. 2002;26(Suppl 5):S63S71.
14. National Cancer Institute. Nutrition in Cancer Care (PDQ ).
http://www.cancer.gov/cancerinfo/pdq/supportivecare/
nutrition/healthprofessional. Accessed November 1, 2008.
15. Unsal D, Mentes B, Akmansu M, et al. Evaluation of nutritional status in cancer patients receiving radiotherapy: a
prospective study. Am J Clin Oncol. 2006;29(2):183188.
374
16. Ogama N, Suzuki S, Umeshita K, et al. Appetite and adverse

effects associated with radiation therapy in patients with head
and neck cancer. Eur J Oncol Nurs. 2009;Sep 4 [Epub ahead
of print].
17. Wilkes C, Ingwersen K, Barton-Burke M. Oncology Nursing
Drug Handbook. Sudbury, Mass: Jones & Bartlett Publishers;
2003.
18. Baltzer CL, Haywood R. Oncology Pocket Guide to
Chemotherapy. 5th ed. Philadelphia, PA: Mosby Medical
Communications/Elsevier Science; 2002.
19. Tyc VL, Vallelunga L, Mahoney S, Smith BF, Mulhern RK.
Nutritional and treatment-related characteristics of pediatric oncology patients referred or not referred for nutritional
support. Med Pediatr Oncol. 1995;25(5):379388.
20. Barber MD, Ross JA, Fearon KC. Cancer cachexia. Surg Oncol.
1999;8(3):133141.
21. National Cancer Institute. Dictionary of Cancer Terms. http://
www.nci.nih.gov/Templates/db_alpha.aspx?CdrID=44111.
22. Martindale RD, Shikora SA, Nishikawa R, et al. The metabolic
response to stress and alterations in nutrient metabolism. In:
Shikora SA, Martindale RG, Schwaitzberg SD, eds. Nutritional Consideration in the Intensive Care Unit. Silver Spring,
MD: American Society for Parenteral and Enteral Nutrition;
2002:1119.
23. Jones MO, Pierro A, Hammond P, Lloyd DA. The metabolic response to operative stress in infants. J Pediatr Surg.
1993;28(1):12581263.
24. Moschovi M, Trimis G, et al. Serial plasma concentrations
of PYY and ghrelin during chemotherapy in children with
acute lymphoblastic leukemia. J Pediatr Hematol Oncol.
2008;30(10):733737.
25. Ovesen L, Allingstrup L, et al. Effect of dietary counseling on food intake, body weight, response rate, survival,
and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study. J Clin Oncol.
1993;11(10):20432049.
26. Cravo M L, Gloria LM, et al. Metabolic responses to tumour
disease and progression: tumour-host interaction. Clin Nutr.
2000;19(6):459465.
27. Argiles JM, Moore-Carrasco R, Busquets S, Lopez-Soriano
FJ. Catabolic mediators as targets for cancer cachexia. Drug
Discov Today. 2003;8(18):838844.
28. Dunlop RJ, Campbell CW. Cytokines and advanced cancer. J
Pain Symptom Manage. Sep 2000;20(3):214232.
29. Bosaeus I, Daneryd P, et al. Dietary intake, resting energy
expenditure, weight loss and survival in cancer patients. J
Nutr. 2002;132(11 Suppl):3465S3466S.
30. Eden E, Edstrom S, et al. Glucose flux in relation to energy
expenditure in malnourished patients with and without
cancer during periods of fasting and feeding. Cancer Res.
(1984) 44(4):17181724.
31. National Cancer Institute. Dictionary of Cancer
Terms.http:w w w.nci.nih.gov/Templates/db_a lpha.
aspx?CdrlD=44111. Accessed November 29, 2008.
32. Lelbach A, Muzes G, et al. Current perspectives of catabolic mediators of cancer cachexia. Med Sci Monit.
2007;13(9):RA168173.
33. National Cancer Institute. Nutrition in Cancer Care (PDQ ):

Depression. Supportive Care. http://www.cancer.gov/cancertopics/pdq/supportivecare/depression/healthprofessional.
Accessed March 20, 2009.
34. Gilbreah J, Inman-Felton A, et al. Medical Nutrition Therapy
Across the Continuum of Care-Client Protocols. 2nd ed. Chicago,
IL: The American Dietetic Association; 1998.
35. Ladas EJ, Sacks N, et al. Standards of nutritional care in
pediatric oncology: results from a nationwide survey on
the standards of practice in pediatric oncology. A Childrens Oncology Group study. Pediatr Blood Cancer.
2006;46(3):339344.
36. Green GJ, Weitzman SS, et al. Resting energy expenditure
in children newly diagnosed with stage IV neuroblastoma.
Pediatr Res. 2008;63(3): 332336.
37. Fuhrman MP, Charney P, et al. Hepatic proteins and nutrition
assessment. J Am Diet Assoc. 2004;104(8):12581264.
38. Rickard KA, Detamore CM, et al. Effect of nutrition staging
on treatment delays and outcome in Stage IV neuroblastoma.
Cancer. 1983;52(4):587598.
39. Lobato-Mendizabal E, Ruiz-Arguelles GJ, et al. Leukaemia
and nutrition. I: Malnutrition is an adverse prognostic factor in
the outcome of treatment of patients with standard-risk acute
lymphoblastic leukaemia. Leuk Res. (1989);13(10):899906.
40. Charuhas PM. Introduction to marrow transplant. American
Dietietics Association, Oncology Nutrition Dietetic Practice
Group Newsletter. 1994;2:29.
41. Andrassy RJ, Chwals WJ. Nutritional support of the pediatric
ocology patient. Nutrition. 1998;14(1):124129.
42. White M, Murphy AJ, et al. Nutritional status and energy
expenditure in children pre-bone-marrow-transplant. Bone
Marrow Transplant. 2005:35(8):775779.
43. Reilly JJ, Odame I, et al. Does weight for height have prognostic
significance in children with acute lymphoblastic leukemia?
Am J Pediatr Hematol Oncol. 1994;16(3):225230.
44. Pedrosa F, Bonilla M, et al. Effect of malnutrition at the time
of diagnosis on the survival of children treated for cancer in
El Salvador and Northern Brazil. J Pediatr Hematol Oncol.
2000;22(6):502505.
45. Rickard KA, Foland BB, et al. Effectiveness of central parenteral
nutrition versus peripheral parenteral nutrition plus enteral
nutrition in reversing protein-energy malnutrition in children
with advanced neuroblastoma and Wilms tumor: a prospective randomized study. Am J Clin Nutr. 1983;38(3):445456.
46. Viana MB, Murano M, Ramos G, et al. Malnutrition as a
prognostic factor in lymphoblastic leukemia: a multivariate
analysis. Arch Dis Child. 1994;71(4):304310.
47. Mejia-Arangure JM, Fajardo-Gutierrez A, Reyes-Ruiz NI,
et al. Malnutrition in childhood lymphoblastic leukemia: a
predictor of early mortality during the induction to remission
phase of treatment. Arch Med Res. 1999;30(2):150153.
48. Hafitz MG, Mannan MA. Nutritional status at initial
presentation in childhood acute lymphoblastic leukemia
and its effect on induction of remission. 2007;17(2
(supplemental)):S46S51.
49. Halton JM, Scissons-Fisher CC. Impact of nutritional status

on morbidity and dose intensity of chemotherapy during
consolidation therapy in children with acute lymphoblastic
leukemia (ALL). J Pediatr Hematol Oncol. 1999;21:317.
50. Obama M, Cangir A, van Eys J. Nutritional status and
anthracycline cardiotoxicity in children. South Med J.
1983;76(5):577578.
51. Hays DM, Merritt RJ, et al. Effect of total parenteral nutrition on marrow recovery during induction therapy for acute
nonlymphocytic leukemia in childhood. Med Pediatr Oncol.
1983;11(2):134140.
52. Bakish JD, Hargrave, et al. Evaluation of dietetic intervention
in children with medulloblastoma or supratentorial primitive
neuroectodermal tumors. Cancer. 2003;98(5):10141020.
53. den Broeder E, Lippens RJ, et al. Effects of naso-gastric tube
feeding on the nutritional status of children with cancer. Eur J
Clin Nutr. 1998;52(7):494500.
54. Barron MA, Duncan DS, et al. Efficacy and safety of radiologically placed gastrostomy tubes in paediatric haematology/
oncology patients. Med Pediatr Oncol. 2000;34(3):177182.
55. Sacks N, Lange B, et al. Pilot study of proactive enteral tube
feedings in children receiving chemotherapy for newly diagnosed AML/MDS, CNS, and high-risk solid tumors. Neuro
Oncol. 2008;10(3):458.
56. Rickard KA, Becker MC, et al. Effectiveness of two methods
of parenteral nutrition support in improving muscle mass of
children with neuroblastoma or Wilms tumor. A randomized
study. Cancer. 1989;64(1):116125.
57. Donaldson SS. Effects of therapy on nutritional status of the
pediatric cancer patient. Cancer Res. 42(2 Suppl)729s736s.
58. Kelly KM, Jacobson JS, et al. Use of unconventional therapies
by children with cancer at an urban medical center. J Pediatr
Hematol Oncol. 2000;22(5):412416.
59. Kemper KJ, Vohra S, et al. American Academy of Pediatrics.
The use of complementary and alternative medicine in pediatrics. Pediatrics. 2008;122(6):13741386.
60. Chwals WJ, Letton RW, et al. Stratification of injury severity
using energy expenditure response in surgical infants. J Pediatr
Surg. 1995;30(8):11611164.
61. Btaiche IF, Marik P, et al. Nutrition in Critical Illness,
Including Immunonutrition. The A.S.P.E.N. Nutrition Support
Practice Manual. 2nd ed. Silver Spring, MD: American Society
for Parenteral and Enteral Nutrition; 2002:263270.
62. Choi K, Lee SS, et al. The effect of oral glutamine on 5-fluorouracil/leucovorin-induced mucositis/stomatitis assessed
by intestinal permeability test. Clin Nutr. 2007;26(1):5762.
63. Cheney CL, Abson KG, et al. Body composition changes in
marrow transplant recipients receiving total parenteral nutrition. Cancer. 1987;59(8):15151519.
64. Ringwald-Smith K, Williams R, et al. Determination of
energy expenditure in bone marrow transplant patient. Nutr
Clin Pract. 1998;13(5):215218.
65. Duggan C, Bechard L, et al. Changes in resting energy
expenditure among children undergoing allogeneic stem cell
transplantation. Am J Clin Nutr. 2003;78(1):104109.
375
66. Duro D, Bechard LJ, et al. Weekly measurements accurately

represent trends in resting energy expenditure in children
undergoing hematopoietic stem cell transplantation. J Parenter
Enteral Nutr. 2008;32(4):427432.
67. Charuhas PM, Lipkin A, et al. Hematopoietic stem cell transplantation. In: Merritt RJ, DeLegge M, Holcombe B, et al,
eds. The A.S.P.E.N. Nutrition Support Practice Manual. 2nd
ed. Silver Spring, MD: American Society for Parenteral and
Enteral Nutrition; 2005.
68. Bechard LJ, McCarthy TC. Oncology and stem cell transplantation. In: Baker SS, Baker RD, Davis AM. Pediatric
Nutrition Support. Sudbury, MA: Jones and Bartlett Publishers;
2007:433445.
69. Charuhas PM. Nutrition management of oncology and
marrow/hematopoietic stem cell transplantation. In:
Amorde-Spalding K, Nieman L, eds. Pediatric Manual of Clinical Dietetics. 2nd ed. Update. Chicago, IL: American Dietetic
Association; 2008:175184.
70. Bunting D, DSouza S. Texas Childrens Hospital Pediatric
Nutrition Reference Guide. 8th ed. 2008.
71. Charuhas PM, Gautier ST. Parenteral nutrition in pediatric
oncology. In: Chernoff R, Baker RD, Baker SS, Davis AM.
Pediatric Parenteral Nutrition. New York, NY: Chapman and
Hall; 1997.
72. Wickham RS, Rehwaldt M, et al. Taste changes experienced
by patients receiving chemotherapy. Oncol Nurs Forum.
1999;26(4):697706.
73. Capra S, Ferguson M, et al. Cancer: impact of nutrition intervention outcome--nutrition issues for patients. Nutrition.
2001;17(9):769772.
74. Roberts S, Thompson J. Graft-vs-host disease: nutrition therapy in a challenging condition. Nutr Clin Pract.
2005;20(4):440450.
75. Centers for Disease Control and Prevention. Food Safety.
http://w w w.cdc.gov/foodsafety/disease.htm.Accessed
November 20, 2008.
76. Moody K, Finlay J, et al. Feasibility and safety of a pilot
randomized trial of infection rate: neutropenic diet versus
standard food safety guidelines. J Pediatr Hematol Oncol.
2006;28(3):126133.
77. VanTiel FH, Harbers MM, et al. Normal hospital and lowbacterial diet in patients with cytopenia after intensive
chemotherapy for hematological malignancy: a study of safety.
Annals of Oncology. 2007;18(6):10801084.
78. August DA, Huhmann MB. A.S.P.E.N. clinical guidelines:
nutrition support therapy during adult anticancer treatment
and in hematopoietic cell transplantation. J Parenter Enteral
Nutr. 2009;33(5):472500.
79. De Santas K, Vlachos A. Care of the hematopoietic stem
cell transplant patient after leaving the transplant center. In:
Altman, AJ. Supportive Care of Children with Cancer: Current
Therapy and Guidelines from the Childrens Oncology Group.
3rd ed. Baltimore, MD: The Johns Hopkins University Press;
2004:286333.
80. Hopman GD, Pena EG, et al. Tube feeding and bone marrow
transplantation. Med Pediatr Oncol. 2003;40(6):375379.
81. Hastings Y, White M, et al. Enteral nutrition and bone marrow
transplantation. J Pediatr Oncol Nurs. 2006;23(2): 103110.
376
82. Papadopoulou A, Nathavitharana K, et al. Diagnosis and

clinical associations of zinc depletion following bone marrow
transplantation. Arch Dis Child. 1996;74(4):328331.
83. Sefcick A, Anderton D, et al. Naso-jejunal feeding in allogeneic bone marrow transplant recipients: results of a pilot study.
Bone Marrow Transplant. 2001;28(12):11351139.
84. Weisdorf SA, Lysne J, et al. Positive effect of prophylactic total
parenteral nutrition on long-term outcome of bone marrow
transplantation. Transplantation. 1987;43(6):833838.
85. Dunn RL, Stettler N, et al. Refeeding syndrome in hospitalized pediatric patients. Nutr Clin Pract. 2003;18(4):327332.
86. Tresley J, Sheean PM.Refeeding syndrome: recognition is
the key to prevention and management. J Am Diet Assoc.
2008;108(12):21052108.
87. Stern J M. Oncology fluid and electrolyte disorders. Support
Line. 2005;27:1927.
88. Gabay C, Kushner I. Acute-phase proteins and other
systemic responses to inflammation. N Engl J Med
1999;340(6):448454.
89. Rodgers C, Wills-Alcoser P, et al. Growth patterns and
gastrointestinal symptoms in pediatric patients after
hematopoietic stem cell transplantation. Oncol Nurs Forum.
2008;35(3):443448.
90. Wasilewski-Masker K, Kaste SC, et al. Bone mineral
density deficits in survivors of childhood cancer: long-term
follow-up guidelines and review of the literature. Pediatrics.
2008;121(3):e705713.
91. Rubenstein EB, Peterson DE, et al. Clinical practice guidelines
for the prevention and treatment of cancer therapy-induced
oral and gastrointestinal mucositis. Cancer. 2004;100(9
Suppl): 20262046.
92. Classen DC, Burke JP, et al. Streptococcus mitis sepsis in
bone marrow transplant patients receiving oral antimicrobial
prophylaxis. Am J Med. 1990;89(4):441446.
93. Filipovich AH, Weisdorf D, et al. National Institutes of
Health consensus development project on criteria for clinical
trials in chronic graft-versus-host disease: I. Diagnosis and
staging working group report. Biol Blood Marrow Transplant.
2005;11(12):945956.
94. Griffith LM, Pavletic SZ, et al. Chronic graft-versus-host
diseaseimplementation of the National Institutes of Health
Consensus Criteria for Clinical Trials. Biol Blood Marrow
Transplant. 2008;14(4):379384.
95. MacMillan ML, Weisdorf DJ, et al. Response of 443 patients
to steroids as primary therapy for acute graft-versus-host
disease: comparison of grading systems. Biol Blood Marrow
Transplant. 2002;8(7):387394.
96. Koc S, Leisenring W, et al. Therapy for chronic graftversus-host disease: a randomized trial comparing
cyclosporine plus prednisone versus prednisone alone.
Blood. 2002;100(1):4851.
97. Martin PJ, Schoch G, et al. A retrospective analysis of therapy
for acute graft-versus-host disease: initial treatment. Blood.
1990;76(8):14641472.
98. Ferrara JL, Levine JE, et al. Graft-versus-host disease. Lancet
2009;373(9674):15501561.
99. Przepiorka D, Weisdorf D, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant.
1995;15(6):825828.
100. Cahn JY, Klein JP, et al. Prospective evaluation of 2 acute
graft-versus-host (GVHD) grading systems: a joint Societe
Francaise de Greffe de Moelle et Therapie Cellulaire (SFGMTC), Dana Farber Cancer Institute (DFCI), and International
Bone Marrow Transplant Registry (IBMTR) prospective
study. Blood. 2005;106(4):14951500.
101. Petersdorf EW, Longton GM, et al. The significance of
HLA-DRB1 matching on clinical outcome after HLA-A, B,
DR identical unrelated donor marrow transplantation. Blood.
1995;86(4):16061613.
102. Barker JN, Wagner JE. Umbilical-cord blood transplantation for the treatment of cancer. Nat Rev Cancer.
2003;3(7):526532.
103. Zecca M, Prete A, et al. Chronic graft-versus-host disease
in children: incidence, risk factors, and impact on outcome.
Blood. 2002;100(4):11921200.
104. Atkinson K. Chronic graft-versus-host disease. Bone Marrow
Transplant. 1990;5(2):6982.
105. Akpek G, Valladares JL, et al. Pancreatic insufficiency in
patients with chronic graft-versus-host disease. Bone Marrow
Transplant. 2001;27(2):163166.
106. Barker CC, Anderson RA, et al. GI complications in
pediatric patients post-BMT. Bone Marrow Transplant.
2005;36(1):5158.
107. Chakrabarti S, Collingham KE, et al. Isolation of viruses from
stools in stem cell transplant recipients: a prospective surveillance study. Bone Marrow Transplant. 2000;25(3):277282.
108. Wingard JR. Opportunistic infections after blood and marrow
transplantation. Transpl Infect Dis. 1999;1(1):320.
109. Burgunder MR, Dickson BJ. Hematopoietic stem cell transplantation. In: Kogut VJ, Luthringer SL. Nutritional Issues
in Cancer Care. Pittsburgh, PA: Oncology Nursing Society;
2005:253263.
110. Richardson PG, Elias AD, et al. Treatment of severe venoocclusive disease with defibrotide: compassionate use results
in response without significant toxicity in a high-risk population. Blood. 1998;92(3):737744.
111. Kumar S, DeLeve L, Kamath P, Tefferi A. Hepatic venoocclusive disease (sinusoidal obstruction syndrome) after
hematopoietic stem cell transplantation. Mayo Clin Proc.
2003;78:589598.
112. Cesaro S, Pillon M, et al. A prospective survey on incidence,
risk factors and therapy of hepatic veno-occlusive disease
in children after hematopoietic stem cell transplantation.
Haematologica. 2005;90(10):13961404.
113. Song JS, Seo JJ, et al. Prophylactic low-dose heparin or prostaglandin E1 may prevent severe veno-occlusive disease of the
liver after allogeneic hematopoietic stem cell transplantation
in Korean children. J Korean Med Sci. 2006;21(5):897903.
114. National Cancer Institute. Nutrition in Cancer Care (PDQ ).
http://www.cancer.gov/cancerinfo/pdq/supportivecare/
nutrition/healthprofessional. Accessed November 1, 2008.
115. Childrens Oncology Group. Long-term Follow-up Guidelines for Survivors of Childhood, Adolescent and Young
Adult Cancers. Version 3.0. Last updated March 2008. http://
www.survivorshipguidelines.org/pdf/LTFUGuidelines.pdf.
116. Schwartz CL. Late effects of treatment in long-term survivors
of cancer. Cancer Treat Rev. 1995;21(4):355366.
117. Castellino S. GI Health - Gastrointestinal Health after Childhood Cancer. Health Link - Healthy living after treatment for
childhood cancer GI health, Version 3.0 - 10/08; 2008.
118. AICR. Nutrition and the Cancer Survivor, Special Population
Series. Washington, D.C.: American Institute for Cancer
Research; 2001.
119. Friedman D, Hudson MM, Landier W. Heart Health
Keeping Your Heart Healthy after Treatment for Childhood
Cancer. Health Link Healthy living after treatment for
childhood cancer Version 3.0 - 10/08; 2008.
120. Chicella MF, Batres LA, et al. Prokinetic drug therapy in
children: a review of current options. Ann Pharmacother.
2005;39(4):706711.
121. Kris MG, Hesketh PJ, et al. American Society of Clinical
Oncology guideline for antiemetics in oncology: update 2006.
J Clin Oncol. 2006;24(18):29322947.
122. Food and Drug Administration. U.S. Food and Drug Administration. 2009. http://www.fda.gov.
123. Food and Drug Administration. Metoclopramide boxed
warning announcement. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm.149533.htm.
124. Curry JI, Lander TD, et al. Review article: erythromycin as
a prokinetic agent in infants and children. Aliment Pharmacol
Ther. 2001;15(5):595603.
125. Cuttica CE, Chicella MF, et al. Comparison of pantoprazole,
omeprazole and ranitidine in children requiring acid suppression: a prospective pilot study. J Pediatr Pharmacol Ther.
2004;9:198201.
126. Khan S, Shalaby TM, et al. The effects of increasing doses of
ranitidine on gastric pH in children. J Pediatr Pharmacol Ther.
2004;9(4):259264.
127. Wedlake LJ, Loader G. Cancer therapy-induced mucositis:
Where are we now? Clin Nutr Highlights. 2007;3:29.
128. Whitworth J, Christensen ML. Clinical management of
infants and children with gastroesophageal reflux disease. J
Pediatr Pharmacol Ther. 2004;9(4):243253.
129. Hatlebakk JG, Katz PO, et al. Proton pump inhibitors: better
acid suppression when taken before a meal than without a
meal. Aliment Pharmacol Ther. 2000;14(10):12671272.
130. Woods DJ, McClintock AD. Omeprazole administration. Ann
Pharmacother. 1993;27(5):651.
131. Olabisi A, Chen J, et al. Evaluation of different lansoprazole
formulations for nasogastric or orogastric administration.
Hosp Pharm. 2007;42(6):537543.
132. Schwartzberg LS. Chemotherapy-induced nausea and
vomiting: which antiemetic for which therapy? Oncology
(Williston Park). 2007;21(8):946953; discussion 954, 959,
962 passim.
377
133. Geling O, Eichler HG. Should 5-hydroxytryptamine-3

receptor antagonists be administered beyond 24 hours after
chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J Clin
Oncol. 2005;23:12891294.
134. Taketomo CK, Hodding JH, et al. Pediatric Dosage Handbook.
Hudson, Ohio: Lexicomp; 2007.
135. Yavuzsen T, Davis MP, et al. Systematic review of the treatment of cancer-associated anorexia and weight loss. J Clin
Oncol. 2005;23(33):85008511.
136. Loprinzi CL, Schaid DJ, et al. Body-composition changes in
patients who gain weight while receiving megestrol acetate. J
Clin Oncol. 1993;11(1):152154.
137. Couluris M, Mayer JL, et al. The effect of cyproheptadine
hydrochloride (periactin) and megestrol acetate (megace) on
weight in children with cancer/treatment-related cachexia. J
Pediatr Hematol Oncol. 2008;30(11):791797.
138. Jatoi A, Windschitl HE, et al. Dronabinol versus megestrol
acetate versus combination therapy for cancer-associated
anorexia: a North Central Cancer Treatment Group study. J
Clin Oncol. 2002;20(2):567573.
139. Strasser F, Luftner D, et al. Comparison of
orally administered cannabis extract and delta-9tetrahydrocannabinol in treating patients with cancerrelated anorexia-cachexia syndrome: a multicenter, phase III,
randomized, double-blind, placebo-controlled clinical trial
from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol.
2006;24(21):33943400.
140. Kardinal CG, Loprinzi CL, et al. A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia.
Cancer. 1990;65(12): 26572662.
141. Keefe DM, Schubert MM, et al. Updated clinical practice
guidelines for the prevention and treatment of mucositis.
Cancer. 2007;109(5):820831.
142. Anderson PM, Ramsay NK, et al. Effect of low-dose oral
glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant. 1998;22(4):339344.
143. Cockerham MB, Weinberger BB, et al. Oral glutamine for
the prevention of oral mucositis associated with high-dose
paclitaxel and melphalan for autologous bone marrow transplantation. Ann Pharmacother. 2000;34(3):300303.
144. Oberbaum M, Yaniv I, et al. A randomized, controlled
clinical trial of the homeopathic medication TRAUMEEL
S in the treatment of chemotherapy-induced stomatitis
in children undergoing stem cell transplantation. Cancer.
2001;92(3):684690.
31
Trauma and Burns

CONTENTS
Nutrition Considerations in the
PediatricTrauma Patient . . . . . . . . . . . . . . . . . . . . . . . . . 378
General Background on Trauma in Childhood
Closed Head Injuries/Traumatic Brain Injury
Spinal Cord Trauma
Blunt Abdominal Trauma/Solid Visceral Injuries
Blunt Abdominal Trauma/Hollow Visceral Injuries
Thoracic Injuries
Summary on Pediatric Trauma
Pediatric Burns. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383

Features Specific to the Pediatric Patient
Energy Estimates in Burn Injury
Clinical Example 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384

Answer/Considerations


378
Learning Objectives
1. Understand the components of the stress response and

how these contribute to hypermetabolism in trauma
and burn patients.
2. Identify childhood conditions that place patients at
risk for trauma and child abuse as well as nutrition
impairment.
3. Understand the injury pattern seen in blunt trauma and
how it impacts the ability to use enteral nutrition.
4. Understand limitations of methods for predicting
energy needs in pediatric patients with significant burn
injury.
Nutrition Considerations in the

PediatricTrauma Patient
Trauma, burn injury, and surgery are known stressors

resulting in hormonal, metabolic, and immune derangements. The initial physiological response to these events
is well studied and is generally described in terms of the
hormonal and cytokine responses. These responses include
the centrally mediated release of adrenocorticotropic
hormone (ACTH), which stimulates cortisol release from
the adrenal glands. This augments the action of epinephrine
and norepinephrine, which are released from the adrenal
medulla via sympathetic stimulation and impact the cardiovascular response. Glucagon is responsible for mobilizing
glucose availability via glycogenolysis and gluconeogenesis.
During the initial resuscitation, tissue perfusion is reduced
and there is an overall (transient) reduction in metabolic rate.
This is promptly followed by the hypermetabolic/catabolic
phase of injury, which is mediated by the hypothalamicpituitary axis and the proinflammatory cytokines (ie, tumor
necrosis factor, interleukin-6). This phase is characterized
TRAUMA AND BURNS
by changes in glucose homeostasis, with insulin promoting

lipolysis and proteolysis to generate glucose, while relative
insulin resistance contributes to elevated serum glucose
levels during this acute phase.
Trauma and burn injury have provided good clinical
models for studying these responses because they are quantifiable injuries in terms of trauma scores and extent of burn
injury. The physiological responses in the pediatric patient
are fundamentally no different than in the adult. The focus
of nutrition management is aligned with the fundamentals
of critical care, which attempt to optimize all organ function
by optimizing perfusion and tissue oxygenation. Support of
this hypermetabolic state, with an aim to control the resultant hyperglycemia and to limit the extent of proteolysis,
becomes the focus of nutrition interventions. The specific
nutrient requirements and whether certain micronutrients
either become conditionally essential or can impact the
elaboration of pro- and anti-inflammatory cytokines and
other agents such as nitric oxide have been the subject of
intense research.
The premise of this chapter on trauma and burns is that
the nutrition support of the child in the critical care unit
follows clinical guidelines that parallel those of the child
presenting with shock and sepsis or respiratory failure.
Distinguishing this surgical scenario is that appropriate
consideration must be given to the actual physical and physiological insult. These patients generally require a much
higher consideration of pain-related issues because of the
associated tissue damage than in the non-physically injured
child. While the use of narcotic and non-narcotic medications contributes to an amelioration of metabolic demands,
it also promotes intestinal dysmotility and ileus and thereby
impacts enteral feeding tolerance. The use of agents such as
propofol, which are solubilized in a lipid solution, requires
reconsideration of the nutrient allocation by parenteral
nutrition.
Because of the nature of organ and skin injury, there are
more frequent interruptions of nutrient delivery as a consequence of surgical interventions. As a result, many patients
remain undernourished in this acute phase of injury when
reliance is placed on enteral feedings alone and frequent
periods of non-feeding are necessary for procedures under
conscious sedation and general anesthesia. In this set of
patients, the goals of energy provision are estimated to be
130% to 160% of resting energy expenditure (REE) with
an expectation to initiate this by day 3 and consistently
deliver this by 7 days postinjury. The route of administration is dependent on patient-specific factors. For instance,
the patient with extensive burn wounds is best served by
379
elimination of multiple vascular access sites and provision

of nutrients via the intact intestinal system. The patient with
blunt abdominal trauma and an extensive pancreatic injury
may not be able to tolerate gastric feedings and should be
considered for jejunal feeding if such access is possible. In
the interim, provision of energy needs should occur by the
parenteral route.
General Background on Trauma in Childhood

Trauma accounts for significant morbidity, mortality, and
long-term disability in children. The patterns of pediatric
trauma are both age and gender related. Mechanisms for
injury in children in the first 3 years of life include falls,
poisoning (including caustic ingestions), transportationrelated injuries, foreign body aspiration or ingestion, burn
injuries, assault/neglect, and submersion/drowning mechanisms. With the older child, falls and bicycle/pedestrian and
transportation-related injuries assume a greater frequency.
These primarily blunt mechanisms are accompanied later
in adolescence by an increasing number of penetrating
injuries. The specific organ injuries are broadly classified as
neurotrauma (closed head injury/traumatic brain injury and
spinal cord injury), thoracic trauma (chest wall, pulmonary,
and cardiac), abdominal-pelvic trauma (solid and hollow
visceral, genitourinary), and musculoskeletal injuries (long
bone and pelvic fractures, craniofacial injuries). An anatomical classification system allows for injury severity scoring,
which has a strong relationship with outcomes including
morbidity, mortality, and length of stay.
While most children are generally healthy prior to
their acute injury, others have underlying diagnoses such as
neuro-developmental delay, disorders on the autism spectrum, or attention deficit disorder. These conditions not only
modify their risk-taking behaviors and place them at risk for
injury but also potentially contribute factors that may result
in nutrition depletion over a shorter period of time than
expected. On the opposite end of the spectrum, children
injured as passive bystanders/occupants of a vehicle may
also present with significant issues related to overweight/
obesity.1 These issues may complicate their acute management and impact their nutrition support in the acute phase.
The sections below provide brief descriptions of the most
common forms of pediatric trauma and serve to provide a
perspective on when, in the course of injury, enteral nutrition is feasible and when there should be an anticipation of
prolonged non-enteral nutrition.
380
Closed Head Injuries/Traumatic Brain Injury

The brain has an inordinately high metabolic demand and
under normal circumstances brain metabolism and cerebral blood flow are generally tightly regulated. When there
is a traumatic brain injury there is frequently a change in
cerebral perfusion as a consequence of intracranial pressure
changes.2 Despite this, the brain remains critically dependent on the uninterrupted delivery of both oxygen and
glucose. Failure to support the brain adequately during this
period likely impacts long-term outcomes. Hypothermia
protocols in pediatric traumatic brain injury aim to reduce
the metabolic needs during periods of relative hypoperfusion. Clearly the nutrition support of such a severely injured
patient will require assurance of glucose provision, however
the concomitant use of medications such as glucocorticoids and development of diabetes insipidus (DI) place this
patient at risk for hyperglycemia. Furthermore, sodium and
water balance are affected by the syndrome of inappropriate
antidiuretic hormone secretion (SIADH) and DI, as well as
by administration of resuscitative fluids which may include
hypertonic saline. These electrolyte and fluid balance issues
may impact the ability to provide proteins, which along with
lipids remain essential during the catabolic phase. Once
neuro recovery is underway, maintenance of muscular tone
for adequate respiratory function and physical rehabilitation
is critical. The use of immune-enhancing diets containing
omega-3 fatty acids, branched-chain amino acids, and
nucleotides has been evaluated in head injury patients and
has not shown benefit over the use of standard nutritional
formulations. 3
With a transition into rehabilitation facilities, nutrition
management is still tightly regulated, because these patients
often have impaired swallowing and airway protection. Estimating caloric needs is difficult and there are many studies
documenting a difference between the calculated needs of
the predictive equations and actual needs based on nitrogen
balance studies.4,5 The concern is that overfeeding will lead
to hyperglycemia for the reasons mentioned above and an
excessive respiratory quotient (RQ ) which will impact the
patients ventilatory management.
Spinal Cord Trauma

This constellation of injuries more often affects the adolescent in the context of sports injuries, diving, and motor
vehicle crashes. Depending on the level of spinal cord
injury, the patient may become dependent on mechanical
ventilation and lose the use of all truncal and extremity
musculature. The peri-injury protection of the spinal cord
remains a topic of active research and controversy and
includes the acute use of steroids in those with incomplete

injury as well as hypothermia protocols. The nutrition
assessment of these patients becomes a very individualized
task due to variability in neuromuscular deficit and metabolic demand despite ongoing perfusion.6,7
Blunt Abdominal Trauma/Solid Visceral Injuries

Solid organ injuries are some of the most frequent injuries encountered in the pediatric patient. In contrast to
the adult population, these injuries are frequently isolated
and can be managed non-operatively. Despite their prevalence, there has been no universally accepted algorithm
for their management. While radiographic parameters
permit grading of injuries to indicate severity of injury, it
is the hemodynamic response to injury that determines
the immediate course of action. Operative intervention is
reserved for those with profound or persistent hemodynamic instability. Simple immobilization with bed rest may
be sufficient in most patients to permit intrinsic mechanisms
for hemostasis to result in formation of a stable hematoma.
Since the stomach is intricately associated with the spleen
via the short gastric vessels, it is usually decompressed or
enteral feedings are at least withheld for 24 hours to avoid
gastric distention and retching. If there has been a significant amount of blood in the abdomen, this not only creates
abdominal pain but also is responsible for a transient ileus.
The period of observation with bed rest is variable and is
generally related to the degree of injury. Hemodynamic
instability despite transfusion is the predominant factor
in determining whether non-operative management will
be successful. With hemodynamically unstable splenic
injuries, splenic salvage can be attempted operatively or
splenectomy may become necessary. Given the role of the
spleen in the immunocompetency of the child, every effort
is made to avoid splenectomy.
Hepatic injuries rarely require operative intervention. In the most severe instances an avulsion of the liver
off the retrohepatic vena cava occurs, and these injuries are
generally immediately fatal. Parenchymal injuries are best
managed non-operatively especially if Glissons capsule
is intact. The abdominal wall provides some compression
and containment, which is lost with laparotomy. When
hemodynamic instability mandates exploration, the liver
is packed with laparotomy sponges to compress the injured
tissues, arterial inflow can be reduced by occluding the
hepatic artery manually, and either injured segments can
be compressed with large sutures or resected. Control of
hemorrhage is as much a surgical as medical event in that
hypothermia and coagulopathy can rapidly obviate any
TRAUMA AND BURNS
surgical advances. In the patient who is or becomes stable,

postoperative management will assess bilirubin levels
which may become elevated for a number of reasons (shed
blood, biloma formation, biliary ascites). Intestinal bleeding
may be from hemobilia in which a fistula forms from the
vascular system into the biliary ductal system. Depending
on the degree of shock, the liver parenchyma may exhibit
some degree of hepatic dysfunction which should be taken
into account when selecting medications. With restoration of adequate perfusion, this is usually only a transient
phenomenon. These solid organ injuries are rarely associated with significant gastrointestinal dysfunction and oral
diets are resumed within several days of injury. Depending
on the severity of injury and on whether there are additional
injuries, these patients may benefit from caloric supplementation. This is because these children may not demonstrate
a normal appetite and may develop constipation due to the
lack of physical activity.
Pancreatic Trauma
The pancreas is typically injured as a consequence of a
compression force to the mid-abdomen. This may be a
bicycle handlebar or another object striking the epigastrium or it can be the consequence of a deceleration injury
associated with the use of a seatbelt. Child abuse must
always be considered when the mechanism is otherwise not
obvious. Complete fractures of the pancreas occur over the
neck of the organ where it crossed the spinal column. Initial
laboratory assessment in the trauma room has been found
to be inadequate for detection of this injury. Amylase and
lipase levels rise typically 8 hours after injury. Computed
tomography (CT) scan of the abdomen is the typical study
that raises concern, but it may not be sufficiently sensitive.
While adult trauma protocols would mandate operative
exploration, there are series in pediatric patients in which
the injury is managed non-operatively with the use of endoscopic retrograde cholangiopancreatography (ERCP) for
stenting of the ampulla and even across a major ductal injury.
These cases are controversial and the most conservative
approach may indeed be exploration with resection of the
tail of the pancreas, thereby eliminating the ongoing leak of
pancreatic enzymes. Resections at this level of the pancreas
are not expected to affect glucose homeostasis, although
there are some reports of late pancreatic exocrine insufficiency, which present with malabsorption as evidenced by
diarrheal stools.
The patient who develops a pancreatic pseudocyst as
a consequence of the trauma can be managed with laparoscopic, open, or endoscopic cyst gastrostomy. This is usually
381
delayed for 4 to 6 weeks to allow the cyst wall to mature.

This allows the cyst content of pancreatic secretions to drain
into the intestinal tract with ultimate expectation that the
ductal defect will heal and that the pseudocyst involutes.
The extent of nutrition support depends on the physiological impact of this traumatic pancreatitis. When jejunal
access can be safely established, it is reasonable to use this
route once there is evidence of return of intestinal motility.
In the most severely injured, with ongoing pancreatitis and
perhaps complications such as tissue necrosis and infection,
parenteral nutrition (PN) is likely essential in the early postinjury period.
Renal Trauma
Injuries to the kidneys are typically unilateral, and assessment must include evaluation of the ureter and bladder.
Typically, delayed phase images on CT scan will identify
urinary extravasation. In the absence of urine extravasation, renal injuries are primarily managed non-operatively.
Patients remain at bed rest until the hematuria subsides. If
urinary extravasation occurs it is classified as contained or
free. The former may permit ongoing non-operative management although placement of a ureteral stent or percutaneous
drainage would be advised in the latter. In rare cases a
primary nephrectomy is performed. Late consequences
of renal injury include the development of renovascular
hypertension. These patients generally experience a transient ileus and then are able to resume an enteral diet. There
are rarely concerns of renal insufficiency that would lead to
consideration of special diets.
Adrenal Hemorrhage
The adrenal glands have an exuberant blood supply from
multiple sources. While generally protected in the retroperitoneum, they are at risk for direct injury, but rarely as
an isolated organ. Injury is generally evident as adrenal
hemorrhage but does not necessarily portend adrenal insufficiency, even when bilateral. When isolated, these injuries
have minimal impact on the overall nutrition management
of the patient.
Blunt Abdominal Trauma/Hollow Visceral Injuries

Duodenal Injuries
Duodenal hematoma and perforation are not infrequently
encountered in pediatric trauma. They occur with blunt
force trauma to the epigastrium (ie, bicycle handlebar
injury, non-accidental trauma). While most duodenal hematomas are dealt with non-operatively, duodenal perforation
382
is a significant injury that demands prompt operative intervention to avoid morbidity and even mortality. Duodenal
hematomas become symptomatic when extraluminal blood
impacts on the luminal caliber, resulting in gastric outlet
obstruction. Passage of a transduodenal feeding tube is
almost always possible, either by radiographic guidance or
endoscopically. This allows the patient to receive enteral
nutrition despite the proximal obstruction, which may
require decompression with a concomitant nasogastric tube.
Operative intervention is rarely indicated in this injury.
Pancreatic injury may be concomitant so it is wise to check
for chemical pancreatitis before initiating feeds. Resolution
of the obstruction can occur within 10 to 14 days of injury
as evidenced by improved gastric emptying.
Duodenal perforation is a much more significant injury
which, depending on its extent, will require either primary
repair with drain placement or sometimes more complicated surgical solutions to protect the duodenal repair from
leakage (ie, pyloric exclusion with gastrojejunostomy).
Typically the pyloric channel will open 4 to 6 weeks later,
which prompts the gastrojejunostomy to close spontaneously. These patients will often require parenteral nutrition
support in the early postoperative phase until the gastrojejunal anastomosis becomes functional.
Small Intestine and Colon Injuries
Jejunoileal perforations or mesenteric injuries resulting in
devascularized segments of small intestine are frequently
associated with seatbelt injuries and other mechanisms
resulting in deceleration forces on the abdomen. These are
most commonly identified in the first 24 hours, however,
later strictures from ischemic injury without perforation
can cause late (> 4 weeks) symptoms of enteral intolerance.
Unless there is an extensive delay in diagnosis, most of these
injuries can be treated with resection and anastomosis.
When peritoneal contamination is extensive, the patients
hemodynamic status is not optimal, and the perfusion of
the involved segment is questionable, it is often prudent to
proceed with stomal diversion. These same principles apply
to colon perforation, which is rare and more commonly
encountered in penetrating mechanisms of injury. These
injuries require a brief period of non-enteral feeding, but
then permit rapid reinstitution of normal dietary habits.
Thoracic Injuries
Thoracic injuries in children may be remarkably unassociated with chest wall signs of trauma. The bony thoracic
case is sufficiently pliable in the young child to permit
complete transduction of the impact energy to the lung
parenchyma, resulting in pulmonary injury which most

often consists of contusion rather than overt tissue disruption. Similarly the pliability of the intrathoracic vessels
results in fewer great vessel injuries than seen in the adult
population. Blunt cardiac trauma is also well-compensated
for with the capacity to offset contractility compromise
with an increased heart rate response. When intrathoracic
injuries occur that require operative intervention, recovery
is supported by the generally healthy state of these organs.
Often these injuries occur in the setting of multiple traumas
and then require mechanical pulmonary support. When in
isolation, they are usually of minimal consequence to nutrition management.
Pelvis and Extremity Trauma
When long bone fractures and pelvic fractures occur in
multiply injured trauma patients these injuries contribute to
the injury severity score and consequently to the nutrition
and metabolic demands of the patient. When these bony injuries are associated with overlying open soft tissue wounds
the risk for infection is increased. Operative management
for limiting the extent of contamination and fixation of the
fracture are routine measures. Even simple immobilization,
whether of a long bone fracture or the pelvis, has metabolic
consequences to the patient. The importance of providing
adequate vitamin D and calcium is emphasized in the
current literature. The focus of the American Academy of
Pediatrics consortium on calcium was to limit the fracture
risk for young children and adolescents.8,9
In the skeletally immature pediatric patient, the
consequences of growth plate fractures, non-union of fractures, and subsequent growth impairment are critical to
address. In the absence of multiple organ injury involving
the abdomen, these patients rapidly resume enteral intake.
Targets for caloric intake should include consideration of
level of activity.
Facial trauma constitutes a specific subset of musculoskeletal trauma but has the added concerns for impacting
enteral alimentation when the mandible and maxilla are
involved.
Summary on Pediatric Trauma

While much pediatric trauma is of a minor and ambulatory
nature, those children with major single-system injuries or
multiply injured pediatric trauma patients require early and
intense evaluation for nutrition support. After restoration
of vital organ perfusion, consistent nutrition support is a
critical intervention to assure meeting the high metabolic
demands imposed by injury.10
TRAUMA AND BURNS
Pediatric Burns
Burn trauma encompasses injuries that occur as a result of

flame, thermal and chemical exposure, inhalation of smoke,
and electrical contact. These continue to inflict significant
morbidity and mortality on patients at the extremes of age.
Young children are particularly vulnerable to both accidental and non-accidental burn injuries. The management
of burns has evolved dramatically in the past 30 years with a
centralization of care for the more severely injured patients.
This has allowed for more concentrated experiences as well
as focused clinical trials. The result of these data has been
significantly improved outcomes, with decreased mortality
attributable to shock and wound sepsis. These patients,
however, require extensive and chronic support from a
multidisciplinary team to return to optimal functional
status. With a better understanding of the metabolic consequences of burn injury on both the animal research as well
as on the clinical research front, the consistent emphasis on
the importance of nutrition support has persisted as one of
the hallmarks of burn care.11
Features Specific to the Pediatric Patient

Children, as compared to adults, will have deeper burn
injuries for a given injury mechanism as a consequence of
the thinner dermal structure and architecture. In contrast
to the older patient, their thermal injury occurs as a consequence of contact with hot liquids in 70% of cases, rather
than flame burn. The percent total body surface area (TBSA)
involvement by second- and third-degree burns remains
a critical determinant of mortality. An understanding
of individualized burn resuscitation, guided by %TBSA
involvement, has led to virtual elimination of burn shock as
a cause of immediate death. With injuries involving > 20%
of TBSA there is an associated stress response which leads
to the hypermetabolic state that has been well described
with burn injury. It is less clear how TBSA impacts the
severity of the stress response invoked when greater areas
are involved,12 although TBSA > 30% to 40% results in
tenfold elevations of urinary catecholamines.13 Attempts
to modulate the severity of this response have been diverse
and have included wound management strategies, enteral
feeding strategies, and the use of pharmacologic agents.
Current therapies that employ early burn wound excision
and grafting have had a significant impact in reducing
wound infections, reducing transdermal losses of fluid and
protein, and achieving earlier healing and rehabilitation.
The improved technologies for coverage of burn wounds
with reduced frequency of painful dressing changes also
will reduce metabolic demands.14,15
383
Use of the intestinal tract for alimentation has been

promoted for burn injuries in particular. Concerns about
mucosal atrophy and impairment of the gut-associated
immune defenses as a consequence of non-use have been
key motivators. While enteral feeding may frequently
require administration via nasoenteric tubes, often oral
supplementation is well received by young children. At
times, simple nighttime supplementation to reach target
caloric goals is sufficient. Choice of formula is typically
based on calculated caloric needs with special emphasis on
protein content. Early enteral feeding has not shown the
benefit demonstrated with delayed enteral feeding and risks
using an underperfused intestinal tract, thereby subjecting
the patient to additional morbidity.16,17 The use of pharmacologic agents such as growth hormone, oxandrolone (a
testosterone analog), and insulin-like growth factor results
in decreased catabolism, but it is unclear how this ultimately
will affect clinical course and outcomes. The use of low-dose
insulin has been described as a useful intervention, which
may be a consequence of control of hyperglycemia in a state
of relative insulin resistance.18
Inhalation injury also has a greater potential for
complications in the young child as a consequence of the
decreased luminal diameter of the trachea and bronchi with
a propensity for formation of obstructive casts and secretion
plugs. Early intubation and respiratory toilet are important
especially in those with associated facial burn injury, given
the rapid and dramatic swelling associated with thirdspace extravasation of resuscitative fluids. These patients
remain at risk for prolonged respiratory support and ventilator-associated pneumonias which further impact their
hypermetabolic state.19 Recent studies document that the
highest mortality is encountered in children under 4 years
of age with TBSA > 30% and inhalation injury.20
Energy Estimates in Burn Injury

Children start off with greater metabolic and specific
nutrient demands (greater caloric demand per kilogram) as
compared to their adolescent and young adult counterparts,
a demand that is amplified by the injury. They generally
have lower energy stores, which are more rapidly depleted.
Their propensity toward fevers, despite the absence of infection, further compounds their energy demands. Despite
the ubiquitous use of the Harris Benedict equation and
other variants to estimate caloric needs for these patients,
these remain very rudimentary tools and there are data that
they do not accurately reflect actual needs as measured by
indirect calorimetry.21 Providing excess calories will not
obviate the proteolysis accompanying the hypermetabolic
384
response, but likely contributes to hyperglycemia. How

hyperglycemia specifically impacts the incidence of wound
infection in burn patients is not known; however, there is
enough suggestive evidence from other models of critical
illness to avoid blatant overnutrition. On the opposite end,
we know that undernutrition negatively impacts wound
healing and maintenance of lean body mass. Muscle catabolism, particularly involving the muscles of respiration, leads
to functional debilitation which can be measured in terms
of prolonged respiratory support; however, physical rehabilitation of the core muscles and extremities is similarly
impacted in the later stages of therapy. Despite the consistent recommendation to assess these patients with indirect
calorimetry, in general, a target of 120% to 130% of REE is
believed to be appropriate.22
The composition of the energy sources is primarily carbohydrate (up to 60% of calories) but with maximum glucose
load limited to 7 mg/kg/min to not only avoid hyperglycemia,
but also to limit lipogenesis which results in increased oxygen
consumption and carbon dioxide elaboration which raises
the RQ. Lipids should initially deliver between 12% to 15%
of total non-protein calories. This lower proportion has been
associated with improved clinical outcomes as compared to
the higher lipid-containing diets (35% calories from fat) in
a randomized clinical trial.23 The use of omega-3 containing
fatty acids is theoretically beneficial from the standpoint of
reducing the precursors for prostaglandin E2 and leukotrienes, thereby limiting further immunosuppression. The
protein needs are exacerbated in burn patients because of
the additional losses via the open wounds in addition to the
standard urine losses and the gluconeogenesis as seen in
other instances of hypermetabolism. Daily intake of 2.5 g/
kg/d and up to 4 g/kg/d may be necessary and is limited by
the patients state of hydration and renal function. Specific
immune-enhancing diets which contain high protein loads,
omega-3 fatty acids, and branched-chain amino acids and
nucleotides have not been shown to be superior to standard
high-protein diets.24,25
The preferred route of nutrition support remains
enteral feedings and these should be instituted as soon as
it is deemed safe to use the intestinal tract. In some institutions the early use of postpyloric feedings is encouraged,
and techniques have been developed to safely place these
devices at the bedside.26 Although initial studies suggested
that early feeding would be beneficial, no clear benefit
has been demonstrated in terms of decreased length of
stay, morbidity, or mortality.17 As with any other invasive
procedure, the risks and benefits must be considered when
initiating enteral feeds. There are case reports of early
aggressive enteral feeding leading to luminal obstruction

and perforation.27 PN support retains a critical role in those
patients with a prolonged ileus or persistent systemic and
visceral hypoperfusion.
Laboratory evaluation using the standard visceral
proteins is limited in the immediate/acute injury period
and may be more useful as a predictor of outcomes, rather
than as a measure of visceral protein status. The degree of
hypoalbuminemia observed in early burn injury is attributable to the losses via the burn wound. Further complicating
their interpretation is that albumin therapy is prevalent in
burn resuscitation and does not reflect intrinsic production.
Weight and other anthropometrics are also invalidated in
the early resuscitative phase given the rapid expansion of
the extravascular space. Trends in prealbumin and other
visceral proteins as well as weight changes once the acute
resuscitative phase is complete are reasonable to monitor.
Clinical Example 1
A morbidly obese 14-year-old is transported to the trauma

center after being involved in a multi-vehicle collision as
a restrained passenger. Although alert and oriented she is
dyspneic and is found to have a pneumothorax. She has a
significant air leak, suggesting a bronchial injury. She is
intubated and undergoes bronchoscopy with subsequent
thoracotomy for repair of a proximal airway injury. Her
initial abdominal exam was unremarkable but limited by
obesity. Focused Assessment with Sonography for Trauma
(FAST) exam was not possible and the urgent intervention
for her airway delayed further evaluation. She develops
abdominal tenderness which prompts CT evaluation and
subsequent laparotomy for a left hepatic duct avulsion with
ischemia to the left lobe of the liver. What are her requirements for energy support in this phase of her acute illness?
How are they best met?
The energy assessment of the overweight and morbidly
obese teenager who requires critical care support is extraordinarily difficult. In this time of metabolic stress, the goal
should not be weight management, but preservation of
protein status. Estimates for caloric intake are best derived
from assessment of metabolically active tissues and these
are more closely related to ideal body weight than actual.
Not only will this patient need to heal her traumatic injuries
but she now has two additional wounds (thoracotomy and
laparotomy) to heal. Indirect calorimetry will likely provide
the best guidance in this scenario. Given the intra-abdominal injuries one would expect a period of ileus to follow
TRAUMA AND BURNS
and thus provision of nutrients should not be delayed and

initially can occur by parenteral route.
Clinical Example 2
A 12-year-old equestrian sustained a kick to her stomach

while grooming her horse. Her initial abdominal CT shows
a hematoma over the neck of the pancreas. There is no free
fluid in the abdomen. She is nauseated and a nasogastric
tube evacuates bilious fluid. Over the next 24 hours she
continues to complain of abdominal pain and her amylase
rises to 950. Do you advise nutritional supplementation at
this point?
It is now 5 days later, an ERCP has been done, and there
is no major ductal injury. Her abdominal pain is improved
and amylase is 200. What do you expect her ability to eat
will be within the next 48 hours?
Pancreatic injuries, despite non-operative management, can
lead to significant metabolic stress as a consequence of the
inflammatory nature of the retroperitoneal injury (hematoma) which is further exacerbated by release of pancreatic
enzymes. While we can expect this patient to have been
active and healthy from a nutrition standpoint, we would
anticipate a return to GI function within perhaps 5 days.
The information related to the ERCP would suggest that
cautious introduction of enteral feeds would be acceptable
and that her response to enteral stimulation of pancreatic
secretions must be monitored. Should she develop recurrent pain and pancreatitis with oral intake, institution of
PN until such time as a jejunal feeding tube can be placed
would be appropriate.
Clinical Example 3
A 2-year-old is brought to the trauma/burn unit with 35%

TBSA injury from a hot oil burn to his face, trunk, and lower
extremities. Within 24 hours, he has developed anasarca,
but is hemodynamically stable and making urine at 1 mL/
kg/h. He is scheduled to undergo burn wound excision on
the following day. When do you consider starting nutrition
support? How do you best determine his caloric needs?
How do you initiate caloric intake?
This child has sustained a significant injury and is expected
to exhibit a stress response leading to catabolism. Nutrition
support will become essential to re-establishing a positive
nitrogen balance. Given the extent of injury this child will
likely have central venous access and provision of glucose
385
and protein can be started early via this route. At the time of
operation it would be ideal to have a nasoenteral tube placed
for subsequent enteral feeding access. Energy requirements
are notoriously difficult to predict and indirect calorimetry
remains the most accurate tool.
1. Blunt abdominal trauma with injury to the liver:

A. Requires prolonged support on parenteral
nutrition
B. Requires specialized formulas to account for hepatic
insufficiency
C. Rarely requires operative intervention
D. Is rare in the pediatric patient
2. Pancreatic trauma may result in all except:
A. Chemical pancreatitis
B. Prolonged intestinal ileus
C. Clinical features of pancreatic insufficiency
D. Diabetes mellitus
3. Closed head injury patients unequivocally benefit from
provision of immuno-nutrients.
A. True
B. False
4. Total burn surface area (TBSA) is most predictive of:
A. Mortality
B. Metabolic stress
C. Energy needs
D. None of the above
References
1. Rana AR, Michalsky MP, Teich S, Groner JI, Caniano

DA, Schuster DP. Childhood obesity: A risk factor for
injuries observed at a level-1 trauma center. J Pediatr Surg.
2009;44(8):16011605.
2. Philip S, Udomphorn Y, Kirkham F, Vavilala M. Cerebrovascular pathophysiology in pediatric traumatic brain injury. J
Trauma. 2009;67(2 Suppl):S128.
3. Briassoulis G, Filippou O, Kanariou M, Papassotiriou I,
Hatzis T. Temporal nutritional and inflammatory changes in
children with severe head injury fed a regular or an immuneenhancing diet: a randomized, controlled trial. Pediatr Crit
Care Med. 2006;7(1):56.
4. Havalad S, Quaid M, Sapiega V. Energy expenditure in children with severe head injury: Lack of agreement between
measured and estimated energy expenditure. Nutr Clin Pract.
2006;21(2):175.
5. Joffe A, Anton N, Lequier L, et al. Nutritional support
for critically ill children. Cochrane Database Syst Rev.
2009(2):CD005144.
386
6. Patt P, Agena S, Vogel L, Foley S, Anderson C. Estimation of

resting energy expenditure in children with spinal cord injuries. J Spinal Cord Med. 2007;30(Suppl 1):S83.
7. Brown RL, Brunn MA, Garcia VF. Cervical spine
injuries in children: a review of 103 patients treated consecutively at a level 1 pediatric trauma center. J Pediatr Surg.
2001;36(8):1107.
8. Baker SS, Cochran WJ, Flores CA, et al. American Academy
of Pediatrics. Committee on Nutrition. Calcium requirements of infants, children, and adolescents. Pediatrics.
1999;104(5):1152.
9. Goulding A. Risk factors for fractures in normally active children and adolescents. Med Sport Sci. 2007;51:102.
10. Hasenboehler E, Williams A, Leinhase I, et al. Metabolic
changes after polytrauma: an imperative for early nutritional
support. World J Emerg Surg. 2006;1:29.
11. Purdue G. American Burn Association presidential address
2006 on nutrition: yesterday, today, and tomorrow. J Burn
Care Res. 2007;28(1):1.
12. Atiyeh B, Gunn SWA, Dibo S. Metabolic implications of severe
burn injuries and their management: a systematic review of
the literature. World J Surg. 2008;32(8):1857.
13. Chan M, Chan G. Nutritional therapy for burns in children
and adults. Nutrition. 2009;25(3):261.
14. Saba S, Tsai R, Glat P. Clinical evaluation comparing the
efficacy of aquacel ag hydrofiber dressing versus petrolatum
gauze with antibiotic ointment in partial-thickness burns in a
pediatric burn center. J Burn Care Res. 2009;30(3):380.
15. Saffle JR. Closure of the excised burn wound: temporary skin
substitutes. Clin Plast Surg. 2009;10;36(4):627641.
16. Venter M, Rode H, Sive A, Visser M. Enteral resuscitation and
early enteral feeding in children with major burnseffect on
McFarlane response to stress. Burns. 2007 6;33(4):464471.
17. Peck M, Kessler M, Cairns B, Chang Y, Ivanova A, Schooler
W. Early enteral nutrition does not decrease hypermetabolism
associated with burn injury. J Trauma. 2004;57(6):1143.
18. Schulman C, Ivascu F. Nutritional and metabolic consequences in the pediatric burn patient. J Craniofac Surg.
2008;19(4):891.
19. Palmieri T, Warner P, Mlcak R, et al. Inhalation injury in children: a 10 year experience at Shriners Hospitals for children. J
Burn Care Res. 2009;30(1):206.
20. Sheridan RL, Schnitzer JJ. Management of the high-risk pediatric burn patient. J Pediatr Surg. 2001 8;36(8):13081312.
21. Suman OE, Mlcak RP, Chinkes DL, Herndon DN. Resting
energy expenditure in severely burned children: analysis
of agreement between indirect calorimetry and prediction
equations using the Bland-Altman method. Burns. 2006
5;32(3):335342.
22. Chan MM, Chan GM. Nutritional therapy for burns in children and adults. Nutrition. 2009 3;25(3):261269.
23. Garrel DR, Razi M, Larivire F, et al. Improved clinical status
and length of care with low-fat nutrition support in burn
patients. J Parenter Enteral Nutr. 1995;19(6):482.
24. Saffle JR, Wiebke G, Jennings K, Morris SE, Barton RG.
Randomized trial of immune-enhancing enteral nutrition in
burn patients. J Trauma. 1997;42(5):793800.
25. Marin V, Rodriguez-Osiac L, Schlessinger L, Villegas J, Lopez
M, Castillo-Duran C. Controlled study of enteral arginine
supplementation in burned children: impact on immunologic
and metabolic status. Nutrition. 2006;22(7-8):705.
26. Cone L, Gilligan M, Kagan R, Mayes T, Gottschlich M.
Enhancing patient safety: the effect of process improvement
on bedside fluoroscopy time related to nasoduodenal feeding
tube placement in pediatric burn patients. J Burn Care Res.
2009;30(4):606.
27. Scaife CL, Saffle JR, Morris SE. Intestinal obstruction
secondary to enteral feedings in burn trauma patients. J
Trauma. 1999;47(5):859.
32
Surgery
CONTENTS
General Nutrition Considerations in
Pediatric Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
General Nutrition Considerations in Neonatal Surgery
Surgical Considerations in Infants with

Congenital Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
Proximal Intestinal Obstruction
Distal Intestinal Obstruction
Abdominal Wall and Diaphragm
Hepatobiliary Disorders
Other (Non-GI) Malformations . . . . . . . . . . . . . . . . . . . . . 400

Nutrition Support in Infants with
Acute GI-Related Disorders. . . . . . . . . . . . . . . . . . . . . . . . 401
Necrotizing Enterocolitis
Isolated Intestinal Perforation
Intestinal Malrotation and Midgut Volvulus
Pyloric Stenosis
Nutrition Support in Children and

Adolescents Requiring Operation. . . . . . . . . . . . . . . . . . . 403
General Principles
Feeding Access in Pediatrics
Insertion of Gastrostomy
Learning Objectives
1. Identify factors that impact the nutrition requirements

associated with the acute metabolic changes in the
pediatric and neonatal surgical patient.
2. Identify methods for optimizing nutrition support
along the entire perioperative period by utilizing
clinical assessment, laboratory analysis, and bedside
calorimetry.
3. Provide a basis for determining when to initiate and
progress enteral feeding in a core group of neonatal
surgical conditions.
4. Delineate the strategies to limit the progression of
cholestatic jaundice in the postoperative infant with
intestinal dysfunction.
General Nutrition Considerations in

Pediatric Surgery
The metabolic consequences of surgical stress have been

extensively studied and show a characteristic/stereotypic
response in terms of hormone and cytokine elaboration. The
resultant hypermetabolic state during the phase of injury
and recovery has been the focus of nutrition support. In
pediatrics, the challenge is not only to provide those nutrients to support the immediate metabolic needs but also to
avert catabolism of limited stores of protein and fat, while
providing substrate for growth and development.
In the surgical patient, wound failure, infection, and
mortality are primary outcome measures that have been
related to the perioperative nutrition condition. The discipline of surgical nutrition arose at a time when nutrition
support was often unavailable to those in the immediate
postoperative period because of a lack of enteral tolerance.
The institution of parenteral nutrition (PN) changed the face
387
388
of postoperative care for this subset of patients. Malnutrition

and consequent complications were the cause of demise for
many neonatal patients with disorders which nowadays one
is hard-pressed to consider lethal. As the ability to provide
PN support has improved, an awareness of its potential for
adverse effects has become apparent, specifically the unique
problem of cholestasis in the pediatric population.
With further advances in the science of intestinal physiology, our appreciation for the complexity of the intestinal
tract in terms of its role in water, electrolyte, and nutrient
assimilation as well as immune sampling functions became
evident. Provision of appropriate nutrition held the promise
of enhanced immune function, fewer complications related
to catabolism, and overall improved outcomes. Studies on
immunomodulatory agents provided either parenterally or
enterally in clinical sepsis have been conducted on adults and
pediatrics alike. In the pediatric literature the focus came
to rest on the components of breast milk, which appeared
beneficial in averting gut-derived sepsis.1 The limitations
of clinical research in pediatrics are evident when it comes
to studies requiring repeated blood sampling and invasive
procedures; however, there is reason to believe that the findings from adult clinical trials can be applied to the pediatric
patient. There is a wealth of knowledge from observational
studies in pediatrics about the growth needs for all age
groups and many congenital/heritable conditions, but these
studies are generally careful to exclude the more complex
surgical patient. The best quantitative neonatal and pediatric data related to the effects of the metabolic response to
stress are derived from studies of a relatively homogenous
group of infants who undergo cardiopulmonary bypass for
repair of congenital cardiac disease or who require extracorporeal membrane oxygenation (ECMO) for pulmonary
support.2,3 These infants, however, cannot represent the
entire spectrum of pediatric surgical conditions and much
work remains to be done.
Nutrition assessment and support of the pediatric
surgical patient requires consideration of the acute impact
of surgical intervention as well as the more chronic consequences of operation. Potential postoperative complications,
as well as the underlying congenital disorder, may further
contribute to persistent impairment of intestinal function.
Associated conditions, such as cholestatic jaundice, which
may be related to the primary problem or occur as a consequence of sepsis or prolonged total parenteral nutrition
exposure, further compromise the recovery of the patient.4
The first section of this chapter will focus on perioperative nutrition support and the general concept of
adjustments in the nutrition considerations of the neonatal
and pediatric patient in response to altered metabolic

demands as a consequence of operation. Patients who experience similar stresses as a consequence of trauma or burn
injury are discussed elsewhere (Chapter 31). The second
section focuses on nutrition support strategies specific to
the various congenital, typically anatomic, gastrointestinal (GI) disorders encountered in the neonatal pediatric
surgery patient.
Surgical care of the newborn infant and extending to
the skeletally mature adolescent requires a fundamental
knowledge of the physiological changes that occur with
growth and maturation. Based on the underlying condition,
these patients will have variable impairments of GI function
that may be related to intestinal motility, surface absorptive
capacity, and immune function. The perioperative state is
a dynamic phenomenon and as the patients clinical status
evolves, constant reassessment and redirection of nutrition care must occur. Because these patients also represent
a spectrum of acute and chronic disease and/or disability,
one uniform set of standards for nutrition care can be difficult to generate.
The principles upon which guidelines are established
should focus on and correspond to the general American
Society for Parenteral and Enteral Nutrition guidelines for
nutrition assessment in pediatrics. These include:
1. Individualized assessment of nutrition status to determine urgency and extent of patient support needs.
2. Consideration of the timing of onset of postoperative nutrition support and the appropriate use of total
parenteral nutrition when the alimentary tract is
compromised, with consideration for provision of
either enteral or parenteral nutrition support within 3
days of hospitalization.
3. Provision of nutrition in a manner (enteral or parenteral) most consistent with safe clinical practice.
4. Avoidance of potential complications by continuous
reassessment of individual risk/benefit ratios including
determining optimal timing for alimentary tract
challenge.
5. Employing methods for determining the adequacy of
nutrition support.
General Nutrition Considerations in Neonatal Surgery

Neonatal Assessment, Nutrient Composition, and Targets for
Nutrition Support in the Early Postoperative Period
Infants with congenital disorders of the abdomen and
especially the intestinal tract have fluid and nutrition
requirements that require frequent reassessment in the
SURGERY
immediate perioperative period. The excess fluid demands

to restore or maintain vital organ perfusion in the perioperative period are not necessarily accompanied by a greater
demand for caloric provision. 57 It is important to consider
these requirements separately and avoid the potential for
overfeeding and hyperglycemia. There are many factors
in the postoperative patient that impact the energy estimates; these include the use of mechanical ventilation,
the provision of external heat support, the use of sedating
agents, and neuromuscular blockers. Pain control has a
tremendous impact on the perioperative hormonal stress
response. Preemptive analgesia, local block, and caudal
blocks all contribute to reducing the stress response and
are part of current surgical practice. For instance, in infants
undergoing patent ductus arteriosus (PDA) ligation it
was demonstrated that a fentanyl anesthetic resulted in
improved protein metabolism. 8,9
While the assessment of volume status can be quantified using weight, fluid balance records, and occasionally
invasive monitoring with central venous pressures, this
process is not as straightforward when assessing metabolic
demands. Unless nitrogen balance studies are readily accessible, the best estimates for caloric provision are made on
the basis of the infants gestational age and formulas for the
resting energy expenditure (REE) of the infant in the acute
phases as well as in the recovery phase, which is best modified with estimated stress factors.
Unfortunately the impact of nutrition interventions is
measured in intervals approaching weeks rather than days
and is generally based on the infants ability to demonstrate
anticipated rates of growth and other anthropometric
measures. Ideally, one would be able to assess parameters
consistently, such as the infants glucose homeostasis, and
verify adequate glycogen stores and a positive nitrogen
balance along with the anticipated weight gain. However,
these are impractical goals in the immediate postoperative
period; therefore one must focus on maintaining euglycemia and avoiding hyperlipidemia and azotemia/uremia,
while providing an escalating amount of balanced macronutrients in the form of carbohydrate, lipid, and protein.
Laboratory parameters are used to assess nutrition
status; however, these must be used as trends rather than
as absolute measures in the infant, for whom there are often
no gestationally appropriate controls.10 In the acute hypermetabolic phase there is whole-body proteolysis to provide
not only substrate for gluconeogenesis but also for protein
synthesis of necessary enzymes and other acute phase reactants. Principal laboratory markers include total protein,
albumin, prealbumin (evaluated in the context of a normal
389
C-reactive protein (CRP)), and retinol-binding protein.

These function as the measures of protein anabolism after
the acute phase of injury and are difficult to interpret earlier.
Whereas one strives for meeting the metabolic needs and
accomplishing weight gain and growth in the healthier
infant, the short-term goals in the postoperative patient
are targeted to provide for sufficient substrate to prevent
catabolism and allow for anabolism in the context of wound
healing. Often, non-protein in an amount of 60 to 80 kcal/
kg/d, perhaps even less, will be sufficient to meet these
initial goals in the neonate.11
It has been documented that preterm neonates often
require a generous protein supply, perhaps as high as 4 g/
kg/d, which primarily serves to provide substrate for tissue
repair and does not independently prevent catabolism of
the existing muscle mass. By counting this protein delivery
as energy-yielding caloric intake, this may result in inadequate caloric provision. This is the basis for calculating and
targeting non-protein calories in the acute perioperative
setting. In order to provide an optimal substrate for nutrient
assimilation, a non-protein calorie-to-nitrogen ratio of
130:1 to 210:1 is generally recommended as the target total
parenteral nutrition solution. Whereas the calculation of
caloric targets in terms of non-protein calories may be
important in the early perioperative phase, this should again
convert to total caloric intake once the acute wound-healing
demands return toward baseline. The time for this transition is perhaps best estimated by normalization of the CRP
and should correspond to clinical indicators such as wound
status, return of intestinal function, and lack of infectious
complications.
Cholestasis: PN-Associated and of Other Origins
In contrast to the adult experience with overfeeding
resulting in steatosis, cholestasis is a significant problem
in pediatric surgical patients, who frequently require
prolonged PN support and are at further risk for hepatic
injury by virtue of their non-enteral feeding status and
susceptibility to sepsis. The generally accepted measure
of significant cholestasis is the direct bilirubin exceeding
2mg/dL.
For those patients anticipated to have a prolonged
dependence on total parenteral nutrition ( > 1 month) this
authors institution initiates cycling of PN when the clinical condition permits, usually after the first month of life
(term gestation infant) when it is predicted that glycogen
stores are adequate and the infant perhaps is receiving
some enteral feedings. Cycling off glucose infusion requires
that the patient can maintain euglycemia to prevent the
390
development of hypoglycemia. Seizures as a consequence of

hypoglycemia carry the most profound risk for neurological
devastation. The procedure for cycling involves reducing the
rate of total parenteral nutrition infusion to 50% for 1 hour
prior to discontinuing infusion and reinitiating the next bag
of PN at a 50% rate for 1 hour before achieving the goal rate
(see Figure 32-1) The targets for cycling on neonates are 4
to 6 hours off infusion; however, this must include consideration of glucose infusion rates, which may be significantly
higher with consolidation of total parenteral nutrition. The
authors institution provides lipid infusions as 24-hour infusions, which helps maintain patency of the catheters without
the need for additional fluid infusions when heparin locking
might not be desirable because of multiple entries into the
catheter hub. Both components are cycled when the patient
is discharged to home on total parenteral nutrition and the
catheter can be heparin locked for an extended period.
Other considerations to limit PN-associated cholestasis
for those infants on complete parenteral nutrition involve
maintaining relative ratios between macronutrients.
Examples of this include targeting a non-protein calorieto-nitrogen ratio of approximately 180:1, and the provision
of lipid calories not exceeding 30% of total non-protein
calories. The role of lipids with a more anti-inflammatory
profile (eg, omega-3 fatty acids) is not yet clear and, in the
absence of a diverse assortment of lipid sources, it may be
wise to use Intralipid (a soy-based and omega-6 fatty acid
based solution) judiciously.12,13 Limitation of lipid calories
may, however, necessitate pushing the glucose infusion rate
(GIR) as high as 15 mg/kg/min to achieve caloric goals.
Clearly the initiation of enteral feeds is one of the most
critical steps14 in this process, and cycling nonabsorbable
enteral antibiotics may additionally be instituted to limit
the potential for bacterial overgrowth and enteral-derived
sepsis which would further compound the cholestatic injury
to the liver. The use of ursodeoxycholic acid is beneficial
when the terminal ileum is in continuity or proximal to a
stoma.
As the infant enters the phase of recovery, absent any
infectious or wound-healing complications, the focus
changes toward the more typical pediatric goals of nutrition
support covering the acute needs as well as those demanded
for growth and development. Here the documentation
of weight gain, resolution of the acute phase reactants
(eg,CRP), and establishment of a trend of increasing prealbumin values become the primary outcome measures for
the efficacy of nutrition support. As mentioned above, the
focus on providing protein purely for wound-related anabolism is reduced at this point.
Initiation and Choice of Enteral Alimentation

Enteral nutrition is incrementally introduced when there
is evidence of GI tract motility and assurance that anastomoses, if performed, have achieved satisfactory healing.
General principles in managing postoperative patients
include a conceptual understanding of normal postoperative events including paralytic ileus, delayed gastric
emptying, the effect of narcotic analgesics, and the perianastomotic edema that may impede transit during the
first 48 hours postoperation. General guidelines for determining the ability to initiate feeding include an assessment
of (1) gastric output both in terms of quality (bilious vs.
gastric or even salivary content) and volume; (2) physical
examination for evaluation of abdominal distention and
the presence of bowel sounds; and (3) assessment of output
whether by stoma or per rectum, remembering that motility
recovers first in the distal intestine and therefore that occasional stool output is not an assurance of actual GI transit.
The recognition of potential intestinal complications such
as anastomotic leak, intraabdominal sepsis, wound failure
at the level of the abdominal wall closure, and even stomarelated problems (eg, stomal stenosis or prolapse) is critical
to those managing these patients.
The timing of initiation of feeds therefore depends on
an assessment of the risks and benefits of providing enteral
nutrients. Choice and mode of feeding are often predicated
by the infants gestational maturity, the history of mucosal
injury/disruption, effectiveness of motility, urgency to transition off PN, and the presence of gastroesophageal reflux
(GER). In general, breast milk should remain the first choice
for all of its innate qualities in optimizing gut mucosal function and immunity. Although donor breast milk will lack
some of the immune benefits, it remains a desirable nutrient
source. When commercial formulas are necessary, infants
who have no history of a compromised intestinal wall
(mucosal damage, transmural edema/fibrosis) can be started
on standard hydrolyzed whey-based formulas for gestational age, whereas those infants who have a positive history
should be started on a more elemental substrate to optimize
absorption in the presence of a compromised mucosal
barrier. Casein hydrolysates (Pregestimil, Alimentum)
are common choices for the surgical infant and the specific
formula is often based on the fat composition and osmotic
load. However, these specialized formulas only provide a
fraction of the calcium and phosphorus needs for a preterm
infant, and this must be taken into consideration with supplementation, when possible. More elemental, extensively
hydrolyzed formulas (Neocate, EleCare), which consist
of amino acids and peptides and were designed to obviate
SURGERY
391
Figure 32-1
392
protein allergies, may in some instances be better tolerated

in those with compromised motility as well. Theoretically
they reduce the luminal content of nutrients reaching the
distal intestine and perhaps limit bacterial overgrowth and
carbohydrate fermentation, which result in excess reducing
substances being excreted along with luminal fluids in the
form of diarrhea or frequent loose stools. As the patients
intestinal tract recovers, transition to a more complex and
age-appropriate formula can be accomplished in a gradual
manner. In contrast, infants with congenital disorders
that do not affect the intestine itself, such as infants with
omphalocele, congenital diaphragmatic hernia, malrotation
without volvulus, pyloric stenosis, and thoracic conditions,
should be able to tolerate standard formulas.
Guidelines for caloric estimates in critically ill surgical
infants requiring respiratory support are difficult to establish, but are best assessed using a metabolic cart.6 Whereas
the acutely, short-term ventilated patient probably does not
require a major revision in energy provision, this is countered
by those infants who are chemically relaxed and actively
ventilated and not participating in their work of breathing.
Most of the recent publications have focused on the subset
of neonatal cardiac surgery patients2,3 who can be analyzed
as a reasonably cohesive group. In between this spectrum
are the infants with congenital diaphragmatic hernia who,
while intubated, are variably assisted in ventilation and
require attention to avoid an inappropriate respiratory
quotient (RQ ) which might adversely impact their ability
to eliminate CO2 . Clearly, each of these patients is unique
and generic formulas cannot be applied. These issues are
more extensively discussed in chapters on critical care and
specific consideration must additionally be placed given the
surgical patients underlying condition.
The goal is to have a patient who is in optimal nutrition
shape. To the surgeon this is a multifactorial evaluation,
which hopefully indicates that the infant has an appropriate weight gain of 1% to 2% of body weight per day and is
demonstrating appropriate somatic growth in length, head
circumference, and triceps skinfold measurement. Furthermore, based on laboratory parameters, the child will either
have achieved a serum albumin within normal limits or at
least show a trend of progressively escalating prealbumin
values. A multifactorial assessment is particularly important when contemplating a secondary surgical intervention,
such as a stoma closure. To achieve these goals one can
ideally provide a balanced enteral and parenteral regimen.
Sufficient enteral nutrition (EN) (trophic or greater) should
be provided to stimulate the mucosa and maintain its health,
promote motility, and avoid recurrent luminal obstruction.
The limits of tolerance are probably best defined by evaluating the volume and nature of the output. Because stool
output is not measured in terms of frequency of stools with
a stoma, the guideline to be used is that output should not
exceed one-third of total enteral intake. Other formulas
include the assessment of normal stoma output on the basis
of weight, with expected output estimated at 1 mL/kg/h
and tolerable amount to allow progression of enteral feeds
set at either 30 mL/kg/d or 2 mL/kg/h.15 Excess outputs
serve as indicators of inadequate absorptive capacity and
osmotic fluid losses and should be further evaluated with
the content of reducing substances and stool pH. Reducing
substances will shed light on carbohydrate malabsorption
with contents of 1% or greater in the presence of loose stools
constituting an indication for intervention, depending on
the type of enteral intake. Stool pH will reflect whether
there are organic acids generated by unabsorbed sugars, and
this can happen independent of the presence of reducing
substances.
Ideally a target caloric goal is established for each patient
and EN is pushed to the limit of tolerance with PN providing
the balance of calories necessary to achieve weight gain and
laboratory goals. While consistently pushing the limits
of the intestinal tract, it is important not to have frequent
setbacks which ultimately delay operation to restore continuity and thereby compromise the best case scenario for
complete adaptation. The use of distal refeeding provides
a valuable adjunct in these situations, at least contributing
to restoring a complete enterohepatic pathway for bile if the
distal ileum has been retained.16 The benefits are, however,
counterbalanced by the often arduous contraptions that
have to be created to collect and reinfuse the stoma output
and the risk of perforating the distal intestine with repeated
catheterization. The decisions involved in these complicated
cases require that all care providers reach consensus on the
short- and long-term plans for the patient. Only then can the
ideal nutrition support plan be instituted.
All surgical patients must be monitored carefully for
the onset of jaundice. Often the default reason for the onset
of direct hyperbilirubinemia is the use of PN; however,
surgical patients can develop intestinal obstruction whether
it be at the level of an anastomosis, at the level of a proximal
stoma, or at a random site due to peritoneal adhesions. These
conditions must remain in the foreground as correctable
causes of obstructive jaundice. Others conditions include
drug-related cholestasis (seen with cephalosporins), lowgrade sepsis, and even secondary disorders such as biliary
tract disease (gallstones and sludge) or pyloric stenosis.
SURGERY
Surgical Considerations in Infants with

Congenital Disorders
Proximal Intestinal Obstruction
A congenital proximal intestinal obstruction is usually
recognized antenatally or immediately postnatally and typically prompts urgent operative intervention. While these
conditions can be temporized with effective nasogastric
suction, delay of operation is reserved for those infants with
suspected congenital heart disease who will require further
evaluation (ie, patients with esophageal atresia and duodenal
atresia) or would benefit from a stabilization of their transitional circulation changes before undergoing anesthesia and
operative stress. Although unusual, the concern for the presence of an underlying non-survivable metabolic disorder or
lethal chromosomal disorder constitutes a second justification for delaying surgical intervention.
Esophageal Atresia
The most complex decision making involves infants who
have esophageal atresia, and are significantly preterm
and/or low birth weight. Operation may safely be delayed
1 to 2 days while postnatal circulation stabilizes and the
child undergoes screening evaluations for disorders in
the VACTERL association (vertebral, anorectal, cardiac,
tracheo-esophageal, renal, and limb). During this time
most neonates will be started on at least peripheral total
parenteral nutrition with a plan to escalate to central total
parenteral nutrition once appropriate venous access has
been established, either via a temporary umbilical venous
catheter, peripherally inserted central catheter (PICC) line,
or surgically placed central venous line inserted at the time
of operative repair. The expectation is that the infant will
not be able to utilize the intestinal tract until approximately
7 days postoperatively when the esophageal anastomosis is
evaluated for patency and absence of leak.
Many surgeons will not place a trans-anastomotic
feeding tube at the time of operation, because gastric feedings will likely be associated with a significant incidence of
GER (on the basis of probable anatomic distortion of the
angle of His) and this should be avoided until the esophageal
anastomosis is shown to be without leak. The association of
trans-anastomotic tubes with anastomotic complications
remains speculative, but unsubstantiated in the literature.17
When there is a leak, the period of non-enteral alimentation may extend for another 5 to 7 days, since there is no
safe esophageal access to the stomach or beyond. The use
of gastrostomy tubes generally has been limited to those
infants with long-gap atresia who will undergo esophageal
393
reconstruction/repair at a later date, or to those infants who

are expected to have poor oral-motor skills or other feeding
dysfunction based on concomitant disorders (trisomy,
retrognathia, etc). Given the reliance on total parenteral
nutrition for a period of 7 days or more, most neonatal
centers will either place central venous access preoperatively (PICC line) or surgically place access at the time of
reconstruction. Because these considerations for alimentation are not based on technique, there is no difference in the
postoperative management in thoracoscopic or open repair
of esophageal atresia.
After the esophageal anastomosis is verified to be free
of leak with a contrast esophagram, the contrast is followed
through the duodenum primarily to establish the absence
of malrotation. Duodenal stenosis due to annular pancreas
and an even duodenal atresia can co-exist with esophageal atresia. This will not be apparent at operation because
the abdominal cavity is not entered. Enteral feeds can be
commenced, preferably by mouth, to avoid repeated instrumentation of the esophagus. It must be kept in mind that
there will be esophageal dysmotility based on the lack of a
progressive peristaltic wave down the esophagus and based
on the perhaps more capacious proximal pouch that empties
as much by gravity as by propulsive esophageal wall activity.
Delayed emptying through the anastomosis will result in
prompt oral regurgitation but also will result in tracheal
compression which becomes evident as desaturation with
feeds. These events are expected even in the absence of a
stricture, and are only further accentuated by any luminal
compromise. Infants must be maintained with the head of
the bed elevated and should be fed as upright as possible.
The goal of oral feeding should be to allow the infant to
practice frequently with low-volume amounts (510 mL
every 3 hours). Once these are tolerated, the progression of
feeds should be gradual, but should remain on a frequent
basis (every 3 hours) as the next barrier to reaching full
feeds will be GER. When breastfeeding is initiated it should
similarly be limited in time, and this interval for feeding is
progressed as the infant tolerates. Although it is difficult
to measure intake, reports of weighing the infant pre- and
postfeed suggest that this may be a method to quantitate
intake.
The stomach capacity will increase with time; however,
any acid reflux is detrimental to the anastomosis and
can result in stricture formation. These infants therefore
should be placed on acid reduction therapy immediately
postoperatively, and this therapy is usually maintained
for 6 to 12 months. The addition of metoclopramide may
be helpful when feeds are first initiated, so as to promote
394
gastric emptying. Optimally the infant will progress to

full feeds over a period of 5 to 7 days, although it is not
unusual for those infants who are more symptomatic with
tracheomalacia to take longer. These infants may require
repeated intubation for mechanical ventilatory support
or they may require support with high-flow nasal cannula
oxygen which compromises their ability to tolerate gastric
feeds. In these instances it may be advisable to place a transpyloric feeding tube to enable the infant to take EN and be
weaned off PN, while his or her airway disability is being
addressed. In severe cases, this may constitute an indication
for placement of a gastrostomy tube. The current reluctance
to place a gastrostomy is that the physical distortion of the
stomach as a result of a gastrostomy may further negatively
impact GER, which in turn may adversely affect healing
of the anastomosis. Surgical therapy of GER, while necessary in a subset of infants, is avoided due to (1) the inherent
dysmotility of the esophagus which may not be able to
overcome any level of obstruction distally and (2) anatomically by the shortened length of the esophagus. While these
concerns can be taken into account surgically with a less
tight fundoplication and esophageal lengthening procedures such as the Collis gastroplasty, these are best avoided,
unless a recalcitrant esophageal stricture forms.18
During infancy, the choice of infant formula should be
based on gestational age. There are no specific intestinal
absorptive defects to prompt the use of more elemental
formulas. Caloric concentration of infant formulas is often
necessary and advisable to accomplish achieving nutrition goals, given the propensity for reflux. Long-term
nutrition problems in esophageal atresia relate to ongoing
problems with GER and proximal strictures. Surveillance
esophagrams are sometimes indicated and mechanical or
hydrostatic fluoroscopic dilatation is usually effective in
treating strictures. With progression to solid foods, these
children must be coached to chew well and to consume
liquids with their meals to overcome any potential residual
esophageal dysmotility. It is not unusual for overly large
pieces of food to become lodged at the level of anastomosis
and result in esophageal obstruction. This problem tends
to resolve with age, the increasing caliber of the esophagus,
and maturity of the child.
Duodenal Atresia
Infants with duodenal atresia are most often identified
antenatally and parents can be advised about their anticipated perinatal course in a prenatal consultation. The focus
of these discussions from a pediatric surgical standpoint is
the operative management of the anatomic defect and the
anticipated need for PN in the pre- and perioperative period

while awaiting healing of the anastomosis, resolution of any
peri-anastomotic swelling, and onset of effective peristalsis
in the dilated proximal duodenal segment. While most
infants can undergo this reconstructive operation within
48 hours of birth, there are some in whom the management
of prematurity and congenital heart disease will dictate
the timing of operation and the provision of total parenteral nutrition will be prolonged in duration. Based on the
specific functional cardiac defect, a decision can be made
with the cardiologists to proceed early with abdominal
operation before the pulmonary pressures rise significantly
and impact the perioperative fluid and cardiac management.
This would reduce the cholestatic consequences of the
combination of anatomic obstruction with prolonged PN, a
combination which may become detrimental with time. For
anatomic reasons, the repair of duodenal atresia involves
no resection, but creates an anastomosis joining the dilated
proximal segment to a segment of the tiny, previously unused
duodenum. At operation an assessment is made of the distal
bowel to assure that there are no further sites of atresia, the
duodenum is assessed in terms of its caliber and contractility
for possible tapering duodenoplasty, and the overall situation is assessed for the potential need for prolonged gastric
decompression via gastrostomy. In a child who requires a
duodeno-duodenostomy, has a reasonable caliber anastomosis, and a not overly dilated proximal pouch, enteral
feeds can generally be started after the fifth postoperative
day. Duodenal leak can be a catastrophic complication due
to the leakage of activated pancreato-biliary secretions.
Often a contrast study for anatomic and functional evaluation is requested in these infants prior to commencing feeds.
In contrast to most postoperative patients, the assessment
for when to start feeds has less to do with the bilious aspirate from the nasogastric (NG) tube or drainage from the
gastrostomy feeding tube (G-tube) than to do with volume.
Because of the congenital obstruction, the pylorus is often
incompetent and bile will flow retrograde into the stomach.
The progressive decrease in output, however, indicates
forward peristalsis through the anastomosis and is the best
indication that it is safe to start enteral feeds. When breast
milk is not available, the choice of infant formula is based on
gestational age. There are no predictable associated absorption disorders to require specialized formulas. The mode of
feeding again is dependent on the childs anatomic and functional considerations. While intermittent oral feeds may be
a successful strategy, often a more rapid transition from PN
to EN is achieved with continuous gastric feeds which are
then transitioned to bolus and oral feeds. Certainly oral
SURGERY
feeds can be added on top of continuous feeds to allow the

infant to acquire oral motor skills. The more complicated
infants have greater duodenal dysmotility and may have
required a tapering enteroplasty. These infants often have a
G-tube inserted to facilitate gastric decompression, thereby
protecting the anastomosis and allowing the infant greater
success in extubating from mechanical ventilation without
a nasogastric tube in place. Given the potentially complex
and prolonged postoperative course in this disorder, PN is
started routinely and converted to central formulation once
central venous access has been established.
Jejunoileal Atresia
As the anatomic site of obstruction extends further distally,
the immediate postoperative problems related to provision of EN generally are less frequent and less severe. These
proximal obstructions can occur in isolation as well as in
various constellations of increasing complexity, culminating
with the type IV apple peel deformity. In the simple mucosal
web or single transmural atresias, operative considerations
are relatively simple if the infant has normal overall intestinal length. A resection of the abnormally dilated jejunal
segment and primary anastomosis to the distal unused bowel
results in the least size discrepancy between adjacent limbs of
intestine and predictably has the least common incidence of
peri-anastomotic obstruction and dysmotility. These infants
would be anticipated to tolerate the onset of enteral feedings once bilious NG output has resolved and volumes have
decreased in concert with the passage of bile-pigmented stool
output. This can occur 5 to 10 days after operation and therefore mandates use of PN in the interim. Infants with multiple
intestinal atresia are likely to have compromise of the overall
bowel length, and operative methods to salvage length
must be considered in relation to the infants gestational
age and how this relates to ongoing longitudinal growth of
the intestine during the third trimester. Infants delivered at
term and diagnosed with multiple intestinal atresia have less
opportunity to compensate for lost intestinal length. The
most proximal segment of intestine will be the only segment
dilated, and length can be preserved by performing a standard longitudinal tapering enteroplasty. Only in the event of
severe congenital short bowel should more novel techniques
such as the serial transverse enteroplasty procedure (STEP) or
Bianchi be considered to optimize salvage of mucosal surface
area while promoting intestinal contractility.19 As many as
possible of the subsequent atretic portions of intestine should
be salvaged using a shish-kebab technique in which continuity is created over a device such as a broviac catheter.20 The
calculated risk, however, is the non-union of segments with
395
either leak or obstruction as a consequence. Surgical clinical

judgment will dictate what is reasonable to salvage.21,22
In the most complex variant of jejunoileal atresia, the
apple peel deformity, there is a complex malformation
of the proximal intestine along with preservation of the
distal ileum on a vascular pedicle that provides retrograde
perfusion for a variable length of intestine. The particular
anatomic appearance of the twisted intestine, may-poled
around the single vascular trunk originating from the distal
ileal arcade, is important to recognize such that inadvertent
further vascular compromise is avoided by torque from a
poorly aligned enteric anastomosis. Furthermore, careful
perioperative fluid management is essential to preserve
adequate perfusion to the distal most intestine. Hypotension
will result in splanchnic vasoconstriction compromising
mucosal flow to particularly this section of bowel.
Nutrition considerations in these infants focus on the
provision of adequate PN calories via central access, with
early consideration of techniques to limit cholestatic disorders since the process to complete conversion to enteral
feeds may be prolonged by dysmotility and complications
such as necrotizing enterocolitis (NEC). With the intent to
gradually stimulate the bowel for adaptation, continuous
feeds are most often initiated and the infants who often
have G-tubes to facilitate this are allowed to sham-feed by
mouth and eventually are later converted to full bolus feeds
by mouth or G-tube.23
Distal Intestinal Obstruction

Distal intestinal obstruction usually involves the terminal
ileum and beyond. These infants will present with
abdominal distention which is not relieved with nasogastric decompression. Distal ileal atresia or obstruction
from inspissated meconium can result in volvulus of the
distended, fluid-filled segment and cause ischemic necrosis
of more extensive regions of the intestine. In the absence
of significant intestinal loss, these conditions are unlikely
to require more than conventional perioperative nutrition
support. Resection of the right colon including the ileocecal
valve is usually well tolerated. The need for replacement of
vitamin B12 must be considered at a later time (age 2 years)
if a significant portion of terminal ileum accompanies the
resection. More extensive colon resections, as might be
encountered in Hirschsprungs disease, have more significant effects on resorption of water and electrolytes. Patients
with Hirschsprungs disease and anorectal malformations
require long-term dietary management with the focus on
achieving optimal evacuation of stool.
396
Colon Atresia
Colon atresia is a rare condition, accounting for only 10%
of all intestinal atresia. Most common is a vascular defect
at the level of the middle colic artery resulting in an interruption of continuity at the mid-transverse colon. The right
colon becomes massively distended since a competent
ileocecal valve may not allow for distribution of the enteric
contents into the terminal ileum. Operatively there are
several solutions for this condition. An extended right hemicolectomy with anastomosis of the ileum to the transverse
colon results in permanent loss of a significant surface area
for nutrient and water absorption. Fortunately the left colon
can compensate for the water absorption with adaptation
and the patient should not have persistent watery stools.
More complicated solutions focus on preserving the right
colon with a proximal diverting stoma in the hopes that it
will decompress and regain its normal caliber and motility.
The nutrition considerations in these patients are generally
simple and are impacted by whether a second reconstructive operation is necessary.
Meconium Ileus and Variants
This is a condition usually associated with cystic fibrosis
(CF), resulting in distal ileal obstruction as a consequence
of the abnormal luminal contents which become inspissated.
Meconium ileus may be complicated further by either (1)
perforation of the obstructed bowel resulting in meconium
peritonitis or (2) volvulus of the distended bowel resulting
in ischemia and stricture formation which may appear identical to an atresia. While simple meconium ileus, in which
there is only luminal inspissation, can be decompressed with
sequential gastrograffin enemas, operation is sometimes
necessary. In the process of attempting to decompress the
obstructed segment with saline or N-acetylcysteine irrigation, it is possible to perforate or excessively traumatize the
intestine. Often the safest choice is placement of a T-tube
that provides access for continued postoperative irrigation
and gradual resolution of the obstruction. In the event of
complicated meconium ileus due to luminal discontinuity,
a resection and primary anastomosis may be possible, but
because of the risk of recurrent distal obstruction, creating
a vented anastomosis (Bishop Koop or Santulli stoma)
provides the greatest assurance of success. This allows
the enteric contents to evacuate per stoma should distal
obstruction re-occur and provides direct access to the
distal bowel to treat with 3% N-acetylcysteine solution. The
most difficult variant to deal with operatively is meconium
peritonitis, in which the site of perforation may be unable
to be identified or mobilized to create a stoma. A proximal
diverting stoma becomes necessary with staged exploration and restoration of continuity at a later date. If the distal
end of the bowel can be identified this is helpful in trying
to prepare it for the subsequent operation and for consideration of distal refeeding of proximal stoma output (see later
section in this chapter).
Nutrition management of these infants requires consideration of the likely underlying diagnosis of CF, which must
be verified by testing. While in the past it was taught that EN
with a protein hydrolysate formula or breast milk did not
require provision of pancreatic enzymes, common practice
now is to provide these enzymes nevertheless, to optimize
whatever enteral intake is available for absorption. This has
to be balanced with the past concerns for mucosal damage
from specific formulations of enzyme dosing. This infant
with a diverting stoma is a classic example of the nutrition
decision-making involved with a child who will require a
second, complicated operation, 6 weeks or more in the future
(see section on management of stoma output). Cholestatic
jaundice is based not only on total PN exposure, but also
on potentially underlying liver disease associated with CF.
Once intestinal continuity to a stoma or the rectum is established postoperatively the goal is to wean total PN support
expeditiously while recognizing that these infants tend to
have a higher than usual caloric requirement.
Hirschsprungs Disease
Hirschsprungs disease is a consequence of the absence of
the ganglion cells from the rectum and distal-most colon,
typically involving the rectosigmoid. The enteric ganglion
cells are essential to receptive relaxation of the intestine and
their absence results in a functional obstruction of the colon
with remarkable dilation of the normal colon proximal to
the transition zone beyond which these neural crest cells
failed to migrate during the embryonic period. The consequence is a functional obstruction at the level of the absence
of ganglion cells (aganglionosis). Hirschsprungs disease
most often affects term or near-term infants and is unusual
in preterm infants. The newborn who is diagnosed and
promptly undergoes reconstructive operationwhether it
be an open operation, laparoscopic assisted, or transanal
is likely to be able to start normal EN within 5 days of
operation. Therefore the provision of even peripheral total
PN, during the first few days of life, once the child has been
diagnosed, is probably sufficient. This scenario, however,
changes with a late diagnosis of Hirschsprungs disease,
which is often associated with significant failure to thrive,
enterocolitis, and long-segment disease. These situations are
independent predictors of a difficult postoperative course
SURGERY
and therefore surgeons will often choose not to operate

immediately and instead to manage these patients medically
(with irrigations if the transition zone is distal) or perform a
stoma at the point where ganglion cells are present. Failure
of the initial reconstruction potentially leads to a lifetime
of anorectal disability. Once diverted, or established on an
effective irrigation program, the alimentary tract can again
be challenged with nutrients and should be able to function
appropriately, allowing the infant to thrive. The infant with
total colon aganglionosis is essentially diverted at the level of
the terminal ileum. He or she may require total PN support
transiently until such time when adaptation has occurred.
The rare infant with aganglionosis extending into the small
intestine often will suffer from severe short bowel syndrome
(SBS) and must be managed accordingly.
Anorectal Malformations
Children with isolated anorectal malformations generally
have no specific nutrition requirements. Their anorectal
defect will either respond to progressive dilation allowing for
a delayed operative intervention or will require a diverting
colostomy. These children grow and develop normally in
the absence of associated disorders.
After reconstruction, children with Hirschsprungs
disease and low variants of imperforate anus will have issues
related to stooling, with some developing severe functional
constipation which may progress to overflow incontinence.
Children with high imperforate anus tend to have problems
with fecal incontinence either due to absence of the sphincter
complex or deficient innervation. Appropriate dietary
management along with a supervised bowel management
program are essential to the well being of children with this
spectrum of disease. Dietary considerations include provision of sufficient non-absorbable fiber intake along with
sufficient liquid intake to assure daily evacuation.
Abdominal Wall and Diaphragm

Omphalocele
Omphalocele and gastroschisis are two very distinct
congenital disorders with completely different considerations in terms of their postnatal GI function. While both
conditions involve the presence of an abdominal wall defect,
the intestine is protected within a membrane in patients
with omphalocele and is not subject to the fascial constriction and amniotic exposure encountered in gastroschisis.
Omphalocele can be associated with genetic disorders as
well as renal and cardiac defects and it is typically these
conditions that determine the outcome of these patients.
397
Beckwith-Wiedemann syndrome is diagnosed when omphalocele is associated with macroglossia, hypoglycemia, and
hemihypertrophy. This is a transient metabolic condition
with no long-term implications for glycemic control, but
places the patient at risk for solid organ tumors. Associated
congenital heart disease may involve various intracardiac
defects or a constellation of defects involving the heart,
pericardium diaphragm, and sternum which are referred to
as the Pentalogy of Cantrell. Depending on the size of the
abdominal wall defect, the liver and intestine are typically
extra-abdominal, and reconstruction can be accomplished
in one vs. several stages.
A small omphalocele can be closed within days after
birth once associated anomalies have been excluded. The
child is typically kept NPO preoperatively, although this
may not strictly be necessary, but convenient for the preoperative evaluations. Once a small omphalocele is closed,
enteral alimentation can be commenced as soon as there
is evidence of GI motility/function. While there are no
predictable GI problems, extrinsic gastric compression from
the oversized liver and GER are not uncommon and may
require transient postpyloric feeding. In the more complicated giant omphaloceles, PN is commonly started to bridge
the childs nutrition needs while multiple operative procedures interfere with consistent EN. Ethical considerations
arise when an infant with omphalocele is diagnosed with
a lethal chromosomal disorder such as trisomy 18. Often
the surgical condition can be managed in a non-operative
manner and EN can be delivered in a relatively non-invasive
manner via a nasogastric feeding tube if the child will not
feed by mouth.
The outcomes of omphalocele should be excellent but
for the most complex disorders.
Gastroschisis
Gastroschisis is frequently the more complex defect from
the standpoint of operative interventions and providing
optimal nutrition support. This abdominal wall defect is
typically a relatively small full-thickness aperture to the
right of the umbilical cord insertion. Much of the GI tract
is extruded through this defect and is bathed in amniotic
fluid through pregnancy. The exposed intestine is at risk
for torsion, vascular impairment from a tight fascial defect
which remains fixed as the intestine and its mesentery
enlarge, and is subject to serosal irritation and trauma by
virtue of its extraperitoneal location. Immediate postnatal
coverage of the intestine is accomplished by either primary
abdominal closure or more commonly by placement of a
temporary silo. This sterile silastic tube accommodates
398
the intestine and is secured via a flexible but reinforced

ring at its open end, which slides under the abdominal wall
fascia, thereby creating a covered extension of the peritoneal
cavity. Gradual compression of the silo from the top down
forces the intestine into the gradually expanding abdominal
space and allows for the ultimate abdominal wall closure.
Although there are multiple variations in the technique to
achieve reduction and closure, there do not appear to be
any remarkable differences in outcome in terms of time to
full feeds and hospital discharge.24 Non-operative, bedside
closure with simple coverage using the umbilical remnant
has also been described and is being evaluated for its longterm outcomes.
The most important predictor of outcomes appears to
be the original condition of the intestine. The intestinal
surface in gastroschisis has a variable appearance and ranges
from non-edematous, pliable, and virtually normal intestine without surface adhesions to stiff, edematous bowel
whose contour and continuity cannot be assessed visually
or even by palpation. Further complicating the presenting
features is the tendency for these children to have a shorter
than normal length of intestine. Fortunately some of these
changes will resolve with time; however, the period of time
to normal intestinal peristalsis can be quite variable. After
an extended period of observation of 4 to 6 weeks, without
evidence of bowel continuity, contrast studies are indicated
to evaluate whether there is an intestinal atresia present.
Evaluation much earlier is without benefit, as the abdomen
will be quite hostile to exploration.
An interesting situation arises when an atretic segment
is recognized at birth. Although the intuitive response
would be to divert at that level to allow for some enteral
stimulation, this is not generally advisable. There is limited
abdominal wall surface area for a stoma and the edema of
the intestine rarely allows it to reach the abdominal wall in
an orientation that is feasible for creation of a stoma. It is
currently considered best practice to close the abdomen and
correct the atresia at a second operation.25,26
Given the primary dysfunction of the intestine on
multiple levels, these infants may require an extended
period of PN support. During the initial few weeks, the
infant remains decompressed with a nasogastric tube.
Again, in contrast to other children who may require
prolonged decompression, there is a reluctance to perform
any visceral procedure, even a gastrostomy, due to abdominal wall constraints and the altered surface characteristics
of the GI tract. Unless these children are extremely preterm,
they usually have an uneventful perioperative course with
a short duration of mechanical ventilation. There are no
known interventions that lead to a more rapid resolution

of wall edema. In general these infants require a generous
amount of intravenous fluid support in the first few days
as they are projected to be relatively volume depleted on
presentation and continue to require good vascular perfusion of the intestine. The peripheral edema which may appear
occurs on a different basis than that of the intestine, which
likely happens as a consequence of vascular and lymphatic
congestion at the level of the fascial ring defect. In contrast
to the peripheral edema, it is unlikely that diuresis affects
this visceral edema in the early phases.
The onset of intestinal feeding must coincide with
evidence of effective full intestinal peristaltic activity as
evidenced by decreasing NG outputs and onset of stooling.
Early feeding into a dysmotile and transmurally altered
intestine likely accounts for the higher incidence of NEC in
gastroschisis than any other gestational age-matched infant
population. While bolus feedings have benefit in stimulating
hormonally regulated secretions from the pancreatobiliary
tract, they are limited by virtue of the initially small capacity
of the stomach. Because cholestasis is common in these
infants, there is a desire to wean them off PN expeditiously;
however, this is best achieved not by starting feeds prematurely, but by providing continuous enteral stimulation via
continuous drip feeds, once motility is evident. These can
certainly be augmented by interval bolus feeds which allow
the child to develop the necessary oral feeding skills and
may stimulate the GI hormones. Vigilance is essential as
the enteral component is advanced. Guidelines for advancement of feeds should take into account the frequency of
stools as well as the pH and reducing substances as these
may indicate poor absorption and/or an excessive osmotic
load. Because of the perceived fragility of the intestine,
this authors practice is generally to use a more elemental
formula and limit the osmolality of the formula, trying not
to increase the caloric density of feeds until the child is
nearly fully established on EN.
Setbacks relate to septic events concerning the central
line, which are usually gram negative in etiology and reflect
the ongoing reduced mucosal barrier defense in the intestine. Given the combination of cholestasis and poor motility,
these patients are great candidates for cycled enteral antibiotics to obviate bacterial overgrowth and its complications.
Gastroschisis is one of the more common causes of neonatal
SBS. The etiologies involve congenital torsion or ischemic
necrosis of entire segments of intestine, simple atresias, and
postnatal loss of intestine due to poor perfusion, NEC, or
surgical catastrophes. Caloric estimates for the needs of
these infants depend on their phase of recovery. In the initial
SURGERY
postnatal period there appears to be an intense inflammatory state as evidenced by elevated CRP which resolves as
the bowel recovers. The incidence of cholestatic jaundice is
likely multifactorial in this population.26
Congenital Diaphragmatic Hernia
Congenital diaphragmatic hernia (CDH) involves a heterotopic location for the viscera within either chest cavity
as well as associated developmental defects in lung and
pulmonary vascular development and maturation. While
the former is a surgically correctable defect, the second
component determines the childs clinical course and ultimate prognosis. Infants with CDH therefore fall into several
categories. There are those with a diaphragmatic defect,
usually first detected postnatally, in whom there is little
hemodynamic and pulmonary compromise; they tolerate
the operation well and can relatively quickly be transitioned to enteral feedings. Infants in whom the defect was
identified early in gestation tend to have a greater degree
of pulmonary hypoplasia and more difficulty with pulmonary hypertension. These infants may require cardiac and
pulmonary support via ECMO. Nutrition support in this
disorder therefore spans the whole spectrum and must be
individualized. The GI tract, although displaced initially, is
fundamentally normal in terms of its motility and absorption capacity. As such there are no specific recommendations
for the type of enteral alimentation. Consideration will
need to be given to the fact that total fluid provision will
likely be restricted in the postoperative patient as he or
she is weaned off ventilatory support. While it is enticing
to provide highly concentrated formulations, this has to be
balanced with the potential for mucosal damage leading to
enteric-derived sepsis in vulnerable infants who likely have
multiple vascular access points. Provision of adequate calories will likely be best accomplished by this means once the
infant has tolerated enteral feedings and becomes limited
in the amount of volume that can be delivered for reasons
of gastric capacity and emptying. All children with CDH
have some degree of foregut dysmotility, which renders
them at risk for GER.27,28 The risk of reflux with aspiration
is particularly pronounced in these patients who already
have a compromised pulmonary system, given the nature
of the congenital defect. This forms the basis for providing
continuous feeds initially to full enteral needs and then
transitioning them to bolus feeds. Again, the provision of
continuous enteral feedings should not be a disincentive to
allow for oral feeds. This can be structured to be the volume
of feeds targeted to be delivered over 1 hour or even more as
the child tolerates.
399
Infants with CDH and severe cardiopulmonary

compromise requiring inotropic support and other medications such as nitric oxide for stabilization of the pulmonary
hypertension present challenges to the provision of even a
fraction of the targeted caloric requirements. The assessment of caloric needs is especially difficult because there
are so many confounding factors such as level of sedation,
possible chemical muscular relaxation, degree of mechanical respiratory support, and level of temperature support
provided. During this phase the goal of nutrition support
is to provide those essential components to allow for basic
metabolic needs and repair of tissues. Calories earmarked
for growth and development become priorities as the
infants clinical condition improves. When these patients
require cardiopulmonary support on ECMO , the assumption was that just as the lungs were being rested, the
metabolic demand would decrease. This has been shown
to be an incorrect assumption; these patients continue to
exhibit the hypermetabolic response, and this even persists
after decannulation.29,30 In the past there has been debate as
to the safety of administering lipids to an infant on ECMO.
The consensus now is that they can safely be administered
via a central line separate from the ECMO circuit, whereas
the dextrose and amino acid solution is typically administered via the cannulae and in this situation only, can safely
exceed dextrose concentrations greater than 20% since
there are sufficiently high flow rates directly into the atrium.
Provision of high glucose loads along with insulin therapy
has been shown to be beneficial in this population in terms
of limiting protein catabolism. 31,32
Hepatobiliary Disorders
Biliary Atresia
Infants presenting with direct hyperbilirubinemia are
promptly evaluated for surgically correctable biliary tract
disorders such as biliary atresia and choledochal cyst.
While other conditions such as neonatal hepatitis also lead
to similar laboratory presentations, they, as well as a host of
infectious disorders and enzymatic defects, require medical
support only. Biliary atresia most often becomes evident at 1
month of life and the infant may have experienced failure to
thrive of unknown etiology. Hallmarks of clinical diagnosis
include jaundice, acholic stools, and dark urine. Ultrasound,
HIDA scan, and percutaneous liver biopsy should confirm
the diagnosis. Once established, preoperative administration of vitamin K is one of the standard recommendations to
optimize coagulation parameters. The diagnosis is further
confirmed intraoperatively by demonstrating lack of the
400
extrahepatic ductular system. Reconstruction involves

creation of a jejunal limb that is anastomosed to the portal
plate, the region of the liver where the hepatic ducts would
be presumed to originate from the liver parenchyma. In
fortunate situations, there is early evidence of bile flow with
resolution of the hyperbilirubinemia. Postoperative steroids
are frequently used as a choleretic and to reduce the parenchymal inflammation within the liver. This postoperative
course is typically a period of 5 days of non-enteral alimentation to allow for healing of the intestinal anastomosis with
subsequent initiation of enteral feedings. With the frequent
delay in diagnosis to 2 months of age, some infants will be
in very poor nutrition condition. On preoperative assessment, some surgeons will opt to place central venous access
at the time of operation, to provide the debilitated child
with some nutrition in the interim so as to optimize healing
and prevent further weight loss. There is no indication for
preoperative nutrition repletion because decompression
of the obstructed biliary tract is the most important goal.
Postoperative feedings are generally breast milk if available,
or a protein hydrolysate formula with approximately 50%
medium-chain triglyceride (MCT) oil to provide MCTs
which are more easily absorbed by the infant with liver
disease. These children have impaired ability to digest fats
and require supplementation of the fat-soluble vitamins A,
D, E, and K. There are reports of these infants requiring
a disproportionately larger caloric intake than for others
their size.
More on the nutrition support of the child with surgically
non-correctable liver disease is discussed elsewhere. 33,34
Choledochal Cyst
Infants with this congenital disorder may present during
the neonatal period or later, but generally before age 5 years.
The acute presentation may include pancreatitis in addition
to hyperbilirubinemia. These children rarely have chronic
malnutrition despite complaints of abdominal pain. Subsequent to resection of the choledochal cyst, which involves
variable portions of the extrahepatic ductal system, and
reconstruction of biliary outflow with a standard roux-en-Y
hepaticojejunostomy, these patients will be able to consume
a normal diet and in the absence of significant underlying
liver disease do not need special nutritional formulations.
Other (Non-GI) Malformations

Thoracic Disorders
Children who require thoracic operations for congenital
lung lesions or even foregut duplications can be treated
by routine postoperative guidelines and have no special

nutritional considerations, other than those imposed by
virtue of prolonged ventilatory support and concern for
reflux with aspiration. Many of these operations can now
safely be achieved with minimally invasive techniques
further reducing the surgical stress, postoperative pain
response, and minimizing wounds to heal. Infants born
with chylothorax, or those who develop it as a consequence
of perioperative complications, are managed depending on
the amount of daily chylous output with gut rest with PN
support and the subsequent introduction of enteral feeds
with high MCT oil concentration.
Urologic, Neurosurgical, and Orthopedic
Infants born with complex urological defects such as bladder
exstrophy and cloacal exstrophy will certainly require a
number of staged surgical interventions by various specialists. The intestinal tract is intact and generally normal in
bladder exstrophy whereas there is imperforate anus with
exteriorization of the hindgut between two bladder halves
in cloacal exstrophy. This portion of the hindgut will need
to be tubularized to create a distal stoma or require proximal diversion. Hydronephrosis, prune belly syndrome,
and other congenital renal anomalies may have evidence of
renal insufficiency or failure that will require adjustments
to the infants nutrient intake as discussed in other chapters.
Congenital neurosurgical and orthopedic interventions
generally do not involve the peritoneal cavity or even the
retroperitoneum and therefore do not impact enteral feeding
status. Depending on the extent of operation and metabolic
stress, adjustments primarily affect caloric goals and will
need to be individualized. A thoughtful consideration of
the impact of general anesthesia, which is virtually uniform
in neonatal patients undergoing surgery, will suggest that
resumption of enteral intake occur in a slightly delayed
manner.
Neonatal Airway Disorders
Infants who require interventions on their airway frequently
have associated aerodigestive disorders that may extend to
foregut dysmotility syndromes. Reconstructive interventions
for laryngomalacia, subglottic stenosis, and tracheomalacia
require protection of the airway from GER. Often tracheostomy can be averted by appropriate management of enteral
feedings along with pharmacologic interventions to limit
exposure of the glottic structures to acid gastric contents.
This may require insertion of a postpyloric feeding tube
to assure continued nutrition support without the risk of
reflux. If chronic in nature, then early consideration for a
SURGERY
Nissen fundoplication is appropriate. Infants with airway

compromise have an increased work of breathing and may
exhibit failure to thrive even despite mechanical feeding.
Once supported with a tracheostomy, the infant will often
show rapid catch-up growth and can sustain a reduction in
what is normally considered caloric goals. It is important to
remember that despite the presence of a tracheostomy, the
airway is not completely protected from either GER or aspiration salivary secretions because the pediatric airway often
does not require a cuffed tracheostomy, and every conscious
effort is made to preserve some airflow past the cords to
prevent progressive subglottic stenosis.
Nutrition Support in Infants with

Acute GI-Related Disorders
Necrotizing Enterocolitis
NEC remains one of the most frequent indications for
emergency operation on preterm neonates. Although the
mortality has decreased over time and management of
intestinal dysfunction has improved, this remains a diagnosis with a significant morbidity and mortality. Although
this is not to be an exhaustive summary on the pathophysiology of NEC, it is important to understand some of the
mechanisms thought to be responsible for its development
as these influence the way surgeons treat infants who have
experienced and may be at further risk for mucosal injury.
NEC is best considered a consequence of exposure
of an immature and nave intestinal tract with potentially
compromised perfusion to pathogenic organisms, which
traverse the intestinal barrier to initiate the gut-derived
sepsis syndrome. The gut mucosal barrier is compromised
on several levels in the premature infant. 35 The normally acid
environment of the stomach serves as an initial barrier to
microbes, yet acid production is often immature and is often
altered iatrogenically by providing acid-suppressing medications, in the hopes of avoiding gastritis and ulceration.
Other factors include the limited supply of luminal protective factors such as the lectins and IgA provided by maternal
milk. Structurally the mucosal surface provides opportunities for attachment of bacteria via a decreased mucus
barrier, tight junctions which may not be as tight as in older,
term infants, and active translocation mechanisms which
optimally are suited for sampling a safer environment than
that provided in a neonatal intensive care unit (NICU). The
mucosal integrity may become further compromised with
decreased visceral perfusion. The mucosa is at greatest risk
with hypoperfusion, and mucosal sloughing as evidenced by
bloody stools is an early indication of potential NEC (Bell
401
stage 1 NEC). Altered perfusion may be the consequence

of primary cardiac events (congenital heart disease, PDA),
pulmonary compromise with consequent hypoxia and
resultant shunting away from the viscera, and other events
such as hemorrhage (pulmonary, intraventricular). Beyond
the mucosal border the immaturity of the host immune
system is overcome due to limited phagocytic and bactericidal activity of neutrophils and other components of the
gut-associated lymphoid tissue (GALT). These speculated
factors would all contribute to facilitating an enteric source
of sepsis. Needless to say the etiology of NEC is manifold
and complex. The radiographic hallmarks are pneumatosis
intestinalis and portal venous gas, both of which portend
that there has been transgression of the mucosa by gasproducing organisms. If the sepsis can be controlled and
the intestine is able to maintain its integrity, no operative
intervention is necessary (Bell stage 2 NEC). However, if
evidence of perforation becomes evident or the abdominal
sepsis fails to come under control, operative intervention
becomes mandatory (Bell stage 3 NEC). The options are
often dictated by the infants size and degree of clinical instability. In the smallest and most unstable infant, placement
of a peritoneal drain may be all that can be safely offered
while in larger or more stable infants a limited laparotomy
at the bedside or in the operating room may allow for more
definitive therapy. At operation the extent of intestinal
involvement becomes apparent. In the least severe circumstances, a limited segment of intestine has transmural
gangrene or has perforated. Resection and diversion with
stoma versus primary anastomosis are decided upon based
on the patients overall condition and specifically the condition of the intestine. In infants with more extensive and
even skip involvement, proximal diversion and only excision of those areas of definite gangrene become the guiding
principles so as to preserve as much intestinal length as
possible. Despite optimal management, these affected areas
may progress to full-thickness gangrene or heal as fibrotic
strictures, further compromising residual length and potentially resulting in SBS. Survival is only possible if the sepsis
is controlled. 36
The acute management focuses on providing adequate
perfusion to the residual intestine in order to allow it to
recover from the initial insult. This results in the generous
provision of intravenous fluids early on and the restriction
of fluids upon resolution of the sepsis in order to optimize
pulmonary function. This compromises the ability to
provide optimal nutrition in a consistent manner. Enteral
feeding would be considered no earlier than 7 days of therapy. As in other complex GI disorders a coherent plan has to
402
be generated by the managing teams so as to best utilize a

combination of EN and PN. Recurrent sepsis and progressive cholestatic jaundice are the predictors of mortality. All
techniques available to limit these complications should be
utilized in these patients. Reconstitution of the full GI tract
is accomplished after 6 weeks to limit operative complications and to have given sufficient time for strictures to form
and to be identified such that they can be treated at the same
operation. 37 Even in those infants managed without operative intervention, the clinicians must maintain suspicion for
developing strictures, particularly if the colon was involved,
which can be difficult to tell non-operatively. Aggressive
feeding of an infant with a distal bowel obstruction will
only lead to recurrence of NEC. 38 While the specific amino
acid composition of neonatal total parenteral nutrition is addressed in other sections, much attention had been focused
on the utility of providing glutamine to this population with
a compromised gut mucosal barrier; however, this does not
appear to be an effective strategy. 39,40
Infants who survive the early postoperative course
associated with NEC are among the highest risk infants
for intestinal dysfunction, SBS, and cholestasis. All nutrition techniques described earlier in relation to initiation of
trophic feedings, enteral antibiotics, and cycling of modulation of total parenteral nutrition should be applied in
this context. The optimal timing of refeeding and stoma
closure remain topics of controversy and are often individually determined or institutional preferences rather than
evidence-based protocol-driven events.
Isolated Intestinal Perforation

This is a condition that closely mimics NEC in that it presents
with evidence of visceral perforation, usually pneumoperitoneum in the absence of pneumatosis, or portal venous gas and
thus requires some surgical intervention. The infants affected
with this disorder are usually extremely low-birth-weight
infants (< 750 g), in their first week of life, and may never have
been fed. Often the diagnosis remains speculative since many
are treated with peritoneal drainage only and isolated involvement of only a small intestinal segment cannot be verified
other than by operation. These infants are generally thought
to have a better prognosis because of limited colonization of
the GI tract during the first week of life, better source control
of sepsis once the abdomen has been drained, a self-sealing
perforation site, and consequently a less profound sepsis
syndrome. The initiating events remain elusive, but may be
related to focal perfusion defects or focal luminal injury by
medications such as indomethacin. The same concerns for
indications for laparotomy, length of NPO status, and length
of antibiotic therapy apply as they do in NEC infants. From

a nutrition standpoint one assumption to be made is that the
remainder of the GI tract will not have experienced the same
generalized mucosal insult as encountered in NEC and that
enteral feedings and rehabilitation should be achievable with
greater success rates.
Intestinal Malrotation and Midgut Volvulus

Midgut volvulus as a consequence of intestinal malrotation
can occur at any age, having been described both prenatally
and in adult patients. The first month of life is, however,
the most common time of presentation. The infant who is
born with intestinal malrotation and experiences a midgut
volvulus can be severely compromised. With timely diagnosis and intervention, the midgut (proximal jejunum to
mid-transverse colon) should be salvageable. At operation the abdomen may be filled with chylous ascites as a
consequence of obstruction and rupture of the mesenteric
lymphatics. Untwisting of the mesenteric pedicle will
restore venous drainage and allow for improved arterial
inflow. Resection is only considered if there are regions of
complete necrosis. Any intestinal segment with borderline perfusion is retained and reassessed at 24 hours with
a second-look laparotomy to avoid unnecessary resection
leading to SBS. Depending on the extent of the intestinal
injury, these infants must initially be fed cautiously to avoid
a second hit to a compromised bowel. The perioperative
nutrition support team again must target metabolic needs
as well as protein substrate for tissue repair. In the absence
of any significant intestinal resection, there should be no
ongoing considerations. The management of the child who
suffers massive intestinal loss is covered in the chapter on
intestinal failure (Chapter 27). As with NEC these infants
are the most likely to have lost the terminal ileum and will
likely require vitamin B12 supplementation in the future.
Pyloric Stenosis
Infants with pyloric stenosis primarily require rehydration
and correction of electrolytes preoperatively but then can
be relied upon to resume a normal infant diet. How this is
initiated varies by institution. In general, no postoperative
feeding tubes are placed as these put the exposed pyloric
channel mucosa to the risk of perforation. The infants are
typically hungry and have good feeding skills. In this authors
institution, our feeding protocol was developed to provide a
consistent algorithm that allows the vast majority of infants
to be discharged to home within 24 hours of operation. We
hold oral feeds for 6 hours, and then test the stomach with 2
small-volume (15 mL) Pedialyte feeds 2 hours apart. If the
SURGERY
child experiences no vomiting, then formula or breast milk

is offered at 30-mL volumes every 3 hours and advanced by
15 mL every second feed to a maximum of 60 mL, which
provides the necessary volumes for the average 3 to 3.5 kg
infant with pyloric stenosis. At this point the infant can be
discharged home and feedings are advanced as tolerated
by the parents with the proviso that individual volumes
should not be excessive so as to minimize reflux. Recurrent vomiting will always raise the spectre of recurrent
stenosis or of an incomplete operation, both of which are
rare events in experienced hands. The infants stomach is
capacious given the preoperative obstruction, but more
frequent limited volume feeds will assure retention of feeds
and optimal absorption. All parents are amazed by the
infants persistent need to feed within the first month postoperation. This resolves spontaneously as the child achieves
catch-up growth. Persistent vomiting should prompt
consideration of gastroesophageal reflux, which can be
ameliorated with antacid therapy including even a dose of
sodium bicarbonate, which may also act to help disintegrate
a mucus plug in the pyloric channel. More serious considerations should include the potential for an intraoperative
bowel injury or wound/fascial dehiscence. Typically these
infants will have other symptoms in addition to persistent
vomiting. If ranitidine was provided perioperatively it can
usually be discontinued at the follow-up visit 3 to 4 weeks
later. Most of these infants have undergone multiple formula
changes prior to their diagnosis; we reassure parents that
the formula is now less important and that they should use
what they have at home and what is most accessible.41
At other institutions the interval of time to feeding may
differ as will the protocol, even to the point of providing the
infant with improvised feeds. The technique (laparoscopic
or open) of pyloromyotomy does not have an impact on
tolerance of feeds or time to discharge.
Nutrition Support in Children and Adolescents

Requiring Operation
General Principles
In the older child and adolescent, many of the surgical
interventions for GI problems are of an acute nature (ie,
appendicitis, Meckels diverticulum, duplications of the GI
tract, and intestinal obstruction due to hernia) where there
are typically no premorbid nutrition impairment concerns.
Those children presenting with more chronic disorders,
such as inflammatory bowel disease, polyposis syndromes,
and chronic GER require a closer evaluation of their nutrition status before elective surgery is contemplated. Some
403
of these chronic conditions can be the consequence of

neonatal interventions with adapted SBS, late stenosis,
and dysmotility in the atresia (duodenal and jejunoileal)
patients. Malignancies affecting the GI tract are generally
rare and most frequently involve lymphomas, although
carcinoid tumors, desmoid tumors, and other solid visceral
tumors will impact the GI tract. Abdominal visceral transplantation is yet another surgical intervention in which
specialized focus on nutrition management must occur.
These more complex topics of irritable bowel syndrome,
malignancy, and transplantation are addressed in individual
chapters elsewhere.
The nutrition management of the acutely ill surgical
patient is generally focused on resumption of enteral intake
and, when this becomes delayed beyond 5 to 7 days, consideration is given to PN support. There is evidence from the
critical care literature to indicate that many of these acutely
ill patients are significantly undernourished while in the
ICU. There is also evidence that simple calculation of REE
without accounting for physical activity underestimates
caloric requirements.42,43 While there is a consistent attempt
to provide medical patients and traumatized patients in the
ICU setting with early enteral feedings, these principles
cannot be applied to the surgical patient who likely is at
higher risk for anastomotic breakdown, abdominal sepsis,
and the development of complications such as surgical site
infections, fascial dehiscence, and enterocutaneous fistulae
which then further complicate clinical and nutrition
management. Despite these surgical concerns, the initiation of enteral feedings should be a clinical goal to allow
transition off PN support at the earliest feasible time. The
ability to handle complex wound failure has been markedly
improved with advances in enterostomal care and with the
use of negative pressure wound devices that contribute to
more rapid closure of open wounds and even enterocutaneous fistulae. The earlier control of fluid and protein losses
from these wounds should impact overall protein balance in
a favorable manner.
The subset of children who present the highest risk for
emergency operation are those with chronic malnutrition.
Examples include children with failure to thrive on the basis
of congenital heart disease or developmental delay resulting
in inadequate oral intake, and children with spine deformities (severe kyphosis and scoliosis) who are at risk for the
superior mesenteric artery (SMA) syndrome in which
there is duodenal obstruction as a consequence of extrinsic
compression of the third portion of the duodenum between
the SMA and the vertebral column. Children with spastic
quadriplegia and seizure disorders may have a limited
404
gastric capacity and poor gastric emptying with a tendency

to reflux, which thereby has limited their enteral intake.
Children with malignancies often are nutritionally depleted
as a consequence not only of the disease process but also the
therapies applied. At childrens hospitals we have become
much more attuned to the preoperative nutrition evaluation
of these patients in an effort to optimize surgical outcomes
from often extensive surgical interventions. Much of the
focus therefore becomes provision of feeding access for
nutrition support.
Feeding Access in Pediatrics

Many children are referred for placement of enteral feeding
devices. If access is required for more than a temporary
situation, the options include the various techniques of
gastrostomy placement (percutaneous endoscopic gastrostomy (PEG), laparoscopic G-tube, open G-tube), insertion
of a gastrojejunal device, and direct jejunal feeding tubes.
Despite their seemingly simple and innocuous nature, these
interventions have the potential for complications and
morbidity.44,45
When placing a gastrostomy, consideration should be
given to the potential for promoting increased reflux on
the basis of anatomic alterations. Children who have typically only consumed small amounts of food may not have
evidence of reflux until larger volumes are directly administered into the gastric lumen. A preoperative evaluation
should be conducted to assess the risks, particularly when
these children are developmentally delayed and at risk for
aspiration. The concomitant construction of a fundoplication may become necessary. Anatomic evaluation will
also determine whether there are impediments to proper
gastric emptying that may be amenable to correction at the
same operation. The principal diagnosis to be considered is
malrotation with partial duodenal obstruction on the basis
of Ladds bands. Typically a pH study or impedance study
is conducted to address the former question and an upper
GI study is performed to exclude all forms of distal obstruction. If consideration is given to an antireflux operation,
a nuclear medicine gastric emptying scan can be useful.
These tests can also provide information regarding reflux
although less quantifiable than those noted above. Gastric
outlet procedures (eg, pyloromyotomy and pyloroplasty)
are occasionally considered in those patients with increased
concern for early failure of a fundoplication.
Insertion of Gastrostomy
When a gastrostomy tube is inserted for the sole purpose of
providing enteral access, enteral feedings can be commenced
within 24 hours of operation. With open and laparoscopic

techniques there may be some initial postoperative ileus;
however, the main reason for decompressing the stomach
or at least avoiding exogenous input is to allow a seal to
form between the gastrostomy and the abdominal wall so
that with retching and vomiting there is no extravasation
between these structures into the peritoneal cavity.
How the enteral feedings are provided depends on the
childs underlying situation. If the enteral feedings are for
supplementation of oral feeds, then oral intake can certainly
be started and G-tube feeds given as small bolus volumes
which are increased according to tolerance. In children
with neurological deficits/developmental delay, initiation of G-tube feeds may be best assessed by open vented
feeds. Rapid egress of formula from the feeding bag into
the stomach with no regurgitation into the tube suggests
a large-capacity stomach that will accommodate additional volumes, whereas slow evacuation into the stomach
suggests a smaller stomach capacity or increased resistance
because of abdominal wall contraction, possibly due to pain
or spasticity. In this latter situation it may turn out to be
more efficient to provide feeds initially as slow continuous
drips rather than bolus volumes. Closed infusion of feeds
certainly is the least cumbersome but risks GER with
potential for aspiration, or requires communication from
the patient that the stomach is full. This may be exhibited
as retching, or visceral pain initiated by overdistention.
In some children with significant reflux there may be
various concerns about proceeding with a fundoplication.
Perhaps the child is so nutritionally depleted that the risks
are not in favor of proceeding with a major operation. In this
situation a gastrostomy tract can become the conduit for a
gastrojejunostomy tube which allows for gastric decompression and jejunal feedings. The disadvantage to the
commercially available tubes is that they have a minimum
size of 16 French and therefore are excessively large and stiff
for infants, but become usable at a patient size of about 10
kg. In smaller patients other devices can be jury-rigged to
achieve the same tasks. These tubes are meant as transient
feeding support devices, and repeated insertion by required
fluoroscopy is not ideal in the pediatric patient. The authors
institution uses them as a bridge to help the patient achieve
an improved nutrition state, thereby becoming a better
candidate for fundoplication.
Children with neurodevelopmental impairment, spasticity, and seizures often have a higher risk for disruption of
their fundoplication and the option of avoiding this operation by the use of jejunal tubes is often enticing. Discussions
with their family and caretakers should evaluate not only
SURGERY
the childs operative risk but also whether continuous feeding

via a GJ tube or J tube will interfere with their daily activity
schedule. These tubes do not allow for bolus feedings other
than through the gastrostomy limb. Often the ability to
provide intermittent bolus feeds is a significant improvement in quality of life for both the child and family.46 With
the advent of the laparoscopic fundoplication, there is less
surgical impact in terms of abdominal wall wound healing
and pain, although early studies showed that surgical stress
in terms of hormone release was not altered. With excellent
short-term results this operation has gained favor; however,
the long-term efficacy of this operation, especially in the
higher risk populations, is still under evaluation.47
Primary jejunostomy tubes have been avoided in all but
the most chronic and perhaps institutionalized patients since
they represent a long-term commitment to continuous enteral
feedings. Operatively a tract is developed through the abdominal wall and an imbricated jejunal limb before the tube enters
the jejunal lumen. This establishes a relatively long tract for
reliable replacement of the tube in the correct orientation and
minimizes risk of leakage. These tubes certainly have their
role in the management of complex surgical patients.
When preoperative nutrition repletion is not feasible
before an urgent surgical intervention, the focus must then be
on providing early nutrition support, which may require the
placement of central venous access or reliable enteral access
for this purpose at the time of operation.
1. Which of the following strategies are considered beneficial in reducing cholestasis?

A. Provision of > 40% of calories as lipid emulsion
B. Maintaining GIR > 15 mg/kg/min
C. Continuous provision of PN
D. Initiation of enteral feedings
2. Which is a contraindication to commencing enteral
feedings?
A. Bilious nasogastric output in jejunoileal atresia
B. Contrast extravasation on postoperative day 7 after
esophageal atresia repair
C. Abdominal distention with lack of stoma output
D. All of the above
3. On a 3-kg infant status post stoma closure after resection for NEC, when should enteral feedings be limited?
A. Number of bowel movements exceeds 8 over
24-hour period
B. Reducing substances < 1/2%
C. Fecal pH > 7
D. Mucoid stools
405
4. Which clinical diagnosis is expected to have impairment of intestinal motility and may require prolonged
total PN support?
A. Gastroschisis
B. Omphalocele
C. Hirschsprungs disease
D. Malrotation without midgut volvulus
References
1. Barlow B, Santulli T, Heird W, Pitt J, Blanc W, Schullinger J.

An experimental study of acute necrotizing enterocolitis - the
importance of breast milk. J Pediatr Surg. 1974;9(5):587.
2. Nydegger A, Bines JE. Energy metabolism in infants with
congenital heart disease. Nutrition. 2006 8;22(7-8):697704.
3. Owens J, Musa N. Nutrition support after neonatal cardiac
surgery. Nutr Clin Pract. 2009;24(2):242.
4. Vaidyanathan B, Radhakrishnan R, Sarala D, Sundaram K,
Kumar R. What determines nutritional recovery in malnourished children after correction of congenital heart defects?
Pediatrics. 2009;124(2):e294.
5. Jaksic T, Shew SB, Keshen TH, Dzakovic A, Jahoor F. Do critically ill surgical neonates have increased energy expenditure?
J Pediatr Surg. 2001 1;36(1):6367.
6. Garza JJ, Shew SB, Keshen TH, Dzakovic A, Jahoor F, Jaksic
T. Energy expenditure in ill premature neonates. J Pediatr
Surg. 2002 3;37(3):289293.
7. Pierro A, Eaton S. Metabolism and nutrition in the surgical
neonate. Semin Pediatr Surg. 2008 11;17(4):276284.
8. Gruber EM, Laussen PC, Casta A, et al. Stress response in
infants undergoing cardiac surgery: a randomized study of
fentanyl bolus, fentanyl infusion, and fentanyl-midazolam
infusion. Anesth Analg. 2001 April 1;92(4):882890.
9. Shew SB, Keshen TH, Glass NL, Jahoor F, Jaksic T. Ligation of
a patent ductus arteriosus under fentanyl anesthesia improves
protein metabolism in premature neonates. J Pediatr Surg.
2000 9;35(9):12771281.
10. Hulst JM, van Goudoever JB, Zimmermann LJI, Tibboel
D, Joosten KFM. The role of initial monitoring of routine
biochemical nutritional markers in critically ill children. J
Nutr Biochem. 2006 1;17(1):5762.
11. Reynolds RM, Bass KD, Thureen PJ. Achieving positive
protein balance in the immediate postoperative period in
neonates undergoing abdominal surgery. J Pediatr. 2008
1;152(1):6367.
12. de Meijer VE, Gura KM, Le HD, Meisel JA, Puder M. Fish
oil-based lipid emulsions prevent and reverse parenteral
nutrition-associated liver disease: The Boston experience. J
Parenter Enteral Nutr. 2009 Sept 1;33(5):541547.
13. Lee SI, Valim C, Johnston P, et al. The impact of fish oil-based
lipid emulsion on serum triglyceride, bilirubin, and albumin
levels in children with parenteral nutrition-associated liver
disease. Pediatr Res. Aug 14 [Epub ahead of print] 2009.
406
14. Javid PJ, Collier S, Richardson D, et al. The role of enteral

nutrition in the reversal of parenteral nutrition-associated liver dysfunction in infants. J Pediatr Surg. 2005
6;40(6):10151018.
15. Boarini JH. Principles of stoma care for infants. J Enterostomal
Therapy. 1989;16(1):2125.
16. Al-Harbi K, Walton JM, Gardner V, Chessell L, Fitzgerald
PG. Mucous fistula refeeding in neonates with short bowel
syndrome. J Pediatr Surg. 1999;34(7):1100.
17. Alabbad SI, Ryckman J, Puligandla PS, Shaw K, Nguyen LT,
Laberge J. Use of transanastomotic feeding tubes during esophageal atresia repair. J Pediatr Surg. 2009 5;44(5):902905.
18. Goyal A, Jones MO, Couriel JM, Losty PD. Oesophageal
atresia and tracheo-oesophageal fistula. Arch Dis Child Fetal
Neonatal Ed. 2006;91(5):F381.
19. Ching YA, Fitzgibbons S, Valim C, Zhou J, Duggan C, Jaksic
T, et al. Long-term nutritional and clinical outcomes after
serial transverse enteroplasty at a single institution. J Pediatr
Surg. 2009;44(5):939.
20. Yardley I, Khalil B, Minford J, Morabito A. Multiple jejunoileal
atresia and colonic atresia managed by multiple primary anastomosis with a single gastroperineal transanastomotic tube
without stomas. J Pediatr Surg. 2008 11;43(11):e45e46.
21. Piper HG, Alesbury J, Waterford SD, Zurakowski D, Jaksic
T. Intestinal atresias: Factors affecting clinical outcomes. J
Pediatr Surg. 2008 7;43(7):12441248.
22. Wales PW, Dutta S. Serial transverse enteroplasty as primary
therapy for neonates with proximal jejunal atresia. J Pediatr
Surg. 2005 3;40(3):E31E34.
23. Stollman TH, de Blaauw I, Wijnen MHWA, van der Staak
FHJM, Rieu PNMA, Draaisma JMT, et al. Decreased
mortality but increased morbidity in neonates with jejunoileal
atresia; a study of 114 cases over a 34-year period. J Pediatr
Surg. 2009 1;44(1):217221.
24. Pastor AC, Phillips JD, Fenton SJ, Meyers RL, Lamm AW,
Raval MV, et al. Routine use of a SILASTIC spring-loaded
silo for infants with gastroschisis: A multicenter randomized
controlled trial. J Pediatr Surg. 2008 10;43(10):18071812.
25. Phillips JD, Raval MV, Redden C, Weiner TM. Gastroschisis,
atresia, dysmotility: Surgical treatment strategies for a distinct
clinical entity. J Pediatr Surg. 2008 12;43(12):22082212.
26. Walter-Nicolet E, Rousseau V, Kieffer F, Fusaro F, Bourdaud N,
Oucherif S, et al. Neonatal outcome of gastroschisis is mainly
influenced by nutritional management. J Pediatr Gastroenterol
Nutr. 2009;48(5):612.
27. Diamond I, Sterescu A, Pencharz P, Kim J, Wales P. Changing
the paradigm: Omegaven for the treatment of liver failure in
pediatric short bowel syndrome. J Pediatr Gastroenterol Nutr.
2009;48(2):209.
28. Muratore CS, Utter S, Jaksic T, Lund DP, Wilson JM. Nutritional morbidity in survivors of congenital diaphragmatic
hernia. J Pediatr Surg. 2001 8;36(8):11711176.
29. Keshen TH, Miller RG, Jahoor F, Jaksic T. Stable isotopic
quantitation of protein metabolism and energy expenditure
in neonates on- and post-extracorporeal life support. J Pediatr
Surg. 1997;32(7):958.
30. Shew SB, Keshen TH, Jahoor F, Jaksic T. The determinants of
protein catabolism in neonates on extracorporeal membrane
oxygenation. J Pediatr Surg. 1999;34(7):1086.
31. Agus MSD, Javid PJ, Ryan DP, Jaksic T. Intravenous

insulin decreases protein breakdown in infants on extracorporeal membrane oxygenation. J Pediatr Surg. 2004
6;39(6):839844.
32. Hulst JM, van Goudoever JB, Zimmermann LJ, Hop WC,
Bller HA, Tibboel D, et al. Adequate feeding and the usefulness of the respiratory quotient in critically ill children.
Nutrition. 2005 2;21(2):192198.
33. Willot S, Uhlen S, Michaud L, Briand G, Bonnevalle M, Sfeir
R, et al. Effect of ursodeoxycholic acid on liver function in
children after successful surgery for biliary atresia. Pediatrics.
2008;122(6):e1236.
34. DeRusso P, Ye W, Shepherd R, Haber B, Shneider B, Whitington P, et al. Growth failure and outcomes in infants with
biliary atresia: A report from the biliary atresia research
consortium. Hepatology. 2007;46(5):1632.
35. Petrosyan M, Guner Y, Williams M, Grishin A, Ford H.
Current concepts regarding the pathogenesis of necrotizing
enterocolitis. Pediatr Surg Int. 2009;25(4):309.
36. Hall NJ, Peters M, Eaton S, Pierro A. Hyperglycemia is
associated with increased morbidity and mortality rates in
neonates with necrotizing enterocolitis. J Pediatr Surg. 2004
6;39(6):898901.
37. Al-Hudhaif J, Phillips S, Gholum S, Puligandla PP, Flageole H.
The timing of enterostomy reversal after necrotizing enterocolitis. J Pediatr Surg. 2009 5;44(5):924927.
38. Bohnhorst B, Mller S, Drdelmann M, Peter CS, Petersen
C, Poets CF. Early feeding after necrotizing enterocolitis in
preterm infants. J Pediatr. 2003 10;143(4):484487.
39. Albers MJIJ, Steyerberg E, Hazebroek FWJ, et al. Glutamine
supplementation of parenteral nutrition does not improve
intestinal permeability, nitrogen balance, or outcome in
newborns and infants undergoing digestive-tract surgery:
results from a double-blind, randomized, controlled trial. Ann
Surg. 2005;241(4):599.
40. Calder P. Immunonutrition in surgical and critically ill
patients. Br J Nutr. 2007;98 (Suppl 1):S133.
41. St. Peter SD, Tsao K, Sharp SW, Holcomb III GW, Ostlie DJ.
Predictors of emesis and time to goal intake after pyloromyotomy: analysis from a prospective trial. J Pediatr Surg. 2008
11;43(11):20382041.
42. van der Kuip M, de Meer K, Westerterp KR, Gemke RJ. Physical activity as a determinant of total energy expenditure in
critically ill children. Clin Nutr. 2007 12;26(6):744751.
43. Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P,
Forbes A, et al. ESPEN guidelines on parenteral nutrition:
Intensive care. Clin Nutr. 2009 8;28(4):387400.
44. Vervloessem D, van Leersum F, Boer D, Hop WCJ, Escher
JC, Madern GC, et al. Percutaneous endoscopic gastrostomy
(PEG) in children is not a minor procedure: Risk factors for
major complications. Semin Pediatr Surg. 2009 5;18(2):9397.
45. Beres A, Bratu I, Laberge J. Attention to small details: Big deal
for gastrostomies. Semin Pediatr Surg. 2009 5;18(2):8792.
46. Veenker E. Enteral feeding in neurologically impaired children with gastroesophageal reflux: Nissen fundoplication and
gastrostomy tube placement versus percutaneous gastrojejunostomy. J Pediatr Nurs. 2008 10;23(5):400404.
47. Kane TD. Laparoscopic Nissen fundoplication. Minerva Chir.
2009;64(2):147.
PART IV
NUTRITION CARE OF
THE PEDIATRIC PATIENT
33.Assessment of Nutrition Status by Age

and Determining Nutrient Needs. . . . . . . . . . . . . . 409
34.Parenteral and Enteral Nutrition Support:
Determining the Best Way to Feed. . . . . . . . . . . . . 433
35. Implementation of the Plan. . . . . . . . . . . . . . . . . . 448
Beth Lyman, RN, MSN
Jodi L. Gamis, OTR
36.Evaluation and Monitoring of Pediatric Patients
Receiving Specialized Nutrition Support . . . . . . . . 460
37. Ethical Issues in the Provision of Nutrition . . . . . . 477
Brian Carter, MD
33
Assessment of Nutrition Status by Age

and Determining Nutrient Needs
Liesje Nieman Carney, RD, CNSD, LDN and Jennifer Blair, MA, RD, CSP, LDN
Learning Objectives
Contents
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
Nutrition Assessment of Premature Infants. . . . . . . . . . 409
Classification Parameters
Special Considerations
Energy Needs
Growth
Nutrition Assessment of Full-Term Infants and Children.411

Nutrition Assessment of Adolescents . . . . . . . . . . . . . . 412
Diet History. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414

Anthropometric Measurements. . . . . . . . . . . . . . . . . . . 414
Weight
Length/Height
Head Circumference
Body Mass Index-for-Age
Mid-Arm Circumference and Triceps Skinfold
Growth Charts
Biochemical Indices
Physical Exam
Appendix 33-1: Estimating Nutrient Needs . . . . . . . . . .

Appendix 33-2: Percentiles of Upper Arm
Circumference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Appendix 33-3: Triceps Skinfold Percentiles. . . . . . . . .
Appendix 33-4: Fetal-Infant Growth Chart. . . . . . . . . . .
Appendix 33-5: NCHS/CDC Growth Charts . . . . . . . . . .
1. Identify the important components of a pediatric nutrition assessment.

2. Describe and differentiate the nutrition needs among
premature infants, full-term infants, children, and
adolescent pediatric populations.
3. Recognize potential nutrition deficiencies and excesses
commonly found among the pediatric population.
Background
Nutrition assessment of infants, children, and adolescents

enables practitioners to identify those at nutrition risk for
weight loss, poor growth, obesity, and nutrient deficits and
excesses. Components of a detailed nutrition assessment
include anthropometric measurements with comparison
to reference standards, a detailed diet history, biochemical
indices monitoring, and physical examination.
Nutrition Assessment of Premature Infants

418
420
421
422
423
Nutrition assessment of premature infants is a critical

component in the medical management of high-risk
neonates. Routine assessment is vital to ensure adequate
nutrition status of the critically ill neonate. Premature
infants are classified according to their birth weight and
gestational age at birth. The goal for the premature infant is
to mimic intrauterine weight gain.1-3
Classification Parameters
Premature infants are classified by the infants gestational
age, growth curve parameters, and maturational examination. The maturational examination, known as the
Ballard score, is a postnatal, indirect method of assessing a
neonates gestational age. It is based upon indicators of fetal
409
410
neuromuscular and physical maturation.4 Premature infants

are defined by their weight at birth. Table 33-1 depicts these
classifications.
Table 33-1 Classification of Preterm Infants by Birth Weight
Low birth weight (LBW)
Very low birth weight (VLBW)
Extremely low birth weight (ELBW)
Micronate
< 2500 g
< 1500 g
< 1000 g
< 750 g
The Lubchenco growth chart is a classification of

newborns based on maturity and intrauterine growth. 5
Along with intrauterine weight charts, these charts allow
the identification of infants with unusual growth patterns.
The Lubchenco growth curve classifies infants as: large
for gestational age (LGA), appropriate for gestational age
(AGA), or small for gestational age (SGA). AGA infants
fall between the 10th and 90th percentile on the weight
per gestational age curve, whereas LGA infants plot greater
than the 90th percentile and SGA infants less than the 10th
percentile.
Reasons infants may present as LGA include genetic
factors, infants of diabetic mothers, and those who have
transposition of the aorta. 5
SGA infants may simply be genetically small or may
have suffered from intrauterine growth restriction (IUGR).
Symmetrical IUGR generally occurs when the unborn baby
experiences a problem during early development; on the
other hand, asymmetrical IUGR is often due to a problem
later in pregnancy. Conditions causing IUGR in infants
include exposure to intrauterine infection; poor intrauterine nutrient provision (eg, placental or umbilical cord
defects); intrauterine exposure to tobacco, narcotics, or
alcohol; chronic lack of oxygen (ie, hypoxia); birth defects
(eg, severe cardiovascular defect), and congenital malformations such as Down syndrome, Turners syndrome, and
trisomy 18. 5
Special Considerations
Specific medical conditions will alter the neonates nutrition needs and ability to feed enterally and by mouth. For
instance, gastrointestinal anomalies such as gastroschisis,
omphalocele, and necrotizing enterocolitis (NEC) will
mandate feeding the infant with parenteral nutrition (PN)
support for longer time periods until after surgical intervention. Furthermore, infants with NEC may suffer from
short bowel syndrome (SBS) postsurgery and may require
long-term PN support. The transition to enteral feeds is
often tenuous and requires slower advancement to full
feeds compared to the premature infant with a healthy gut.

These conditions often require protein hydrolysate or free
amino acid formulas while the gastrointestinal tract adapts.
Protein hydrolysates and free amino acid formulas do not
provide the higher nutrient components provided with
premature formulas. This may require additional nutrient
supplementation, such as calcium and phosphorus, to meet
the needs of the premature infant.
Long-term PN support in the premature infant places
the infant at increased risk for osteopenia of prematurity.
This is due to the inability to match intrauterine calcium
and phosphorus accretion rates, without precipitation of the
parenteral solution.
The premature infants respiratory status may alter his
or her energy requirements and the ability to feed orally.
For instance, chronically ventilator-dependent infants
may require decreased energy requirements since they are
not working to breathe. Conversely, infants may have
increased energy expenditure during times of weaning
from respiratory support. Appropriate caloric provisions
are often difficult to determine, and are best estimated
by closely monitoring daily weight changes. Infants with
chronic lung disease (CLD) and bronchopulmonary
dysplasia (BPD) often require fluid restrictions, requiring
formula concentration and the use of modular supplements
to meet their increased energy and nutrient requirements
within the constraints of fluid restrictions.
Energy Needs
The premature infants weight may decrease 10% to 15%
in the first week of life due to decreased water content of
the extracellular volume. Until the weight is regained, the
infants birth weight should be used to estimate energy and
nutrient needs.
Growth
The premature infant should be weighed nude, at the same
time of day, on the same scale, on a daily basis to evaluate
nutrition status. The infants average daily weight gain is
compared (in grams per kilogram daily or grams per day)
to expected intrauterine weight velocity charts. Please refer
to Table 33-2.6 Extreme weight changes may be due to fluid
shifts or medical conditions, and these factors should be
considered before modifying an infants nutrition support
regimen.
ASSESSMENT OF NUTRITION STATUS BY AGE AND DETERMINING NUTRIENT NEEDS
Table 332 Average Daily Intrauterine Weight Gain7

Age Interval
(weeks)
Average Daily
Weight Gain
(g/d)
Mean Weight
(g)
Average Daily
Weight Gain
(g/kg/d)
2425
2526
2627
2728
2829
2930
3031
3132
3233
3334
3435
3536
3637
3738
Mean
11.4
15.7
18.6
21.4
22.6
23.1
24.3
25.7
27.1
30
31.4
34.3
35.7
31.4
25.2
904961
9611001
10011065
10651236
12361300
13001484
14841590
15901732
17321957
19572278
22782483
24832753
27532866
28663025
12.2
16
18
18.6
17.8
16.6
15.8
15.5
14.7
14.2
13.3
13.1
12.7
10.7
14.9
Nutrition Assessment of Full-Term Infants

and Children
The purpose of the nutrition assessment of infants and children is to (1) evaluate growth, body size measurements, and
composition as compared to national standards; (2) determine an estimation of nutrient needs; and (3) evaluate the
adequacy of the nutrition regimen. Infants experience a more
rapid growth velocity as compared to children. The need
for medical care may impact the childs nutrition status by
altering metabolic requirements and nutrient intake, and can
result in weight loss and decreased height or length velocity.8
Refer to Table 33-3 for reference standards of growth velocity,
both weight and length, in healthy children.9
411
a reference standard for other children the same age in the

United States and can aid in the determination of conditions
such as malnutrition and obesity. Evaluation of growth is
best monitored over a period of time.
Poor weight gain is an indicator of acute malnutrition
(ie, wasting) while inadequate length or height velocity is
indicative of chronic malnutrition (ie, stunting). Tables 33-4
and 33-5 provide wasting and stunting criteria.11 Waterlow
developed these standards to classify children as either
stunted (ie, low height-for-age) or wasted (ie, low weightfor-height). Frisancho12 argues that although the Waterlow
criteria have the advantage of being based on easily obtainable information, measurements of height and weight, the
criteria are ineffective for distinguishing the truly malnourished child from those who are simply underweight. For
instance, a child suffering from protein malnutrition will
present with a low weight-for-height, but so will a tall and
normally lean child.12 Additionally, an obese child will
present with a high weight-for-height, as might a muscular,
large-frame child.12
Table 33-4 Waterlow Criteria for Degree of Wasting11 (wt/ht %std)
> 120%
Obese
110120%
Overweight
90110%
Normal variation
8089%
Mild wasting
7079%
Moderate wasting
< 70%
Severe wasting
Table 33-5 Waterlow Criteria for Degree of Stunting11 (ht/age %std)
> 95%
Normal
9095%
Mild
85-89%
Moderate
< 85%
Severe
Table 33-3 Recommendations for Weight and Length Gain

for Healthy Children8,9
Age
Weight (g/d)
Length (cm/mo)
< 3 mo
36 mo
612 mo
13 y
46 y
710 y
2535
1521
1013
410
58
512
2.63.5
1.62.5
1.21.7
0.71.1
0.50.8
0.40.6
Infants and childrens weights, length or height, head

circumference (measured for those less than 3 years of
age), and weight-for-length or body mass index (BMI)-forage should be plotted on the National Center for Health
Statistics (NCHS) and Centers for Disease Control and
Prevention (CDC) standard growth charts.10 This provides
412
Table 33-6 Recommended Dietary Allowances13,15

Age
kcal/kg
1989 RDAs
Protein g/kg
2002 DRIs
06 mo
712 mo
13 y
46 y
710 y
Males
1114 y
1518 y
108
98
102
90
70
1.52 (AI)
1.2
1.05
0.95 (48 y)
0.95 (913 y)
55
45
0.85 (1418 y)
47
40
0.85 (1418 y)
Females
1114 y
1518 y
Estimation of energy requirements can be determined

using the 1989 Recommended Dietary Allowance (RDA)
or the 2002 Dietary Reference Intake estimated energy
requirements (EER). Both of these methods represent
energy needs of the healthy child. Refer to Table 33-6 for
the RDAs for energy.13 The resting energy expenditure
(REE) can be estimated using the World Health Organization (WHO) equation (Table 33-7).14 Using the WHO
equation to determine the REE with an activity factor (see
Table 33-8) may be more helpful in estimating energy needs
of the acutely ill child. Refer to Appendix 33-1 Estimating
Nutrient Needs for a comprehensive description of the
various methods to estimate energy needs.
Table 33-7 WHO Equation14
Age
Males
03
310
1018
1830
Females
03
310
1018
1830
kcal/d
60.9W 54
22.7W + 495
17.5W + 651
15.3W + 679
61W 51
22.5W + 499
12.2W + 746
14.7W + 496
Table 33-8 Activity and Stress Factors14

Activity/Stress Adjustment Factors
REE x 1.3: For a well-nourished child at bedrest with mild to moderate

stress
REE x 1.5: For a normally active child with mild to moderate stress; an
inactive child with severe stress (ie, trauma, stress, cancer), or a child
with minimal activity and malnutrition requiring catch-up growth
REE x 1.7: For an active child requiring catch-up growth or an active
child with severe stress
The DRI for protein, as outlined in Table 33-6, is used to

estimate protein needs15 for both the healthy child as well as
the hospitalized child. However, clinical conditions should
be considered when estimating protein requirements. Some
situations may require protein intakes greater than the DRI
to achieve a positive nitrogen balance. Examples include
major surgery, wound healing, infection, and catch-up
growth. Conversely, the critically ill patient with acute renal
failure may benefit from a moderate protein restriction (but
not less than the DRI for age).
Maintaining adequate hydration is crucial in both the
healthy and hospitalized infant and child. Guidelines for
determining maintenance fluid requirements are outlined
in Table 33-9.16,17
Table 33-9 Fluid Requirements16,17
110 kg
1020 kg
> 20 kg
100 mL/kg
1000 mL + 50 mL each kg
over 10 kg
1500 mL + 20 mL for each kg
over 20 kg
Nutrition Assessment of Adolescents
Nutrition assessment of adolescents should include

measurements of weight, height, and BMI-for-age with
plotting on CDC growth curves, an estimation of nutrient
needs, diet history, and analysis of biochemical indices.
Refer to Tables 33-6 through 33-9 for the RDAs for kilocalories, the DRIs for protein, the WHO equation, activity
factors, and maintenance fluid guidelines, respectively.
Special conditions during adolescence that need to
be considered include the increased energy and nutrient
requirements that occur during puberty, as well as the
behavioral, social, and emotional changes that occur during
adolescence.18,19 Increases in lean body mass result in an
increased demand for energy, protein, calcium, and iron
intakes.18 Dietary habits during adolescence that pose a
risk for nutrient deficiencies or overnutrition include the
following: skipping meals, eating more meals outside the
home (often high in fat with low-nutrient density), binge
eating, following fad diets, and taking dietary supplements.18,19 Adolescents are at risk for inadequate calcium
and vitamin D intake due to skipping meals, avoidance
related to dieting behaviors, and replacing milk intake with
sodas and sports drinks. Females are at increased risk of
iron deficiency due to the onset of menses.
A comprehensive diet history will aid in the identification of nutrition concerns such as nutrient deficiencies,
unhealthy dietary practices, the use of dietary supplements,
and potential eating disorders. Please refer to the Diet History

section of this chapter for a more detailed explanation.18,19

Calcium
According to the American Academy of Pediatrics (AAP),
the primary need for dietary calcium in otherwise healthy
infants, children, and adolescents is to enhance bone
mineral absorption.20 Maintaining adequate calcium intake
during childhood is necessary for maximizing peak bone
mass and decreasing the risk of osteoporosis later in adulthood.20 Exercise, in addition to calcium intake, is important
for achieving peak bone mass. Wyshak and Frisch21
reported a positive relationship between cola consumption
and bone fractures. However, it is uncertain if this may be
attributed to the potential excess phosphorus content found
in colas, or due to the diminished calcium intake related
to decreased consumption of dairy products (specifically
milk). Currently, dual-energy radiograph absorptiometry
(ie, DEXA scan) is the method used in many studies to
measure bone mineral content and bone mineral density of
specific areas or the entire skeleton, with notably negligible
levels of radiation exposure.20
According to the AAP, the optimal primary nutritional
source during the first year of life is human milk. No available evidence shows that exceeding the amount of calcium
retained by the exclusively breastfed term infant during the
first 6 months of life or the amount retained by the human
milk-fed infant supplemented with solid foods during the
second 6 months of life is beneficial to achieving long-term
increases in bone mineralization. 20 The exception to this is
premature infants, who benefit from fortified human milk
and premature infant formulas that have additional mineral
supplementation. Data demonstrate that the bioavailability
of calcium in human milk is greater than that found in
infant formulas and cows milk. Therefore, infant formulas
contain increased concentrations of calcium content to be
more comparable to that found in human milk.
According to the AAP, calcium retention is relatively
low in toddlers and increases as puberty approaches. 20 Most
available data conclude that calcium intakes of 800 mg daily
are adequate for bone mineral accretion in pre-pubescent
children. The majority of bone formation and the efficiency
of calcium absorption are highest during puberty. Data from
balance studies suggest that maximal net calcium balance
is achieved with intakes of 1200 to 1500 mg daily in most
healthy adolescents.20
Calcium intakes on food labels are indicated as a
413
percentage of the Daily Value (DV) in each serving. The DV

is currently set at 1000 mg daily. Calcium supplementation
should be considered for children who are unable to achieve
adequate dietary sources of calcium. Calcium supplements
vary in their bioavailability, and may be comparable to or
greater than that of dairy sources.20
Iron
Iron deficiency is the most common nutrition deficiency in
the world.22 The incidence of iron deficiency anemia peaks
in children between the ages of 6 and 20 months, or earlier
with premature infants, with a second peak around puberty.
Iron deficiency may adversely affect the childs psychomotor development and cognitive function.22 Those at risk
for developing iron deficiency include premature and low
birth-weight infants, overweight children, children with
caregivers of low socioeconomic status, adolescent females,
and athletes.22 Additionally, toddlers are often at a risk for
iron-deficiency anemia due to transitioning from iron-fortified formula to cows milk.
More than 80% of the iron stores of the term infant are
accreted during the third trimester of pregnancy. Therefore,
infants born premature require more iron postnatally during
the first year of life to catch up to infants born at term. 23
Iron intake requirements for premature infants range from
2 mg/kg/d for infants with birth weights between 1500 and
2500 g to 4 mg/kg/d for infants weighing less than 1500g
at birth.24,25 Adequate iron stores are needed for optimal
growth and development. According to the AAP Infants
who are not breastfed or who are partially breastfed should
receive an iron-fortified formula (containing between 4 to
12 mg of iron per liter) from birth to 12 months.23
The recommended treatment dose for iron deficiency
anemia is 3 to 6 mg/kg/d in 3 divided doses, ideally with
concomitant vitamin C intake to enhance iron absorption.
Prophylactic iron supplementation is recommended for those
identified at an increased risk of iron deficiency anemia.22
Vitamin D
Cases of rickets continue to be reported in the United States
and other Western countries. One of the causes of rickets is
vitamin D deficiency. Vitamin D deficiency is attributed to
exclusively breastfed infants due to breast milks low vitamin
D content and those with decreased sun exposure due to an
inadequate conversion within the body to the active form
of vitamin D. As a result, the AAP recently issued updated
guidelines for vitamin D intake for infants, children, and
adolescents to prevent vitamin D deficiency which in turn
will reduce the incidence of rickets. These new guidelines
414
replaced the 2003 AAP recommendations for a daily intake

of 200 International Units of vitamin D for infants in the
first 2 months of life, children, and adolescents. The 2008
guidelines recommend a daily intake of 400 International
Units of vitamin D for all infants, children, and adolescents
starting from the first few days of life.26,27
Fluoride
According to the CDC, dental caries may be the most prevalent of infectious diseases in our nations children. Primary
tooth decay can affect childrens growth, lead to malocclusion, and result in pain and potentially life-threatening
swelling.28,29 Recommendations to aid in the prevention of
dental caries include the establishment and maintenance
of good oral hygiene, optimizing systemic and topical fluoride exposure, and the elimination of prolonged exposure
to simple sugars in the diet.28 The American Academy of
Pediatric Dentistry (AAPD) reports that the adjustment of
fluoride levels in community water to the optimal concentration is the most beneficial and inexpensive method of
reducing the incidence of dental caries. However, when
drinking water fluoridation is not possible, the AAPD
supports the intake of daily fluoride supplements and the
use of fluoride-containing preparations (eg, toothpastes,
gels, and mouth rinses). Topical fluoride use in children is
cautioned, due to the risk of excessive exposure to fluoride. 30
Table 33-10 details recommendations for fluoride supplementation based on levels found in community drinking
water. 31
Table 33-10 Level of Fluoride in Community Drinking Water (ppm)* and
Recommended Fluoride Supplementation
Measured Levels
< 0.3
< 0.30.6
> 0.6
None
0.25 mg/d
0.5 mg/d
1 mg/d
None
None
0.25 mg/d
0.5 mg/d
None
None
None
None
Age
06 mo
6 mo3 y
36 y
616 y
*1 ppm = 1 mg/L31
Diet History
A detailed diet history is an important component of the

nutrition assessment. Methods of obtaining diet histories
include usual intake patterns, 24-hour recall, written diet
records provided by the caregiver, and calorie counts for
the hospitalized pediatric patient. Of these, the most accurate method of diet intake assessment is to obtain a 3- to
5-day diet record, which can then be analyzed for nutrient
composition. This will enable the practitioner to gain

insight into energy, protein, micronutrient deficiencies, and
excesses. When interviewing the caregiver, the practitioner
must be diligent in obtaining information regarding food
and formula preparation, food availability, and behavioral
eating patterns. This will aid in providing insight to potential barriers such as improper formula preparation, potential
food insecurities related to poor socioeconomic status, and
behavioral conditions affecting the childs diet.
Anthropometric Measurements
Anthropometric measurements are a crucial component of

the nutrition assessment. A series of measurements obtained
over a period of time provides a more accurate and comprehensive indication of a childs growth.
Weight
Weights of children under the age of 2 should be measured
on a leveled scale that is frequently calibrated. The scale
should be calibrated regularly with appropriate standards.
The nude infant is placed on the scale, making sure the
weight is evenly distributed on either side of the center of
the scale. Weight is recorded to the nearest 10 g.12,32
For children older than 2 years of age, the weight should
be measured using a standing scale. The calibration of the
scale should also be done regularly with appropriate standards. Subjects are to stand still in the middle of the scale,
with their body weight evenly distributed between both
feet. Light indoor clothing should be worn. Weights should
be recorded to the nearest 100 g.12,32
Length/Height
With children under 3 years of age, length should be
obtained in the recumbent position using a length board.
This is a device consisting of a flat board and a moveable
footboard, which are perpendicular to the table surface. A
fixed measuring tape is present with the 0 end at the edge
of the headboard. The infants length should be recorded
as the distance between the headboard and the footboard.
An assistant should hold the infant/toddlers head with the
child looking upward and the crown of the childs head
against the headboard. The examiner holds the infants
legs straight with the feet against the board and the toes
facing up. The footboard is placed flat against the infant/
toddlers feet. The measurement is recorded to the nearest
0.1 cm.12,32
Children older than 3 years of age are to be measured,
without shoes, using a standiometer. A standiometer is a
metric tape affixed to a vertical surface and a moveable
block that is attached to the vertical surface at a right angle,

that can be brought down to the crown of the head. Stature
can also be measured on a platform scale, but it is a less
accurate measure than that obtained with a standiometer.
The subject should stand with heels together and his or her
back as straight as possible. The heels, buttocks, shoulders,
and head should touch the wall or vertical surface of the
measuring device. The subjects weight should be evenly
distributed between both feet with the head positioned
horizontally. The arms should hang freely at the sides, with
palms facing the thighs. The moveable block is brought down
until it puts sufficient pressure on the head to compress the
hair. Measurements are recorded to the nearest 0.1 cm.12,32
When a subjects stature cannot be obtained standing,
either due to the inability to stand or excessive spinal
curvature, stature can be extrapolated from measuring
knee height or tibial length. Knee height is obtained with a
sliding broad-blade caliper. While lying in a supine position,
the subjects knee and ankle are bent to form a 90-degree
angle. The fixed blade of the caliper is placed under the heel
of the foot, and the other blade is placed over the anterior
surface of the thigh, over the condyle of the femur. The shaft
of the caliber is held parallel to the tibia shaft, with pressure
applied to compress the tissue. Measurements are recorded
to the nearest 0.1 cm and then converted to stature12,32 by
using the following equations:
Males: 64.19 (0.04 age) + (0.02 knee height)
Females: 84.88 (0.24 age) + (1.83 knee height)

Tibial length is unique from knee heightit is a valid
measurement in children with lower extremity contractions. Unfortunately, knee height is unable to be obtained
when the feet are contracted because it is not possible for
the fixed blade of the caliper to be placed under the heel of
the foot. To obtain a tibial length, one measures from the
superomedial edge of the tibia to the inferior edge of the
medial malleolus using a flexible steel tape. The following is
a formula33,34 for the estimation of stature in children with
cerebral palsy using tibial length:
(3.26 tibial length in cm) + 30.8 = estimated stature (cm)

Genetic influences should be considered when evaluating
any linear growth abnormality. Obtaining parental stature
is essential to help differentiate when a growth pattern is
normal for the childs genetic potential or not. Adjustments
for parental stature are based on the average height of the
415
childs biological parents, called the mid-parental height,

which is calculated as follows:
Mothers height + fathers height 2 = mid-parental
height
The impact of mid-parental height on a childs growth can
be evaluated by using one of two methods:
Garn and Rohmann defined percentile ranges for
corrected height of children35; and
Himes et al36 formulated adjustment factors that are
added to the childs measured stature.
Head Circumference
Occipital-frontal circumference (OFC) should be obtained
in infants and children until 3 years of age. Head circumference is measured with a narrow, non-stretchable measuring
tape. The tape should cross the forehead, just above the
supraorbital ridges, passing around the head at the same
level on both sides to the occiput. The tape should be moved
up and down until maximum circumference is obtained.
Sufficient tension should be placed on the tape to press the
hair against the skull. 37
Body Mass Index-for-Age

Body mass index-for-age (BMI-for-age) is an indicator of
potential nutrition-related health concerns. The BMI can
be used to define patients as obese, overweight, adequately
nourished, at risk for underweight, and underweight. The
BMI (kg/m 2) is derived by taking the subjects weight in
kilograms and dividing by height in meters squared. BMI is
most useful when measurements are taken periodically and
compared over time for trends. Table 33-11 outlines BMI
criteria.10,12
Table 33-11: Interpretation of BMI for Ages 218 Years34
Percentile
Interpretation
< 5th %ile

515th %ile
1585th %ile
8594th %ile
95th %ile
Underweight
At risk for underweight
Adequate
Overweight
Obese
Mid-Arm Circumference and Triceps Skinfold

Mid-arm circumference (MAC) and triceps skinfold
measurements (TSF) are utilized to assess fat and muscle
mass. These measurements should be monitored over a
period of time to evaluate for changes. These measurements
416
are useful for further evaluating fat and muscle mass of

children whose weight-for-height or BMI-for-age fall less
than the 5th percentile or above the 95th percentile, and for
those suffering from malnutrition. Skinfold measurements
may also be obtained on other sites of the body, such as
subscapular and suprailiac.12,32,37 Refer to Table 33-12 for
methods to calculate MAC and TSF.
Table 33-12 Anthropometric Equations12
Arm Muscle Area (AMA) =
[(MAC in cm 10) - (3.14 TSF)]
12.56
Upper Arm Area =
[(MAC in cm 10)] 0.785
[3.14]
Arm Fat Area (AFA) = Upper Arm Area AMA
To measure mid-upper arm circumference, the subjects

right arm is bent to a 90-degree angle at the elbow, with the
upper arm held parallel to the body. The distance between
the acromion, the bony protrusion on the posterior of the
upper shoulder, and the olecranon (ie, the tip) of the elbow
is measured. Mark the midpoint between these two landmarks with ink. The subjects arm should be relaxed and
hanging loosely by the side of the body. The metric tape
should be positioned around the upper arm at the marked
midpoint. The tape should be snug, but not pinching the
skin. Record the measure to the nearest 0.1 cm.12,32 Refer to
Appendix 33-2 for the MAC measurement tables to interpret measurements obtained. 38
Triceps skinfold thickness is measured with a skinfold
caliper. Skinfold thickness is measured at the midpoint upper
arm circumference (refer to mid-upper arm circumference
measure above). The subjects arm should hang loosely at
the side and the examiner should grasp a vertical pinch of
skin and subcutaneous fat between the thumb and forefinger, about 1 cm above the previously marked midpoint.
The skinfold is pulled away from the muscle and the caliper
is placed on the marked midsection. Three readings should
be taken, and the average of the 3 is recorded in millimeters. The reading is measured as soon as the calipers come in
contact with the skin and the dial reading stabilizes.12,32 See
Appendix 33-3 for triceps skinfold percentiles.
Growth Charts
Fenton for Premature Infants
The Babson and Benda 1976 fetal-infant growth graph
for premature infants was commonly used to assess growth
of premature infants in the neonatal intensive care unit
(NICU). Limitations of this curve included the small sample

size, the 26-week gestational age start, and the 500-g graph
increments. In 2003, Tanis R. Fenton6 created an updated
growth chart, which allows for a comparison of infants
growth from 22 weeks gestation through 10 weeks postterm. Data compilation was also based on a larger sample
size. Comparisons were made between the new chart and
the Babson and Benda chart. Growth results from the
National Institute of Child Health and Human Development Research Network (NICHD) were then superimposed
on the new chart to validate growth results. Additionally, a
large-scale grid was used for accuracy of plotting. The increments are 100 g of weight, as opposed to Babson and Bendas
500 g, 1 cm for both head circumference and length, and
1-week intervals for time. Refer to Appendix 33-4 for this
growth chart. It can also be downloaded from http://www.
biomedcentral.com/1471-2431/3/13.
While in the NICU, infants weights should be plotted
daily. Head circumference and length should be measured
and plotted weekly. The optimal body composition of
growing premature infants is unknown. However, the most
comprehensive growth assessment uses the calculation of
growth velocity and size in relation to correlating gestational ages on the growth chart.6
CDC Curves (Birth to 36 Months and 2 to 20 Years)
The National Center for Health Statistics (NCHS) growth
curves are references of height and weight used to evaluate
growth and nutrition status of infants, children, and adolescents. The NCHS curves were compiled from a combined
sample of data derived from the NCHSs Health Examination Survey, conducted during 1963-1965 and 1970-1974,
and data from the Fels Research Institute.12 The 2000 CDC
growth charts represent the revised version of the 1977
NCHS growth charts.10 Please refer to Appendix 33-5 for
the CDC Growth Curves for Males (birth to 36 months),
Females (birth to 36 months), Males (2 to 20 years), and
Females (2 to 20 years).
Biochemical Indices
Biochemical parameters are also an essential component of
a comprehensive nutrition assessment. Routine laboratory
monitoring with the pediatric population includes complete
blood counts and blood lead levels to rule out lead exposure. Abnormal hemoglobin (Hgb) and hematocrit (Hct)
levels can aid in the detection of iron, vitamin B12, and folate
deficiencies.
A complete blood count can identify the degree and
features of anemia. Red cells are microcytic and hypochromic
in iron deficiency anemia. In early phases of iron deficiency,

decreased levels of mean corpuscular volume (MCV) and
mean hemoglobin content (MCH) are seen. As the iron deficiency progresses, decreased levels of Hgb and Hct develop.22
If iron deficiency is suspected, a complete iron profile should
be ordered. A low serum iron concentration with an elevated
total iron-binding capacity (TIBC) and decreased levels of
ferritin are a diagnostic indicator of iron deficiency.22
However, if Hgb and Hct are low with an elevated
MCH, vitamin B12 and folate deficiencies should be considered. Serum vitamin B12 and folate levels should be drawn.
Those consuming a vegetarian diet or having undergone
ileocecal valve resection (from gastrointestinal surgery) are
at a greater risk of developing vitamin B12 deficiency.
417
Serum albumin, transferrin, and prealbumin are indicators of visceral protein status. Depleted levels can be an
indication of visceral protein depletion and malnutrition.
However, other clinical conditions (eg, altered fluid status,
inflammation, acute infection) may falsely decrease levels.
Physical Exam
Physical examination of the pediatric patient is also a vital
component of the nutrition assessment. Physical examination can provide insight into conditions such as malnutrition,
obesity, edema, dehydration, and vitamin deficiencies and
excesses. Table 33-13 outlines some nutrition concerns
based on physical examination.2,33,39
Table 33-13 Nutrition Concerns Based on Physical Examination1,27,33

Site
Potential Nutritional/Metabolic Status
Skin Integrity
Pallor
Iron, folate, or vitamin B12 deficiency
Dry, scaly skin
Vitamin A or essential fatty acid deficiency
Dermatitis
Essential fatty acid deficiency; zinc, niacin, riboflavin, or tryptophan deficiency
Spoon shape
Iron deficiency
Lackluster, dull
Protein deficiency
Mottled, pale, poor blanching
Vitamin A or C deficiency
Moon face
Protein-calorie malnutrition
Bilateral temporal wasting
Protein-calorie malnutrition
Neck
Enlarged thyroid
Iodine deficiency
Mouth
Dry, cracked, red lips
Riboflavin, niacin, or vitamin B6 deficiency
Bleeding gums
Vitamin C deficiency
Inflammed mucosa
Vitamin B complex, iron or vitamin C deficiency
Magenta color
Riboflavin deficiency
Beefy red color and diminished taste
Niacin, folate, riboflavin, iron, or vitamin B12 deficiency
Night blindness; dull, dry appearance

to sclerae or inner lids; dull, milky
appearance of the cornea
Vitamin A deficiency
Cracked, red corners
Riboflavin or niacin deficiency
Dull, lackluster, thin, sparse
Protein, iron, zinc, or essential fatty acid deficiency
Easily pluckable
Protein deficiency
Dentition
Excessive dental caries
Excessive simple carbohydrate intake
Abdomen
Rounded, distended
Gas, edema, ascites, obesity
Temperature
Increased temperature
Increased energy and fluid requirements
Respiration
Increased respiratory rate
Altered calorie and protein requirements

Energy needs may be increased if weaning from ventilator support or decreased if
chronically ventilator dependent
Nails
Face
Tongue
Eyes
Hair
418
Appendix 33-1 Estimating Nutrient Needs

Name of Equation
or Formula
ENERGY
1989
Recommended
Daily Allowance
(RDA)
Description
Calculations for the Equation or Formula
Infants:
00.5 y:
108 x Wt (kg)
0.51 y: 98 x Wt
Children:
13 y: 102 x Wt
46 y: 90 x Wt
710 y: 70 x Wt
Males:
11-14 y: 55 x Wt
15-18 y:
45 x Wt
Females:
11-14 y: 47 x Wt
15-18 y: 40 x Wt
Estimated Energy
Replaces the 1989 Recommended
EER = TEE + energy deposition
Requirements
Dietary Allowances (RDA).
Ages 0-36 mo:
(EER) (new DRI/
0-3 mo: (89 x wt [kg] - 100) + 175
Energy needs were determined from
IOM equation) &
4-6 mo: (89 x wt [kg] - 100) + 56
children with normal growth, body
Physical Activity (PA) composition, and activity, and who are 7-12 mo: (89 x wt [kg] - 100) + 22
Co-Efficients
13-36 mo: (89 x wt [kg] -100) + 20
also metabolically normal.
Ages 3-8 yBoys:
EER = 88.5 - (61.9 x age [y]) + PA x (26.7 x wt [kg] + 903 x ht[m]) + 20 kcal
PA = 1 if PAL is estimated to be > 1 < 1.4 (sedentary)
PA = 1.13 if PAL is estimated to be > 1.4 < 1.6 (low active)
PA = 1.26 if PAL is estimated to be > 1.6 < 1.9 (active)
PA = 1.42 if PAL is estimated to be > 1.9 < 2.5 (very active)
Ages 3-8 yGirls:
EER = 135.3 - (30.8 x age [y]) + PA x (10 x wt [kg] + 934 x ht [m]) + 20 kcal
Ages 9-18 yBoys:
EER = 88.5 - (61.9 x age [y]) + PA x ( 26.7 x wt [kg] + 903 x ht [m]) + 25 kcal
Ages 9-18 yGirls:
EER = 135.3 - (30.8 x age [y]) + PA x (10 x wt [kg] + 934 x ht [m]) + 25 kcal
EER (new DRI/IOM
Weight Maintenance TEE in Overweight Boys Ages 3-18 y:
equation) & obesity
TEE = 114 - (50.9 x age [y]) + PA x (19.5 x weight [kg] + 1161.4 x height [m])
co-efficients/factors
Weight Maintenance TEE in Overweight Girls Ages 3-18 y:
TEE = 389 - (41.2 x age [y]) + PA x (15 x weight [kg] + 701.6 x height [m])
Schofield
A predictive equation for calculating
Males:
basal metabolic rate (BMR) in healthy 0-3 y: (0.167 x wt [kg]) + (15.174 x ht [cm]) - 617.6
children that was developed by analysis 3-10 y: (19.59 x wt [kg]) + (1.303 x ht[cm]) + 414.9
of Fritz Talbot tables.
1018 y: (16.25 x wt [kg]) + (1.372 x ht[cm]) + 515.5
> 18 y: (15.057 x wt [kg]) + (1.0004 x ht[cm]) + 705.8
Females:
0-3 y: (16.252 x wt[kg]) + (10.232 x ht [cm]) - 413.5
3-10 y: (16.969 x wt [kg]) + (1.618 x ht [cm]) + 371.2
1018 y: (8.365 x wt [kg]) + (4.65 x ht [cm]) + 200
>18 y: (13.623 x wt [kg]) + (23.8 x ht [cm]) + 98.2)
FAO/WHO
The WHO equation was developed
Males:
for use in healthy children; however, it
03 y: (60.9 x wt [kg]) - 54
is commonly used to predict resting
310 y: (22.7 x wt [kg]) + 495
energy expenditure (REE) of acutely ill 1018 y: (17.5 xwt [kg]) + 651
patients in the hospital setting.
Females:
03 y: (61 x wt [kg]) - 51
310 y: (22.5 x wt [kg]) + 499
1018 y: (12.2 x wt [kg]) + 746
Based on the median energy intakes of
children followed in longitudinal growth
studies
It can overestimate needs in non-active
populations (eg, bedridden) and does
not provide a range of energy needs.
Though an outdated reference, still
widely used.
Applicable to Which
Patient Populations?
Source
Most often used for

healthy infants and
children
Committee on Dietary Allowances,

Food and Nutrition Board, National
Research Council. Recommended
Dietary Allowances. 10th ed.
Washington, DC: National Academy
Press; 1989.
Children with
normal growth, body
composition, and
activity, and who are also
metabolically normal.
National Academy of Sciences,

Institute of Medicine, Food and
Nutrition Board. Dietary Reference
Intakes for Energy, Carbohydrate,
Fiber, Fat, Fatty Acids, Cholesterol,
Protein, and Amino Acids
(Macronutrients) (2005).
Overweight children who National Academy of Sciences,

are metabolically normal Institute of Medicine, Food and
Healthy children, acutely Schofield WN. Predicting basal

ill patients in the hospital metabolism rate, new standards and
setting
review of previous work. Hum Nutr:
Clin Nutr. 1985;39C:591.
Healthy children who are World Health Organization. Energy

acutely ill patients in the and Protein Requirements. Report
hospital setting
of a Joint FAO/WHO/UNU Expert
Consultation. Technical Report Series
724. World Health Organization,
Geneva, 1985.
Source: Ludlow V, Randall R, Burritt E, Rago D. Estimating Nutrient Needs, Pediatric Module. A.S.P.E.N. Enteral Nutrition Practitioner Tutorial Project, pending publication.
419

Name of Equation
or Formula
Estimating
calorie needs for
developmental
disabilities
Description
Calculations for the Equation or Formula
Cerebral palsy (age 5-11 y*):

Mild-moderate activity: 13.9 kcal/cm height
Severe physical restrictions: 11.1 kcal/cm height
Severe restricted activity: 10 kcal/cm height
Athetoid Cerebral Palsy: Up to 6,000 kcal/day (adolescence)
Down Syndrome (5-12 y*):
Boys 16.1 kcal/cm height
Girls 14.3 kcal/cm height
Prader-Willi Syndrome (for all children and adolescents):
10-11 kcal/cm height for maintenance
8.5 kcal/cm height for weight loss
Myelomeningocele (Spina bifida) (Over 8 years of age and minimally active):
9-11 kcal/cm height for maintenance
7 kcal/cm height for weight loss
Approximately 50% RDA for age after infancy
Petersons Failure to This calculates nutrients in excess of the [RDA for weight age (kcal/kg) x Ideal body weight for height] Actual weight
Thrive (FTT)
requirements of the RDA.
Concerns with using this equation
include refeeding syndrome.
FAO/WHO/UNU
Food and Agriculture Organization, World Boys 1018 y BMR = 16.6 weight (kg) + 77 height (m) + 572
(aka Dietz
Health Organization, United Nations
equation)
University
Girls 1018 y BMR = 7.4 weight (kg) + 482 height (m) + 217
Children with developmental disabilities
(DD) may have a slower basal energy
need due to a decreased muscle tone,
growth rate, and motor activity.
The recommendation to calculate
energy needs in children with DD per
cm of height is based on the fact that
they tend to have a shorter height when
compared to children with normal
growth.
White equation
Developed for use in the pediatric

critical care population by including
temperature as a gauge of the bodys
inflammatory response.
It is not commonly used in clinical
practice, and recent studies have
shown decreased accuracy especially in
smaller, younger patients.
This equation should not be used in
patients less than 2 months of age.
STRESS FACTORS FOR ENERGY
Stress Factors
The use of stress factors along with
predictive energy equations should
be considered for use in hospitalized
children whose energy requirements
may be altered due to metabolic stress.
PROTEIN
A.S.P.E.N. Clinical
Guidelines: Nutrition
Support of the
Critically Ill Child
Metabolic stress increases catabolism

and breakdown of lean body mass.
To meet the increased demands of
metabolic stress and spare the use of
endogenous protein stores, a greater
amount of protein is needed in this
population until the underlying stress
has been overcome.
Recommendations are based on limited
data.
For the injured child Metabolic stress increases catabolism
and breakdown of lean body mass.
To meet the increased demands of
metabolic stress and spare the use of
endogenous protein stores, a greater
amount of protein is needed in this
population until the underlying stress
has been overcome.
Dietary Reference
Replaces the 1989 Recommended
Intake (DRI)
Dietary Allowances (RDA).
Protein needs were determined from
children with normal growth, body
composition, and activity, and who are
also metabolically normal.
Applicable to Which
Patient Populations?
Children with
developmental
disabilities
*This reference applies
to the specific ages
listed. Please refer to
another equation for
ages outside of the
referenced ages, and
apply an appropriate
activity/stress factor.
Rokusek C, Heindicles E. Nutrition

and Feeding of the Developmentally
Disabled. Brookings, SD: South
Dakota University Affiliated
Program, Interdisciplinary Center for
Disabilities;1985.
Infants and children who Peterson K, et al. Team Management

present underweight and of Failure-to-thrive. J Am Diet Assoc.
need to achieve catch-up 1984;84:810.
growth
Overweight/obese
adolescents in an
outpatient setting
EE (kJ/day) = (17 age [mo]) + (48 weight [kg]) + (292 body temperature
[C]) - 9677
Pediatric critical care

population
Starvation 0.700.85
Surgery 1.051.5
Sepsis 1.21.6
Closed head injury 1.3
Trauma 1.11.8
Growth failure 1.52
Burn 1.52.5
Pediatric hospitalized
population
02 y: 23 g/kg/d
Pediatric critical care

population
213 y: 1.52 g/kg/d
Source
Dietz WH, Brandini LG, Schoeller DA.

Estimates of metabolic rate in obese
and non-obese adolecents. J Pediatr.
1991;118:146149.
White MS, Shepherd RW, McEniery JA.
Energy expenditure in 100 ventilated,
critically ill children: improving the
accuracy of predictive equations.Crit
Care Med. 2000;28(7):23072312.
Leonberg B. ADA Pocket Guide to

Pediatric Nutrition Assessment.
Chicago, IL: American Dietetic
Association; 2007.
TABLE 8.10
1318 y:1.5 g/kg/d
Mehta NM, Compher C, A.S.P.E.N.

Board of Directors. A.S.P.E.N. Clinical
Guidelines: Nutrition Support of the
Critically Ill Child. J Parenter Enteral
Nutr. 2009;33(3):260276.
0-2 y: 2-3 g/kg/d

2-13 y: 1.5-2 g/kg/d
Adolescents: 1.5 g/kg/d
Pediatric critical/surgical Jaksic T. Effective and efficient

care population
nutritional support for the injured
child. Surg Clin North Am.
2002;82(2):379391, vii.
06 mo: 1.52 g/kg/d

*This is an Adequate Intake recommendation, not enough research has been
conducted to establish an RDA for this age group.
Children with
normal growth, body
composition, and
National Academy of Sciences,

Institute of Medicine, Food and
Children with
normal growth, body
composition, and
Committee on Dietary Allowances,

Food and Nutrition Board, National
Research Council. Recommended
Dietary Allowances.10th ed.
Washington, DC: National Academy
Press; 1989.
612 mo: 1.2 g/kg/d

1236 mo: 1.05 g/kg/d
413 y: 0.95 g/kg/d
1418 y: 0.85 g/kg/d
>18 y: 0.8 g/kg/d
1989
Based on the median nutrient intakes
06 mo: 2.2 g/kg/d
Recommended
of children followed in longitudinal
612 mo: 1.6 g/kg/d
Dietary Allowance
growth studies
13 y: 1.2 g/kg/d
(RDA)
It can overestimate needs in non-active 46 y: 1.1 g/kg/d
populations (eg, bedridden) and does 714 y: 1 g/kg/d
1518 y (males): 0.9 g/kg/d
not provide a range of energy needs.
1518 y (females): 0.8 g/kg/d
Though an outdated reference, still
widely used.
Petersons Failure to This calculates nutrients in excess of the [Protein Required for Weight Age (g/kg/d) x Ideal Weight for Age (kg)] Actual
Thrive (FTT)
requirements of the RDA.
Weight (kg)
Concerns with using this equation
include refeeding syndrome.
It can be calculated using a method
similar to the one for calories above.
Infants and children who Peterson K, et al. Team Management

present underweight and of Failure-to-thrive. J Am Diet Assoc.
need to achieve catch
1984;84:810.
up growth
420
Appendix 33-2 Percentiles of Upper Arm Circumference
Reprinted with permission from Frisancho AR. New norms of upper limb fat and muscle areas for assessment of nutritional status.
Am J Clin Nutr. 1981;34:25402545.
421
Appendix 33-3 Triceps Skinfold Percentiles
Reprinted with permission from Frisancho AR. New norms of upper limb fat and muscle areas for assessment of nutritional status.
Am J Clin Nutr. 1981;34:25402545.
422
Appendix 33-4 Fetal-Infant Growth Chart

A new fetal-infant growth chart for preterm infants developed through a meta-analysis of published reference studies.
Fenton TR. Fetal-infant growth chart for preterm infants. BMC Pediatrics. 2003 Dec 16;3(1):13. Reproduced with permission from BioMed Central.
423
Appendix 33-5
424
425
426
427
428
429
430
1. Important components of the nutrition assessment of

the pediatric population include(s):
A. Dietary history
B. Anthropometric measurements
C. Physical examination
D. All of the above
2. The American Academy of Pediatrics recommends the
following for vitamin D intake:
A. 200 International Units daily for all age groups
B. 400 International Units daily, starting at 2 months
of age
C. 400 International Units for all infants, children, and
adolescents, starting at birth
D. 200 to 400 International Units per day, based on
deficiency symptoms and risk of rickets
3. Spoon-shaped nails and depleted Hgb and Hct levels
may be an indication of:
A. Folate deficiency
B. Vitamin B12 deficiency
C. Vitamin C deficiency
D. Iron deficiency
References

Kleinman RA, ed. Pediatric Nutrition Handbook. 5th ed. Elk
Grove, IL: American Academy of Pediatrics; 2004:149154.
2. Faulhaber D. Nutrition assessment of premature infants. In:
Nevin-Folino N, ed. Pediatric Manual of Clinical Dietetics.
2nd ed. Chicago, IL: Pediatric Nutrition Practice Group;
2003:127144.
3. Ziegler EE, Thureen PJ, Carlson SJ. Aggressive nutrition of the very low birthweight infant. Clin Perinatol.
2002;29:225244.
4. Ballard JL, Khoury JC, Wedig K, et al. New Ballard Score,
expanded to include extremely premature infants. J Pediatr.
1991;119:417423. http://www. Ballardscore.com. Accessed
September 17, 2008.
5. Lubchenco LO, Hansman C, Boyd E. Classification of
newborns based on maturity and intrauterine growth. Pediatrics. 1966;37:403.
6. Fenton TR. A new growth chart for premature babies: Babson
and Bendas chart updated with recent data and a new format.
BMC Pediatrics. 2003;(3)13. http://biomedcentral.com/14712431/3/13. Accessed September 17, 2008.
7. Katrine KF. Anthropometric assessment. In: Groh-Wargo S,
Thompson M, Hovasi-Cox J, eds. Nutritional Care for HighRisk Newborns. 3rd ed. Chicago, IL: Precept Press; 1994:13.
8. Faulhaber D. Nutrition assessment of infants and children.
In: Nevin-Folino N, ed. Pediatric Manual of Clinical Dietetics.
2003:145162.
431
9. Fomon SJ, Haschke F, Ziegler EE, Nelson SE. Body composition of reference children from birth to age 10 years. Am J Clin
Nutr. 1982;35:1169.
10. National Health and Nutrition Examination Survey. CDC
Growth Charts: United States. http://www.cdc.gov/nchs/
about/major/nhanes/growthcharts/background.htm.
Accessed October 18, 2008.
11. Waterlow JC, Buzina R, Keller W, Lane JM, Nichamon MZ. The
presentation and use of height and weight data for comparing
the nutritional status of children under the age of 10 years. Bull
World Health Organization. 1977;55(4):489498.
12. Frisancho AR. Anthropometric Standards for the Assessment of
Growth and Nutritional Status. Ann Arbor, MI: The University
of Michigan Press; 2004.
13. Food and Nutrition Board, Committee on Dietary Allowances. Recommended Dietary Allowances. 10th ed. Washington
DC: The National Academies Press; 1989.
14. World Health Organization. Energy and Protein Requirements. Report of a Joint FAO/WHO/UNU Expert
Consultation. Technical Report Series 724. World Health
Organization, Geneva; 1985.
15. Otten JJ, Pitzi Hellwig J, Meyers LD, eds. Dietary Reference
Intakes: The Essential Guide to Nutrient Requirements.
16. Holliday MA, Segar WE. The maintenance for water in parenteral fluid therapy. Pediatrics. 1957;19:823832.
17. Oh TH. Formulas for calculating fluid maintenance requirements. Anesthesiology. 1980; 53:351353.
Adolescent nutrition. In: Kleinman RA, ed. Pediatric Nutrition Handbook. 5th ed. Elk Grove, IL: American Academy of
Pediatrics; 2004:149154.
19. Faulhaber D. Nutrition assessment of adolescents. In:
Nevin-Folino N, ed. Pediatric Manual of Clinical Dietetics.
2003:163172.
Calcium requirements of infants, children, and adolescents.
Pediatrics. 1999;104:11521157. http://aappublications.org/
cgi/content/full/pediatrics;104/5/1152. Accessed October
11, 2008.
21. Wyshak G, Frisch RE. Carbonated beverages, dietary calcium,
the dietary calcium/phosphorus ratio, and bone fractures in
girls and boys. J Adolesc Health. 1994;15:210215.
22. Borgna-Pignatti C, Marsella M. Iron deficiency in infancy and
childhood. Pediatric Annals. 2008;37(5):329337.
23. American Academy of Pediatrics, Committee on Nutrition. Iron fortification of infant formulas. Pediatrics.
1999;104:119123. http://aappublications.org/cgi/content/
full/pediatrics;104/1/119. Accessed October 12, 2008.
24. American Academy of Pediatrics, Committee on Nutrition. Iron supplementation for infants. Pediatrics.
1976;58:765768.
25. Siimes MA, Jarvenpa AL. Prevention of anemia and iron
deficiency in very-low-birth-weight infants. J Pediatr.
1982;101:277280.
26. Pupillo J. Bone up on new vitamin D recommendations: all
infants, children, adolescents should get at least 400 IU a day.
AAP News. 2008;29:1.
432
27. Wagner CL, Greer FR, and the Section on Breastfeeding and
D deficiency in infants, children, and adolescents. Pediatrics. 2008;122:11421152. http://aappublications.org/cgi/
content/full/pediatric;122/5/1142. Accessed November 13,
2008.
28. American Academy of Pediatrics, Section on Pediatric
Dentistry. Policy statement: Oral health risk assessment
timing and establishment of the dental home. Pediatrics.
2003;111:11131116.
29. US Department of Health and Human Services; National
Institute of Dental and Craniofacial Research. Oral health
in America: A report of the surgeon general. Rockville, MD:
National Institutes of Health; 2000.
30. American Academy of Pediatric Dentistry, Council on Clinical Affairs. Policy statement on the use of fluoride. Adopted
5/2000; revised: 5/2001. http://www.aapd.org/members/
referencemanual/pdfs/Fluoride.pdf. Accessed October 11,
2008.
31. US Department of Health and Human Services. Recommendations for using fluoride to prevent and control dental caries
in the United States. MMWR Recomm Rep. 2001;50(-14).
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5014a1.
htm. Accessed November 13, 2008.
32. Lohman TG, Roche AF, Martorell R, eds. Anthropometric

Standardization Reference Manual. Champaign, IL: Human
Kinetics Books; 1998.
33. Splender Q , Cronk C, Charney E, et al. Assessment of
linear growth of children with cerebral palsy: use of alternative measures of height or length. Dev Med Child Neurol.
1989;31:206214.
34. Stevenson RD. Use of segmental measures to estimate stature
in children with cerebral palsy. Arch Pediatr Adolesc Med.
1995;149:658662.
35. Garn S, Rohmann C. Interaction of nutrition and genetics
in the timing of growth and development. Pediatr Clin North
Am. 1966;13:353379.
36. Himes J, Roche A, Thissen D, et al. Parent-specific adjustments
for evaluation of recumbent length and stature of children.
Pediatrics. 1985;75:304313.
37. Leonberg BL. ADA Pocket Guide to Pediatric Nutrition Assessment. Chicago, IL: American Dietetic Association; 2008.
38. Frisancho AR. New norms of upper limb fat and muscle
areas for assessment of nutritional status. Am J Clin Nutr.
1981;34:25402545.
39. Hammond K. The nutritional dimension of physical assessment. Nutrition. 1999;15:412417.
34
Parenteral and Enteral Nutrition Support:

Determining the Best Way to Feed
Liesje Nieman Carney, RD, CNSD, LDN, Andrea Nepa, MS, RD, CSP, LDN, Sherri Shubin Cohen, MD, MPH, Amy Dean, MPH, RD, LDN,
Colleen Yanni, MS, RD, LDN, and Goldie Markowitz, MSN, CRNP
CONTENTS
When to Use Enteral versus
ParenteralNutrition Support. . . . . . . . . . . . . . . . . . . . . . . 431
Determining the Best Enteral Approach. . . . . . . . . . . . . . 432
Functional Barriers to Oral Enteral Nutrition
Structural Barriers to Enteral Nutrition
Candidates for Enteral Nutrition
Inadequate Oral Intake and Prematurity
Inadequate Oral Intake and BronchopulmonaryDysplasia
Inadequate Oral Intake and Cystic Fibrosis
Inadequate Oral Intake and Congenital Heart Disease
Inadequate Oral Intake and Renal Disease
Inadequate Oral Intake in Burns, Sepsis/Critical Illness, and HIV
Enteral Nutrition: Routes of Administration

Gastrointestinal Conditions
Prematurity
Anorexia Nervosa
Relative Indications for PN
Access for Administering PN
Macronutrients
Electrolytes
Vitamins, Minerals, and Trace Elements
PN Additives: Heparin, Carnitine, and Cysteine
Complications of PN
Monitoring
Aluminum in PN
Feeding Teams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440

Etiologies of Feeding Disorders
Evaluation and Treatment of Feeding Disorders
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443
Learning Objectives
1. Discuss indications for nutrition support in infants and

children.
2. Identify when it is appropriate to utilize parenteral
nutrition versus enteral nutrition.
3. Name examples of structural or functional barriers to
safe oral intake in medically compromised children.
4. Explore the types of enteral nutrition formulas, access
options, and administration modalities.
5. Distinguish between a feeding disorder and an eating
disorder.
6. Explore why an interdisciplinary approach is necessary
to treat feeding disorders.
When to Use Enteral versus

ParenteralNutrition Support
The decision to utilize enteral versus parenteral nutrition

primarily depends upon whether the gastrointestinal (GI)
tract can be used safely or not. Peripheral parenteral nutrition (PPN) is generally reserved for patients for a short
period of time who cannot use their GI tracts, whereas
central parenteral nutrition (CPN) is appropriate for longterm needs.1 Whenever possible, oral feeding or enteral
nutrition (EN) is preferred over parenteral nutrition (PN)
to maintain GI mucosal integrity, absorptive ability, and
immune function.2
Medical conditions that usually require PN support
include the following: necrotizing enterocolitis (NEC),
diaphragmatic hernia, omphalocele, meconium ileus,
intestinal atresia, gastroschisis, and short bowel syndrome
(SBS). 3,4 There are some clinical situations in which enteral
feeding may be contraindicated, but this must be evaluated on a case-by-case basis. Examples of clinical situations
433
434
where PN may be warranted due to an increased risk for

poor bowel perfusion include hemodynamic instability or
use of high-dose vasopressors. Severe pulmonary disease,
cystic fibrosis, congenital heart disease, chylothorax, renal
disease on peritoneal dialysis, severe sepsis, and anorexia
nervosa are additional conditions in which PN support has
been utilized in special circumstances. 3,4
Determining the Best Enteral Approach
Infants and children with a variety of disorders may be

unable to meet their nutrient needs via exclusive oral intake.
Some medical conditions make it difficult or impossible to
safely consume food and hydration by mouth, or to digest
and/or absorb food effectively. Other diagnoses are associated with high energy needs, making it is difficult for the
infant or child to consume adequate amounts orally. In
general, children who require EN support are those who are
unable to obtain more than 80% of caloric needs by mouth,
or who require an extended period of time to eat (ie, more
than 4 hours per day). Children who are malnourished or
exhibit poor growth also benefit from EN support. Children
under the age of 2 who have poor growth or weight gain for
more than 1 month or children over the age of2 with weight
loss or lack of weight gain for 3 months also require nutrition support. A child who has decreased 2 or more weight or
height growth channels, or persistently has a triceps skinfold
(TSF) of less than the 5th percentile, is likely malnourished
enough to warrant nutrition support as well. 3
Patients with congenital anomalies such as tracheoesophageal fistula (TEF), esophageal atresia, cleft palate, and
Pierre Robin syndrome require a source of nutrition that
bypasses the oral route, at least until the condition is surgically repaired.4 EN support would also be indicated in cases
of obstruction of the oral cavity and surrounding areas such
as cancer of the head/neck, or mechanical ventilation. Injuries such as caustic ingestion, trauma, or burns to the head/
neck area may impede ability to consume oral intake as
well.4 Other types of severe oral injury that may warrant EN
support include mucositis and Stevens-Johnson syndrome
cases that involve oral lesions.
Candidates for Enteral Nutrition
Functional barriers to safe oral intake may include neurological or neuromuscular diseases, genetic/metabolic
syndromes, and prematurity.4 For example, bulbar dysfunction is common in patients with severe spinal muscular
atrophy, which can lead to problems with eating and swallowing, as well as aspiration pneumonia. Reflux related to
delayed gastric emptying can also occur. 5 Chewing and
swallowing difficulties are common in children affected
by neuromuscular disorders, and can lead to aspiration.6
In fact, most children with cerebral palsy benefit from tube
feedings.6 Children with neurological impairments, such
as severe seizure disorders or anoxic brain injury, usually
require enteral feeding long-term. 3 Infants or children with
neurological impairments may also develop oral aversions
due to sensory integration disorders.
Candidates for EN vary in the degree to which they depend

upon the tube. Children with the ability to eat yet are stunted
in growth or malnourished may only need tube feedings as
a supplement to oral intake, which may be administered
nocturnally or as bolus feedings between meals. Tube feedings can also be administered on an as-needed basis, such
as only when intake of a meal is poor or when the child
goes through a period of feeling poorly (eg, during chemotherapy). Likewise, children with significant oral aversions
who consume a limited variety and/or volume of food may
need supplemental tube feedings to provide the remainder
of their daily nutrient needs.
On the other hand, children who are not capable of
consuming food orally receive tube feedings as their sole
source of nutrition. Children with neuromuscular disorders
often fall into this category. Children who require highly
specialized diets, such as the ketogenic diet or formulas
indicated for metabolic disorders, may require EN. This
is usually due to the unpalatable formulas or the absolute
need for the child to receive 100% of the daily formula
prescription.
Children who have experienced delayed introduction
of oral feeding (eg, when tube feedings are required for a
long period of time in infancy) or unpleasant oral-tactile
experiences (eg, frequent or prolonged oral intubation and
suctioning) are especially at risk. 3,7 It appears that there is
a window of opportunity in which the infant learns how
to eat by mouth. 3 When infants are unable to take anything
orally for a prolonged time (eg, prolonged oral intubation)
they are at risk for long-term oral aversion due to tactile
defensiveness.
Structural Barriers to Enteral Nutrition
Inadequate Oral Intake and Prematurity
Structural barriers to oral intake include congenital anomalies, obstructions, injuries, and some types of surgery.
In premature infants, the inability to coordinate the suckswallow-breathe pattern may prevent safe oral feedings. 8
Functional Barriers to Oral Enteral Nutrition
PARENTERAL AND ENTERAL NUTRITION SUPPORT: DETERMINING THE BEST WAY TO FEED
Although historically it was thought that the ability to

coordinate sucking and swallowing with breathing did not
develop until 32 to 34 weeks gestation, studies are presently
investigating the theory that there is a positive association
between attainment of successful oral feedings at less than
32 weeks gestation and the implementation of oral stimulation protocols. Multiple medical issues in the premature
infant, such as long-term dependency on mechanical
ventilation, make it difficult to achieve normal oral intake.
One study demonstrated a significant correlation between
prematurity and feeding disorders.9 Children with feeding
disorders had significantly lower birth weights for gestational age, and infants born before 34 weeks gestation had
more GI and oral sensory problems.9 It has been observed
that a very small percentage of premature infants require
long-term EN because they are unable to meet all their
nutrient needs orally.10
Inadequate Oral Intake and

BronchopulmonaryDysplasia
Bronchopulmonary dysplasia (BPD) occurs relatively
frequently in infants who are born prematurely.11 Infants and
young children with BPD are at increased risk for growth
failure and nutrient deficits. This is thought to be a result
of the excessive energy expenditure required for breathing
and/or poor nutrition intake. Poor oral intake is common
due to oral aversion, fatigue secondary to increased work
of breathing, and anorexia secondary to chronic illness.12
Therefore, patients with BPD often require EN support to
promote normal growth and maintain good weight gain.
Inadequate Oral Intake and Cystic Fibrosis

Due to increased work of breathing and pancreatic insufficiency, infants and children with CF have increased caloric
needs, as much as 200% above that of the general population. 3,13 Pancreatic insufficiency occurs in most (85%90%)
individuals with CF, which causes malabsorption of nutrients.14 The CF Foundation recommends that children with
CF who have growth deficits receive oral and enteral supplements to achieve better weight gain, and recommend a BMI
of at least the 50th percentile.13 The initiation of enteral
feedings is suggested when oral supplementation does not
achieve adequate weight gain.14 This is especially important because studies have demonstrated that better weight
status is associated with better lung function and improved
survival rates.13
435
Inadequate Oral Intake and Congenital Heart Disease

Children with congenital heart disease often show growth
failure for a variety of reasons. Anorexia, hypermetabolism, frequent respiratory infections, decreased circulation,
malabsorption, and pulmonary hypertension are all factors
that contribute to poor nutrition status. 8 Increasing respiratory effort as a result of accumulation of pulmonary fluid
can cause feeding difficulties as well. In this case EN may
be required to prevent excessive energy expenditure from
occurring during oral feedings. Infants and children may
have delayed feeding skills as a result of chronic illness and
prolonged hospitalization. Chronic malnutrition is especially common in children with cyanotic heart disease.15
Depending on the degree of malnutrition and the ability
to tolerate oral feedings, infants and children with congenital heart disease may need supplemental EN to maintain
adequate nutrient intake. Energy needs may be increased
20% to 33% due to congenital heart disease.7
Inadequate Oral Intake and Renal Disease

Infants and children with renal disease often exhibit poor
appetite. In addition, the need for a restrictive diet (eg, low
sodium, low potassium, and low phosphorus) may decrease
the childs intake since preferred foods must be limited. The
decision to provide nutrition support needs to be considered on an individual basis, depending upon many factors
some of which include nutrition status and willingness to
eat.7 It is generally accepted that most infants and young
children on peritoneal dialysis need supplemental tube
feedings to maximize their growth potential.16 At this time,
there are limited data regarding the use of nutrition support
in infants and children on hemodialysis. Therefore, general
nutrition support recommendations for this population are
not available.
Inadequate Oral Intake in Burns,

Sepsis/Critical Illness, and HIV
Children with severe burns, sepsis, or advanced HIV may
have extremely high metabolic rates that demand full or
supplemental tube feedings. 3 Calorie, protein, and micronutrient needs are increased in burn patients to allow wound
healing. Individuals with burns affecting over 20% surface
area are more likely to require supplemental tube feedings to
meet their needs.17 Small bowel feedings are often preferred
due to the risk of gastric ileus in this population.17
Enteral Nutrition: Routes of Administration

The route chosen for the administration of EN depends
upon the anticipated length of time that tube feeding will
436
Table 34-1 Indications for Enteral Nutrition1

Inadequate Oral
Intake
Increased
Nutrient Needs
Increased
GI Losses
Primary
Therapy
Oral Motor
Dysfunction
Structural or
Functional Abnormality
of GI Tract
Injury/Critical
Illness
Anorexia nervosa
Cystic fibrosis
Pancreatic
insufficiency
Metabolic
diseases
Prematurity
Congenital malformation
Burn
Anorexia related
to medical
condition
BPD
FTT (requires
catch-up growth)
SBS
Intolerance to
fasting
Neuromuscular
disorders
Trauma
Anorexia due
to treatment/
medications (eg,
chemotherapy)
Congenital heart
disease
Renal disease
Cholestatic liver
disease
Biliary atresia
Unpalatable diet
(eg, elemental
or metabolic
formula)
Neurological
impairment (eg,
cerebral palsy)
TEF
Proximal fistula with
highoutput
Surgery
Food aversion
Mucositis
Infection
Malabsorption
IBD
Proximal intestinal
obstruction
Oral intubation
be required, the anatomy of the patient, and the disease

state. 3 Short-term EN can be administered via nasoenteric
route (eg, nasogastric, nasoduodenal, or nasojejunal tube)
or placed orally (eg, orogastric). Examples of long-term
enteral access include percutaneous endoscopic gastrostomy (PEG), percutaneous endoscopic jejunostomy (PEJ),
surgical jejunostomy, or surgical gastrostomy.18 When
choosing enteral access one should consider the following:
(1) indication for EN, (2) duration of EN, (3) anatomical
integrity of the GI tract, (4) functional integrity of the GI
tract, and (5) risk of aspiration.1
Gastrointestinal Conditions
Infants born with congenital anomalies of the GI tract
generally require PN. Children who develop GI disorders
that prohibit the use of enteral feedings rely on PN for their
nutrition, either temporarily or permanently. For instance,
SBS may result from major surgical resection of the GI
tract, or may develop in infants born with gastric anomalies.19 Intestinal atresia that requires extensive resection or
gastroschisis that causes necrotic bowel can lead to SBS.
Necrotizing enterocolitis (NEC), trauma, and volvulus are
other examples of conditions in which SBS can occur. PN
is always indicated for SBS in the immediate postoperative
period.19,20 Eventually, many individuals with SBS can adapt
to enteral feeds with the successful weaning of PN.19 NEC
in infants requires PN, as enteral feedings are withheld for a
period of time to support bowel healing and recovery. 3,21,22
Those with intestinal failure, as defined by inability of
the gut to digest or absorb an adequate amount, or extensive lesions and/or motor dysfunction, usually require
PN. However, in some pediatric intestinal failure cases a

semi-elemental or elemental diet may be tolerated. 23,24 The
removal or absence of a part of the GI tract will impact the
ability to tolerate enteral feeding; for some this intolerance
is transient and for others it is long term.23
Obstruction of the GI tract and major surgery that
impairs the GI tract also require PN. Other GI conditions
such as severe inflammatory bowel disease, severe reflux,
motility disorders of the GI tract, severe/acute pancreatitis,
intractable diarrhea, intussusception, volvulus, high output
fistulas, severe Hirschsprungs disease, and severe GI side
effects of chemotherapy including radiation enteritis (as
well as cancer cachexia) can in extreme cases require PN
support. 3,4,23
Prematurity
Premature and low birth weight infants need a source
of nutrition immediately after birth due to low nutrient
reserves, increased energy expenditure, immaturity of the
GI tract, as well as their increased propensity for acute and
chronic illness.8,21 Infants should receive PN if it is anticipated that they will be unable to receive enteral feedings
for more than 2 to 3 days. Infants have very limited fat and
glycogen stores, and when these have been depleted infants
begin to catabolize protein stores for energy. However,
EN is commonly withheld if the following conditions are
present: severe respiratory failure associated with hypoxia
and acidosis; hypotension treated with vasopressors; peri
natal asphyxia with signs of organ involvement; clinical
signs of NEC or intestinal obstruction; congenital heart
disease with decreased left-sided outflow; patent ductus
arteriosus with left to right shunt or requiring Indomethacin
or surgical ligation; or sepsis-associated paralytic ileus.
PN is typically provided, as premature infants may

be unable to digest nutrients enterally due to immature
intestinal development and low digestive enzyme production. These infants are also prone to reflux, generalized
GI dysmotility and delayed gastric emptying.8,21 These GI
issues are particularly prevalent in infants who weigh less
than 1500 g.4,21 Organized gut motility does not begin
until 32 to 34 weeks gestation.25 PN is weaned slowly as
EN and/or oral intake increases, so that overall the nutrient
intake remains optimal during this transition.

In infants and children with congenital heart disease, PN
may be used until tolerance to EN is established, especially
postoperatively due to increased nutrient needs to support
recovery.7 In addition to supporting postoperative recovery,
the infant or child needs to be anabolic to promote growth;
therefore nutrient requirements are especially high in
the chronically ill infant and child with congenital heart
disease.26 In patients who are receiving vasopressor medications (eg, dopamine, dobutamine, epinephrine), EN may be
contraindicated, but this remains an area of controversy. 27
PN is occasionally needed to treat individuals with chyle
leaks (ie, chylothorax, chylous effusion, chylous ascites, or
chylopericardium) who do not respond to diets restricted in
long-chain triglycerides (LCTs) and high in medium-chain
triglycerides (MCTs).28 Because the lipids in PN go directly
into the bloodstream and bypass the lymph system, they do
not increase the volume of chyle produced.
Anorexia Nervosa
Severely malnourished patients with anorexia nervosa who
require urgent nutrition rehabilitation may more readily
accept PN than EN support. However, this is a last resort
because PN is more expensive and carries increased risk for
complications.7
Relative Indications for PN

Treatment with extracorporeal membrane oxygenation
(ECMO) and use of vasopressor support may not be absolute contraindications to enteral feedings; however, many
clinicians are hesitant to enterally feed infants and children with hemodynamic instability due to risk of bowel
ischemia. Concerns about NEC and the possible effect of
hypoxia on the gut during ECMO have led to the use of
PN as the main source of nutrition support in pediatrics.
However, a study was done in which infant subjects on
ECMO received full-strength, continuous enteral feedings
administered via either nasogastric or post-pyloric feeding
437
tubes.27 There were no documented cases of NEC or intestinal perforation. Although the parenteral group achieved
goal calories first (3.07 days 2.1 days for PN; 4.25 days
2.6 days for enteral), the benefits of EN far outweigh the
risks of PN. Pettignano et al concluded that vasoactive drug
infusions should not be considered a contraindication to
enteral feeding.27
Access for Administering PN

Venous access is not defined by the initial point of entry,
but by the position of the catheter tip. With central venous
lines (CVL) the catheter tip terminates in the superior
vena cava (SVC) or the right atrium of the heart. PN can be
administered through a peripheral vein; however, the final
osmolality is limited to 900 mOsm/kg to minimize risk of
phlebitis and infiltration.29 To do this the dextrose concentration is limited to 10% to 12.5%; this means that the PPN
requires a relatively large volume to supply adequate administration of nutrients. In the critically ill infant or child,
nutrient requirements often cannot be met with PPN due
to the fluid restriction. Adequate PN requires a CVL and
allows for administration of a solution with a high osmolality (ie, > 900 mOsm/kg).
Macronutrients
Parenterally, carbohydrates are administered in the form
of dextrose, which provides 3.4 kcal/g. Protein is administered as a crystalline amino acid solution, which provides
4 kcal/g. Specialized amino acid solutions are available for
infants and children; these include TrophAmine 6% and
10% (B.Braun), Premasol 6% and 10% (Baxter Healthcare),
and Aminosyn-PF 7% and 10% (Hospira). These specialized solutions contain high concentrations of essential
amino acids, including histadine and tyrosine; low concentrations of phenylalanine, methionine, and glycine; as well
as glutamic acid, aspartic acid, taurine, and N-acetyl-Ltyrosine. The amino acid solutions for infants are designed
to replicate plasma amino acids in breastfed infants. They
also have a lower pH, which allows higher levels of calcium
and phosphate to be added to the solution.
Using a more concentrated amino acid solution allows
for a smaller volume to be administered, which then allows
for a greater volume to be allotted for other solutions (ie,
dextrose), as well as electrolytes, minerals, trace elements,
vitamins, and intravenous fat emulsion (IVFE). Using a
less concentrated amino acid solution may sometimes be
necessary because of the difficulty in measuring extremely
small volumes of the more concentrated solutions. When an
infant or child is severely fluid restricted, it may be difficult
438
Table 34-2. Chart Comparing Various Pediatric Amino Acid Solutions
Comparison of Various Pediatric AA Solutions

Ten percent pediatric amino acid formulations
Company
Product
Introduction date (FDA approval date)
Amino acid content (gm/100mL)
Essential amino acids
Isoleucine
Leucine
Lysine
(added as lysine acetate)
Methionine
Phenylalanine
Threonine
Tryptophan
Valine
Cysteine
(as cysteine HCI H2O)
Histidine
Tyrosine
(added as tyrosine
and N-acetyl-L-tyrosine)
Nonessential amino acids
Alanine
Arginine
Proline
Serine
Glycine
L-Aspartic acid
L-Glutamic acid
Taurine
Sodium metabisulfite NF (as an antioxidant)
pH adjusted with glacial acetic acid USP
pH: Average and (range)
Calc. osmolarity (mOsmol/L)
Total amino acids (gm/L)
Total nitrogen (gm/L)
Protein equivalent (gm/L)
Electrolytes (mEq/L)
Sodium
Acetate
Chloride
B. Braun (McGaw),
Bethlehem, PA
Hospira (Abbott),
Abbott Park, IL
Baxter,
Deerfield, IL
TrophAmine
July 20, 1984
Aminosyn PF
Sept. 6, 1985
PremaSol
June 23, 2003
0.820
1.400
0.820
1.200
0.340
0.480
0.420
0.200
0.780
<0.016
<0.024
0.480
0.240
0.044
0.240
0.760
1.200
0.677
-0.180
0.427
0.512
0.180
0.673
--0.312
0.044
---
0.820
1.400
0.820
-0.340
0.480
0.420
0.200
0.780
<0.016
-0.480
0.240
---
0.540
1.200
0.680
0.380
0.360
0.320
0.500
0.025
<0.050
0.698
1.227
0.812
0.495
0.385
0.527
0.820
0.070
0
0.540
1.200
0.680
0.380
0.360
0.320
0.500
0.025
0
5.5 (5.0-6.0)
875
100
15.5
97
5.5 (5.0-6.5)
788
100
15.2
100
5.5 (5.0-6.0)
865
100
15.5
--
5
97
<3
None
46
None
-94
<3
Source: FDA, US Food and Drug Administration
Reprinted with permission from: Nieman Carney L. Neonatal Nutrition Support (CEU Self-Study Course),
Nutrition Dimension, Ashland, OR. 2009.
439
TABLE 34-3: Comparison of Selected Intravenous Fat Emulsions
Comparing ofofSelected
Comparison
SelectedIntravenous
IntravenousFat
Fat Emulsions
Emulsions
Product and
distributor
Intralipid
10% and 20%
(Clintec)
Liposyn II
10% and 20 %
(Abbott)
Liposyn III
10% and 20%
(Abbott)
Soybean
50% Soybean and

50% safflower
Soybean
50
26
10
9
3.5
65.8
17.7
8.8
4.2
3.4
54.5
22.4
10.5
8.3
4.2
1.1
2.0
1.2
2.25
1.1
2.0
1.2
2.5
1.1
2.0
1.2
2.5
260
260
276
258
284
292
Oil base
Fatty acid content (%)
Linoleic
Oleic
Palmitic
Linolenic
Stearic
Calories/ml
10%
20%
Egg yolk phospholipids (%)
Glycerin (%)
Osmolarity mOsm/L
10%
20%
Source:Drug
Drugfacts
facts
and
comparisons.1998
1998ed.
ed.St.St.Louis:
Louis:
Wolters
Kluwer
Co.
Source:
and
Comparisons.
Wolters
Kluwer
Health.
Reprinted with permission from: Nieman Carney L. Neonatal Nutrition Support (CEU Self-Study Course),
Nutrition Dimension, Ashland, OR. 2009.
to meet the estimated nutrient needs via PN due to the lack

of a concentrated infant amino acid solution (ie, 15%).
Research has shown a potential decrease in PN-associated cholestasis with the use of TrophAmine, as compared
to Aminosyn- PF. 30 Another benefit of TrophAmine is that
when L-cysteine is added, there is an increased solubility
of calcium and phosphorus. TrophAmine is the only infant
amino acid product available in the United States that has
been utilized when conducting stability studies for the addition of cysteine to PN solutions.
IVFE consists of either soybean oil or a combination
of safflower and soybean oil. These products provide 10
kcal/g, regardless of the product concentration, and are
available in 10% (1.1 kcal/mL), 20% (2 kcal/mL), and 30%
concentrations. The 20% concentration is preferred over
the 10% product because it allows adequate lipid intake in
less volume. The 10% solution has a higher phospholipid/
triglyceride weight ratio than the 20% solution, and this
higher ratio may affect the activity of lipoprotein lipase,
the primaryenzyme for lipid clearance, resulting in higher

triglycerides and other plasma lipids in infants.22 In recent
years some institutions have been utilizing 30% lipid solutions without adverse effects, but this is not a common
practice.
IVFE not only supplies a concentrated source of calories but also provides essential fatty acids (EFAs) for cell
membrane integrity and brain development. IVFE also
helps to prolong the integrity of peripheral lines because of
their lower osmolality. It is crucial to provide infants and
children a minimum amount of lipids (0.51 g/kg/d) to
prevent essential fatty acid deficiency (EFAD). However,
premature infants require at least 0.6 to 0.8 g/kg/d.1 EFAD
was historically defined as a triene:tetraene ratio equal to
or greater than 0.431; however, Mayo Clinical Laboratories
recently developed a new set of standards for assessing the
triene:tetraene ratio for various age groups, but this is only
applicable if the test is run by its laboratory.
440
Table 34-4 Recommendations for Initiation and Advancement of Parenteral Nutrition

Initiation
Advance By
Infants (< 1 y)
Protein (g/kg/d)
CHO (mg/kg/min)
Preterm
1.53
57
Term
1.53
69
Fat (g/kg/d)
12
12
Children (110 y)
Protein (g/kg/d)
CHO (mg/kg/min)
Fat (g/kg/d)
Adolescents
Protein (g/kg/d)
CHO (mg/kg/min)
Fat (g/kg/d)
Goals
Preterm
1
12.5% dextrose
per day
0.51
Term
1
12 or 2.55%
dextrose per day
0.51
Preterm
34
812 (Max 1418)
Term
23
12 (Max 1418)
33.5 (Max
0.17g/kg/hr)
3 (Max 0.15g/
kg/hr)
12
10% dextrose
12
1
5% dextrose per day
0.51
1.53
810
23
0.81.5
3.5 or 10% dextrose
1
1
12 or 5% dextrose per day
1
0.82.5
56
12.5
Electrolytes
Close monitoring of electrolyte status is essential. In
newborns, the addition of electrolytes to PN may be
deferred until the second day of life in some cases. Potassium is generally added once normal kidney status and good
urine output are established, and sodium is often added once
diuresis begins.22 Daily adjustments to electrolyte intake
are often necessary. Electrolyte requirements of preterm
and full-term infants are generally similar, with the exception of calcium and phosphorus. Electrolytes are typically
prescribed per kilogram in infants and younger children,
and as units per day in larger children and adolescents.
Table 34-5 PN Electrolyte Dosing Guidelines*
Electrolyte
Preterm
Neonates
Infants/
Children
Adolescents &
Children > 50kg
Sodium
Potassium
Calcium
Phosphorus
Magnesium
Acetate
Chloride
2-5 mEq/k
2-5 mEq/k
1-2 mEq/kg
2-4 mEq/kg
2-4 mEq/kg
1-2 mEq/kg
0.5-4 mEq/k
10-20 mEq/d
2-4 mEq/kg
0.5-2 mmol/kg 10-40 mmol/d
1-2 mmol/kg
0.3-0.5 mEq/kg 0.3-0.5 mEq/kg 10-30 mEq/d
As needed to maintain acid base-balance
As needed to maintain acid base-balance
*Assumes normal organ function and losses

Reprinted with permission from Mirtallo J, Canada T, Johnson D, et
al. Safe practices for parenteral nutrition. J Parenter Enteral Nutr.
2004;28(6):S-39S70.
Vitamins, Minerals, and Trace Elements

Standard infant and pediatric trace element commercial
products are available. However, in cases of specific medical
conditions, such as renal or hepatic disease, some may use

custom trace elements.
Table 34-6 Comparison of MTE Products (quantity per 1 mL of solution)
Mineral
Multitrace-4
Neonatal
Multitrace-4
Pediatric
Multitrace-5
Concentrate
(Adolescent/
Adult)
Zinc (as Sulfate)

Chromium
(as Chloride)
Selenium
(as Selenious Acid)
Copper (as Sulfate)
Manganese
(as Sulfate)
1.5 mg
0.85 mcg
1 mg
1 mcg
5 mg
10 mcg
none
none
60 mcg
0.1 mg
25 mcg
0.1 mg
25 mcg
1 mg
0.5 mg
Source: American Regent Product Catalog

http://www.americanregent.com/multiple_trace.html
Zinc is important for the maintenance of cell growth

and development. When PN is supplemental to EN or of
short duration, zinc is the only trace element that requires
supplementation. Some conditions that require additional
zinc intake include elevated urinary zinc excretion (eg,
high-output renal failure) and increased GI excretion (eg,
high-volume stool loss and fistula/stoma losses).
Copper is an essential constituent of many enzymes.
Current daily recommendations are adequate to prevent
deficiency. Clinical manifestations of copper deficiency
include hypochromic anemia that is unresponsive to
iron therapy, neutropenia, and osteoporosis. Conditions
requiring higher copper intake include increased biliary
losses due to jejunostomy and losses via external biliary
441
Table 34-7 Trace Element Requirements*

Trace Element
Preterm Neonates
< 3 kg (mcg/kg/d)
Term Neonates 3-10 kg

(mcg/kg/d)
Children 10-40 kg
(mcg/kg/d)
Adolescents > 40 kg
(per day)
Zinc
Copper
Manganese
Chromium
Selenium
400
20
1
0.05-0.2
1.5-2
50-250
20
1
0.2
2
50-125
5.0-20
1
0.14-0.2
1.0-2
2-5 mg
200-500 mg
40-100 mcg
5-15 mcg
40-60 mcg
*assumes normal organ function and losses

In order to meet these trace element needs, one would need to use individual trace element products. Commercially available multi-trace element products
would not meet these needs.
Reprinted with permission from Mirtallo J, Canada T, Johnson D, et al. Safe practices for parenteral nutrition. J Parenter Enteral Nutr. 2004;28(6):S-39S70.
drainage. Historically, copper was withheld in PN for

patients with cholestasis; however, cases of copper deficiency have recently been reported when copper was
withheld in PN. 32 In patients with cholestasis, it is recommended to reduce supplementation by 50% of the amount
typically provided for age, monitor serum copper levels and
ceruloplasmin, and adjust supplementation accordingly. 33
Manganese is an important component of several
enzymes. 34 Manganese deficiency has not been documented in humans. However, manganese toxicity has been
reported. Manganese supplementation in PN should be
withheld in patients with cholestasis or other liver function
impairment. 34,35 Fok et al. provided evidence suggesting
that high manganese intake contributes to the development
of cholestasis. 35 Manganese should therefore be used with
caution in PN provided to infants because they are more
susceptible to cholestasis. 35 It is recommended to monitor
serum manganese levels and adjust supplementation as
needed.
Selenium is a component of the enzyme glutathione
peroxidase, which is involved in protecting cell membranes
from peroxidase damage through detoxification of peroxides and free radicals. 34 Supplementation with selenium is
recommended when a patient is on long-term PN (ie, longer
than 1 month). It is recommended to decrease selenium
intake when renal dysfunction is present. 33
Chromium potentiates the action of insulin and plays
a role in glucose, protein, and lipid metabolism; therefore,
chromium is essential for growth. 34 It is also recommended
to decrease chromium intake with renal dysfunction.
Molybdenum supplementation is recommended in cases
when exclusive PN exceeds 4 weeks. Deficiency of molybdenum has not been reported in pediatrics; however, one
adult case of deficiency has been documented. 34 Iodine is
often omitted from PN since iodine-containing disinfectants and detergents are used on the skin and absorbed.
Iron supplementation should be considered only among

long-term PN-dependent patients who are not receiving
frequent blood transfusions. Monitoring iron status is
imperative with iron supplementation as there is a risk of
iron overload. 36
Parenteral vitamin products for infants and children
(<11 years of age) have not been reformulated since their
inception in the 1970s and 1980s.1 Currently available
commercial products do not meet the vitamin needs of
malnourished patients, those affected by renal or liver
disease, premature infants, and children with SBS.1 Greene
at al explored this issue in depth in 1998; however, new
parenteral vitamin products intended for infants and
younger children have yet to be released. 37
Table 34-8 Dosing Recommendations for Pediatric Parenteral Multiple
Vitamins (MVI-Pediatric)*
Manufacturer Recommendations
NAG-AMA Recommendations
Weight (kg)
<1
3-Jan
>3
Weight (kg)
< 2.5
> 2.5
Dose (mL)
1.5
3.25
5
Dose (mL)
2 mL/kg
5 mL
*Assumes normal organ function

Nutrition Advisory Group-American Medical Association
PN Additives: Heparin, Carnitine, and Cysteine

Heparin is added to PN solutions to reduce the formation of
a fibrin sheath around the catheter and may reduce phlebitis
and increases the duration of catheter patency. 22 Heparin
also stimulates the release of lipoprotein lipase, which may
improve lipid clearance. It is recommended to add heparin
in units of 0.25 to 1/mL PN solution. 22 There is an increased
risk of anti-coagulation with the higher doses of heparin.
Carnitine is responsible for the transport of fatty acids
into the mitochondria for oxidation. Carnitine deficiency
442
results in impaired fatty acid oxidation and can present

as hypertriglyceridemia. Carnitine synthesis and storage
are not optimal at birth, when compared to older children
and adults. Premature infants less than 34 weeks gestation receiving PN without carnitine can develop carnitine
deficiency 6 to 10 days after birth. 38 Carnitor (Sigma-Tau
Pharmaceuticals) is available for PN supplementation.
An initial, safe dose to consider for infants on exclusive
PN for more than 4 weeks is 8 to 10 mg/kg/d.22 A recent
study revealed that parenteral supplementation of 20 mg/
kg/d carnitine resulted in plasma total carnitine concentrations that exceeded the reference range, which supports
the use of smaller doses of carnitine supplementation. 39
It is recommended to monitor carnitine levels and titrate
supplementation from 8 to 10 mg/kg/d, up to a maximum
of 20 mg/kg/d.
Cysteine, a conditionally essential amino acid, is not a
component of crystalline amino acid solutions because it is
unstable and will form an insoluble precipitate. 22 In adults,
cysteine can be synthesized from methionine; however,
preterm infants lack adequate hepatic cystathionase to
facilitate this conversion. Commonly recommended dosing
for L-cysteine hydrochloride is 40 mg per gram of amino
acids. Current practice suggests supplementation with
L-cysteine hydrochloride for the first year of life, although
practice varies widely. 36 One benefit of the addition of
L-cysteine hydrochloride to PN is the decrease in the pH of
the solution, which increases the solubility of calcium and
phosphorus. It should be noted though that the addition
of cysteine to PN warrants close monitoring of acid-base
status as it may increase risk for acidosis, and acetate may
need to be added to the solution.
Complications of PN
Short-term potential adverse effects of PN include the
following: infection, hyperglycemia, electrolyte abnormalities, disturbance of acid-base balance, hypertriglyceridemia,
phlebitis, bacterial translocation, and compromised gut
integrity. With long-term PN support adverse effects
may include infection, PN-associated cholestasis, metabolic complications, disturbance of acid-base balance,
osteopenia, risk of vitamin/mineral deficiency or toxicity,
and continued risk of bacterial translocation. Nosocomial
infections appear to result either from improper care of the
catheter and/or frequent use of the catheter for purposes
other than delivery of nutrients (eg, blood draws, medication administration).1
Monitoring
Prior to initiation of PN support, it is recommended to
check the following biochemical indices: basic metabolic
panel (BMP), calcium, magnesium, phosphorus, liver function tests (ie, Alk Phos, ALT, AST, GGT), total bilirubin,
conjugated or direct bilirubin, prealbumin, albumin, and
triglyceride. Following the initiation of PN the patients
require close biochemical monitoring. The monitoring
is then slowly decreased in frequency depending on the
patients demonstration of stable parameters. Patients on
long-term PN, such as those with SBS, need regular monitoring of vitamin and mineral status.
Aluminum in PN
It has come to light that various products utilized during
PN compounding contain high levels of aluminum, which
can be especially dangerous for infants and children.
Preterm infants are extremely vulnerable to aluminum
toxicity due to immature renal function and the likelihood
for long-term PN. 36 As of July 2004, the Food and Drug
Administration (FDA) mandated that products used in
compounding PN should state the aluminum content on
the label. The FDA identified 5 mcg/kg/d as the maximum
amount of aluminum that can be safely tolerated and
amounts exceeding this limit may be associated with central
nervous system or bone toxicity. 36 It is essential for pharmacists, dietitians, physicians, and nurses to collaborate
to minimize the use of higher aluminum content products. However, it is difficult to achieve the recommended
aluminum intake level set by the FDA when patients are
receiving multiple medications and PN.
Providing PN is wrought with unique potential risks
and complications and calls for a diligent interdisciplinary
team approach. Initiating EN as soon as medically appropriate is the key to minimizing the potential adverse effects
of PN support.
Feeding Teams
Pediatric feeding disorders are common, affecting 25% of

typically developing children and up to 80% of developmentally delayed children.40 Prolonged feeding disorders have
significant short- and long-term medical consequences,
including poor growth and development, severe malnutrition, increased susceptibility to illness, and even death.40
Feeding disorders are often confused with eating
disorders. The American Psychiatric Association has
established criteria for the diagnosis of eating disorders,
anorexia nervosa and bulimia, based on DSM-IV criteria
that focuses on weight loss, attitudes and behaviors, and
amenorrhea displayed by patients with eating disorders.41

Eating disorders are more commonly seen in older children
with a dysmorphic body image; they do not eat because
their focus is the intent to be thin. A feeding disorder has
been defined as the inability or refusal to consume certain
foods in sufficient quantity or variety to maintain normal
growth.42,43 Generally, feeding disorders involve younger
children whose intent is not centered on body image
they refuse to eat due to lack of desire or lack of oral-motor
skills.
Etiologies of Feeding Disorders

Feeding disorders have numerous causes, which are often
inter-related. Organic, environmental, and behavioral
issues can all adversely impact feeding. Organic factors
can be categorized as those affecting the ability to eat,
the desire to eat, and the developmental readiness to eat.
The ability to eat is a complex process and there are many
potential impediments to functional chewing and swallowing. The following are examples of organic causes of
feeding disorders: anatomical defects, genetic disorders/
syndromes, and GI issues. Anatomic abnormalities within
the oral cavity and airway include aspiration syndromes,
micrognathia, cleft lip and palate, vocal cord paralysis
(frequently as a complication of cardiac surgery), laryngomalacia, asthma, and Treacher-Collins Syndrome. Many
syndromes and chromosomal abnormalities have a high
risk for feeding difficulties. Examples include Trisomy
21, Williams syndrome, CHARGE syndrome, WAGR
Syndrome, 22 q deletions, Trisomy 13, and Trisomy 18.
Some gastroesophageal pathologies that impact feeding
include tracheoesophageal fistula, esophageal strictures,
malrotation, gastroesophageal reflux, esophagitis (including
eosinophilic esophagitis), dysmotility, constipation, cystic
fibrosis, and irritable bowel syndrome. Some conditions
warrant interventions whose iatrogenic effects adversely
impact the desire to eat. These may include side effects from
some chemotherapeutic agents and medications for attention deficit hyperactivity disorder, or oral aversion after the
prolonged intubation of premature infants. Supplemental
tube feedings can also affect the desire to eat orally. Impaired
developmental readiness to eat arises from developmental
delays and sensory and oral-motor issues. These impact the
ability to accept foods, advance textures, and eat in an ageappropriate manner, which is frequently seen in children on
the autistic spectrum.
Environmental factors impact feeding. The parent-child
interaction around food creates the environment in which
the child eats. Poor interactions during feeding may present
443
at any period in an infant or childs lifetime; if this occurs

early in life there is an increased risk for long-lasting effects.
Examples of inadequate parent-child interaction during
feeding may include: a parent not looking at an infant or
reading hunger cues during a bottle feeding, and feeding
a meal to a toddler separate from the family.44 The familys
cultural and religious beliefs surrounding food change
how eating and weight is perceived. In addition, the ability
to buy food, the quality of food available, and the feeding
equipment within the home can impact the success of the
feeding experience.
Behavioral issues can stem from a combination of any
of the aforementioned concerns. Internationally adopted
children frequently have feeding issues likely related to the
feeding conditions they experienced before adoption. A
child with GI pathology may develop a learned avoidance
and/or feeding-related anxiety, resulting in limited intake of
volume and inconsistent acceptance. An infant who required
prolonged intubation may have an oral aversion and food
refusal. Patients with significant food allergies may refuse
to eat foods to which they are not allergic. Parents who have
difficulty setting limits can lose control of the meal and be
unable to establish a consistent mealtime structure.
Table 34-9 Commonly Utilized Behavioral Strategies for Treating Feeding
Disorders
Offer liquids primarily between meals, and limit drinking during meals
Encourage a structured and consistent schedule for 3 meals
and2to 3 snacks daily
Limit meals to 2030 minutes
Eliminate grazing behavior on liquids and foods between meals
Use a timer to have a child sit at the table for a finite period of time
Offer foods on a divided plate
Offer 1 new or non-preferred food with 1 to 2 preferred foods
Continue to offer non-preferred foods in a positive way (as with all
children, repeated exposure to new foods increases acceptance)
Encourage exploration of a non-preferred food (touching to lips,
touching with fingers)
Establish a non-food reward system (for children older than
1215months) where positive behavior is praised and negative
behavior is ignored
Be as consistent as possible
Encourage training and cooperation of all caregivers to support
acohesive treatment approach
Encourage family mealtimes
Provide age-appropriate portions and developmentally
appropriatetextures
Evaluation and Treatment of Feeding Disorders

Feeding disorders are best evaluated and treated by interdisciplinary teams with expertise in the complexities inherent
444
Figure 34-1
to feeding disorders. Feeding teams usually include medical

and behavioral health specialists, registered dietitians, and
a variety of therapists and social support personnel. The
medical team may consist of a physician (often with specialized training in gastroenterology, neurology, neonatology,
otolaryngology, or child development), nurse practitioner,
and/or registered nurse. The behavioral health practitioner
is commonly a psychologist or family counselor, who may
be aided by feeding therapists with training in psychology.
The therapists may include occupational therapists, speech
pathologists, physical therapists, and respiratory therapists. Social support personnel include social workers, case
managers, and child life or recreational therapy specialists.
The composition of the team varies by facility and by the
needs of the patient (Figure 34-1).
Services offered by feeding teams also vary by facility.
They range from an initial evaluation with referrals to

outside therapists to intensive inpatient feeding therapy. At
the initial evaluation, various members of the team interview the child and primary caregivers. The child undergoes
a physical examination, and team members observe the
child being fed and eating. The team then collaborates at the
end of the evaluation to discuss their findings and synthesize family-centered goals and recommendations.
Teams frequently refer patients to other sub-specialists
and clinics for evaluation and/or treatment of feedingrelated medical issues if they cannot be addressed within
the team setting. Some hospital-based teams offer additional services such as inpatient consults or diagnostic
testing (eg, modified barium swallow study, gastrointestinal endoscopy).
Most teams either provide or refer patients to outpatient
or home-based therapies including occupational, speech,

nutrition, and individual or group psychological therapy.
These services focus specifically on behavioral feeding
issues, sensory processing difficulties, development of selffeeding skills, and oral-motor swallowing function. Therapy
goals may include increasing a childs acceptance of a variety
of foods, managing food refusal behaviors, texture progression (ie, smooth puree to lumpy puree to soft solids), and
establishing developmentally appropriate manipulation
of liquid and food. Therapists are also able to recommend
adaptive equipment, if appropriate.
Table 34-10 Common Feeding Problems
Excessive liquid intake, impeding acceptance of solid foods
Grazing, unstructured meals/snacks
Prolonged feeding time (> 30 minutes)
Inadequate or immature oral-motor skills (unable to handle complex
textures)
Sensory integration issues (will only consume foods/liquids of one
color and/or texture)
Table 34-11 Nutrition Interventions for Children with Feeding Disorders

Initiate a multivitamin with mineral (or age-appropriate vitamin
supplement)
Offer nutrient-dense snacks and increase the caloric concentration
infoods (add butter/oils, modulars)
Limit juice to 4-oz per day
Recommend using pureed table food in place of jarred baby food
toincrease caloric density
Gradual increase of the thickness of the pureed food may help
advance children with difficulty to advance to more complex textures
Initiate nutrition supplementation, either orally or via enteral nutrition,
if the patient is unable to sustain age-appropriate weightgain
Initiate enteral nutrition immediately if the child is < 80% ideal
bodyweight
Adjust tube feeding regimen in conjunction with behavioral
strategiesto increase oral acceptance
Eating is an integral part of our social interactions, and

families can experience significant difficulty coping with
the stress of caring for a child with a feeding disorder. Families are therefore commonly referred to support groups,
where they may discuss building social supports, strategies
for establishing mealtime structure at home, coping mechanisms for handling stress, and strategies for implementing
behavior management. 43
For patients who require more intensive intervention,
some teams offer outpatient day hospital treatment or inpatient treatment, which allow therapists to work with children
at every meal and to monitor their nutrition and medical
status closely. For outpatient evaluations and therapies, as
445
well as intensive programs, caregivers are typically present

for follow-up appointments to monitor the childs progress, support the childs advancement towards long-term
treatment goals, and engage with the team to address any
questions or concerns. The frequency of follow-up is determined on an individualized basis.
Conclusion
Every child should be evaluated individually when determining the best way to provide optimal nutrition to promote
growth and development. What works for one child and
caregiver may not work for another. One must consider
many factors when initiating nutrition support including,
but not limited to, the patients baseline nutrition status, the
functionality of the GI tract, access options, administration
schedule, and modality. In pediatrics, one must consider the
effect that the nutrition support regimen will have on the
infant/child and the caregivers. It is essential to be flexible
and supportive when working with caregivers to develop a
nutrition plan of care that is best for their child and their
lives.
1. Which of the following are common behavioral strategies to address picky eating?
A. Offer foods on a divided plate
B. Offer 1 new or non-preferred food with 1 or 2
preferred foods
C. Be consistent
D. Encourage family mealtimes
E. All of the above
2. All of the following findings may justify nutrition
support in a toddler except:
A. Height at the 25th percentile on the growth curve
since infancy
B. No weight gain for 4 months
C. Decrease in 2 weight percentiles channels over the
past 6 months
D. Eats very slowly
3. A child with CF who has a very good appetite, yet is
moderately underweight, should receive:
A. PN in addition to oral feedings
B. Tube feedings only
C. No nutrition intervention
D. Oral nutrition supplements in between meals
446
References
1. Baker S, Baker R, Davis A. Pediatric Nutrition Support. Boston,

MA: Jones & Bartlett; 2007.
2. Mahesh C, Sriram K, Lakshmiprabha V. Extended indications
for enteral nutritional support. Nutrition. 2000;16:129130.
3. Axelrod D, Kazmerski K, Iyer K. Pediatric enteral nutrition. J
Parenter Enteral Nutr. 2006;30(1):S21S26.
4. Samour PQ , King K. Handbook of Pediatric Nutrition. 3rd ed.
Lake Dallas, TX: Helm Publishing; 2005.
5. Wang C, Finkel R, Bertini E, et al. Consensus statement for
standard of care in spinal muscular atrophy. J Child Neuro.
2007;22:10271049.
6. Ramelli G, Aloysius A, Davis T, Muntoni F. Gastrostomy
placement in paediatric patients with neuromuscular disorders: indications and outcome. Dev Med & Child Neuro.
2007;49:367371.
7. Ekvall S, Ekvall V. Pediatric Nutrition in Chronic Diseases and
Developmental Disorders. 2nd ed. New York, NY: Oxford
University Press; 2005.
8. Watkins JB, WalkerW , Duggan C. Nutrition in Pediatrics: Basic
Science and Clinical Applications. 3rd ed. Hamilton, Ontario:
BC Decker Inc; 2003.
9. Rommel N, De Meyer AM, Feenstra L, Veereman-Wauters G.
The complexity of feeding problems in 700 infants and young
children presenting to a tertiary care institution. J Pediatr
Gastroenterol Nutr. 2003 Jul;37(1):7584.
10. Geggie JH, Dressler-Mund DL, Creighton D, CormackWong ER. An interdisciplinary feeding team approach for
preterm, high-risk infants and children. Can J Diet Pract Res.
1999;60(2):7277.
11. Bott L, Beghin L, Hankard R, Pierrat V, Gondon E, Gottrand
F. Resting energy expenditure in children with neonatal
chronic lung disease and obstruction of the airways. British J
Nutr. 2007;98:796801.
12. Guimber D, Michaud L, Storme L, Deschildre A, Turck D,
Gottrand F. Gastrostomy in infants with neonatal pulmonary
disease. J Pediatr Gastroenterol Nutr. 2003;36:459463.
13. Stallings V, Stark L, Robinson L, Feranchak A, Quinton H.
Evidence-based practice recommendations for nutritionrelated management of children and adults with cystic fibrosis
and pancreatic insufficiency: results of a systemic review. J Am
Diet Assoc. 2008;108:832839.
14. Borowitz D, Baker R, Stallings V. Consensus report on
15. Da Silva V, de Oliveira Lopes M, de Araujo T. Growth and
nutritional status of children with congenital heart disease. J
Cardiovasc Nurs. 2007;22(5):390396.
16. Ledermann S, Spitz L, Moloney J, Rees L, Trompeter R.
Gastrostomy feeding in infants and children on peritoneal
dialysis. Pediatr Nephrol. 2002;17:246250.
17. Merritt R, ed. The A.S.P.E.N. Nutrition Support Practice
Manual. 2nd ed. Silver Spring, MD: The American Society for
Parenteral and Enteral Nutrition; 2005.
18. Pearce CB, Duncan HD. Enteral feeding. Nasogastric, nasojejunal, percutaneous endoscopic gastrostomy, or jejunostomy:
its indications and limitations. Postgraduate Medical Journal.
2002;78:198204.
19. Abad-Sinden A, Sutphen J. Nutrition management of pediatric

short bowel syndrome. Pract Gastroenterol. 2003; Nutrition
Issues in Gastroenterology, series #12:2848.
20. Serrano M, Schmidt-Sommerfeld E. Nutrition support
of infants with short bowel syndrome. Nutrition.
2002;18:966970.
21. Puntis JWL. Nutritional support in the premature newborn.
Postgraduate Med Journal. 2006;82:192198.
22. Groh-Wargo S, Thompson M, Cox J, ed. Nutritional Care for
High-Risk Newborns, Revised. 3rd ed. Chicago, IL: Precept
Press, Inc; 2000.
23. Okada A. Clinical indications of parenteral and enteral
nutrition support in pediatric patients. Nutrition.
1998;14(1):116118.
24. Vanderhoof J. New and emerging therapies for short bowel
syndrome in children. J Ped Gastr Nutr. 2004;39:S769S771.
25. Thureen PJ, Hay WW. Early aggressive nutrition in preterm
infants. Semin Neonatol. 2001;6:403415.
26. Dudrick S. Early developments and clinical applications of total parenteral nutrition. J Parenter Enteral Nutr.
2003;27(4):291299.
27. Pettignano R, Heard M, Hart M, Davis R. Total enteral
nutrition versus total parenteral nutrition during pediatric
extracorporeal membrane oxygenation. Crit Care Med.
1998;26(2):358363.
28. Parrish C, McCray S. When chyle leaks: Nutrition management options. Pract Gastroenterol. 2004; Nutrition Issues in
Gastroenterology, series # 17: 6076.
29. American Academy of Pediatrics, Committee on Nutrition. Commentary on parenteral nutrition. Pediatrics.
1983;71(4):547.
30. Wrught K, Ernst KD, Gaylord MS, et al. Increased incidence of
parenteral nutrition-associated cholestasis with Aminosyn PF
compared to Trophamine. J Perinatol. 2003;23(6):444450.
31. Kerner JA. Parenteral nutrition. In: Walker WA, Durie PR,
Hamilton JR, Walker-Smith JA, Watkins JB, eds. Pediatric
Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. Vol 2. St. Louis, MO: Mosby; 1996:19041951.
32. Hurwitz M, Garcia MG, Poole RL, Kerner J. Copper deficiency during parenteral nutrition: a report of four pediatric
cases. Nutr Clin Pract. 2004;19:305308.
33. McFarland C. Evaluating trace element status in long-term
parenteral nutrition-dependent pediatric patients. Building
Block for Life. 2009; 32(2):35.
34. Reifen RM. Microminerals. In: Tsang RC, ed. Nutritional
Needs of the Preterm Infant: Scientific Basis and Practical Guidelines. 2nd ed. Digital Educational Publishing, Inc.; 2005.
35. Fok TF, Chui KKM, Cheung R, Ng PC, Cheung KL, Hjelm
M. Manganese intake and cholestatis jaundice in neonates
receiving parenteral nutrition: a randomized controlled study.
Acta Paediatr. 2001;90(9):10091015.
36. Mirtallo J, Canada T, Johnson D, et al. Safe practices for parenteral nutrition. J Parenter Enteral Nutr. 2004;28(6):S39S70.
37. Greene HL, Hambidge KM, Schanler R, Tsang RC. Guidelines

for the use of vitamins, trace elements, calcium, magnesium,
and phosphorus in infants and children receiving total parenteral nutrition: report of the Subcommittee on Pediatric
Parenteral Nutrition Requirements from the Committee on
Clinical Practice Issues of the American Society for Clinical
Nutrition. Am J Clin Nutr. 1998;48(5);13241342.
38. Schmidt-Sommerfield E, Penn D, Wolf H. Carnitine blood
concentrations and fat utilization in parenterally alimented
premature newborn infants. J Pediatr. 1982;100:260.
39. Crill CM, et al. Relative bioavailability of carnitine supplementation in premature neonates. J Parenter Enteral Nutr.
2006; 30(5):421425.
40. Manikam R. Pediatric Feeding Disorders. J Clin Gastroenter.
2000;30(1):3446.
41. American Academy of Pediatrics. Identifying and treating
eating disorders. Pediatr. 2003;111(1):204211.
42. Piazza C, Carrol-Hernendez T. Assessment and Treatment
of Pediatric Feeding Disorders. Encyclopedia of Early Childhood Development; 2004. http://www.enfant-encyclopedie.
com/Pages/PDF/Piazza-Carroll-HernandezANGxp.pdf.
447
43. Tobin S, Cheng V, Schumacher C, et al. The role of an interdisciplinary feeding team in the assessment and treatment of
feeding problems. Building Block for Life. 2005;28(3):111.
44. Satter E. Child of Mine; Feeding with Love and Good Sense. Bull
Publishing; 2000.
Additional Readings
Cloud HH. Recent trends in care of children with special needs:

nutrition services for children with developmental disabilities and special health care needs. Topics in Clinical Nutrition.
2001;16(4).
Puntis JWL. Specialist feeding clinics. Arch Dis Childhood.
2008;93:164167.
Rudolph C, Link T. Feeding disorders in infants and children.
Pediatr Clin North Am. 2002;49(1):97112, vi.
Implementation of the Plan
35
Beth Lyman, RN, MSN, Jennifer M. Colombo, MD, and Jodi L. Gamis, OTR
CONTENTS
Learning Objectives
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 446
Type of Intravenous Catheter Needed
Site Care
Safety Issues
Nursing Care
Enteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Enteral Route Selection
Types of Tubes
Tube Insertion
Verification of Placement
Bolus vs. Continuous Feeds. . . . . . . . . . . . . . . . . . . . . . . .
Bolus Feedings
Continuous Feedings
Combination Feedings
Initiation and Advancement of Feedings . . . . . . . . . . . . .
Bolus Feedings
Continuous Feedings
Safety Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Preparation
Hang Time for Formula
Feeding Pumps
Nursing Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Securing the Tube
Site Care
Checking Residual Volumes
Flushing the Tube
Use of Sterile vs. Non-Sterile Water
Reflux
Aspiration Precautions
Intake and Output
Weights
Assessment of Feeding Tolerance
Medication Administration
Oral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
448
449
1. Evaluate the patient for specific issues that can impact

the plan of care.
2. Implement an evidence-based nutrition plan of care
that blends parenteral, enteral, and oral intake as appropriate for that patient.
3. Discern the key safety measures that are age appropriate
and patient specific when implementing the nutrition
plan of care.
Background
452
452
453
454
456
Implementation of a nutrition plan of care may involve a

combination of parenteral nutrition (PN), enteral nutrition
(EN), or oral nutrition therapies in pediatric patients.
Inorder to stimulate intestinal growth and adaptation, pediatric
patients who require PN need some amount of EN, oral intake,
or both. Depending on the patient-specific characteristics that
have been discussed elsewhere, a balancing of PN nutrients with
EN and/or oral intake is the accepted mode of intervention for
most pediatric patients. Goals for each of these interventions
are constantly redefined based on patient assessment
by all involved health care providers and the parents (or
caregivers). Clear communication of the plan and goals is
essential for successful implementation of any nutrition
support plan. These patients are medically complex and
require close observation to accurately assess how they
tolerate the interventions.
For pediatric patients who receive nutrition support
the goal of therapy is to first wean off of PN and on to full
enteral feedings. Oral feeding is introduced as developmentally and physiologically appropriate. This careful balance
of all 3 modalities requires skilled observation and evaluation by everyone involved with the patient.
IMPLEMENTATION OF THE PLAN
Malnourished children need PN if they cannot tolerate or

safely receive EN for > 3 days.1 Implementation of a nutrition care plan that involves PN begins with the goals of
therapy and considers fluid status, appropriate intravenous
(IV) access and nutrition needs, and anticipated length
of therapy. Fluid status and PN solution composition is
discussed previously (see Chapter 34). The anticipated
length of therapy often dictates the IV access choice. Generally, the longer the need for PN, the more likely a patient
will need a more permanent central vascular access device
(VAD). In pediatrics, the use of peripheral parenteral nutrition (PPN) may be the initial nutrition intervention.
Type of Intravenous Catheter Needed

Neonatal and pediatric patients may receive a short course of
PPN prior to the initiation of PN. Peripheral intravenous vein
(PIV) selection is important in these patients. Avoidance of
the antecubital fossa is recommended if peripherally inserted
central catheter (PICC) placement is anticipated. PPN use is
the most common cause of infiltration-related tissue necrosis
in pre-term infants so diligent site assessment is crucial.2
Ideally, PIVs should not be placed in the scalp or feet of infants
who receive PPN.2 One study documented an average of 2.2
attempts per PIV for PPN placement with an average duration
of 2.19 days in neonates receiving PPN.3 Investigators recommended PICC placement as soon as possible.3
When PICC placement is needed for PPN, placement
of the tip in the superior vena cava, right atrium, or inferior
vena cava above the level of the diaphragm is recommended
to prevent complications such as occlusion and leakage.4 Also,
a PICC that has been in place for an extended period of time
before being used for PN should have tip placement verified
before use as this type of VAD is associated with a higher rate
of malposition than other central venous catheters (CVCs). 5
Case reports in the literature document intracranial malpositioning resulting in seizures and stroke in pediatric patients
who had a PICC for PN.6,7
As PICCs are the preferred VAD for neonates receiving
PN, it is important to discern the best placement; ie, upper
extremity (UE) versus lower extremity (LE). One retrospective
study documented a preferred site placement of UE by nearly
3 to 1 with UE placement at an average of day of life (DOL) 6
compared to LE placement around DOL 8. This study found a
significantly longer duration of usefulness for PICCs placed in
the LE. There was also a lower incidence of coagulase-negative
Staphylococcus (CoNS) in the LE group.8 Care should be taken
in site selection for PICCs in neonates. The antecubital fossa or
above is the preferred site for PICC placement in children.
449
PICCs should be secured to the skin. The use of sutures

to secure a PICC has been documented to result in less
migration, occlusion, and leakage when compared to the use
of tape.9 However, sutures can become inflamed requiring
removal. The use of an adhesive securement device has
been shown to be easier to place and associated with fewer
complications than sutures in pediatric patients.10
Critically ill children who require PN will typically
have a temporary VAD placed via the subclavian or internal
jugular veins. Reduction of bloodstream infections (BSIs)
related to CVCs continues to be an ongoing focus in all health
care settings, including critical care units. One approach has
been to coat CVCs with antibiotics. This is controversial in
pediatrics due to concerns of sensitization and development
of drug resistance. One study using antibiotic-coated CVCs
shows comparable infection rates but the antibiotic-coated
CVCs were in place an average of 18 days compared to 5
days for the non-coated CVCs before infection occurred.11
Many critical care units advocate removal of a temporary
CVC after 7 days. The use of antibiotic-coated CVCs in
pediatric patients remains controversial.
When it is clear long-term PN is needed for a patient,
plans for the most appropriate VAD need to be made. A
patient who will go home for up to 6 weeks of PN can often
use the same PICC already in place. A surgically placed
tunneled catheter is most often used for infants and children
who require home PN for an extended period of time. Occasionally an implanted VAD is placed when intermittent PN
or a few nights per week infusions are prescribed. This VAD
has definite benefits for adolescents who are already struggling with body image issues.
Once a CVC is in place for PN, it is also used to obtain
lab specimens to avoid venipuncture. Vigorous cleaning
of the injection cap prior to accessing the CVC is essential
to prevent intraluminal contamination. The approaches to
obtaining lab specimens are compared in Table 35-1. Two
studies in the literature document the safe and reliable
method of blood sampling involving repeated pushing and
pulling of blood into an empty syringe before obtaining a
specimen in a new syringe.12,13 Nursing should have options
for specimen collection based on what is best for that patient.
It is important for nursing staff to stop all infusions when
using a multi-lumen catheter to assure accurate lab sample
results. When the waste approach is used, one study does
validate the safety of 3 mL versus 5 mL of waste when blood
samples are obtained from a tunneled or implanted VAD.14
Regardless of the method used to obtain a blood specimen
through a CVC, it is recommended to change the injection
cap after every blood sample or within 24 hours.
450
Table 35-1 Comparison of Techniques Used to Obtain Blood Samples from a VAD
Type of Technique
Description
Pros
Cons
Traditional
1. Stop infusion
2. Flush VAD with NS
3. Obtain a waste specimen of 35 mL
4. Obtain blood needed for labs ordered
6. Restart infusion
1. Fill a syringe with heparin and remove it
2. Stop infusion
4. Obtain a waste specimen of 35 mL
5. Have a nurse rotate the waste specimen
6. Obtain blood needed for labs ordered
7. Return the waste specimen to the patient
9. Restart infusion
1. Stop infusion
2. Aspirate 35 mL of blood into a syringe
3. Reinfuse that blood and repeat the aspiration/
reinfuse procedure a total of 3 times
4. Place a new syringe on the VAD and obtain blood
needed for ordered labs
Gold standard procedure at

this time
Increases blood loss when doing

frequent blood sampling
Increases exposure of staff to
blood
Potential for confusing the waste
syringe with the sample syringe
Return the Waste
Push-Pull Method
Site Care
Once the CVC is in place, routine skin disinfection and
dressing changes are necessary. In 2002, the Guidelines for
the Prevention of Intravascular Catheter Infections recommended the use of chlorhexidine gluconate (ChloraprepTM )
for skin antisepsis for all patients over the age of 7 days or 26
weeks gestation.15 Since that time, this product has become
the standard antiseptic used for routine VAD dressing
change skin antisepsis in this country. It is generally well
tolerated. Transparent dressings that are replaced every 7
days or when loose or soiled are the dressing of choice over
gauze and tape as the insertion site can easily be inspected.
A trial of chlorhexidine gluconate-impregnated dressings
(BiopatchTM) in neonates resulted in contact dermatitis
making it not recommended for use in this population.16
Another key aspect of the dressing is to place a stress
loop in the VAD if it is tunneled or in the extension tubing
and tape to provide another method to prevent accidental
dislodgement of the CVC.
Safety Issues
BSIs related to the CVC are known to be associated with an
increase in cholestasis in infants on PN.17 Therefore, many
measures must be in place to assure adequate infection
control processes to prevent CVC-related BSIs. Table 35-2
When done properly, low risk

of infection associated with
obtaining labs.
Decreases the blood loss for the
patient
Potential for reinfusion of blood

clots
Potential for contamination of
blood being reinfused
Limits patient blood loss from

blood sampling
Potential for hemolysis due

to turbulence created by the
pushing and pulling
May not be feasible for some
VADs that are difficult to
drawfrom
summarizes these recommendations. Aside from institution processes to safeguard the patient, individual patients
will require infection prevention measures as well. Attempts
must be made to prevent contamination of the catheter hub
by draining gastrostomy tubes, a leaking ostomy bag, or
other body fluids. Babies who are teething need to have a
pacifier to prevent them from sucking on their IV tubing.
Children who are suspected or known to be self-destructive
should be carefully monitored. Siblings need to be supervised when visiting their brother or sister.
For children who have a parent in the room at all times
monitoring of the parent and any activity with the CVC is
warranted. Parents should not be allowed to access or care
for a CVC unless specifically trained to do so and only with
the permission of the nurse.
One of many reports in the literature described the use
of a CVC by parents with Munchausen Syndrome by Proxy.18
This condition is now referred to as Pediatric Condition Falsification which is a form of child abuse where the caregiver is
the perpetrator. Because this condition can be life threatening for the child, any suspicion of this condition needs to
be addressed prior to placement of a CVC for PN. While this
condition is difficult to prove, certain typical behaviors seen
in the caregivers include doctor shopping to different health
care facilities, discrepancy between reported symptoms and
451
Table 35-2 Prevention of CVC-Related Bloodstream Infections

Aspect of Care
Action
Hand Hygiene
Use an antiseptic skin soap to wash hands before placing or accessing a VAD or
use an alcohol-based hand sanitizer.
Staff involved in CVC placement must be competent to do this procedure.
Use maximal sterile barriers including masks, gowns, drapes, sterile gloves, and a kit with all
needed supplies.
Allow nursing to call a time out for an observed break in sterile technique.
Avoid placement of a CVC in a febrile patient.
Avoid guidewire replacement of a CVC.
Vigorously clean the hub of the catheter with 70% alcohol or chlorhexidine wipes before entering the line.
Have a policy on routine injection cap changes.
Avoid stopcocks on CVCs.
Use sterile, prefilled syringes for CVC flushing.
Limit accessing for labs to 1 time per day if possible.
Use a kit with all supplies needed.
Use ChloraprepTM as preferred skin disinfectant.
Use a mask and gown for PICC dressings.
Use a transparent dressing preferentially over a gauze and tape dressing to allow for the site
to be assessed.
Restrain the patient as needed to prevent accidental dislodgement.
Place a stress loop in the VAD tubing or extension tubing.
Obtain a peripheral and central blood culture.
Staff obtaining blood cultures should be specially trained and competent to avoid contamination.
Draw a minimum of 1mL for the blood culture.
Use clinical and other labs to validate diagnosis.
Do not necessarily remove the CVC.
Lipidsevery 24 h
PNevery 72 h unless a 3-1 solution, then every 24 h or if cycled off a few hours/day
Evaluate all supplies used on CVCs for defects that could lead to infections.
When using outside pharmacies, surveillance of possible IV fluid related infections is needed.
Have a surveillance plan within the institution to trend infections and look for a root cause.
Catheter Insertion
Catheter Accessing
Catheter Dressing Changes
Diagnosis of BSI
IV Tubing Changes
Other
what is observed, caregiver reluctance to leave the child and

to allow others to provide care, and overzealous attachment
to certain healthcare providers.19
Nursing Care
In addition to prevention of VAD-related infections, the
nursing care of a child requiring PN is extensive. Table 35-3
summarizes the nursing activities required when taking care
of a child who requires PN. Most hospitals and other care
settings require competencies in the areas of CVC dressing
changes, obtaining lab specimens, and appropriate flushing,
etc. Meticulous nursing care for any patient receiving PN is
absolutely essential in the pediatric care setting.
Enteral Nutrition
Enteral Route Selection
Enteral nutrition should be considered in all children with
an intact and functional gastrointestinal (GI) tract who can
not take in enough calories orally to meet their needs for
growth and development. Ideally a multidisciplinary team
including a pediatric physician, a nurse, a dietitian, a speech
therapist, and/or an occupational therapist should assess
each patient and develop a feeding plan. Balancing caloric
needs with the childs ability to digest and absorb nutrients
is a dynamic process that may necessitate low rates of EN
via feeding tube.
Once a clearly identified indication for enteral tube
feeding has been established, several ways to administer EN
exist. Enteral access can be obtained through a nasogastric
452
Table 35-3 Nursing Care of the Patient Requiring PN

Action
Frequency
Weigh patient using the same scale

Weigh babies nude
Assure the competency of staff who weigh patients
Repeat any weight that is clearly aberrant
Vital signs
Notify physician for temp > 38.5C
Monitor intake and output
Note stool/ostomy output and notify physician for excessive losses
Assess CVC site
Assure the CVC is secure
Flush the CVC with the appropriate amount of NS and Heparin if TPN
cycled off a few hours/day
Only use the appropriate concentration of heparin if needed for pt
Change injection cap
Shower or bathe patient with consideration for the safety of the CVC
Assure the safety of the CVC as age appropriate
Infuse the PN as orderedmatch the order with the bag
Double check the pump settings to assure the PN is infusing as ordered
If the CVC comes out or becomes dysfunctional, contact the physician for
orders for dextrose-containing solution
Monitor lab results and redraw when results look contaminated by PN
Monitor blood glucose
Promote normal growth and development of the patient
Daily at approximately the same time.
tube, orogastric tube, gastrostomy tube, nasoduodenal

tube, nasojenunal tube, gastro-jejunostomy, and jejunostomy. The choice of access is dependent on several factors
(described below) and should be made with the guidance of
the multidisciplinary team.20 The family and the older child
should be involved in the decision-making process to ease
potential fears and concerns related to providing EN and to
improve compliance.
The expected duration of therapy for EN is key in
selecting the most appropriate feeding tube. A child
expected to require EN for less than 3 months should have
a temporary means of providing formula, such as a nasogastric tube, nasoduodenal tube, or an orogastric tube. More
permanent access should be considered in a child requiring
enteral formula for greater than 3 months.
Anatomic abnormalities of the GI tract may dictate the
most appropriate feeding tube for the patient, especially if
there are known strictures. The GI tract should be free of an
obstruction that would impede normal movement of enteral
nutrients. There should be appropriate length to allow for
digestion and absorption of nutrients.
Proper functioning of the GI tract is necessary for
successful administration of EN. Feeding directly into the
stomach is preferred as it provides a more normal physiological process, digestively and hormonally. Delayed gastric
As needed
As needed
As needed but usually at least every 12 h
Every shift and as needed
At least every 4 h and more often if warranted
At least every 4 h and more often if warranted
After every interruption in TPN
As needed
Within 24 h of drawing blood and per hospital policy
Daily
At all times
Daily
Hourly
As needed
As needed
Per hospital policy
Ongoing
emptying or severe gastroesophageal reflux will impair

tolerance. Bypassing the stomach by way of nasoduodenal,
nasojejunal, gastrojejunal, or direct jejunal feedings may be
necessary at times.
The last factor that should be considered is aspiration
risk. Any patient with a potential risk of aspiration should
be evaluated. Preventive measures, such as bypassing the
stomach by using nasoduodenal, nasojejunal, gastrojejunal,
or jejunal tubes, or by operative fundoplication should be
considered by the healthcare team.
Types of Tubes
Nasogastric Tube
Nasogastric (NG) tubes are indicated for children who have
an intact and functional GI tract and will only require enteral
formula for a short period of time. These patients should have
minimal gastroesophageal reflux, normal gastric emptying,
and low risk of aspiration.20 NG tubes are soft flexible tubes
made of Silastic or polyurethane ranging in size from 5 Fr.
to 12 Fr. The tube size is chosen based on the patients age,
size, and type of formula needed. Small-diameter tubes are
more comfortable for the patient, but can become clogged,
particularly if the patient receives fiber-containing formula
or additives to the formula.
Nasogastic tubes can be easily placed by the family.

However, they can be dislodged as well, especially by an
active or agitated child. NG tubes should be replaced or
changed every 30 days. Children with NG tubes can be
encouraged to eat orally while receiving NG tube feedings.
Orogastric Tube
Orogastric (OG) tubes are not used as frequently because
they restrict oral feedings. Orogastric tubes are most useful
in infants to avoid nasal obstruction or in children where an
NG tube cannot be passed (ie, choanal atresia).
Nasojejunal Tube
Nasojejunal (NJ) tubes are similar to NG tubes, but longer
for passage through the pylorus, duodenum, and into the
jejunum. Nasojejunal tubes are necessary when there is
delayed gastric emptying, severe gastroesophageal reflux, or
risk of aspiration.20 These tubes are challenging to place and
require either a skilled nurse, gastroenterologist, or interventional radiologist to place. They can migrate back into
the stomach or duodenum or clog with thickened formulas
or medication administered in the tube. Feeding tubes in
the small bowel must be given as continuous drips since the
reservoir function of the stomach is bypassed.
Gastrostomy Tube
Gastrostomy (G) tubes or buttons are a more permanent
way of administering EN, and are recommended for any
child who requires long term (greater than 3 months) EN.20
Formula is directly administered into the stomach similar
to an NG tube. These tubes can be placed either endoscopically or surgically. The gastrostomy tube size is usually 14 Fr.
to 24 Fr.; however, smaller and larger tubes are available.
Gastrostomies are soft pliable devices made of silicone
or polyurethane. They are less noticeable to the general
public, which is important to some patients and families.
The primary gastrostomy may be a G-tube or primary placement G-button. Once the gastrostomy tract has matured
(in 2 to 3 months), the gastrotomy may be replaced with a
low-profile, skin-level device (Mickey button) that the caregivers can change themselves.
Gastrojejunostomy Tube
Gastrojejunostomy (GJ) tubes are also permanent tubes
that are inserted into the wall of the stomach similar to a
G-tube; however, there are two ports: one into the stomach
for fluids, medication, and venting and the other into the
jejunum. They are recommended for patients who require
long-term EN and who cannot tolerate feedings into their
453
stomach because of delayed gastric emptying, gastroesophageal reflux, or risk of aspiration.20 These must be
administered as continuous drip feedings.
Jejunostomy Tube
Jejunostomy (J) tubes are surgically placed jejunal tubes.
These tubes can be inserted directly into the jejunum endoscopically or surgically. Typically, they are used in patients
who will require enteral nutrition access for the small bowel
for more than 6 months.20 The negative side to jejunostomy
tube use includes mandatory continuous feedings as well as
surgical emergencies (volvulus) around the tube.
Tube Insertion
Most NG tubes are placed at the bedside. An attempt is made
to make the child as comfortable as possible. An infant or
young child should be swaddled for comfort and to prevent
their arms from flailing about during tube insertion. The
cervical spine of the child should be slightly flexed and not
hyperextended.21 A small amount of lubricant is applied to
the tip of the tube or water may be used. The tip is inserted
into a nostril and then slid carefully down the nasopharynx,
oropharynx, esophagus, and into the stomach. It is then
secured into place at the nares. Parents are taught the technique of inserting NG tubes so the tubes can be replaced at
home when necessary.
Nasojejunal tubes are inserted in a similar manner;
however, they usually require the assistance of radiology or
fluoroscopy for accurate placement or confirmation. These
tubes cannot be replaced at home. If the tube migrates back
into the stomach, it must be replaced.
Gastrostomy tubes, gastrojejunostomy tubes, and
jejunostomy tubes must be placed endoscopically by a
pediatric gastroenterologist, radiologist, or by a pediatric
surgeon. If a tube is dislodged, families should be instructed
to insert a replacement tube or temporary tube in the tract
immediately to avoid premature closure of the tract until a
more permanent tube can be replaced.
Verification of Placement
Verifying correct placement of an enteral tube is imperative
prior to administering enteral formula. A tube accidentally
inserted into the respiratory tract will certainly have disastrous or even deadly consequences.
Radiology
A chest and abdominal x-ray which identifies the length of
the tube is the gold standard for confirming placement. The
tip of the feeding tube can be seen within the stomach or
454
jejunum. There is concern regarding increasing exposure to

X-rays, and alternative methods have been used to confirm
placement of feeding tubes.22
Air Insufflation
Air is pushed through an NG tube using a syringe, with
auscultation over the patients left upper quadrant. If the air
bolus is heard in the left upper quadrant, then placement is
thought to be in the stomach. This method is inexpensive,
but is also the least sensitive. Air pushed into a feeding
tube that is mistakenly placed in the thoracic cavity can be
heard in the abdomen. 23 Many case reports describe the
inability of clinicians to determine gastric versus respiratory placement.22
Gastric Aspirate/pH Testing
Aspirating gastric contents and confirming pH is an
alternative to the gold standard radiograph and is the recommended bedside method to confirm NG placement. 22,23 The
Childrens Hospital in Boston recommends use of gastric
pH performed at the bedside. Correct placement may be
confirmed if the gastric pH measures less than 5. The use
of medications for acid suppression is widely used in pediatrics and would invalidate the confirmation of placement.
Delivery of feeds, time of last feed, and medications also
impact gastric pH. If the gastric pH is greater than 5, gastric
aspirate cannot be obtained, the patient clinically deteriorates during placement, or develops low oxygen saturation,
an x-ray would be necessary to confirm placement.24
Colorimetric CO2 Detector
The colorimetric CO2 detector was initially used to determine placement of an endotracheal tube within the trachea.
It has been used in adults to assess appropriate feeding tube
placement. Unfortunately, there are no published studies in
children regarding the reliability and validity of colorimetric
CO2 detectors verifying placement of enteral feeding tubes.25
Electromagnetic Tube Placement
The Cortrak SystemTM assists with feeding tube placement
by displaying the approximate location of the feeding tube
during real-time placement. This system uses feeding tubes
with a specialized stylet that has an electromagnetic transmitter. A receiver unit is placed on the patients xiphoid
process and acquires the signal from the stylet. It tracks the
course of the stylet as the feeding tube is inserted and displays
it on a monitor. Pediatric patients who can tolerate an 8 Fr. or
larger feeding tubes are candidates for this device.25
Bolus vs. Continuous Feeds
Enteral formulas can be given through bolus feedings, continuous feedings, or a combination of both depending on a
number of factors. These factors include the childs condition
and nutrition status, anatomy, type of tube selected, indication for tube feedings, and family schedule. It is important to
consider family lifestyle when implementing a feeding plan.
The goal is to maximize the benefit of enteral feeding while
minimizing the complexity of nutrition support.
Bolus Feedings
Bolus feedings imitate regular mealtimes and, therefore,
are more physiologic compared to continuous feedings. A
feeding schedule is determined by a dietitian and pediatric
physician depending on the childs caloric and fluid requirements. Bolus feedings can only be administered into the
stomach and should never be administered past the pylorus.
Formula can be administered by gravity or over a pre-determined period of time by a feeding pump. Bolus feedings are
often more convenient for the patient and family because
the schedule is more flexible and the child is not tethered to
an infusion pump.
Continuous Feedings
Continuous feedings are infusions of enteral formula over
time. Patients, who cannot tolerate large volumes because
of delayed gastric emptying, GERD, or dumping syndrome,
are given slow continuous feeds. The continuous feedings
are generally smaller volumes infused slowly. A feeding
pump is required for these infusions which may limit the
childs ability to move. For ambulatory patients, there are
smaller feeding pumps that can be carried in a backpack
allowing for more flexibility and mobility.
Combination feedings are ideal for patients who need a
significant amount of calories but cannot tolerate large
volumes. Smaller bolus feedings can be given during the
day and the remainder can be administered continuously
overnight. This method also allows the child and parents to
sleep at night.21
Initiation and Advancement of Feedings
Enteral feedings are often started in a hospital to observe

feeding tolerance and monitor for complications. A feeding
schedule is designed by the health care team which may
include a dietitian, attending physician, and an occupational
therapist, and a GI nurse. The family receives support and
reassurance during the hospitalization from all members
of the team. The family learns about the formula, feeding

schedule, enteral device, and safety concerns regarding
feedings.
Choice of formula is discussed in other chapters. Fullstrength formula should be used. There is no need to dilute the
formula for initiation or advancement of feedings.21 For neurologically intact children, it is important to encourage the child
to eat orally to maintain oral motor skills. If oral feeding cannot
be done, a referral for occupational therapy is warranted for oral
stimulation while receiving enteral feeding.
Bolus Feedings
The total calculated volume of formula is based on the childs
caloric needs and requirements. This volume is divided into
6 to 8 boluses. It is recommended to give 25% of the childs
caloric needs on day 1 and advance by 25% each day until
the final caloric goal is achieved.21 The child is monitored
closely for tolerance to the increased volume. Signs of intolerance include vomiting, abdominal distention, or pain.
Bolus feedings are given over 15 to 20 minutes, however,
longer times may be required.
Once the child is doing well with the initial feeding
schedule and is meeting the caloric goal, boluses can be
compressed to 4 to 6 feedings. This allows for ease and
flexibility of administration by the family at home. Again,
the child is monitored for tolerance during this transition.
Boluses may need to be given more frequently in infants or
children who have metabolic disorders or increased caloric
needs (ie, burns, catch-up growth).
Continuous Feedings
It is recommended to start continuous feedings at 1 to 2
mL/kg/h for 24 hours and increase by 0.5 to 1 mL/kg/h
every 8 to 12 hours until the final caloric goal is met. 22
When the final goal is achieved, compressing the feeding
into a shorter time interval should be considered so the
child can have a few hours each day free from the feeding
tube. Generally 16 to 18 hours each day should enable a full
daily caloric requirement. The child is monitored closely for
tolerance to each increase in volume and during compression of feedings.
When a child cannot tolerate large volumes of bolus feedings, combination feedings should be considered. The total
daily caloric requirement is divided between 3 to 4 smaller
bolus feedings during the day followed by a continuous
infusion overnight. This can be accomplished starting with
continuous feedings and working up to the caloric goal.
455
Daytime feedings are compressed by 1 to 2 hours each day

until the desired number of boluses is given (3 to 4 hours
apart). Boluses may be given over 30 to 60 minutes if intolerance presents.
Safety Issues
Preparation
Formula should be prepared by personnel and family
members who are trained to prepare formula in a clean
environment.21 Good hand washing is imperative prior
to preparation.21 The warm and nutrient-rich environment of enteral formulas promote the growth of bacteria.
Using appropriate handling, hygiene, and adherence to
guidelines for hang time will prevent most episodes of
contamination.26
Ready-to-feed and formulas from liquid concentrate
are and should remain sterile; however, bacteria and other
micro-organisms can populate rapidly if the right conditions
are met. Powdered, reconstituted formulas or those with
additives tend to grow more bacteria and therefore require
meticulous attention to principles of aseptic technique in
the preparation and administration of the formula. 21
Hang Time for Formula

Contamination of enteral formula can occur at any time,
even after it is prepared and placed in a container or bag and
ready to be given to the child. Hang time refers to the length
of the time that the formula flows through an administration
set. During this time, it is possible for bacteria to populate
and contaminate the formula. Because bolus feedings are
usually administered within 1 hour and have a lower risk of
contamination, hang time usually refers to a continuous or
overnight feeding.
Liquids in an open system, human breast milk, and
powdered formula that is reconstituted should not hang for
more than 4 hours. Sterile, ready-to-feed formula may hang
for up to 8 hours. Liquid formula in a closed system can be
safely hung for 24 hours.21,27
Feeding Pumps
Feeding pumps are useful for delivering continuous feedings or slower infusions for bolus feedings. Some feeding
pumps are small enough to be worn in a small backpack
for ease of mobility and flexibility of schedules. The ideal
pediatric pump is not position sensitive, can be increased
in increments of 0.1 mL up to 5 mL/h, and is relatively
light weight. Providers and caregivers need to be aware
that enteral feeding pumps are not free of malfunctions.
456
Most manufacturers of feeding equipment and pumps have

safeguards in place to prevent flow errors. Pumps should
accurately administer formula within 5% of the ordered
amount. Periodic calibration of the pump is important to
ensure the accuracy of the delivery system.21
Nursing Care
Securing the Tube
Nasoenteric tubes can easily be pulled out of the nose by an
infant or a child tugging on the tube, sneezing, or vomiting.
To prevent dislodgement, the tube is secured in place on the
childs face. It is recommended to fix the excess tubing to
the back of the infants or childs shirt (ie, with a tape tab
and safety pin). This helps to keep the tube out of sight and
prevents the child from grabbing it.
Transparent dressing is usually applied to the cheek on
the same side of the face as the nasoenteric tube. The enteral
tube is inserted as described previously. The portion of the
tube that remains outside the body is laid across the DuodermTM and then a transparent dressing is applied over the
tube and Duo-dermTM securing the tube to the face. This
method protects the childs skin from harsh adhesive tape
that may tear the skin.28
J tubes, G tubes, and low-profile skin-level G buttons
can also be pulled out by the child, although it is less likely.
Most types of permanent feeding devices have an internal
retaining device which may be a collapsible rubber stopper
or a water-filled balloon. Many permanent feeding devices
also have an external retaining device.
A similar technique can be used to secure a G or J tube
to the childs stomach. There are commercially available
products to help keep some tubes in place.
Site Care
Keeping the site clean and dry is the most important aspect
of caring for an enteral feeding tube. Washing the nose and
face with mild soap and water daily is enough to keep the
nasoenteric tubes clean.
Ostomy sites should be monitored for cleanliness
daily. Mild soap and water is enough to keep these sites
clean, gently scrubbing off any crusted areas. A 22 gauze
dressing that is cut half way through can be placed between
the device and the skin to keep the ostomy site dry if there is
some leakage. For the most part, a dressing is not required.
Antibiotic ointment may be needed if the site becomes
erythematous or tender. Caregivers are taught to apply the
ointment for up to 3 days and if the symptoms persist, a
physician should be contacted.
Checking Residual Volumes

It is not recommended to check residual volumes as there is
much debate over their significance. Intolerance to feedings
is demonstrated by mood (ie, fussy or irritable), vomiting,
retching, or abdominal distention. Residuals are influenced
by enteral formulation, gastric emptying, gastroesophageal
reflux, respiratory embarrassment, timing of measurement
in relation to feed, and delivery method. Residuals that are
collected should be re-fed to the patient as this can be a
significant source of calorie loss.
Flushing the Tube

In general, routine flushing of enteral tubes after each bolus
feeding or interrupting continuous feeding for water flushes
is not recommended in children.21 If a tube becomes clogged,
water is readily available and is the preferred flushing solution. Sterile or purified water is preferred over tap water
when flushing the tube.21
It is important to take the childs age into account when
flushing an enteral feeding tube with water. Immature
kidneys cannot remove excess water and too much free
water can dilute normal sodium levels causing hyponatremia. Hyponatremia may promote complications (eg,
seizures). Typically, 3 to 5 mL is enough to flush an NG tube
in children. Smaller volumes may be used in premature and
smaller infants.
Use of Sterile vs. Non-Sterile Water

It is generally recommended to use sterile or purified water
when preparing formulas for infants or immunocompromised children.26
Reflux
Severe gastroesophageal reflux may be an indication for
enteral tube feeding when frequent emesis results in food
refusal and failure to thrive. Gastroesophageal reflux can
be frustrating and anxiety provoking for both the child
and caregivers. Frequent episodes of emesis are a source of
calorie loss in young children.
Reflux can worsen with enteral tube feedings. Children
are unable to self-limit their intake. Their stomach may not
be able to accommodate their goal volumes. Also, in older
children, the diet is changed from relatively thickened or
solid feeds to liquid formula, which can predispose them to
more reflux.20
Worsening reflux may be a sign of intolerance to a
feeding schedule or formula. Sepsis, respiratory embarrassment, or metabolic abnormalities have an impact on the
number of reflux episodes.
The cause and extent of GERD affects nutrition

management. Common tests in the evaluation include an
esophagram, upper GI study, pH/impedance probe study,
or esophagogastroduodenoscopy with biopsies. Changing
the enteral formula, slowing the rate of the bolus feedings, or changing to continuous feedings may need to be
considered.
Medications to treat reflux such as H2 blockers or
proton pump inhibitors may be prescribed. If delayed
gastric emptying is the cause for increased reflux, prokinetic
medications, changing formula, or post-pyloric feeding may
be considered.20 If all other methods have failed, a surgical
consultation for fundoplication procedure or JT may be
necessary.
Aspiration Precautions
Infants and children lying flat are at increased of refluxing
and aspirating. It is important to position the infant or child
in a manner to prevent aspiration episodes with the head of
the child elevated at least 30 while receiving a feed.20,21 It
may also be necessary to feed the child at risk for aspiration
transpylorically.
Intake and Output

During the initiation and advancement of enteral feeding,
intake and output should be measured frequently, accurately,
and recorded for each 24-hour period. This information
helps monitor the childs caloric adequacy and fluid balance,
and assists the multidisciplinary teams decision making
regarding needed changes to the nutrition plan.
Intake should be documented as both oral and enteral
feeding. Caregivers should record the name and the amount
that was given. They also should include if the feeding was
held or for medications or intolerance, or decreased.
Output can be in the form of vomiting, voiding, and
elimination. A normal voiding pattern ensures that the child
is receiving enough fluid and that the childs kidneys are
functioning properly. A normal stooling pattern indicates
that the child is tolerating the feedings and likely absorbing
the appropriate macro- and micronutrients. Patients with
an ostomy should have written parameters for when to call
the physician. Diarrhea is a cause for concern as it is source
of significant fluid and calorie loss.
Maintaining a strict intake and output diary can be challenging especially for the family at home. When the child is
tolerating maintenance or caloric goal feeds, monitoring of
intake and output can be more flexible. The parents or caregivers should note modifications to the feeding schedule,
episodes of vomiting, or changes in the voiding or stooling
457
patterns of the child and be able to discuss them with the

multidisciplinary team at follow-up visits. For patients with
ostomies, ostomy output should be recorded and a contact
given if that amount is exceeded.
Weights
Weights should be monitored daily during the initiation and
advancement phases of a feeding plan. The infant or child
should be weighed without clothing and on the same scale
every day at the same time. Ostomy bags should be emptied
just prior to the weight measurement. Individual weights
are less important than an overall weight trend.
Monitoring a childs weight at every follow-up visit
ensures that the child is receiving appropriate calories for
growth. If the child fails to gain weight or loses weight,
healthcare providers should investigate any potential
sources of calorie loss.
Assessment of Feeding Tolerance

Successful enteral nutrition will allow a child to grow in
both weight and length without significant distress. Tolerance to a feeding plan should be assessed during initiation,
advancement, and maintenance of feedings. Any issues with
feeding intolerance should be addressed early to minimize
interruption of nutrition support.
Monitoring parameters that should be assessed routinely
include vital signs, intake and output, daily weights, enteral
access, and physical exam with close attention to abdominal
assessment. Laboratory assessment including electrolytes,
glucose, calcium, magnesium, and phosphorus should be
obtained prior to initiating enteral nutrition. They may need
to be monitored frequently until they are stable, especially
in the severely malnourished child at risk for refeeding
syndrome.21
Parents and caregivers should be made aware of the
signs and symptoms of feeding intolerance so that they
may seek medical attention in a timely manner. Signs and
symptoms of feeding intolerance include changes in mood
or behavior (ie, fussiness during feeds), coughing, choking,
retching, abdominal distention, vomiting, or diarrhea.
Modifications to the feeding plan can be made to decrease
these problems.
Medication Administration
Enteral feeding tubes can be utilized for medication administration. Some medications can be given via enteral tube
easily (eg, liquid suspension or solution, crushed solid
tablets, and capsules). More complex formulations including
extended or sustained released products are problematic.
458
Liquid forms of medications are preferred. Some solutions and suspensions may be too viscous or thick to safely
put through an enteral tube. These medications must be
diluted with sterile water. Suspensions must be shaken thoroughly prior to administration.21 Improper administration
can lead to inaccurate medication provision.
Medications in the solid form such as tablets or capsules
must be crushed or opened and mixed with purified water
prior to administering through an enteral feeding tube. It
is important to mix the medication well to prevent underdosing or overdosing of the prescribed medication.
After administering medications through an enteral
feeding tube, the tube must be flushed with purified water to
prevent the feeding tube from being clogged and to ensure
that the entire dose of medication is given to the child.
Caregivers should be aware of what medication is being
administered and where the medication is being administered. Certain medications including vitamins and minerals
require activation in the stomach or are predominantly
absorbed in the upper small intestine. Medications that alter
gastric pH may also affect the activity of concomitant medications. A consultation with a pharmacist is warranted when
deciding to give medications through an NJ tube or a GJ tube
as these tubes bypass the stomach and upper small intestine altogether. A pharmacist will also provide information
regarding medication compatibility if the decision is made to
add the medication directly to an enteral formula.21
Oral Nutrition
A patient is ready to have the tube feedings reduced when

he or she can tolerate the amount of calories needed for
growth. In transition off tube feeds, it is typical for the child
to receive more bolus feedings and to get those feedings in
30 minutes or less. An established meal schedule offered
before bolus feedings provides the opportunity to eat
orally before tube feeds. Table 35-4 is an example of a tube
weaning program.
The goal of tube reduction should not be to just get off
the tube but to be able to eat a variety of age-appropriate
foods with age-appropriate skills and growth. Progress is
determined by many factors (eg, ongoing medical complications, cooperation and consistency of caregivers, and
realistic expectations). Communication, consistency, and
commitment are needed by all providers and the family to
achieve the goal of oral eating.
Table 35-4 Weaning Off Tube Feedings

Using spoon foods, baby foods, or blenderized table food aim for 12
bites swallowed with no vomiting.
Increase bite amount if reaching goal 75% of the time, about every 34
days
Once 10 bites achieved per meal, go to amounts/quantity.
Taking 14 oz per meal consumed, start tube reduction
Reduce the tube feeding early in the day to benefit meals. Reduce the
bedtime/evening tube feedings last.
Continue to advance oral motor and oral sensory but not at mealtimes.
Begin activating chewing skills while continuing to spoon feed
Introduce cup and straw.
When swallowing of chewables is established, offer finger foods at each
meal before the spoon feeding.
Offer liquid by cup or straw throughout the meal but do not leave on
the tray.
Naked weights will be needed monthly. This will help determine tube
reduction. Reduce 48 oz depending on weight gain/loss.
Increase finger foods as skill allows.
Add water to tube feedings as needed during reduction.
Need 23 months of normal growth without tube use before removing
the tube.
1. A patient who has a documented weight loss of 5%,

whose body mass index is < 3rd percentile, and is not
expected to have normal gut function for at least 7 more
days should receive PN via:
A. Peripheral IV
B. PICC
C. Surgically placed CVC
D. No PN
2. A baby with short bowel syndrome is anemic and needs
daily lab specimens. The most appropriate technique to
obtain the lab specimens for this patient is:
A. Return the waste
B. Push Pull method
C. Traditional method using the least amount of waste
possible
3. A toddler with failure to thrive who plots at < 3rd
percentile for body mass index needs nasogastric tube
feeds due to presumed postviral food aversion. The
most appropriate approach to feeding this child is:
A. Continuous drip feedings
B. Bolus feedings during the day only
C. Daytime bolus, nighttime drip
D. None of the above. Do an occupational therapy
consult for food aversion.
References
1. Duggan C, Rizzo C, Cooper A, et al. Effectiveness of a clinical

practice guideline for parenteral nutrition: a 5-year follow-up
study in a pediatric teaching hospital. J Parenter Enteral Nutr.
2002;26:377381.
2. Wilkins CE, Emmerson AJB. Extravasation injuries on
regional neonatal units. Arch Dis Child Fetal Neonatal Ed.
2004;89:F274275.
3. Franck LS, Hummel D, Connell K, et al. The safety and efficacy
of peripherally inserted intravenous catheters in ill neonates.
Neonatal Network. 2001;20(5):3338.
4. Racadio JM, Doellman DA, Johnson NA, et al. Pediatric
peripherally inserted central catheters: complication rates
related to catheter tip location. Pediatrics. 2001;107(2):14.
5. DiChicco R, Seidner DL, Brun C, et al. Tip position of
long-term central venous access devices used for parenteral
nutrition. J Parenter Enteral Nutr. 2007;31(5):382387.
6. Anderson C, Graupman PC, Hall WA. Pediatric intracranial
complications of central venous catheter placement. Pediatr
Neurosurg. 2004;40:2831.
7. Parikh S, Narayanan V. Misplaced peripherally inserted
central catheter: an unusual cause of stroke. Pediatr Neurol.
2004;30(3):210212.
8. Hoang V, Sills J, Chandler M, et al. Percutaneously inserted
central venous catheters for total parenteral nutrition in
neonates: complication rates related to upper versus lower
extremity insertion. Pediatrics. 2008;121(5):11521159.
9. Graf JM, Newman CD, McPherson ML. Sutured securement of peripherally inserted central catheters yields fewer
complications in pediatric patients. J Parenter Enteral Nutr.
2006;30(6):532535.
10. Frey AM, Shears GJ. Why are we stuck on tape and suture? J
Infusion Nurs. 2006;29(1)3438.
11. Chelliah A, Heydon KH, Zaoutis TE, et al. Observational trial
of antibiotic-coated central venous catheters in critically ill
pediatric patients. Pediatr Infect Dis J. 2007;26(9):816820.
12. Barton SJ, Chase T, Latham B, et al. Comparing two methods
to obtain blood specimens from pediatric central venous catheters. J Pediatr Oncol Nurs. 2004;21(6):320326.
13. Adlard K. Examining the push-pull method of blood sampling
from central venous access devices. J Pediatr Oncol Nurs.
2008;25(4):200207.
14. Cole M, Price L, Parry A, et al. A study to determine the
minimum volume of blood necessary to be discarded from a
central venous catheter before a valid sample is obtained in children with cancer. Pediatr Blood Cancer. 2007;48:687695.
15. Centers for Disease Control and Prevention. Guidelines for
the prevention of intravascular catheter-related infections.
MMWR Morb Mortal Wkly Rep. 2002;51(RR10):126.
459
16. Garland JS, Harris MC, Naples M, et al. A randomized trial

comparing povidone-iodine to chlorhexidine gluconateimpregnated dressing for prevention of central venous catheter
infections in neonates. Pediatrics. 2001;14311437.
17. Sondheimer JM, Asturias E, Cadnapaphornchai M. Infection and cholestasis in neonates with intestinal resection and
long-term parenteral nutrition. J Pediatr Gastroenterol Nutr.
1998;27:131137.
18. Feldman KW, Hickman RO. The central venous catheter as a
source of medical chaos in Munchausen syndrome by proxy. J
Pediatr Surg. 1998;33(4):623627.
19. Ayoub CC, Alexander R. Definitional issues in Munchausen
by proxy. APSAC Advisor. 1998;11(1):710.
20. Baker SS, Bakers RD, Davis AM. Pediatric Nutrition Support.
Sudbury, MA: Jones and Bartlett Publishers; 2007.
21. Bankhead R, Boullata J, Brantley S, et al. Enteral nutrition practice recommendations. J Parenter Enteral Nutr.
2009;33(2):122167.
22. Wilkes-Holmes C. Safe placement of nasogastric tubes in children. Paediatr Nurs. 2006;18(9):1417.
23. Westhus N. Methods to test feeding tube placement in children. Am J Matern Child Nurs. 2004;29(5):282287.
24. Richardson DS, Branowicki PA, Zeidman-Rogers L, Mahoney
J, MacPhee M. An evidence-based approach to nasogastric
tube management: special considerations. J Pediatr Nurs.
2006;21(5):388393.
25. Ellett ML. What is known about methods of correctly placing
gastric tubes in adults and children. Gastroenterol Nurs. 2004
Nov-Dec;27(6):253259.
26. Smith SL. Guidelines for safety and quality assurance
when preparing infant feedings. Newborn Infant Nurs Rev.
2008;8(2):101107.
27. Hustler D. Delivery and bedside management of infant
feedings. In: Robbins ST, Beker LT, eds. Infant Feedings:
Guidelines for Preparation of Formula and Breastmilk in Health
Care Facilities. Chicago, IL: American Dietetic Association;
2003:8895.
28. Guenter P, Silkroski M. Tube Feeding: Practical Guidelines and
Nursing Protocols. Sudbury, MA: Jones and Bartlett Publishers;
2001.
36
Evaluation and Monitoring of Pediatric Patients

Receiving Specialized Nutrition Support
Elaina Szeszycki, PharmD, BCNSP, Wendy Cruse, MMSc, RD, CNSD and Michelle Strup, PharmD
CONTENTS
Management of Pediatric Patients Receiving
Nutrition Support Therapy. . . . . . . . . . . . . . . . . . . . . . . . . 460
Nutrition Monitoring and Evaluation. . . . . . . . . . . . . . . . . 461
Enteral Nutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461
Monitoring
Evaluation of Growth and Nutrition Adequacy
Evaluation of Formula Tolerance
Monitoring Laboratory Values
Oral Feeding
Revision of Enteral Plan
Evaluate for Infusion-Related Incidents
Evaluate Tolerance of Volume
Evaluate Tolerance of Macronutrients
Monitoring the Integrity of PN Formulations
Comparison of 3-n-1 and 2-n-1 Formulations
Combination Enteral and Parenteral Nutrition
Reassessment of the Plan. . . . . . . . . . . . . . . . . . . . . . . . . 466
Evaluate Drug and Nutrient Interactions. . . . . . . . . . . . 466

Compatibility of Medications
Guidelines for Monitoring Nutrition Laboratory Values in Children
Receiving Enteral and Parenteral Nutrition
Physical Data
Chemistry Profile Monitoring
Nutrition-Related Laboratory Tests
Liver Function Tests and Bilirubin
Trace Elements
Iron Studies and Anemia
Vitamins
Metabolic Bone Disease
Infectious Complications. . . . . . . . . . . . . . . . . . . . . . . . . . 470
Appendix 36-1: PN Limits . . . . . . . . . . . . . . . . . . . . . . . . . 471
Appendix 36-2: Neonatal and Pediatric

PN Monitoring Form. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472
Appendix 36-3: Long-Term PN Lab Tracking Sheet . . . . . 473
460
Learning Objectives
1. State objective and subjective data necessary for a

thorough evaluation of currently stated nutrition
support goals.
2. Identify parameters utilized to evaluate gastrointestinal
tolerance of enteral nutrition.
3. Identify parameters utilized to evaluate tolerance to
parenteral nutrition.
4. List factors affecting calcium and phosphorus
solubility.
5. Discuss the laboratory monitoring required for patients
receiving specialized nutrition support.
Management of Pediatric Patients Receiving

Nutrition Support Therapy
Management of pediatric patients receiving nutrition support

therapy is based on continuously assessing the tolerance and
efficacy of the nutrition intervention based on the initial
nutrition care plan. The nutrition care plan must consist of
nutrition goals that are both short term and long term. The
patient-specific set of goals must be continually monitored to
assess the efficacy of therapy and adequacy of growth.
When initiating any form of nutrition support in a
severely malnourished child, careful monitoring must take
place to avoid refeeding syndrome.1 Hypophosphatemia
has been reported to be associated with malnutrition in
children and in the first 10 days of intensive care hospitalization.2 Although hypophosphatemia is most commonly
associated with refeeding syndrome, careful monitoring of
phosphorus as well as potassium and magnesium is critical
when initiating nutrition support in severely malnourished
patients. 3 Baseline electrolyte levels should be obtained
and depleted mineral and electrolytes should be replaced
EVALUATION AND MONITORING OF PEDIATRIC PATIENTS RECEIVING SPECIALIZED NUTRITION SUPPORT
before initiation of nutrition therapy.1 It has been suggested

that electrolyte levels should be monitored thereafter every
6 hours, 12 hours, then daily for the first 3 days or until
levels are stable.4,5 Daily monitoring of serum electrolytes,
minerals, and vital signs during advancement of nutrition
support would be a minimum expectation in malnourished
patients. Oral supplements can be administered by mouth
or feeding tube as tolerated when patients are being fed
enterally. Intravenous (IV) electrolytes can be provided
when patients are receiving primarily parenteral nutrition
(PN). Should the child experience diarrhea when receiving
oral therapy or serum levels are moderately to severely
depleted, electrolyte replacement may need to be switched
to IV infusion.
It is also critical to avoid providing excess or inadequate
calories during controlled feeding situations when the child
is not utilizing hunger and satiety cues. Children receiving
tube feeding do not have the ability to choose more or
less calories as their growth and nutrition needs change;
therefore, it is critical to monitor growth frequently. It is
important to utilize growth charts with serial measurements
and growth velocity.6,7 Excessive calories from PN may
contribute to cholestatic liver disease, which is discussed
later in this chapter.
The route of nutrition support needs to be reevaluated
frequently. Enteral nutrition (EN) is the preferred route
when possible. PN should be used when the gastrointestinal
(GI) tract is not functional or if inadequate absorption is
apparent and thus adequate nutrition support is not possible
via the enteral route.8 Adequacy and appropriateness of the
route for nutrition support must be reassessed frequently
and adjusted as needed.
Nutrition Monitoring and Evaluation
Complications associated with the delivery of EN and

PN can be prevented with monitoring and timely formula
adjustments based on the patients tolerance. Development
of enteral and parenteral monitoring guidelines is critical
to assure all parameters are being assessed. Monitoring
parameters are based on nutrition goals set in the nutrition care plan as well as patient tolerance. Initially, baseline
weight, height or length, and head circumference should be
plotted on age-appropriate growth curves. Monitoring will
include the patients growth, fluid status, clinical status,
tolerance to EN and PN, medication changes, and laboratory values. Frequency of monitoring depends on the age,
severity of illness, tolerance of specialized nutrition support
(SNS), comorbid diseases, and degree of malnutrition.
Preterm neonates, infants, critically ill patients, and severely
461
malnourished children at risk for refeeding syndrome or

during the transition periods between PN, EN, and oral diet
may require more frequent monitoring.
Enteral Nutrition
Monitoring
There are many parameters that can be used to monitor
patients receiving EN. During the initiation and advancement of EN, monitoring will be more frequent and become
less frequent as the child becomes more stable. A proposed
monitoring protocol for infants and children receiving EN
initially and then stable, both while in hospital and at home,
is provided in Table 36-1.9,10
Evaluation of Growth and Nutrition Adequacy

Baseline anthropometric data must be assessed initially,
followed by periodic monitoring of growth velocity. Calorie,
protein, vitamin, mineral, and fluid intake must be assessed
initially, then monitored daily then weekly and later monthly
as needed. Fluid status can be assessed by balancing fluid
intake with fluid output including urine, stool, or ostomy
output, emesis, wound losses, and tube drainage.
Evaluation of Formula Tolerance

Monitoring tolerance to EN includes monitoring changes
in GI function. Stool frequency and consistency as well as
presence of blood should be recorded daily. If a patient has
an ostomy, consistency and volume of ostomy output should
also be recorded daily. Volume goal may be < 40 mL/kg/d
or < 30% of formula volume.11 A large amount of stool or
ostomy output may indicate the need to reduce formula
volume or avoid advancement of feeding volume. Large
stool volume or ostomy output may require the initiation
of IV fluids to avoid dehydration. If small bowel bacterial
overgrowth is present based on the presence of D-lactate or
a positive breath hydrogen test, a low-carbohydrate formula
may be beneficial. Measuring stool for reducing substances
also identifies when a patient is experiencing small bowel
bacterial overgrowth. Antibiotics administered enterally in a cyclical fashion, probiotics, and avoidance of acid
suppression may also be beneficial in patients with bacterial
overgrowth. 5 The presence of blood in the stool may require
an elemental formula with lower allergenicity or in extreme
cases an amino acid-based formula. Other symptoms of GI
intolerance may include nausea, vomiting, gastric residuals,
abdominal distention, and increase in abdominal girth.
462
Monitoring Laboratory Values
Oral Feeding
Routine laboratory monitoring may include serum electrolytes,

glucose, blood urea nitrogen (BUN), creatinine, calcium, phosphorus, magnesium, albumin, prealbumin, complete blood
count with differential, and iron indices as well as assessment of
acid-base status. Routine monitoring of laboratory values is not
indicated for medically stable pediatric patients receiving EN
at advised levels and achieving adequate growth.9 Serum zinc
may need to be monitored when fat malabsorption is present.
Physical assessment including clinical signs of nutrient excess
or deficiency must be assessed periodically.
Introduction to oral feeding is critical in all infants receiving

EN. Allowing the infant to take a minimal volume of
formula orally may reduce the amount of oral aversion so
commonly seen in these children. It is also critical in older
children receiving tube feeding to be allowed to eat and
drink once safety has been established either via observation or oximetry-swallow study.
Table 361 Suggested Parameters to Monitor for Infants and Children Receiving Enteral Nutrition9,10
Growth Parameters
Weight
NICU
Infants
Children
Length
NICU
Infants
Children
Height
(> 36 mo)
Head circumference
(< 36 mo)
Weight gain
Linear growth
Intake Parameters
Intake
Calories
Protein
Vitamins
Minerals
Fluid balance
GI Tolerance
Abdominal girth
Gastric residuals
Emesis
Stool
(volume, frequency,
consistency, color)
Ostomy
(volume, consistency)
Physical
Temperature
Tube placement
Tube site care
Initial Week
During Hospitalization
Outpatient EN-Only
Patient
Outpatient PN and/
or EN Patient
Daily
Daily
Daily
Daily
Daily
DailyTwice Weekly
WeeklyMonthly
WeeklyMonthly
Weekly to Every Clinic
Weekly
Weekly
Weekly
Baseline
Baseline
Baseline
Baseline
Weekly
Monthly
Monthly
Monthly
Monthly or at Clinic
Monthly or at Clinic
Baseline
WeeklyMonthly
Monthly or at clinic
Monthly or at clinic
DailyWeekly
Monthly
DailyWeekly
Monthly
WeeklyMonthly
Monthly
Weekly
Monthly
Daily
Weekly
Monthly
Weekly
As indicated
As ordered or reported
As reported
Daily as reported
As indicated
As reported
Daily as reported
As indicated
As reported
Report changes in stool
pattern
As indicated
As reported
Report changes in stool
pattern
Per nursing policy
Per nursing policy
Prior to each feeding

Daily

Daily
Report when > 101F

(38.5C)
Daily
Report when > 101F

(38.5C)
Daily
Revision of Enteral Plan

Revision of the EN care plan will be based on patients tolerance of the EN regimen and achievement of goals. If goals
are not being met, the nutrition care plan must be adjusted
according to patients tolerance. When the child has grown
and is older the formula type and volume will need to be
adjusted based on the childs needs, recommended daily
allowance (RDA), and dietary reference intake (DRI). If the
EN plan is not supporting appropriate growth and making
adjustments to the EN plan does not support the nutrition
goals, then supplementation with PN or a transition to all
PN may be required. It is important to assess if the patient
has achieved the nutrition goals. EN can be transitioned to
oral diet should the child be able to tolerate an oral diet.
If nutrition goals are unattainable by EN then PN will need

to be considered. As with EN, patient allergy information
or any history of infusion-related incidents should be evaluated prior to the initiation of PN.
Evaluate for Infusion-Related Incidents

Patients with an egg allergy may require a test dose of lipid
emulsion to better evaluate for any reaction.12 The emulsifier
in currently marketed long-chain triglyceride lipid emulsions contains egg phospholipid. Even though reactions to
PN components are rare, there are case reports suggesting
that multivitamins, lipid emulsions, iron dextran, or
preservatives may be the causative agent.13,14 If a reaction
does occur and PN is suspected, eliminating 1 agent at a
time helps to determine the causative ingredient. If PN is
required for more than a week with no EN then alternate
routes may need to be identified to provide the particular
causative agent. Vitamins may be administered orally or
via a feeding tube or topical safflower oil in the case of lipid
intolerance.
Once the patient allergy profile has been reviewed, IV
access needs to be identified. Peripheral parenteral nutrition
(PPN) is limited based on osmolarity due to the vesicant
properties of PN ingredients. Institutions generally set
osmolarity limits for neonatal PPN at 900 to 1200 mOsm/L
and pediatric PPN at 600 to 900 mOsm/L.10 Maximum
dextrose concentration for pediatric and neonatal PPN is
12.5% but ultimately the osmolarity of the solution dictates
the amount of nutrients, electrolytes, and minerals that
can be ordered.15 Lower concentrations of dextrose may be
necessary in children with poor peripheral access. Amino
acids, dextrose, calcium, sodium, and potassium are the
main determinants of osmolarity. If PPN is utilized, the IV
463
site needs to be monitored closely (every 3 to 4 hours) for

early signs of infiltration. It is difficult to provide 100% of
nutrition goals with a peripheral solution but may be effective for a short period of time. If EN cannot be initiated and
advanced to goal within 5 to 7 days, serious consideration
should be given to placement of a catheter for central venous
access.10
Once central access is obtained it is helpful to note the
date of insertion, location, type of catheter, and number of
lumens. These initial data will be useful when monitoring for
catheter-related complications. Heparin is routinely added
to neonatal and pediatric PN solutions to maintain patency
of the central venous catheter.16 Lower flow volumes, smaller
catheters, and frequent interruptions of PN solutions may
play a roll in increased incidence of catheter clotting than
in adults.17 Preliminary data suggest that a heparin concentration of 0.5 units/mL in neonatal PN solutions may be as
effective for maintaining catheter patency as 1 unit/mL.18
Prospective data are currently being collected to further
validate these preliminary results (Elaina Szeszycki,
personal communication).
Evaluate Tolerance of Volume

Generally PN volume is based on a patients maintenance
volume requirement (refer to Chapter 9). Fluid volume may
be restricted or increased depending on disease processes
and clinical condition. There are a number of subjective and
objective data that can be evaluated to aid in determining if
the volume of PN or total fluid intake is appropriate. Weight,
intake from all sources, output from all sources, laboratory
results (refer to Table 36-7), vitals, and physical assessment
should be evaluated on a daily basis initially when PN is
started (Table 36-2). Routine weights and laboratory results
can be decreased as the patient stabilizes. If a patient is going
home on PN or has limited access, total fluid requirement
may be incorporated into the PN solution as possible.
Evaluate Tolerance of Macronutrients

Amino acid tolerance can be evaluated by monitoring
the BUN level.19 If an elevated BUN cannot be explained
by changes in renal function, medications (eg, highdose steroids, amphotericin, aminoglycosides, and
diuretics), bleeding, or dehydration then the non-protein
calorie:nitrogen (NPC:N) ratio needs to be evaluated. The
ideal NPC:N ratio in stable patients is 150250:1.20 The ratio
may be less in critically ill patients or higher in renal failure
patients. Ammonia levels and mental status are monitored
in liver disease patients. Please refer to Chapter 26.
464
Table 36-2 Parameters to Evaluate Adequacy of PN Volume

Parameter
DehYDRATION
FLUID OVERLOAD
Weight Change: Real

versus fluid
Rapid weight
Rapid weight
Intake: Intravenous
fluids, PN,
blood products,
medications, EN
Output: Urine,
gastric, stool, bile,
chest tube, wound,
skin
Laboratory
Total intake < total

output
Total intake > total

output
Decreased urine
output, dark urine
Increased urine
output in patients
with normal renal
and liver function
sodium, serum
osmolality, urine
specific gravity
albumin or Hgb
Vitals
Medications
Physical Exam
Blood urea
nitrogen, sodium,
serum osmolality,
urine specific
gravity, albumin
or Hgb
Heart rate,
losses with fever
Addition of diuretic
or change in
frequency
Thirst, dry lips, dry
mucous membranes,
dry skin, headache,
dizziness
Respiratory rate
Fluid retention with
steroids or excessive
sodium intake
Peripheral, facial,
and orbital edema,
abdominal girth,
shortness of breath
Dextrose is best monitored by venous blood glucose and

capillary glucose. The frequency of venous or capillary
glucose monitoring depends on history of glucose intolerance, presence of diabetes, or concurrent medications
affecting blood glucose control. Capillary glucose monitoring is useful for frequent monitoring so that the central
line does not have to be accessed an inordinate amount of
times during the day or when verifying an abnormal glucose
level from a venous sample. The frequency of monitoring
can be modified once the patient has established good blood
glucose control on the goal PN formula. Ordering dextrose
in PN as final dextrose concentration has been the standard
for years but there is a push to order dextrose in mg/kg/min
or g/kg/d as a glucose infusion rate (GIR).
Maximal dextrose infusion varies according to age
and there is growing information about the maximal GIR
range for differing age groups.21 This should allow for more
appropriate dextrose ordering and potentially decrease
complications associated with excess carbohydrate intake
(eg, hyperglycemia, elevated liver enzymes, cholestasis, and
ultimately fatty liver).22 Unexplained hyperglycemia should
prompt the calculation of the GIR from the PN solution
and other dextrose-containing solutions. Pediatric patients
receiving PN for > 2 weeks on a stable regimen may be
cycled 12 to 22 hours per day in an effort to ease daily activities and decrease hepatic complications related to PN. 23
Initially, blood glucose levels should be obtained during the
high rate of cyclic PN infusion and 1 to 2 hours after cycle
completion to evaluate for hyper- and hypoglycemia. Levels
> 150 mg/dL will require a decrease in dextrose amount or
lengthening of cyclic infusion to decrease the GIR. Levels
< 60 mg/dL or any symptoms of hypoglycemia will require
a longer taper period off of the cyclic PN or adjustment of
insulin if present in PN solution.24
Triglyceride levels are monitored daily as lipid intake is
increased and then decreased to weekly once dose is stable
and levels are adequate. Maximal lipid infusion for adults
is 0.125 g/kg/h.25 There is limited information regarding
maximal infusion rate for pediatrics but it is well-documented that longer infusion rates, 12 to 24 hours, improve
tolerance to lipid infusions.26 Decreasing the lipid dose or
infusing lipids every other day or 3 to 5 times a week instead
of daily in long-term PN patients will allow for further clearance of the lipid and possibly avoid triglyceride levels > 200
mg/dL. Limiting the dose and therefore decreasing phytosterol intake may also reduce the cholestasis commonly
noted in pediatric patients receiving long-term PN. 27 Calculating the lipid infusion rate in g/kg/h would be helpful if
hypertriglyceridemia is an issue.
Monitoring the Integrity of PN Formulations

Changes in any of the PN ingredients may affect the stability
or solubility of the formulation and thus warrants constant
surveillance during compounding and administration.
There are a number of factors that influence solubility
of minerals such as calcium and phosphorus, the compatibility of PN solutions, and the integrity of total nutrient
admixtures (TNA). Factors that influence calcium and
phosphorus solubility are listed in Table 36-3. The pH of the
amino acid solution drives the pH of the PN solution. The
ideal pH for calcium and phosphorus solubility is ~ 56.28
Solubility will decrease as the pH becomes more acidic or
alkaline. Higher concentrations of amino acid allow for
higher calcium and phosphorus doses to be admixed in
a 2-n-1 or 3-n-1 solution. There is a myth that the amount
of lipid emulsion influences how much calcium and phosphorus that can be admixed together in PN solutions but
the concentration of lipid emulsion is not a variable evaluated in calcium/phosphorus solubility graphs. Solubility
graphs in Trissels and Kings reference texts have been a
primary source for determining adequacy of calcium and
phosphorus amounts ordered in various PN solutions. 29,30
Today, some of the order-entry software utilized with the
automated compounding hardware has incorporated the

calcium/phosphorus solubility graphs into alerts. The
order entry pharmacist is alerted when the solubility graphs
are exceeded. This feature eliminates manual plotting of
concentration points but still requires critical evaluation of
all graphs to determine if each individual solution is appropriate for compounding.
Table 36-3 Factors Affecting Calcium and Phosphorus Solubility
Temperature
Concentrations of calcium and phosphorus
Type of amino acid product and concentration
Dextrose concentration
pH of final solution
Cysteine
Lighting
Order of mixing
Calcium and phosphorus amounts are limited in PPN

solutions when low amino acid concentrations are ordered
(initial PN solutions, renal insufficiency or disease, and
dilute solutions). Once amino acid concentrations can
be safely advanced, calcium and phosphorus solubility
should improve and these mineral doses can be increased.
Increasing concentrations of dextrose affects the solubility
curve positively as well.29 Some institutions set maximum
concentrations allowed for calcium and phosphorus in addition to evaluating the solubility curves to avoid excessive
dosing and avoid infiltrations with PPN (Appendix 36-1).
Practitioners were reminded in a tragic fashion how
important order of mixing is when compounding PN
solutions. At least 2 deaths have been associated with calciumphosphorus precipitation in PN solutions. 31 Temperature
and lighting also play a role and need to be investigated when
precipitation occurs, PN solutions look abnormal or become
discolored, PN filters occlude, and when the solution otherwise meets all solubility and stability limits. Neonatal PN
solutions are particularly at risk for stability issues due to bilirubin lights, heat from the extensive amount of equipment
utilized in these units, and frequent co-infusion of medications with limited intravenous access.
TNAs are complex solutions that require additional
scrutiny and compounding limits due to their opaque nature.
Factors involved for ensuring the integrity of the emulsion
are listed in Table 36-4. Minimum concentrations of the
macronutrients should be determined, especially for TNA,
to maintain the integrity of the emulsion. 32,33 A minimum
amount of IV lipid is required to provide adequate emulsifier for a TNA. 34 It is yet to be determined how product
packaging of current lipid formulations will affect the
465
integrity of TNA. 35 Refer to Appendix 36-1 for an example

of institutional-derived dosing and stability limits.
Table 36-4 Factors Affecting Total Nutrient Admixture Stability
Final pH (56)
Optimal pH for stability
Divalent cation concentration
Maximum concentration limits
(calcium, magnesium, zinc)
required
Trivalent cations (iron dextran)
Not stable in TNA
Type of amino acid &
Higher concentrations improve
concentration
stability
Dextrose concentration
Lower concentrations will limit
stability
Anionic emulsifier
Protects emulsion integrity
Multivitamin products
Protects emulsion integrity
Temperature
Avoid administration in warm areas
Order of mixing
Critical to avoid precipitation &
instability
Product packaging
Lipids in plastic ? affect on
stability
Comparison of 3-n-1 and 2-n-1 Formulations

PN is a general term referring to IV PN whereas 2-n-1 refers
to PN compounded with amino acids and dextrose. TNA or
3-n-1 refers to PN solutions compounded with amino acids,
dextrose, and lipids. The opaque nature of a TNA or 3-n-1 is
considered a disadvantage due to the inability to see obvious
precipitates. Calcium and phosphorus intakes are felt to be
less with TNA but again lipid is not a limiting factor in the
solubility of these two minerals. Divalent cations such as
calcium, magnesium, and zinc may be somewhat limited
in TNA due to the anionic nature of the lipid emulsions. 33
It may be difficult to provide higher doses of these divalent
cations in low-volume solutions or for patients receiving
magnesium-wasting medications.
As with calcium and phosphorus solubility, higher
concentrations of amino acid and dextrose provide a
protective effect on the emulsion. The amino acids form a
protective layer around the lipid globules while the hypertonicity of the dextrose prohibits excessive movement and
possible coalescence of globules. 36 The most problematic
TNAs are the initial neonatal formulations for extremely
low birth weight (ELBW) infants with low dextrose and
lipid concentrations. Centers that compound TNAs or
3-n-1 formulations must invest in automated compounding
systems that interface with advanced order-entry software
containing multiple manufacturer and institutional limits.
These dosing and stability limits will aid in identifying solutions potentially unsafe for patient administration.
Although TNAs require rigorous review, they do
allow for all nutrients to be in one bag and therefore only
466
one infusion pump. Nursing time is less compared to lipids

administered separately in syringes every 12 hours and
co-infused with a 2-n-1 solution. Some institutions infuse
lipids in syringes over 24 hours but the latest Centers for
Disease Control and Prevention (CDC) recommendation
states IV lipids should not be infused longer than 12 hours
to avoid microbial growth. 37 There is a concern for increase
in lipid peroxidation once lipids are transferred from their
original container. 38 Clinical consequence is not known at
this time and it is not clear whether peroxidation occurs at
a quicker rate in TNA or lipids administered via syringe.
Another advantage of TNA is 24-hour infusion of lipid
and decreased risk of microbial growth compared to lipid
alone. 37 Table 36-5 outlines the advantages and disadvantages of 3-n-1 or TNA over 2-n-1 solutions. Each institution
needs to determine which mode of PN ordering works best
for its patient populations.
Table 36-5 Advantages and Disadvantages of Total Nutrient Admixtures
Advantages
Disadvantages
Allows for 24-hour lipid infusion

Decrease labor costs
Decreased equipment and
supplycost
Decreases microbial growth
opportunity
Prohibits visual inspection

Limited compatibility information
Minimum macronutrient amount
required forstability
surgical history, feeding tolerance, or any sign/symptoms of

nutrient deficiencies. Transitioning from EN via a feeding
tube to oral nutrition requires periodic monitoring of weight,
length or height, and skinfold thickness to determine how
quickly the transition can occur and its success. A key point
for monitoring is follow-up once a plan is in place.
Reassessment of the Plan
Patients receiving SNS require periodic reassessment of their

progress and goals. Pediatric patients differ from adults in
that growth and development is a dynamic process and these
2 elements should be taken into account when assessing the
patient. Weight, fluid, calorie, protein, vitamin, and mineral
goals all need to be adjusted as the patient grows, with
subsequent adjustment in his or her SNS regimen. Ideally
these restated goals and therapy recommendations should
be communicated to all physicians involved in the patients
care so that evaluation of changes can be monitored. If the
current nutrition regimen is not successful, an alternative plan needs to be developed, initiated, and monitored.
Assessment, recommendation of a plan, activation of the
plan, and evaluation of the plan is a continuous cycle that
needs to be followed by practitioners involved with patients
requiring SNS.
Figure 36-1
Combination Enteral and Parenteral Nutrition

Once EN is initiated along with current PN, the amount of
monitoring and evaluation of specialized nutrition support
(SNS) increases during this transition phase. The plan is to
advance EN to goal as soon as possible while scaling back on
PN but still maintaining adequate nutrition intake. Monitoring of weight, enteral tolerance, linear growth, skinfold
thickness, protein stores, electrolytes, minerals, and other
laboratory values will aid in determining if the EN regimen
is appropriate. This can occur through once or twice weekly
lab draws and communication with parents or caregivers.
This is in addition to monthly clinic visits. Frequent communication regarding the patients progress with the medical
team will allow for quicker advancement of enteral feedings
per patient tolerance. When adequate nutrient intake can
be achieved enterally and/or orally and appropriate growth
demonstrated, then PN can be discontinued and vascular
access removed. EN can be gradually decreased as oral
intake improves. When the patient is stable on a goal EN
regimen and PN is discontinued, the frequency of monitoring can be decreased. Laboratory monitoring is required
periodically depending on other pertinent medical history,
Evaluate Drug and Nutrient Interactions
The process of evaluating for drug-nutrient interactions

begins with the patient medication profile and nutrition regimen. There are a number of excellent published
resources and pharmacy computer databases that can be

utilized to identify drug-drug and drug-nutrient interactions. 39,40 Pharmacy order entry systems can provide alerts
for particular medications (eg, fluoroquinolones and
phenytoin) when patients are receiving enteral feedings.
Once an interaction is identified, the severity along with
the source of the interaction needs to be evaluated closely
to determine a course of action. A number of interactions
may be avoided by administering the drug and the particular nutrient, vitamin, or mineral at separate times during
the day. If enteral formula ingredients interfere with drug
absorption, consultation with a pharmacist and dietitian
can aid in developing a revised enteral regimen for the
patient that will allow for improved drug absorption.
Particular medications may induce certain electrolyte and mineral wasting or retention. Oral, enteral, or
parenteral electrolyte and mineral supplementation may
be required while a patient is receiving these offending
agents. PN is not meant to be a vehicle for acute electrolyte
and mineral replacement but can aid in supplementing
patients with chronic electrolyte and mineral abnormalities. Electrolyte and mineral supplementation should not
be added directly to enteral formulas due to the potential
for instability but should be diluted and given orally or
flushed via a feeding tube. Table 36-6 lists some common
drug-induced metabolic disorders.41,42 Patients on these
particular medications require at least weekly laboratory
monitoring. Frequency of monitoring is dependent on
renal and hepatic function as well.
Table 36-6 Drug-Induced Metabolic Disorders
Loop Diuretics
hyponatremia, hypokalemia, hypocalcemia,
metabolic alkalosis
H2 antagonists
hyponatremia
Corticosteroids
hypokalemia, hypocalcemia,
hypophosphatemia, metabolic alkalosis
Amphotericin B
hypokalemia, hypomagnesemia, metabolic
acidosis
Cyclosporine, Tacrolimus hypomagnesemia, hyperkalemia,
hypertriglyceridemia
Aminoglycosides
metabolic acidosis
Citrate
hypocalcemia
467
and compatible medications that can be safely added to

PN solutions. Certain medications may be co-infused
with PN or TNA if no other access is available. There are
a number of published compatibility charts but it is still a
good practice to compare your own institutions PN solutions against published charts and studies.43,44 A range of
PN solutions and TNA have been tested but there is no
way to test each individual solution for stability that may
be prescribed in clinical practice.
Guidelines for Monitoring Nutrition Laboratory Values

in Children Receiving Enteral and Parenteral Nutrition
The goals for monitoring patients receiving SNS are to
ensure the efficacy of the regimen and to identify and
prevent potential complications. It is important that the
nutrition support team (physician, nurse, pharmacist, and
dietitian) establish goals for the patient prior to initiating
SNS. The monitoring of patients requiring EN and/or PN
must include both clinical data and laboratory testing.
Sample patient data sheets are included (Appendices 36-2
and 36-3). Appendix 36-2 may be utilized for patients
started on PN or a combination of PN/EN. Appendix
36-3 can be utilized in addition to Appendix 36-2 for those
patients receiving PN for greater than 3 months. Every
patient must have documented baseline data in order for
appropriate evaluation and monitoring to take place.
It is important to note that it is impossible to create a
one size fits all set of monitoring guidelines. Each patients
monitoring regimen must be created based on the specific
disease state and individualized long-term goals. New
patients will require the most frequent monitoring, while
stable long-term SNS patients may require less intense
monitoring. EN-only patients will require less laboratory
monitoring while those on PN will require regular laboratory testing. The following information should be used as
a general guideline and can be customized to the specific
patient needs. Please refer to disease-specific chapters in
this book for additional monitoring that may be required.
Tables 36-7 and 36-8, which appear at the end of this
chapter, are examples of suggested monitoring for shortand long-term laboratory testing.
Compatibility of Medications
Physical Data
In addition to calcium and phosphorus solubility, stability

of the PN solution needs to be evaluated at order entry.
Critical review of available PN stability literature, parenteral product manufacturer studies, and in-house stability
studies are what nutrition support practitioners rely on to
determine maximum concentrations for micronutrients
There are a number of objective physical pieces of data

that can be collected to aid in evaluating adequacy and
tolerance to SNS. Developing standards of practice, order
sets, policies, and procedures in all institutions caring for
patients requiring SNS can assist those individuals responsible for monitoring these complex patients. Table 36-1
468
delineates some general guidelines but individual patient

needs and clinical situation should dictate specific monitoring parameters and the frequency.
The monitoring of electrolytes, minerals, renal function,
glucose, and acid-base balance is essential in PN. When
initiating a patient on PN, a baseline basic metabolic panel
(BMP), magnesium, phosphorous, and triglyceride level
should be ordered and monitored daily until the patient
has reached the calorie goal established at initial assessment. The frequency may be decreased to twice weekly
in which one day includes the comprehensive metabolic
panel (CMP), which encompasses the hepatic function
along with the BMP. As the patient stabilizes, labs may be
decreased to weekly. Finally, these labs may be reduced to
every 2 to 4 weeks when the PN formula is stable and if
appropriate goals are being met for the current condition
and growth needs.
patient receiving PN for > 7 days. 56 Although most EN

formulas contain adequate dietary carnitine, supplementation can be considered in EN patients with malabsorption
or bowel resection if deficiency is suspected or confirmed
by laboratory testing. A carnitine profile, including ester/
free ratio, should be monitored every 3 to 6 months if the
patient is being supplemented. A yearly carnitine profile is
sufficient for patients not receiving supplementation.
There are 2 fatty acids in humans that must be supplied via the diet primarily from plants. They are linoleic
and -linolenic acid and are known as essential fatty acids
(EFAs). Patients receiving EN and PN must be adequately
supplemented with both EFAs because their oral intake
may be minimal. If inadequate amounts are provided, an essential fatty acid deficiency (EFAD) may eventually occur.
If lipid-free PN is provided for a significant amount of time
or there is clinical manifestation of an EFAD, it is possible to order an EFA profile. The resulting triene:tetraene
ratiocan determine if an EFAD exists. 26,6062
Nutrition-Related Laboratory Tests
Liver Function Tests and Bilirubin
(see also Chapters 4 and 5)

Prealbumin is commonly used to monitor protein status
due to its shorter half-life of 2 to 3 days in comparison
to albumin. 51 However; there are other factors that can
influence prealbumin levels such as inflammatory states,
end-stage liver disease, untreated thyroid disease, renal
disease, and zinc deficiency. These limitations should
be considered when interpreting a patients prealbumin
level. 5254 Monitoring of prealbumin levels can be helpful
especially for long-term stable patients. Prealbumin can
be monitored on a weekly basis initially and then monthly
in stable patients.
Changes in triglyceride levels can be influenced by a
variety of factors including disease state, organ function,
medications, nutrition status, and current nutrient intake.
They should be monitored daily when SNS is initially
started, followed by a weekly level, and then increased to
monthly.19,26,45,55
Carnitine is often supplemented in the formula of PN
patients, particularly neonates and infants due to their
inability to synthesize an adequate amount. In addition,
premature neonates will also have limited carnitine stores
that are needed for long-chain fatty acid transport. 56 A
deficient patient may present with increased triglyceride
levels, hyperbilirubinemia, or decreased weight gain along
with a multitude of other clinical symptoms. 5759 Currently
a carnitine dose of 10 to 20 mg/kg/d is recommended for
IV or oral supplementation and should be initiated in any
Liver complications are a well-documented adverse

effect of PN in children. 6366 It is necessary to monitor
liver function enzymes, which generally include alkaline
phosphatase, aspartate aminotransferase, and alanine
aminotransferase, on a weekly basis when initiating PN.
A total bilirubin should also be followed. If prolonged PN
is anticipated or the patient becomes jaundiced, a direct
or conjugated bilirubin level is helpful to monitor for
cholestasis. 24 A direct bilirubin > 2 mg/dL may prompt
earlier monitoring of the trace elements, copper, and
manganese. 67 The liver function enzymes and total bilirubin are included when ordering the CMP as previously
discussed. Once stabilized these laboratory tests can be
monitored every 2 to 4 weeks.
Gamma glutamyl transpeptidase (GGTP) is another
liver enzyme that is more specific for liver and biliary tract
problems. 24 GGTP is the most sensitive liver enzyme for
detecting biliary obstruction, cholangitis, or cholecystitis. 51 It can be ordered for further diagnosis when the
traditional liver enzymes are elevated or as a regularly
monitored monthly test if the patient is at risk for biliary
problems.
The prothrombin time (PT) and international normalized ratio (INR) can be utilized in long-term monitoring
of PN. The PT can be elevated in a patient who is developing hepatocellular disease or obstructive biliary disease
or more rarely a vitamin K deficiency. 24,68,69 A baseline and
then monthly check of the PT/INR is adequate.
Chemistry Profile Monitoring4550
Trace Elements
(see also Chapter 6)
When a patient is receiving PN for several months, it is
important to assess the status of trace elements due to
the standardized way in which they are initially ordered
in PN patients and the known contamination of commercial products used to compound PN.70 After 3 consecutive
months on PN (unless clinically indicated earlier),71 a
patient should be assessed for zinc, selenium, manganese, copper, and chromium.45 Long-term use of standard
multi-trace products can result in both excessive and
deficient concentrations, especially in patients who have
abnormalities in the GI tract. Although measuring blood
concentrations of these trace elements is not necessarily
the most accurate due to the bodys ability to store these
elements, it is generally the easiest and least costly way to
monitor.72 It is also important to note that these elements
should not be checked during times of acute inflammatory
type conditions due to the bodys sequestration of some
elements during this time. Levels may be falsely decreased
in these types of situations.73
Assessment of these elements should occur every 3
to 12 months while receiving PN.45,72 If a patient is found
to have an elevated level of any standard element, the
multi-trace element of the PN can be omitted and separate elements may be added. Additionally, if any element
is found to be deficient, it can be added in addition to the
standard multi-trace. There are limits to concentrations of
trace elements in PN so this must be considered, and in that
situation, oral supplementation may be an option. After
altering the dosage of any element it should be rechecked
in approximately 1 to 3 months. If a patients condition
has completely stabilized, it is reasonable to monitor only
once per year.
Aluminum, considered an ultratrace element, is a
known contaminant of PN products. It is important to
monitor due to the patients continued exposure and risk
for toxicity. It is reasonable to check an aluminum level
each year during PN therapy. If the aluminum is elevated,
the PN pharmacist can look at the current PN components and make adjustments if possible since aluminum
contamination varies even between different PN product
manufacturers.74
Molybdenum deficiency is rare but can occur in a PN
patient, especially those with decreased intestinal absorption.75,76 If desired, a molybdenum level may be checked
yearly unless otherwise clinically indicated. If a deficiency
is detected, molybdenum may be supplemented via PN in
the form of ammonium molybdate.
469
Iodine is an element not supplied by standard multitrace products in PN. Therefore it is possible, although
unlikely, for a SNS patient to become deficient.77,78 This
can routinely be assessed with a yearly thyroid stimulating
hormone (TSH), triiodothyronine (T3) test, or urine
iodine concentration.
Iron Studies and Anemia

(see also Chapters 68)
When patients are dependent on EN and/or PN, there is
always the potential for the patient to become anemic.
The 4 nutrients that are most likely to be the reason for
an anemia are iron, copper, vitamin B12 , and folic acid.
Standard PN contains 3 of the previous nutrients with
the exception being iron. Enterally fed patients typically
are provided with all 4 nutrients. However, the standard
quantities provided may not always be adequate for the
specific disease process that is being treated. For example,
a patient who has shortened bowel will generally have less
absorption of the nutrients from EN and may become deficient over time.
Iron deficiency can be recognized by abnormalities
in the complete blood count (CBC). In general there is
a decrease in hemoglobin and mean corpuscular volume
(MCV).45 It may take some time for the deficiency to
occur so a routine CBC (at least monthly) is recommended to monitor for these changes.46,47,50 When these
abnormalities are present an iron panel can be ordered if
indicated to confirm the deficiency. An iron panel should
include serum iron, ferritin, transferrin saturation, and
iron-binding capacity. In a deficient patient, the iron and
ferritin may be reduced and the binding capacity elevated.
After confirming the deficiency, the iron may be supplemented orally. If the patient does not respond to oral iron,
parenteral iron may be used as a separate infusion or added
to the PN. The only parenteral iron that may be used in
PN is iron dextran, and it can only be used in the absence
of lipids in the formulation for stability reasons.44 Monitoring of iron status should occur every 3 to 6 months in a
deficient patient or a patient receiving supplementation.
Copper deficiency can also present with anemia and
neutropenia.79,80 This can result from decreased absorption or increased losses from the intestinal tract. Copper
deficiency can also occur due to high zinc, vitamin C,
or iron supplementation or from the use of gastric acid
suppressing medications. 81 Iatrogenic copper deficiency
may occur with inadequate amounts in PN due to concern
for accumulation in patients with cholestasis. Measuring
serum copper or serum cerulosplasmin levels can assess
470
the patients copper status.72 This can be performed with

the other multi-trace elements as previously discussed.
Both vitamin B12 and folic acid deficiencies can
present as a macrocytic anemia with an elevated MCV.
Because these 2 nutrients have an intertwined relationship in the body, it is recommended to assess the status
of both whenever either is measured. Patients without an
ileal cecal valve are particularly at risk for development of
vitamin B12 deficiency since this is a site for absorption.
It is possible for the body to maintain serum vitamin B12
levels even though storages have been depleted. Therefore,
it can also be beneficial to check methylmalonic acid and
homocysteine levels when vitamin B12 deficiency is truly
suspected. These 2 tests will be elevated in most patients
even with a minimal vitamin B12 deficiency. 82 However,
homocysteine levels may also be elevated in the presence
of folic acid and vitamin B6 deficiency, therefore it is not
a specific indicator of vitamin B12 deficiency. 83 A yearly
measure of these vitamins is normally sufficient unless
deficiency is suspected71 or in evaluating after increased
supplementation.
Vitamins
(see also Chapters 7 and 8)
Fat-soluble vitamins A, D, E, and K are standard components of most parenteral multivitamin products and EN
products. It is possible for a patient to accumulate excessive amounts due to the bodys storage of these vitamins,
but it is also possible for deficiency to occur with certain
disease states. Monitoring the levels of vitamins A, D, and
E once yearly is recommended unless otherwise clinically
indicated.45 Vitamin K status is more commonly assessed
by the PT as previously discussed.
The water-soluble vitamins including B1, B2 , B6, B12 ,
niacin, folic acid, pantothenic acid, biotin, and vitamin
C are also components of parenteral multivitamins and
EN. Routine monitoring of these vitamins is not indicated
(except for B12 and folic acid as previously discussed)
unless there is a clinical reason to believe that there is a
deficiency or toxicity.71
Metabolic Bone Disease

Metabolic bone disease (MBD) is a complication that may
result from long-term PN. It may present as osteomalacia, osteopenia, or osteoporosis. Several factors may
increase the incidence of MBD. Those include medications, calcium, and vitamin D malabsorption, metabolic
acidosis, high aluminum concentrations in PN, and other
nutrient deficiencies. In addition to the presence of bone
pain or non-traumatic fracture, the following laboratory

tests may indicate MBD: low to normal PTH, elevated
alkaline phosphatase, altered vitamin D levels, changes in
serum calcium levels, and hypercalciuria. 50,84,85 Therefore,
monitoring a yearly PTH along with vitamin D may be
indicated in long-term PN patients.
Infectious Complications
Catheter-related bloodstream infections (CRBSIs) are a

well-known complication of vascular access devices. By
monitoring for fever and changes in the CBC, potential
infections can be identified and treated promptly.45 The
most recent CDC guidelines for catheter maintenance were
published in 2002.86 The replacement of the infected catheter is recommended in most CRBSIs. However, continual
replacement of the catheter can lead to the loss of venous
access sites. This can be problematic for many PN patients
due to their long-term need for a vascular access device.
One strategy used to prevent CRBSIs has been the use of
agents to sterilize the catheter lumen. The first of these was
antibiotic lock therapy (ALT), which has been studied since
the late 1980s.87 This method involves using concentrated
antibiotic solutions and dwelling the solution in the catheter lumen for a period of time. Problems associated with
ALT are the development of antibiotic resistance with
long-term use, lack of documented stability, and expense. 88
A newer agent that has been shown to reduce CRBSI is
ethanol. Opilla MT et al specifically studied the use of
ethanol for the home PN patient and showed a statistically
significant reduction in CRBSIs and catheter exchanges. 89
The use of an ethanol lock has been shown to be safe for
the pediatric patient.9092 Currently, there is not a standardized dose, concentration, frequency, or dwell time for the
use of ethanol lock. Factors that must be considered when
choosing to utilize an ethanol lock include catheter material, catheter age, and compliance.93
Bacterial overgrowth can be a complication of patients
with intestinal failure receiving PN and requires treatment
when identified. Abdominal discomfort, bloating, cramps,
gas, changes in stool color, consistency, and odor are
common signs and symptoms. When the preceding signs
and symptoms are identified, the patient should be treated.
If a fever is also present, the patient should be evaluated for
bacteremia due to possible translocation from the GI.45 (See
Chapter 27.)
Table 36-7
471
Table 36-8
Parameter
Initial
Followup
Parameter
Initial
Followup
BMP
CMP
Magnesium
Phosphorous
Prealbumin
Triglycerides
PT/INR
CBC differential/
platelets
GGT
Daily
Weekly
Daily to Weekly
Daily to Weekly
Weekly
Daily to Weekly
Weekly
Weekly
Included in CMP
Every 1 to 4 weeks
Every 1 to 4 weeks
Every 1 to 4 weeks
Monthly
Monthly
Monthly
Every 1 to 4 weeks
Baseline if indicated
Monthly
Iron Studies
Zinc
Selenium
Manganese
Copper
Chromium
Vitamins A, D, and E
Vitamin B12 and Folate
Carnitine
TSH
3 mo
3 mo
3 mo
3 mo
3 mo
3 mo
6 mo
6 mo
3 mo
Baseline if indicated
Every 36 mo
Every 36 mo
Every 36 mo
Every 36 mo
Every 36 mo
Every 36 mo
Every 12 mo
Every 12 mo
Every 312 mo
Every 12 mo
Appendix 36-1 PN Limits
Na
K
Ca
PO4
Mg
Cl
Ac
Zn
Cysteine
Vitamin K
Ranitidine
Famotidine
Adult
Pediatric
NICU
180
180
06
150
06
30
02
30
02
24
00.5
250
08
250
08
5
300
40
10
100
06
n/a
180
06
150
05
30
04.5
30
02
13
01
250
010
250
010
5
400
120
n/a
100
2
n/a
1000
500
50
2.5
10
1000
700
50
2.5
10
1000
700
50
Min 10 g/L or
DC Lipids
150
30
35
24
300
300
10
10
n/a
Folic Acid
Heparin
Vitamin C
Carnitine
Stability
mEq/L
mEq/kg
mEq/L
mEq/kg
mEq/L
mEq/kg
mmol/L
mmol/kg
mEq/L
mEq/kg
mEq/L
mEq/kg
mEq/L
mEq/kg
mg/L
Mcg/kg
mg/kg
***mg***
mg/L
mg/kg
mg/L
mg/kg
***mg***
mg/d
units/L
mg/d
mg/kg/d
Usual Dose
Comments
Osmolarity
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Total zinc
or DC fat
mg/day
X
X
X
Not mg/L
X
X
X
X
Amino Acid
Min 20 g/L
Min 10 g/L or
DC Lipids
Dextrose
Min 50 g/L
Min 50 g/L
Min 50 g/L
Lipid
Min 5 g/L
Min 5 g/L
Min 5 g/L
Total dose
X
Need 20 g/L if
Dextrose
< 10% or DC
Lipids
DC Lipids if
< 50 g/L
DC Lipids if
< 5 g/L
472
Appendix 36-2 Neonatal and Pediatric PN Monitoring Form

Name:
MRN:
DOB:
Age:___y____m____d
Goals: Calories (kcal/d):_ ___________________

Protein (g/d):_______________________

Fluid (mL/d):_ ______________________
Formula
Rate/Cycle
Route
MD:
Date:
wt_____ :____%ile
ht/lt_ __ :____%ile
wt/ht________%ile
dry wt__________
kcal/kg: ________________________________
g/kg: __________________________________
mL/kg:_ ________________________________
LABS
Date
Weight (kg)
Sodium / Potassium
Chloride / Carbon Dioxide
BUN / Creatine
Glucose / Calcium
Phosphorous / Magnesium
Total/conj. Bilirubin
Cholesterol / Triglyceride
AST / ALT
AlkPhos / GGT
Hgb / Hct
WBC / platelets
INR
Zinc
Albumin / Prealbumin
AA/Dex/lipid
Na (mEq/kg)
K (mEq/kg)
Cl (mEq/kg)
Anions (A,C)
Ca (mEq/kg)
P (mmol/kg)
Mg (mEq/kg)
Heparin
MVI:Peds/Adult
TMS:Peds/Adult
Zinc (mcg/kg)
Copper (mcg/kg)
Manganese (mcg/kg)
Chromium (mcg/kg)
Selenium (mcg/kg)
Carnitine (mg/kg)
Rate/Cycle
Total Volume/day
Total Calories/day
kcal/kg
GIR
NPC:N
Wt used for script
kcal/mL
Admit Date:
DX:
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
TPN SCRIPT
/
/
WA_______
HA________
BMI_______
IBW_______
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
/
ENTERAL
/
mL PN/EN
kcal / kcal/kg
% PN/EN
Protein (g)
Protein (g/kg)
UOP mL/kg/h
Emesis
Stool
Ostomy mL/d / mL/kg
Total mL
TOTALS
OUTPUT
473
Appendix 36-3 Long-Term PN Lab Tracking Sheet

Patient:
D.O.B.
Physician:
Diagnosis:
Medical Record Number:
Fax:
Phone:
Home Health Care:
TPN start date:
Pager:
Lab Location / Phone:
Enteral Formula:
Other Contact:
Family Contact:
Lab Location:
Date:
Every Month
Pre-Albumin
Triglyceride
GGT
MCV
Every 3 Months
Selenium
Manganese
Copper
Chromium
Zinc
Ferritin
Iron Serum
TIBC
Transferrin Saturation
Carnitine Total
Carnitine Free
Carnitine Ratio
Every 12 Months
Vitamin A
Vitamin D
Vitamin E
Vitamin B12
RBC Folate
TSH
Free T4
Aluminum
Recorded By:
Reviewed By:
Date Faxed to Physician:
474
1. Meeting a weight goal is the primary goal for SNS patients.

A. True
B. False
2. Bloating, fullness, and abdominal cramping may be
related to the rate of enteral nutrition infusion.
A. True
B. False
3. Examining the GIR from PN may provide insight to
hyperglycemia of unknown etiology.
A. True
B. False
4. Final amino acid and dextrose concentrations do not
affect calcium and phosphorus solubility.
A. True
B. False
5. Only selenium and zinc levels should be monitored
periodically in patients receiving PN with cholestasis
or specifically a direct bilirubin > 2 mg/dL.
A. True
B. False
References
1. A.S.P.E.N. Enteral Nutrition Practice Recommendations

Task Force. Enteral nutrition practice recommendations. J
2. Santanan e Meneses JF, Leite HP, de Carvalho WB, et
al. Hypophosphatemia in critically ill children: prevalence and associated risk factors. Pediatr Crit Care Med.
2009;10:234238.
3. Dickerson R. Refeeding syndrome in the intensive care unit.
Hosp Pharm. 2002;37(7):770775.
4. Parrish CR. The refeeding syndrome in 2009: prevention is
the key to treatment. J Support Oncol. 2009;7:2021.
5. McCray S, Walker S, Parrish CR. Much ado about refeeding.
Practical Gastroenterol. 2005;30(1):2644.
6. Danner E, Joeckel R, Michalak S, et al. Weight velocity in
infants and children. Nutr Clin Pract. 2009;24:7679.
7. Guo S, Roche AF, Fomon SJ, et al. Reference data on gains in
weight and length during the first two years of life. J Pediatr.
1991;119:355362.
8. A.S.P.E.N. Board of Directors and Task Force on Standards
for Specialized Nutrition Support for Hospitalized Pediatric
Patients. Standards for specialized nutrition support: hospitalized pediatric patients. Nutr Clin Pract. 2005;20:103116.
9. Moyer-Mileur L. Anthropometric and laboratory assessment
of very low birth weight infants: the most helpful measurements and why. Semin Perinatol. 2007;31:96103.
10. A.S.P.E.N. Board of Directors and the Clinical Guidelines
Task Force. Guidelines for the use of parenteral and enteral
nutrition in adult and pediatric patients. J Parenter Enteral
Nutr. 2002;1SA.
11. Wessel JJ, Kocoshis SA. Nutritional management of

infants with short bowel syndrome. Semin Perinatol.
2007;31:104111.
12. Intralipid 20% A 20% I.V. Fat Emulsion [package insert].
Clayton, NC: Kabi Pharmcia; 1991.
13. Bullock L, Etchason E, Fitzgerald JF, et al. Case report of an
allergic reaction to parenteral nutrition in a pediatric patient. J
14. Market AD, Lew DB, Schropp KP, et al. Parenteral nutrition-associated anaphylaxis in a 4-year-old child. J Pediatr
Gastroenterol Nutr. 1998; 26(2):229231.
15. Seashore JH, Hoffman M. Use and abuse of peripheral
parenteral nutrition in children. Nutr Support Serv. 1983;
3(10):813.
16. Imperial J, Bistrain BR, Bothe A Jr, et al. Limitation of central
vein thrombosis in total parenteral nutrition by continuous
infusion of lowdose heparin. J Am Coll Nutr. 1983;2:6373.
17. Kakzanov V, Monagle P, Chan A. Thromboembolism in infants
and children with gastrointestinal failure receiving long-term
parenteral nutrition. J Parenter Enteral Nutr. 2008;32:8893.
18. Szeszycki E, Kastner A, Mobley L, Gervasio J. A comparison
of the efficacy of 0.5 units/mL versus 1 unit/mL of heparin
in neonatal parenteral nutrition. A.S.P.E.N. 2009, Nutrition
Practice Poster Presentation.
19. Shulman RJ, Phillips S. Parenteral nutrition in infants and
20. Wesley JR, Coran AG. Intravenous nutrition for the pediatric
patient. Semin Pediatr Surg. 1992;1:212.
21. Koletzko B, Goulet O, Hunt J, et al. 1. Guidelines on paediatric
parenteral nutrition of the European Society of Paediatric
Gastroenterology, Hepatology and Nutrition (ESPGHAN)
and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of
Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr.
2005;41:S28S32.
22. Burke JF, Wolfe RR, Mullany CJ, et al. Glucose requirements
following burn injury. Ann Surg. 1979;190(3):274285.
23. Jensen AR, Goldin AB, Koopmeiners JS, et al. The association of cyclic parenteral nutrition and decreased incidence of
cholestatic liver disease in patients with gastroschisis. J Pediatr
Surg. 2009;44(1):183189.
24. Btaiche IF, Khalidi N. Parenteral nutrition-associated
liver complications in children. Pharmacotherapy.
2002;22:188211.
25. Mirtallo J, Canada T, Johnson D, et al. Task Force for the
Revision of Safe Practices for Parenteral Nutrition. Safe
practices for parenteral nutrition. J Parenter Enteral Nutr.
2004;28(6):S39S70. Erratum 2006; 30:177.
26. Kerner JA, Poole RL. The use of IV fats in neonates. Nutr Clin
Pract. 2006;21:374380.
27. Pianese P, Salvia G, Campanozzi A, et al. Sterol profiling in
red blood cell membranes and plasma of newborns receiving
total parenteral nutrition. J Pediatr Gastroenterol Nutr.
2008;47(5):645651.
28. Clintec Nutrition Company in cooperation with Wagner DR
and Atkins J. Total Nutrient Admixtures: Clinical and Practical
Guidelines. USA: Clintec Nutrition Co; 1992.
29. Trissel LA, ed. Handbook on Injectable Drugs. 11th ed.

Bethesda, MD: American Society of Health-System Pharmacists; 2001:195205.
30. IV Compatibility. King Guide to Parenteral Admixtures.
Lexi-Comp Online. Lexi-Comp, Inc. Hudson, OH. Available
at: http://online.lexi.com/crlonline. Accessed January 2009.
31. Food and Drug Administration. Safety Alert: Hazards of
precipitation associated with parenteral nutrition. Am J Hosp
Pharm. 1994;51:14271428.
32. Bullock L, Fitzgerald JF, Walter WV. Emulsion stability in
total nutrient admixtures containing a pediatric amino acid
formulation. J Parenter Enteral Nutr. 1992;16:6468.
33. Driscoll DF, Bhargava HN, Zaim RH, et al. Physicochemical
stability of total nutrient admixtures. Am J Health Syst Pharm.
1995;52:623634.
34. Driscoll DF, Giampietro K, Wichelhaus DP, et al. Physicochemical stability assessments of lipid emulsions of varying
oil composition. Clin Nutr. 2001;20:151157.
35. Driscoll DF, Ling PR, Bistrain BR. Physical stability of 20%
lipid injectable emulsions via simulated syringe infusion:
effects of glass vs. plastic product packaging. J Parenter Enteral
Nutr. 2007;31:148153.
36. Warshawsky KY. Intravenous fat emulsions in clinical practice. Nutr Clin Pract. 1992;7(4):187196.
37. OGrady NP, Alexander M, Dellinger EP, et al. Guidelines for
the prevention of intravascular catheter-related infections.
Infect Control Hosp Epidemiol. 2002;23:759769.
38. Neuzil J, Darlow BA, Inder TE, et al. Oxidation of parenteral lipid emulsion by ambient and phototherapy lights:
potential toxicity of routine parenteral feeding. J Pediatr.
1995;126:785790.
39. Nyffeler MS, Frankel E, Hayes E, et al. Drug-nutrient interactions. In: Merritt R, DeLegge MH, Holcombe B, et al., eds.
The A.S.P.E.N. Nutrition Support Practice Manual. 2nd ed.
USA: American Society for Parenteral and Enteral Nutrition;
2005:118136.
40. Drug Interactions. Thomson Micromedex. Greenwood
Village, CO. http://thomsonhc.com. Accessed January 2009.
41. Navaneethan SD, Sankarasubbaiyan SG, Jeevanantham VM.
Tacrolimus-associated hypomagnesemia in renal transplant
receipients. Transplantation Proc. 2006;38(5):13201322.
42. Brown RO. Drug-nutrient interactions. In: Cresci G., ed.
Nutrition Support for the Critically Ill Patient: A Guide to Practice. Boca Raton, FL: CRC Press; 2005:341355.
43. Robinson CA, Lee JE. Y-site compatibility of medications
with parenteral nutrition. In: Phelps SJ, Hak EB, Crill CM,
eds. Teddy Bear Book: Pediatric Injectable Drugs. 8th ed.
Bethesda, MD: American Society of HealthSystem Pharmacists; 2007:459463.
44. Trissel LA. Compatibility of medications with 3-in-1 parenteral
nutrient admixtures. J Parenter Enteral Nutr. 1999;23:6774.
45. Siepler J. Principles and strategies for monitoring home parenteral nutrition. Nutr Clin Pract. 2007;22:340350.
46. Kovacevish D, Canada T, Lown D. Monitoring home and
other alternate site nutrition support. In: Gottschlich M,
ed., Fuhrman M, ed, et al. The Science and Practice of Nutrition Support. Dubuque, IA: Kendell/Hunt Publishing Co;
2000:731756.
475
47. Vanderhoof J, Young R. Overview of considerations for the

pediatric patient receiving home parenteral and enteral nutrition. Nutr Clin Pract. 2003;18:221226.
48. Sacks G, Mayhew S, Johnson D. Parenteral nutrition implementation and management. In: Merritt R, ed, et al. The
A.S.P.E.N. Nutrition Support Practice Manual. 2nd ed. USA:
American Society for Parenteral and Enteral Nutrition;
2005:108117.
49. American Society for Parenteral and Enteral Nutrition Board
of Directors and the Standards for Specialized Nutrition
Support Task Force, Kovacevich DS, Frederick A, Kelly D,
Reid N, Young L. Standards for specialized nutrition support:
home care patients. Nutr Clin Pract. 2005;20:579590.
50. Ireton-Jones C, DeLegge MH, Epperson LA, et al. Management of the home parenteral nutrition patient. Nutr Clin Pract.
2003;18:310317.
51. Pagana KD, Pagana TJ, eds. Mosbys Diagnostic and Laboratory
Test Reference. 8th ed. St Louis, MO: Mosby; 2007:755756.
52. Fuhrman MP, Charney P, Mueller CM. Hepatic proteins and
nutrition assessment. J Am Diet Assoc. 2004;104:12581264.
53. Marshall WJ. Nutritional assessment: its role in the provision
of nutrition support. J Clin Pathol. 2008;61:10831088.
54. Johnson AM, Merlini G, Sheldon J, et al. Clinical indications for plasma protein assays: transthyretin (prealbumin)
in inflammation and malnutrition. Clin Chem Lab Med.
2007;45:419426.
55. Crook MA. Lipid clearance and total parenteral nutrition:
the importance of monitoring plasma lipids. Nutrition.
2000;16:774775.
56. Crill CM, Helms RA. The use of carnitine in pediatric nutrition. Nutr Clin Pract. 2007;22:204213.
57. Borum PR. Carnitine in neonatal nutrition. J Child Neurol.
1995;10(suppl):2S252S31.
58. Winter SC, Szabo-Aczel S, Curry CJ, et al. Plasma carnitine
deficiency: clinical observations in 51 pediatric patients. Am J
Dis Child. 1987;141:660665.
59. Tao RC, Yoshimura NN. Carnitine metabolism and its
application in parenteral nutrition. J Parenter Enteral Nutr.
1980;4:469486.
60. Hamilton C, Austin T, Seidner DL. Essential fatty acid deficiency in human adults during parenteral nutrition. Nutr Clin
Pract. 2006;21:387394.
61. Postuma R, Pease PW, Watts R, et al. Essential fatty acid deficiency in infants receiving parenteral nutrition. J Pediatr Surg.
1978;13:393398.
62. Panel on Macronutrients, Panel on the Definition of Dietary
Fiber, Subcommittee on Upper Reference Levels of Nutrients,
Subcommittee on Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific
Evaluation of Dietary Reference Intakes. Dietary Reference
Intakes for Energy, Carbohydrate, Fat, Fatty Acids, Cholesterol,
Protein, and Amino Acids. Washington DC: The National
Academies Press; 2005:422541.
63. Postuma R, Trevenen CL. Liver disease in infants receiving
parenteral nutrition. Pediatrics. 1979;63:110115.
64. Kelly DA. Liver complications of pediatric parenteral nutrition-epidemilogy. Nutrition. 1998;14:153157.
476
65. Quigley EM, Marsh MN, Shaffer JL, Markin RS. Hepatobiliary complications of total parenteral nutrition.
Gastroenterology. 1993;104:286301.
66. Payne-James JJ, Silk DB. Hepatobiliary dysfunction associated with total parenteral nutrition. Dig Dis. 1991;9:106124.
67. McMillan NB, Mulroy C, MacKay MW, et al. Correlation of
cholestasis with serum copper and whole-blood manganese
levels in pediatric patients. Nutr Clin Pract. 2008;23:161165.
68. Duerksen DR, Papineau N. The prevalence of coagulation
abnormalities in hospitalized patients receiving lipid-based
parenteral nutrition. J Parenter Enteral Nutr. 2004;28:3033.
69. Deitcher SR. Interpretation of the international normalized
ratio in patients with liver disease. Lancet. 2002;359:4748.
70. Pluhator-Murton MM, Fedorak RN, Audette RJ, et al. Trace
element contamination of total parenteral nutrition. 1.
Contribution of component solutions. J Parenter Enteral Nutr.
1999;23:222227.
71. Jensen GL, Binkley J. Clinical manifestations of nutrient deficiency. J Parenter Enteral Nutr. 2002;26:S29S33.
72. Fuhrman MP. Micronutrient assessment in long-term
home parenteral nutrition patients. Nutr Clin Pract.
2006;21:566575.
73. Prelack K, Sheridan RL. Micronutrient supplementation
in the critically ill patient: strategies for clinical practice. J
Trauma. 2001;51:601620.
74. Poole RL, Hintz SR, Mackenzie NI, et al. Aluminum exposure
from pediatric parenteral nutrition: meeting the new FDA
regulation. J Parenter Enteral Nutr. 2008;32(3):242246.
75. Heimburger DC, McLaren DS, Shils M. Clinical manifestations of nutrient deficiencies and toxicities: a resume. In: Shils
ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern
Nutrition in Health and Disease. 10th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2006:595612.
76. Nielsen FH. Boron, manganese, molybdenum, and other
trace elements. In: Bowman BA, Russel RM, eds. Present
Knowledge in Nutrition. 8th ed. Washington, DC: ILSI Press;
2001:384400.
77. Ibrahim M, Morreale de Escobar GM, Visser TJ, et al.
Iodine deficiency associated with parenteral nutrition in
extreme preterm infants. Arch Dis Child Fetal Neonatal Ed.
2003;88:F5657.
78. Moukarzel AA, Buchman AL, Salas JS, et al. Iodine supplementation in children receiving long-term parenteral nutrition.
J Pediatr. 1992;121:252254.
79. Nagano T, Toyoda T, Tanabe H, et al. Clinical features of
hematological disorders caused by copper deficiency during
long-term enteral nutrition. Intern Med. 2005;44:554559.
80. Fuhrman MP, Herrmann V, Masidonski P, et al. Pancytopenia

after removal of copper from total parenteral nutrition. J
81. Beshgetoor D, Hambidge M. Clinical conditions
altering copper metabolism in humans. Am J Clin Nutr.
1998;67:10171021S.
82. Hoffbrand AV. Chapter 100 Megaloblastic anemias. In: Harrisons Online. http://www.accessmedicine.com/content.
aspx?aID=2893392. Accessed October 21, 2009.
83. Clark SF. Vitamins and trace elements. In: Gottschlich MM,
DeLegge, MH, Mattox T, Mueller C, Worthington P, eds. The
A.S.P.E.N. Nutrition Support Core Curriculum: A CaseBased
Approach The Adult Patient. Silver Spring, MD: American
Society for Parenteral and Enteral Nutrition; 2007:129159.
84. Ferrone M, Geraci M. A review of the relationship between
parenteral nutrition and metabolic bone disease. Nutr Clin
Pract. 2007;22:329339.
85. Klein GL. Metabolic bone disease of total parenteral nutrition. Nutrition. 1998;14:149152.
86. Centers for Disease Control and Prevention. Guidelines for
the Prevention of Intravascular Catheter-Related Infections.
MMWR Recomm Rep. 2002;51(RR10):129.
87. Messing B, Peitra-Cohen S, Debure A, Bernier J. Antibioticlock technique: a new approach to optimal therapy for
catheter-related sepsis in home-parenteral nutrition patients.
J Parenter Enteral Nutr. 1988;12:185189.
88. Bestul MB, VandenBussche HL. Antibiotic lock technique:
review of the literature. Pharmacotherapy. 2005;25:211227.
89. Opilla MT, Kirby DF, Edmond MB. Use of ethanol lock
therapy to reduce the incidence of catheter-related bloodstream infections in home parenteral nutrition patients. J
90. Mouw E, Chessman K, Lesher A, Tagge E. Use of an ethanol
lock to prevent catheter-related infections in children with
short bowel syndrome. J Pediatr Surg. 2008;43(6):10251029.
91. Onland W, Shin CE, Fustar S, Rushing T, Wong WY.
Ethanol-lock technique for persistent bacteremia of long
term intravascular devices in pediatric patients. Arch Pediatr
Adolesc Med. 2006 Oct;160(10):10491053.
92. Dannenberg C, Bierbach U, Rothe A, Beer J, Korholz D.
Ethanol-lock technique in the treatment of bloodstream infections in pediatric oncology patients with broviac catheter. J
Pediatr Hematol Oncol. 2003;Aug;25(8):616621.
93. Crnich CJ, Halfmann JA, Crone WC, Maki DG. The effects
of prolonged ethanol exposure on the mechanical properties
of polyurethane and silicone catheters used for intravascular
access. Infect Control Hosp Epidemiol. 2005;26:708714.
Ethical Issues in the Provision

ofNutrition
37
Patrick M. Jones, MD, MA and Brian Carter, MD
CONTENTS
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485
Clinical Care as a Team Approach . . . . . . . . . . . . . . . . . . 486
Approaching the Pediatric Patient: WhatShould
We Let Them Know?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 486
The Good Shepherds
The Liberators
The Educators
Natural versus Medical Provision ofNutrition . . . . . 487

Determining the Goals of Nutrition. . . . . . . . . . . . . . . . . . 487
Values Ascribed to Feeding. . . . . . . . . . . . . . . . . . . . . . . . 488
Do we tend to see medical feeding in a
different light from other interventions?
Why is unique value assigned to feeding?
Ethical Dimensions of Clinical Nutrition Issues. . . . . . . . 489

The Intensive Care Environment: Neonatal and Beyond
Palliative Care
The Special Needs Infant and Toddler
Vegetarian Diets, Fad Diets, and Feeding Disorders
Childhood Obesity
The Adolescent
Summary
Case Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491

A Decision Not to Start Medical Nutrition Support?
The Withdrawal of Nutrition Support
Learning Objectives
1. Explain 3 models of sharing information with a pediatric patient.

2. Define natural versus medical provision of nutrition.
3. Review the importance of determining goals of treatment.
4. Examine the unique values associated with providing
nutrition to children.
Introduction
There are ever-expanding clinical applications to ethics in the

practice of the healing arts. The uniqueness of the pediatric
patient, who is dynamic in her growth, development, and
communication and cognitive capacities, requires special
sensitivity on the part of all healthcare professionals. Similarly, decisional processes that early on rely solely on parents/
guardians gradually must change to incorporate the child
and, ultimately, yield to the child as a maturing and autonomous young adult. As interdisciplinary team members work
together to bring about cure, prolong function, and provide
comfort to children living with acute and chronic health
care conditions, a common approach, language, and understanding of values that are important to patients, families,
and health care professionals will serve everybody.
Like other specialty areas, pediatric nutrition comes
with its own set of ethical challenges. Approaching these
challenges requires that the clinician be able to communicate effectively with patients, families, and other caregivers.
This chapter is not intended to make a person competent to
handle any or all situations, but instead it intends to help the
reader become more comfortable when engaging in conversations regarding ethics so that the important voice of the
nutritionist is heard by families and caregivers discussing
these issues.
477
478
Clinical Care as a Team Approach
The practice of medicine, even when dealing with decisions that raised fundamental ethical and social questions,
was historically the domain of an individual physician.
Physicians would decide if a critically ill baby had enough
potential to continue on the ventilator, whether an organ
should be given to a patient in heart failure, or if the elderly
womans pneumonia should be treated with antibiotics.
However, events such as abuses in human experimentation and the formation of a national commission to explore
medical ethics in the late 1960s and early 1970s began to
change the number of persons gathering around the bedside.
During the 1970s and 1980s, institutional review boards
(IRBs) examined research protocols to ensure subject
protection; orders to limit life-saving interventions began
to be documented and justified in the medical chart; and
ethics committees discussed situations that spurred moral
disagreement in the medical staff and/or the family. The
result has been a dramatic shift in how health care interacts
with the medical patient.1
Today, health care is not only affected by this history
but also the increasing role of the medical specialist. Any or
all of the following caregivers may be found participating in
the care of a sick child and her family: bedside nurse, charge
nurse, respiratory therapist, physician (including various
physician subspecialists and trainees), dietitian, physical
therapist, occupational therapist, speech pathologist, social
worker, case manager, psychologist, nurse practitioner,
physician assistant, chaplain, child life specialist, and music
therapist. The potential for benefit is high, as many professionals focus on specific aspects of that patients care, but
an obvious, and frequent, drawback is a lack of true teamwork. Most of the time, this problem originates from a lack
of defined roles mixed with poor communication; the result
may be conflicting messages presented to the family.
It is important to acknowledge that within the team lies
people with individual experiences and personal circumstances. Cultivating an environment where the team can
openly discuss concerns about patient care is a formidable,
but extremely valuable undertaking. As a participating
member of a health care team, it is each persons responsibility to form this team environment by communicating
effectively, understanding the underlying issues at hand,
and maintaining a complete picture of the goals and objectives of the clinical care of a patient.
Approaching the Pediatric Patient:

WhatShould We Let Them Know?
Pediatric medicine has at its core a unique figure: the

ever-changing and developing child. Most of the time, the
medical communitys interaction with children is brief
they get sick, they recover, they blissfully run off to their
old routines. Occasionally, however, the encounters last
much longer and involve illnesses that do not allow a quick
recovery or even a return home. A foundational concern
for the caregivers of these patients is that of knowing what
information, if any, to give the child regarding an illness.
There are certain children for which this question is rather
straightforward; an example being a child who is unable to
comprehend the world around her (eg, a newborn or a child
with severe traumatic brain injury). However, an 8-yearold with leukemia is able to understand some aspects of
her illness, and may need to participate in conversations
regarding her disease and its treatment.
To help summarize the best approach to involving the
pediatric patient, it is useful to turn to the work of Robert
Cassidy in his chapter on truth-telling.2 Cassidy describes
3 broad communication strategies for communicating with
a sick child. His first 2 models are described as the good
shepherd and the liberator models. After discussing the
history of these approaches and providing critiques, he
offers up a compromise, the educator model of pediatric
engagement, which best describes the approach used by
most pediatricians today.
The Good Shepherds

This model is rooted in the historical model of patient-physician interaction in which the physician, because of his or her
special knowledge concerning health and the human body,
primarily made all decisions regarding a patients treatment,
sometimes even choosing not to inform the patient of an
underlying medical condition. With the emphases of patient
autonomy in the late 1960s and early 1970s, this paternalistic
practice began to disappear, and patients became intimately
involved in choices regarding their medical care.
However, the autonomy movement was not quick
to trickle down to the pediatric population, as medical
providers and parents continued to treat children in a
similar manner. These adults viewed it as their duty to take
responsibility for all decisions, due to their more advanced
level of knowledge and maturity. Caregivers feared that
telling the truth to a sick child about her condition would
be harmful, and therefore selfish and irresponsible, so they
adamantly guarded the child from any discussions about
their medicalcare.
ETHICAL ISSUES IN THE PROVISION OFNUTRITION
The Liberators
Cassidy describes the liberators are those who fought to
counter the arguments of the Good Shepherds, especially
as researchers in the medical and social sciences made the
following important discoveries:
Withholding illness-related information from children
tends to increase their anxiety and fear. 3
Some sick children feel pressure to continue the faade
of not knowing about their illness in order to protect
their parents.4
Children are exceptionally observant and adept at
discovering the truth, regardless of the intent of parents
or health care providers to shield them from it. 5,6
Although a mature concept of death was thought to
be unattainable by a child, a majority of children reach
such an understanding by the age of 7 years.7
While this information argued for children to be given
information about their illness, the liberators erred in
assuming that the solution was to apply adult standards to
the pediatric population. The result was a standoff between
2 approaches that stood at opposing ends of the spectrum:
either tell children nothing in order to protect them from
a harsh reality, or tell children everything and potentially
bombard them with age-inappropriate information.
The Educators
A compromise is forged by approaching the patient in a
manner that makes use of a skill already rooted within the
practice of pediatrics: the assessment of a childs development. In this approach, caregivers interact with the pediatric
patient in a manner that is appropriate to her level of development; autonomy is not given fully and freely to the child,
but caregivers act in a manner that will inform and foster
the development of her increasing autonomy. This gradual
approach, especially in children with chronic, yet survivable
medical conditions (eg, diabetes) makes the transition to
adulthood more realistic than the sudden placement of full
responsibility upon a patient when she becomes an adult.
Used within this model is the concept of obtaining
assent from the pediatric patient. The American Academy
of Pediatrics (AAP) describes assent as having 4 elements:
1. Helping the patient achieve a developmentally appropriate awareness of the nature of his or her condition
2. Telling the patient what he or she can expect with tests
and treatment(s)
3. Making a clinical assessment of the patients understanding of the situation and the factors influencing
how he or she is responding (including whether there is
appropriate pressure to accept testing or therapy)
479
4. Soliciting an expression of the patients willingness to

accept the proposed care. 8
A frequent objection to obtaining assent is the fear that the
child may refuse to assent to a needed procedure. However,
as noted by Cassidy, this potential roadblock for the care
team may be extremely beneficial for the patient. As children are typically eager to please the important figures in
their lives, a refusal to give assent could be an important
signal that a misunderstanding or fear needs to be addressed
by the parent or care team prior to the procedure being
performed. The result is improved communication and
trust (and potentially an improved outcome).2
Natural versus Medical Provision

ofNutrition
When discussing ethical issues it is helpful to begin the

conversation by making sure that the terms and phrases
being used are understood in the same manner. Therefore,
prior to looking at individual clinical examples, it is important to discuss what is meant by the natural provision of
nutrition as opposed to the medical provision of nutrition.
These terms can be used in various manners, but for the
purposes of this chapter, the definitions put forth by Nicolas
Porta and Joel Frader are helpful as they describe their
typical usage in the clinical and bioethical literature.9 The
natural provision of nutrition refers to all feedings that do
not require medical intervention, specifically breast, bottle,
cup, and other oral feedings. Medical provision of nutrition
refers to nutrition that requires a special physician order (eg,
the usage of a nasogastric tube, central intravenous catheter, or the placement of a gastrostomy feeding tube). As
they are quick to point out, these classifications into natural
and medical do not connote that one is ethically optional
while the other is not.9 For example, medical nutrition is
frequently used in premature infants until they develop the
ability to suck and swallow safely; discontinuation of such
feedings to a child without another complication (such as a
fatal underlying condition) would be unacceptable.
Determining the Goals of Nutrition
Another useful practice prior to discussing an ethical question, particularly one that focuses on the use or disuse of
a particular medical intervention, is to define the goals of
the act in question. For instance, when a child is placed on a
ventilator, certain goals are set for the usage of that intervention (although this process is rarely formalized). Often the
goal is the provision of oxygen and the removal of carbon
dioxide until appropriate lung healing, or maturation, can
take place. Once that goal is no longer served because the
480
lungs have developed enough to sustain life, the ventilator

is discontinued. On a similar, yet more tragic vein, if the
infant is found to have a genetic condition that will prevent
the lungs from ever healing or maturing to the point that
the ventilator is unnecessary, it can be said that the intervention (assisted ventilation) is not serving the initial goal.
The physiological purpose of the ventilator, to provide
oxygen and remove carbon dioxide, is still being met, but
the overarching goal of using the ventilator to support the
infant until lung healing or maturation is achieved is no
longer applicable. While the ventilator may be continued,
it is now with a completely different set of goals in mind.
This may be to sustain life at all costs; however this longterm management goal is often fraught with complications.
The new goal might be to briefly continue physiological
support until the family has adjusted to the terminal nature
of the childs condition. This could include waiting for other
family members to come together, perhaps from a distance,
to provide emotional support and assist with funeral plans.
Regardless of the decision made, it should be recognized
that the underlying goal has changed, and it is no longer to
support until a cure.
Thus, when discussing nutrition in light of ethical
dilemmas posed by individual cases, it is important to
consider the underlying goal of providing nutrition. In its
very basic form, the goal of providing pediatric patients with
nutrition (natural or medical) is to provide them with the
substrate, vitamins, and minerals needed to meet basic metabolic demands for appropriate growth and development. Of
course, there are many other goals for nutrition in addition
to this rather basic purpose. For example, in the patient with
cystic fibrosis, adequate nutrition to meet increased needs
becomes a key factor in decreasing morbidity and mortality.
Also, in a patient with liver failure, the goals of providing
nutrition include optimizing his chance for a successful
transplant. However, just as in the aforementioned example
with the ventilator, should the clinical situation change, it is
important to reevaluate the goals of nutrition therapy as they
may no longer apply and the team may find itself pursuing
a nutritional strategy based on an outdated set of goals. As
an example of this, if a child with liver failure suffers a new
complication that makes transplant impossible, the goal
of nutrition would no longer be to optimize the patient for
surgery. The realization of new goals, such as improving
quality of life, may allow the team to be less aggressive (no
central lines, less emphasis on caloric intake) and begin to
de-medicalize the family and the child during the final
months of life.
Values Ascribed to Feeding

Do we tend to see medical feeding in a different light
from other interventions?
Although identifying the goals of medically provided nutrition is critical, to limit the discussion to this process alone
fails to address the complete picture. Outside of the intended
goals, the provision of nutrition to a pediatric patient often
has values assigned to it that make this intervention unique
from other life-sustaining interventions. An example of this
assignment of value can be seen in the description of withholding nutrition as starving the patient to death. This is a
phase rather unique to discussions on nutrition; rarely is the
removal of a ventilator described as suffocating the patient
to death or the decision to forgo dialysis as drowning the
patient to death. The tendency to use this language shows
that a certain value is being placed upon the provision of
medical feeding.10
Another example of this perspective of value assigned
to feeding and nutrition is seen in a pair of surveys done
with pediatric health care providers. The Pediatric Section
of the Society for Critical Care Medicine found that 98% of
physicians were apt to withhold cardiopulmonary resuscitation (CPR), 86% withdrew ventilators, but only 42% would
withdrawal tube feedings.11 Likewise, a survey of pediatric
residents in their third year of training demonstrated that
100% would withhold CPR and vasoactive medicines, 97%
would withdraw ventilator support, but only 45% would
withdrawal fluids and nutrition.12 Again, it appears that
there are underlying values assigned to providing a child
with nutrition that reach beyond the set medical goals.
Because of this, ethical issues involving the provision or
withholding of nutrition often take place in a unique and
complex social dynamic, charged with emotion.
Why is unique value assigned to feeding?

What is it about feeding that makes it more likely to have
additional value ascribed to it as opposed to dialysis? A
possibility is that providing nutrition to a child is a fundamental responsibility of the caregiver. A child is born unable
to provide himself with nutrition, and several years of development must take place before he is able to independently
obtain and consume nutrition. Perhaps this responsibility is
so ingrained in the caregivers being, that limiting its provision, no matter how beneficent the motives, causes feelings of
guilt or neglect in attending to care-giving duties. Contrast
this to the act of breathing: should assistance be needed
with this life-sustaining function, its provision is beyond the
usual parental duty. Therefore, while the discontinuation of
a ventilator is difficult for all who care for the child, perhaps
the feeling that all natural caregiving responsibilities have
been fulfilled allows this to be more palatable limitation of
treatment than the withholding of nutrition.10
Another potential reason for the uniqueness of feeding
is the typical time course and physical appearance of a
person who dies from starvation or dehydration. This is not
to imply that starvation is not a natural part of the dying
process, in fact the bodys reaction to a deprivation of nutrition may actually serve to ease a persons death. However,
for families who are caring for a child who is not being
adequately fed, the visual appearance and the prolonged
time course prior to death may be too difficult to endure
regardless of any medical considerations. Additionally,
the supportive care programs that could provide palliative
care throughout the dying process for these children are
unavailable in many geographic locales.13,14 Therefore, it is
understandable why the medical provision of nutrition may
be seen as such an essential element of care.
Ethical Dimensions of Clinical Nutrition Issues

The Intensive Care Environment: Neonatal and Beyond
Common practice in the neonatal intensive care unit
(NICU) includes a nutrition plan that facilitates growth,
development, healing, and immune function. All newborns
are born dependent upon caregivers for nutrition support.
Those with special considerations such as prematurity,
congenital anomalies requiring surgery, and numerous
disease states all may require medically delivered nutrition
and hydration. In a similar light, pediatric intensive care
unit (PICU) patients may also be in need of nutritional
support as infants, surgical patients, trauma victims, or
because of chronic and debilitating conditions that may be
associated with increased energy and nutrient demands or
special needs for nutritional delivery.
In the ICU, medically administered nutrition may well
be the norm. As such, its goals and decided benefits must
be reexamined as the patients condition changes. Risks (or
burdens), as well as benefits of nutritional delivery systems
must be acknowledged and clarified for the pediatric patient
and his/her parents.15,16 The mere capability to do something does not equate with the absolute medical indication,
or prerogative, to do so.
Ethical challenges in nutrition management for neonatal
and pediatric ICU patients, then, can be evaluated in the
context of goals and values, and warrant open communication and a collaborative approach among the medical team
involved. In a family-centered context, parental input may
481
be important in making certain choices about the appropriateness of medically delivered nutrition in the hospital or
at home. At the very least, open and transparent decisional
processes and communication with parents that allow for
their understanding of why, and how, and for how long a
certain method may be used, is required.
When surgically placed devices (eg, central venous
catheters, gastrostomy, or jejunostomy feeding tubes) are
considered, the risks and benefits require special attention
as the potential for pain, wound healing, aspiration, infection, thrombosis, or other complications must be weighed
against the patient and family goals. For most patients the
benefits are clear and the health care team makes reasonable decisions with the family to proceed with placement of
such devices. But on occasion, the initial placement, or their
replacement, become burdensome and cause all involved
to pause and reconsider their appropriateness. This may be
especially true in the terminal stages of many chronic and
debilitating conditions. In these cases, adequate time needs
to be devoted to discerning the best interests of the pediatric patientoften addressed differently by the patient,
parents, and clinicians. Clinicians sensitivity to parental or
patient goals and values that differ from their own, whether
in matters of culture and custom, faith and religious tradition, or social and family norms and expectations must be
present and allow for considerations beyond what may be
simply metabolically or physiologically apparent as a best
course of action. With long-term care and chronic debilitation, one may need to ask Does more always equate
to better?17
Perhaps the most heated ethical debates in nutrition
management of patients dependent upon medically delivered
nutrition and hydration are in the context of the withholding
or withdrawal (WH/WD) of such nutrition. For children,
especially those in whom a cognitive capacity is not appropriate for them to participate in decisions, parents normally
serve as surrogate decision makers as they are entrusted by
society with discerning and acting upon their childs best
interests. These interests, though not always knowable,
certainly include not being treated as mere passive objects,
and the same ethical and legal posture toward WH/WD
medical nutrition is due them that is due adult patients.10
Decisions that are made concerning medical nutrition
should be made like all other decisions about WH/WD
life-sustaining treatments, although as previously noted
these decisions may be fraught with greater psychological
and emotional duress among all partiesespecially when
the patient is not imminently dying.18, 19 As noted by Porta
and Frader, clinicians should neither demand nor reject
482
medical nutrition without examining and considering each

situations context (eg, goals, values, burdens, and benefits),
through which the provision of medical nutrition may be
found morally optional.9
Palliative Care
The subject of palliative, and end-of-life, care has been of
increasing interest in pediatric medicine over the past decade.
Among resources that address what pediatric palliative care
should entail, the 2003 Institute of Medicine Report When
Children Die is among the most often cited.20 Among issues
noted therein, the attention to medically administered [artificial] nutrition and hydration (ANH) is noted as one that
warrants acknowledgement by clinicians of some residual
controversy and continued need for inquiry. The recent AAP
Clinical Report, Forgoing Medically Provided Nutrition and
Hydration in Children, helps by providing further guidance
in this sensitive area.21 Both of these resources, and numerous
articles that have been published in the peer-reviewed
medical literature, address aspects of ANH in the context
of life-limiting or threatening conditions, and specifically at
the end of life.22,23 Matters of values, open communication,
assigned meanings to feeding, and the overall goals of care
require attention in addressing this matter as much as any
other life-sustaining interventions.
The dietician may need to be a resource for parents,
families, other care team members, and for physicians in
particular as the issue of ANH is examined in the acute care
setting (hospital or clinic), home health, or home palliative and
hospice care. Attention to the normalcy of assisted feeding
devices, such as gastrostomy feeding tubes, is another sensitive
area that may require education as well as a values clarification. Petersen and colleagues reported a different perspective
on feeding through a gastrostomy tube by a majority of daily
caregivers of children with cerebral palsy.24
The Special Needs Infant and Toddler

Among the varied special needs children cared for by dieticians, perhaps the most labor-intensive and demanding are
graduates from the NICU. These children may be followed
by an interdisciplinary team in NICU Graduate Follow-up
Clinics that include a dietitian, may be seen only by primary
care clinicians (pediatricians, family physicians, nurse practitioners, physician assistants), in county health department
clinics, or they may be altogether lost to follow-up. Their
nutrition needs are fundamental to their care as continued
growth, physical development, neurodevelopment, resilience with acute illness, and overall health are all predicated
on good nutrition.25,26
On occasion an ethical dilemma may arise in determining that the placement of a medical nutrition device
(feeding gastrostomy tube), is in the best interests of the
patient. The dietician as a key interdisciplinary health care
team member, or consultant, may bring clarity to decisions
to go forward with such a plan, or to reconsider it. Goals
clarification may be the greatest contribution to be made.
The dietician may also be called to advocate for correct
ethical action in beginning, sustaining, or advancing nutrition support for special needs children. She may find herself
in tension with primary or specialty clinicians who have
not prioritized nutrition for the NICU graduate, missed
faltering growth, or are uncertain about what to do next
for a child in whom a medical feeding device is not being
used and oral nutrition is inadequate to secure the goals of
health. Ethical action here requires professional competence, self-confidence, and a stance of advocacy for the child.
Effectively communicating with involved clinicians, and
parents, may include the provision of past and present goals
of nutrition, observed and documented failures (growth
curves, illness, and other outcomes), and recommendations
with evidence-based expectations for measurable outcomes
in an appropriate timetable.
Additionally, some NICU graduates have chronic
gastrointestinal illnesses such as cholestatic jaundice, liver
disease, or short bowel syndrome (SBS) following neonatal
surgery. The care of the child with SBS requires attentiveness to detail and elements of psychosocial support for the
child and family that complement the necessary medical,
nutrition, and pharmacy (home parenteral nutrition)
management of this condition. Those who await eventual
liver-bowel transplantation have lengthy waiting periods
and high morbidity and mortality.27
Other children with special nutrition needs include
those born with an inborn error of metabolism. Perhaps
diagnosed prenatally, or even after discharge home from the
hospital, many metabolic conditions result in acute illness
and nearly all have significant impact upon child growth
and development. The nutritionist must remind himself that
he is part of a team and work collaboratively in addressing
parent education, child health, and the provision of special
nutrition products. In extreme cases, such as certain urea
cycle disorders, liver transplantation may be the ultimate
goal and nutrition assessment and daily management brings
the nutritionist in close and frequent contact with the family.
Should such contact lead to shared feelings about the childs
illness, goals, and values, it is the nutritionists duty to raise
issues that might seem contrary to the goals of the current
care plan with the responsible physician or team leader.
Vegetarian Diets, Fad Diets, and Feeding Disorders

The dietician is a key team member in addressing nutrition
education for children of all ages. While this chapter cannot
address the broad concerns raised and management issues
required for children with feeding disorders such as bulimia
and anorexia (Chapter 19), the dietician must attend to the
priority of care being focused on the patients well-being
and best interests as they can best be discerned. In conjunction with other clinicians and behavioral health specialists,
the nutritionist may need to address facts, falsehoods, and
fallacies about the goals of nutrition, nutrition essentials,
and how all concerned parties may help children attain and
maintain good health.
When addressing vegetarian diets, it may be important
to understand the rationale for such dieting can be clinical
(eg, improved cardiovascular health and longevity), a means
of addressing weight control, upholding religious tenets, or
ethical life-style choices (addressing concern for the ecosystems on the planet, and for animal well-being).28 At the
same time vegetarianism may be a marker for disordered
eating practices (or tendencies) and a preoccupation with
weight that may not serve the childs overall interests. 29 The
dietician must balance appropriate support of choices and
dieting habits with responsibilities of addressing potential
clinical and behavioral health matters.
Childhood Obesity
The recent increase in childhood obesity may be seen by
some as a mere medical, or strictly nutrition, condition.
This is far from the reality of complex social, behavioral,
educational, and even economic contributors to this
growing concern. Some have raised the issue of obesity
constituting medical neglect, and thereby warranting interventions that include social and legal actions akin to those
expected in physical or sexual child abuse, or gross parental
neglect of meeting a childs due needs (eg, food, clothing,
shelter, education, and health care). Recently, Varness and
colleagues have addressed the nature of these concerns and
how they are rarely borne out in such a manner that obesity
could legitimately be considered neglect. 30
The Adolescent
The period of adolescence is accompanied by major developmental and cognitive goals, not the least of which are
individuationthe process in which the young person
engages in developing his or her own self-identity and
strives to become an individual, distinct from parents and
siblingsand independence, whereby the young person
takes actions that allow for not only a separate identity
483
from parents and siblings but also a claim to independent

thinking. For some, this may include the choice of separate
dietary preferences, vegetarian dieting (while the remainder
of their family, or even circle of friends continue omnivorous
dieting), or participation in fad dieting that may actually
reflect issues of reckoning with bodily changes of adolescence, or even self-image and psychological well-being.
In this period of life, clinicians need to attend to the
complexity of intersecting issuesclinical, social, and
behavioralwhich affect dieting and overall nutritional
well-being. A balance of respect for the adolescent accomplishing individual identity and independence must be
met with informing and educating the young person about
healthy habits and avoidance of negative behaviors. While
matters of eating disorders exceed the subject of this chapter
and are discussed elsewhere (Chapter 19), ethical precepts
of respect for persons, doing good and avoiding harm, and
attending to the fine line of confidentiality for and with the
adolescent patient and his or her family must be recognized
by all health care team members.
Summary
The timely, appropriate, and beneficial provision of pediatric nutrition requires attention to the pediatric patient and
his or her parents and family. Ethical challenges may best
be met with open dialogue, respectful listening, clarity of
communication, and sensitive provision of support directed
toward mutually derived nutrition goals. The dietician has
an integral role to play in these matters as a valued interdisciplinary team member across diverse diagnostic categories,
care environments, and the age continuum of pediatrics.
Case Studies
A Decision Not to Start Medical Nutrition Support?
A term infant is delivered by emergency cesarean section
for fetal bradycardia to a 25-year-old gravida I mother
with diabetes mellitus. He required extensive resuscitation
and had Apgar scores of 0, 0, and 3 at 1, 5, and 10 minutes
after birth, respectively. He is admitted to the NICU with
respiratory distress and hypoglycemia. His birth weight is
4.5 kg. He has poor cardiovascular function, hypotension,
and metabolic acidosis. His respiratory depression and
apnea require assisted ventilation. At 2 hours of age he has
a convulsion and after receiving an anticonvulsant he is
placed on a head-cooling protocol for severe birth asphyxia.
An MRI confirms diffuse and devastating ischemic brain
injury. On postnatal day 4 he fails a trial of extubation due
to apnea and inability to handle his own secretions. He has
484
no urine output for 7 days and after receiving initial intravenous dextrose the question of providing parenteral nutrition
or a trial of nasogastric tube feedings is raised on morning
ICU rounds. A discussion follows in which his prognosis
for recovery is described as bleakhis future survival is
contingent on the provision of a tracheostomy and placing
a feeding gastrostomybut his potential for future neurological function (motor, cognitive, and communicative) and
development is gone and he will remain infantile.
This infant presents a number of opportunities for
evaluating nutrition support: a large for gestational age
infant of a diabetic mother (complicated by hypoglycemia),
birth asphyxia (with circulatory shock, acidosis, and likely
impaired gastrointestinal perfusion, mucosal barrier function, and poor gut motility), neurological injury, and renal
failure. At a week of age he evidences multiple organ system
injury and failure of function. His prognosis for successful
oral feeding is nil, and in the face of renal failure the provision of parenteral nutrition must be questioned.
1. What is the ethical rationale for placing a central line
and providing parenteral nutrition?
2. What is the burden:benefit analysis of pursuing a
feeding gastrostomy and fundoplication?
3. What are the goals of nutrition support for this baby?
4. Can palliative care be provided without a specific
feeding regimen?
The Withdrawal of Nutrition Support

Jill, a 3-year-old girl with severe cerebral palsy (spastic
quadriplegia), seizures, and mental retardation after infantile meningitis, has recently required management in the
PICU following a fourth episode of aspiration pneumonia.
She is sedated in order to allow adequate assisted ventilation, and has been receiving medically administered
intravenous nutrition and hydration for the past 5 days. Her
parents meet with the PICU team to discuss the prognosis
and plan of care. The team states they are hoping for the best
for Jill, as nobody knows how long she was hypoxic after she
arrested at home. A trial of lifting her sedation, reducing
ventilator support, extubating Jill, and providing enteral
nutrition through a transpyloric nasal feeding tube is agreed
to by Jills parentswho are anxious to see any signs of Jill
getting better. Two days later, however, Jills respiratory
condition worsens after failing a trial of extubation and a
tracheostomy must now be considered.
Jills mother and father are overwhelmed by her decompensation following this most recent aspiration event. She is
not responding to their voice or touch. At a follow-up family
meeting her attending physician discusses his concern for
Jills neurological status. Unlike prior hospitalizations with

aspiration pneumonia, this time she has never opened her
eyes, is only reflexively responsive to pain, and he fears she
may never improve, or even assume her prior level of infantile function. He also believes that Jills overall condition
warrants not only the tracheostomy but that she will need
a fundoplication to protect her airway if she were to receive
gastric feedingsstating for clarification that feeding
should now only be pursued via a gastrostomy tube. In
realizing the extent of Jills injury and poor prognosis, the
parents begin to sob, We knew this day might come. After
a minute, the physician re-appraises the matter of nutrition
support for Jill, stating, Just because we can place a feeding
gastrostomy does not necessarily mean we should. And
frankly, that is true for the tracheostomy as well. This gives
the parents initial pause, but then they express a desire to
speak with extended family members, their church, and be
given some time. The physician leaves them alone to talk
with the unit social worker.
1. What are the key considerations for this family to
consider in making their decision for Jill?
2. How does the ethical standard of doing what is in the
childs best interest pertain to this case?
3. What level of burden, pain, or suffering might be acceptable in doing surgery for Jill?
4. If the parents elect not to have a gastrostomy, fundoplication, and tracheostomy done, what nutrition support
goals should exist for this patient?
1. When a developmentally appropriate child with cystic

fibrosis asks questions to the medical team regarding his
or her disease, the method of communication thought
to be most beneficial is to:
A. Carefully talk to the child, trying to stay positive, while also avoiding any potentially negative
information.
B. Try to give the child the worse case scenarios in
hopes of preparing him or her for the worst.
C. Tell the child that you are going to focus on todays
plan of care, but that you will schedule an appointment with the nurse educator.
D. With the guardians permission, try to answer the
questions in an honest, but developmentally appropriate, manner.
E. All of the above.
2. How do Porta and Frader distinguish between natural

and medical nutrition?
A. Natural nutrition is a mandatory act.
B. Medical nutrition is a mandatory act.
C. Natural nutrition is always optional.
D. Medical nutrition is always optional.
E. None of the above.
3. Which of the following actions is not recommended as
a way to help reach an ethical decision regarding the
provision of nutrition?
A. Make sure everyone on the team is using the same
definition for commonly used medical and ethical
terms.
B. Avoid talking to the family or the patient until a
decision is made so that the team does not appear
uncertain.
C. Define the long-term goal of providing nutrition to
the patient.
D. Discuss with the family their views and beliefs
regarding feeding and/or the provision of
nutrition.
E. Carefully examine the context (goals, values,
burdens, and benefits) of the nutrition dilemma.
References
1. Rothman DJ. Strangers at the Bedside. New York, NY: Walter

de Gruyter, Inc; 2003.
2. Cassidy RC. Tell all the truth? Shepherds, liberators, or educators. In: Cassidy R, Fleischman A, eds. Pediatric Ethics: From
Principles to Practice. Amsterdam, The Netherlands: Harwood
Academic; 1996:6782.
3. Slavin LA, OMalley JE, Koocher GP, Foster DJ. Communication of the cancer diagnosis to pediatric patients: Impact on
long-term adjustment. Am J Psychiatry. 1982;139(2):179183.
4. Bluebond-Langner M. The Private Worlds of Dying Children.
Princeton, NJ: Princeton University Press; 1978.
5. Spinetta JJ, Rigler D, Karon M. Anxiety in the dying child.
Pediatrics. 1973; 52(6):841845.
6. Spinetta JJ, Maloney MS. Death and anxiety in the outpatient
leukemic child. Pediatrics. 1975;56(6):10341037.
7. Speece MW, Brent SB. Childrens understanding of death:
A review of three components of a death concept. Child Dev.
1984;55:16711686.
8. American Academy of Pediatrics, Committee on Bioethics.
Informed consent, parental permission, and assent in pediatric practice. Pediatrics. 1995;95(2):314317.
9. Porta N, Frader J. Withholding hydration and nutrition in
newborns. Theor Med Bioeth. 2007;28:443451.
10. Carter BS, Leuthner SR. The ethics of withholding/
withdrawing nutrition in the newborn. Semin Perinatol.
2003;27(6):480487.
485
11. Society of Critical Care Medicine, Task Force on

Ethics. Consensus report on the ethics of forgoing lifesustaining treatments in the critically ill. Crit Care Med.
1990;18(12):14351439.
12. Rubenstein JS, Unti SM, Winter RJ. Pediatric resident attitudes about technologic support of vegetative patients and
the effect of parental inputa longitudinal study. Pediatrics.
1994;94(1):812.
13. Contro N, Larson J, Scofield S, Sourkes B, Cohen H. Family
perspectives on the quality of pediatric palliative care. Arch
Pediatr Adolesc Med. 2002;156:1419.
14. Liben S, Papadatou D, Wolfe J. Paediatric palliative care: Challenges and emerging ideas. Lancet. 2008;371(9615):852864.
15. Hobbs N. Decisions for a baby in foster care. J Clin Ethics.
2004;15(3):292295.
16. Mello M. The experience of a community representative on an
Ethics Consult Team. J Clin Ethics. 2004;15(3):296301.
17. Essex C. More is not necessarily better. Arch Dis Child.
2006;91:202.
18. Mitchell C, Truog RD, Ethics Advisory Committee at Childrens Hospital Boston. Excerpts from the ethics consult
report: MT. J Clin Ethics. 2004;15(3):302306.
19. Johnson JA. Withdrawal of medically administered nutrition
and hydration: the role of benefits and burdens, and of parents
and ethics committees. J Clin Ethics. 2004;15(3):307311.
20. Field MJ, Behrman RE, eds. When Children Die: Improving
Palliative and End-of-Life Care for Children and Their Families.
Washington, DC: National Academies Press; 2003:39, 143,
298299.
21. Diekema DS, Botkin JR, American Academy of Pediatrics
Committee on Bioethics. Clinical ReportForgoing medically provided nutrition and hydration in children. Pediatrics.
2009;124(2):813822.
22. Levi BH. Withdrawing nutrition and hydration from children: legal, ethical and professional issues. Clin Pediatr.
2003;42:139145.
23. Truog RD, Cochrane TI. Refusal of hydration and nutrition:
irrelevance of the artificial vs natural distinction. Arch
Intern Med. 2005;165:25742576.
24. Petersen MC, Kedia S, Davis P, Newman L, Temple C. Eating
and feeding are not the same: caregivers perceptions of
gastrostomy feeding for children with cerebral palsy. Dev Med
Child Neurol. 2006;48:713717.
25. Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage
LA, Pool WK and the NICHD Neonatal Research Network.
Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth
weight infants. Pediatrics. 2006;117(4):12531261.
26. Bhatia J. Post-discharge nutrition of preterm infants. J Perinatol. 2005;25:S15S16.
27. Horlsen S. Organ allocation for liver-intestine candidates.
Liver Tranpl. 2004;10:S86S89.
28. Klopp SA, Heiss CJ, Smith HS. Self-reported vegetarianism
may be a marker for college women at risk for disordered
eating. J Am Diet Assoc. 2003;103:745747.
29. Perry CL, McGuire MT, Neumark-Sztainer D, Story M. Characteristics of vegetarian adolescents in a multiethnic urban
population. J Adolesc Health. 2001;29:406416.
486
30. Varness T, Allen DB, Carrel AL, Fost N. Childhood obesity

and medical neglect. Pediatrics. 2009;123:399406.
Additional Readings of Interest

Ethical Issues and Nutrition Therapy in General
Carrese JA. Refusal of care: patients well-being and physicians

ethical obligations. JAMA. 2006;296(6):691695.
Ferrie S. A quick guide to ethical theory in healthcare: solving
ethical dilemmas in nutrition support situations. Nutr Clin
Pract. 2006 21:113117.
Fine RL. Ethical issues in artificial nutrition and hydration. Nutr
Clin Pract. 2006;21:118125
MacDonald C. Treatment resistance in anorexia nervosa and the
pervasiveness of ethics in clinical decision making. Can J
Psychiatry. 2002;47:267270.
OSullivan Maillet J, Vyas A, Rodrigues J. Ethical issues in nutrition and human immunodeficiency virus. Nutr Clin Pract.
2004;19:365374.
Sayers GM, Lloyd DA, Gabe SM. Parenteral nutrition:
ethical and legal considerations. Postgrad Med J. 2006
Feb;82(964):7983.
Sharp HM, Bryant KN. Ethical issues in dysphagia: When
patients refuse assessment or treatment. Semin Speech Lang.
2003;24(4):285299.
Thomson C, Diekman C, Fragakis AS, Meerschaert C, Holler
H, Devlin C. Guidelines regarding the recommendation and sale of dietary supplements. J Am Diet Assoc.
2002;102:11581164.
Unknown. Artificial feeding for a child with a degenerative
disorder: a familys view. The mother and grandmother of
Frances. Arch Dis Child. 2005 Sep;90(9):979.
Ethical Issues and Nutrition Therapy:

Pediatric End of Life
Donnelly JP, Huff SM, Lindsey ML, McMahon KA, Schumacher

JD. The needs of children with life-limiting conditions: a
healthcare-provider-based model. Am J Hosp Palliat Care.
2005;22(4):259267.
Fleischman AR, Collogan L. Addressing ethical issues in everyday
practice. Pediatr Ann. 2004;33(11):740745.
Frader JE. Discontinuing artificial fluids and nutrition: discussions
with childrens families. Hastings Cent Rep. 2007;37(1):49.
Glover JJ, Caniano DA, Balint J. Ethical challenges in the care of
infants with intestinal failure and lifelong total parenteral
nutrition. Semin Pediatr Surg. 2001;10(4):230236.
Heine RG, Bines JE. New approaches to parental nutrition in infants
and children. J Paediatr Child Health. 2002;38(5):433437.
National Hospice and Palliative Care Organization. Standards of
Practice for Pediatric Palliative Care and Hospice. Alexandria,
VA: National Hospice and Palliative Care Organization;
2009.
Nelson LJ, Rushton CH, Cranford RE, Nelson RM, Glover JJ, Truog
RD. Forgoing medically provided nutrition and hydration in
pediatric patients. J Law Med Ethics. 1995;23(1):3346.
Repenshek M, Slosar JP. Medically assisted nutrition and hydration: a contribution to the dialogue. Hastings Cent Rep.
2004;34(6):1316.
Saad L. Americans choose death over vegetative state: most would
have feeding tube removed for their child, spouse, or themselves. In: Gallup A, Newport F, eds. The Gallup Poll: Public
Opinion March 29, 2005. Lanham, MD: Rowman & Littlefield; 2006:116118.
Velez G Jr. Death of John Paul II and the basic human care for the
sick and the dying. Ethics Med. 2005;Fall;21(3):167177.
Test Your Knowledge Answers
Chapter 1: Mechanics of Nutrient Intake
Chapter 4: Fats
1. The correct answer is C.

2. The correct answer is B.
3. The correct answer is A.
1. The correct answer is B. The problems of overweight and

obesity are the result of excess calories and not simply
too much fat. In addition to customizing the caloric
intake to meet the individual patients needs, the ideal
nutritional support will provide appropriate ratios of
preformed LA, -LA, ARA, EPA, and DHA that cannot
be made in adequate amounts by the patient.
2. The correct answer is D. Medium-chain fatty acids and
long-chain fatty acids are oxidized in mitochondria.
Very long-chain fatty acids are oxidized in peroxisomes
and mitochondria. Although it is normally a minor
pathway, omega-oxidation in the endoplasmic reticulum of the cytoplasm becomes important if there is
mitochondrial dysfunction.
3. The correct answer is D. The neonate cannot synthesize LA or -LA. Although the enzymes are present to
convert LA to ARA and -LA to EPA and DHA, the
capacity to do so is not adequate to meet the needs of
the neonate.
Chapter 2: Gross Digestion Principles: Gastric Grinding

and Gastrointestinal Motility
1. The correct answer is C. Liquids empty from the
stomach faster than solids; feeding higher in fiber, fat,
and protein will empty more slowly.
2. The correct answer is B. The other three answers each
describe characteristics of one of the 3 phases of the
migrating motor complex seen in the fasting state.
3. The correct answer is D. It has been demonstrated that
even small amounts of enteral feeding in the premature
infant will encourage maturation of intestinal motility.
Bolus feeds will actually cause a cessation of contractions in the proximal small bowel of the premature
infant. Both gastric emptying and intestinal transit are
slower in the premature infant.
Chapter 3: Carbohydrates: Changes with Development

1. The correct answer is D. Lactose, sucrose, and maltose
are disaccharides. Amylose is a polysaccharide consisting
of multiple glucose units and is a component of starch.
3. The correct answer is B. Lactase activity at the start of
the third trimester is < 25% of that at term.
4. The correct answer is D. The prevalence of hypolactasia
amongst individuals of different ethnic backgrounds is
as follows: 90% Asians, 80% African-Americans, 53%
Hispanics, and 15% to 25% non-Hispanic whites.
Chapter 5: Protein Digestion, Absorption, and

Metabolism
1.
2.
3.
4.
The correct answer is C.

The correct answer is A.
Chapter 6: Minerals
1.
2.
3.
4.
The correct answer is E.

The correct answer is D.
487
488

6. The correct answer is A.
Chapter 7: Water-Soluble Essential Micronutrients

1.
2.
3.
4.
5.

Chapter 8: Fat-Soluble Vitamins

1.
2.
3.
4.
5.

Chapter 9: Fluids and Electrolytes

1. The correct answer is C. Fluid gains in the body
compartments depend on the volume and osmolarity of
the fluid administered. Administering 100 mL of 0.9%
sodium chloride (154 mEq/L of sodium) will not alter
the plasma osmolarity because it is iso-osmotic. The
sodium will be held in the ECF by the Na+-K+-ATPase
pump, and the water stays with the sodium. Therefore,
all of the administered volume (100 mL) will stay in the
ECF compartment. Because 25% of the ECF compartment is intravascular volume, the intravascular volume
will increase by 25 mL.
2. The correct answer is A. A low serum sodium concentration is the result of either an increase in TBW or
a decrease in total body sodium with a subsequent
decrease in TBW. The weight has not changed significantly over the past 3 days and the sodium intake
(3 mEq/kg/d) may not be sufficient for a 1250-g
neonate. Therefore, the renal and GI losses are probably
exceeding the sodium intake, resulting in the decreased
serum sodium concentration. The correct treatment
would be to increase the sodium concentration in the
maintenance IV fluids.
3. The correct answer is C. The low serum phosphorus
concentration is cause for concern and needs to be
treated acutely. A supplemental IV infusion of sodium
phosphate would be more appropriate than adding
sodium phosphate to the maintenance IV solution. A
serum potassium concentration of 3.4 mEq/L does not
necessitate acute treatment; increasing the potassium
in the maintenance IV fluids would be most appropriate
to address this issue.
Chapter 10: Nutrition and Early Development

1. The correct answer is D.
Chapter 11: Human Milk

1. The correct answer is E. Some of these infants have
been shown to have an insufficient suck and negative
pressure needed for good milk extraction. They may
fool mothers and as this problem persists, the mothers
milk supply may dwindle. This may cause dehydration
as well as poor growth and create a cycle that can lead
to lactation failure. Encouraging mothers to pump to
stimulate milk supply is helpful; also, the use of teat
weights to determine whether there is sufficient milk
transferred can also be helpful. Further information is
included in references 39 and 40.
2. The correct answer is B. Although calories are important which will be supplied in greater amounts with the
higher fat content of hind milk, the premature infant
needs fortification for protein, calcium, phosphorus,
magnesium, and zinc.
3. The correct answer is A. Donor banked human milk
may often be from donations of mothers of term
infants. This milk would have lower protein content
than the milk from a mother of a preterm infant. The
pasteurization process alters some of the properties of
human milk as well. There will be increased needs for
supplemental protein, calcium, and phosphorus.
Chapter 12: Infant Formulas and

ComplementaryFeeding
1.
2.
3.
4.

The correct answer is B.
Chapter 13: Growth Assessment and Monitoring

1. False. BMI not available for children age < 2 years. BMI
patterns after age 2 years can be linked to adolescent.
2. False. BMI percentile 85th 95th represents risk
for overweight. BMI percentile > 95th represents
overweight.
3. True. The CDC recommends using terminology
obesity for BMI 95th percentile or calculated BMI
30 kg/m2 . This is a change from Expert Committee
recommendations in 1998 that discouraged use of
obesity terminology in children. The term obesity
denotes excess body fat and the associated serious health
TEST YOUR KNOWLEDGE ANSWERS
4.
5.
6.
7.
risks. It also provides continuity with adult definitions

and avoids the vagueness of previous terminologies of
risk for overweight for BMI 85th to 94th percentile
and overweight for BMI > 95th percentile.
The correct answer is D. FTT or wasting is an involuntary decline falling below 2 or more major percentile
channels. The major percentile channels are 90th, 75th,
50th, 25th, 10th, and 5th.
The correct answer is C. The 50th percentile is the mean
and median value. This corresponds to a z score of 0.
The correct answer is D. Timeline of progression was
not given; otherwise, answer B is also potentially life
threatening if rapid in onset (ie, < 1 to 2 months).
The correct answer is B. Length refers to linear
measurements taken with the subject in a supine position. Lengths are longer than heights. Linear growth
in the birth to age 36-month growth reference charts
is based on length measurements. Linear growth in the
2- to 20-year growth reference charts is based on height
measurements.
Chapter 14: Obesity and Metabolic Disorders

1. The correct answers are A, B (as relates to cut-points),
D, and E.
3. The correct answers are E and F.
Chapter 15: Lipid Disorders

Chapter 16: Use of Popular and Fad Diets

1. The correct answer is C. The ADA evidence-based
analysis of pediatric overweight literature on intervention programs reported positive effects from 2 specific
kinds of interventions: multi-component, family-based
programs for children between the ages of 5 and 12
and multi-component school-based programs for
adolescents. The components included were behavioral counseling, promotion of physical activity, parent
training/modeling, dietary counseling, and nutrition
education.
2. The correct answer is A. Interventions should be based
on the familys readiness to change and include the
following recommendations: consumption of 5 servings of fruits and vegetables per day; minimization or
elimination of sugar-sweetened beverages; limits of 2
hours of screen time per day, no television in the room
489
where the child sleeps, and no television if the child is <

2 years of age; and 1 hour of physical activity per day.
3. The correct answer is B. The Traffic Light Diet was
designed to promote weight loss, provide adequate
kilocalories and nutrients for growth and development, and be easy to follow. The Food Guide Pyramid
was designed as a general guide for diet and exercise
in adults; however it was used as a dietary component
in childhood weight management in one study of
adolescents.
4. The correct answer is D. For children and adolescents,
these diets have not been studied due to potential risks
for growing children and adolescents from elimination
of key food groups, greater than recommended caloric
restriction, adverse behavioral patterns of eating and/
or lack of scientific evidence for the basis of the diets
recommendations. The key requirement for dietary
treatment of overweight children and adolescents is to
initiate and maintain lifelong healthy eating habits that
focus on unhealthy weight in the short term and foster
improved health outcomes in the long term.
Chapter 17: Sports Nutrition

1.
2.
3.
4.

Chapter 18: Developmental Delay

Chapter 19: Eating Disorders

1. The correct answer is C. Physical presentation of a
person with anorexia nervosa includes lanugo-type
hair, muscle wasting, dry skin, cyanosis of extremities,
bradycardia less than 60 beats/min, and cachexia. When
anorexia develops in childhood, the first clinical sign
may be failure to make weight gains while continuing to
grow in height as opposed to documented weight loss.
Growth charts should be evaluated for typical growth
patterns of the individual
2. The correct answer is B. Parenteral nutrition (PN) is
only indicated in cases of digestive inability as it leads
to a continued loss of hunger cues in the eating-disordered individual.
3. The correct answer is A. Patients with a weight loss of
10% within 2 to 3 months or those at or below 70%
490
ideal body weight are at the greatest risk. Categories

of patients who may meet these criteria include those
with anorexia nervosa, alcoholics, cancer patients, postoperative patients, the elderly, uncontrolled diabetics,
marasmus, prolonged fasting, morbid obesity with
profound weight loss, patients NPO greater than 5 to
7 days, malabsorptive syndrome (such as pancreatitis,
cystic fibrosis, short bowel), prolonged antacid use (due
to binding of phosphorus), and long-term diuretic use
(due to electrolyte losses).
Chapter 20: Food Allergies

1. The correct answer is D. Allergens are usually proteins
or glycoproteins. Allergies do not develop to carbohydrates. Allergies to intravenous lipid, amino acid
solution, and the multivitamin solution have all been
described.
2. The correct answer is B. Children under 2 years of age
and avoiding milk and soy protein are at increased
risk of consuming insufficient fat, protein, calcium,
vitamin D, zinc, iron, and total energy. Enriched rice
milk provides adequate vitamin D and calcium but
does not provide appropriate fat, protein, and energy
intake. Appropriate substitute for liquid intake would
be a hydrolysate formula or if that is not tolerated, an
elemental formula.
3. The correct answer is D. In a patient with a history of
anaphylaxis to a food, a food challenge at home should
never be recommended. Follow-up with an allergist is
the only safe way to assess if a patient has outgrown
or developed tolerance to the food. Annual follow-up
assessment with an allergist is recommended for children with food allergies. The nutrition assessment of a
these children should always review growth and nutrient
intake. By obtaining a 24-hour recall and reviewing
common foods consumed, exposures to food allergens
can be identified. If a patient is tolerating exposures
to foods that were allergenic, again the patient must
follow up with the allergist to clarify the allergen list.
Liberalizing a patients diet will provide more options
for improving the overall nutrition intake.
4. The correct answer is A. In IgE-mediated anaphylaxis,
there are usually cutaneous signs such as an urticarial
rash. The absence of cows milk-specific IgE on RAST
testing makes an IgE-mediated mechanism unlikely.
This clinical scenario is consistent with food proteininduced enterocolitis syndrome and avoidance of cows
milk is the most important therapy. A protein hydrolysate formula would be an effective substitute and if
not tolerated, an elemental formula.
Chapter 21: Diabetes Mellitus and Other

EndocrineDisorders
1. The correct answer is D. The concentration of dextrose
used in the PN should be chosen based on the optimal
formulation of the PN, rather than on the fact that the
child has diabetes mellitus.
2. The correct answer is A. The hospitalized child with
CF-related diabetes mellitus often has increased insulin
resistance and therefore requires a larger amount of
insulin to control blood glucose excursions.
3. The correct answer is C. Acceptable blood glucose
control in children with diabetes mellitus on EN can
usually be obtained by using subcutaneous insulin.
Insulin is usually not administered enterally.
4. The correct answer is D. Acceptable serum sodium
concentrations in a child with diabetes insipidus on
nutrition support can usually be obtained by using an
intravenous drip of aqueous vasopressin.
Chapter 22: Inborn Errors of Metabolism

1. The correct answer is D. Disorders selected for newborn
screening programs must be cost-effective and reliably
detected by population-based screening methods.
Realistic and effective treatment modalities should be
available for the disorder to prevent severe sequelae of
the disease.
2. The correct answer is C. Specialty total parenteral nutrition solutions for MMA provide all essential amino
acids except met, val, ile, and thr. As metabolic control
improves, standard total parenteral nutrition may need
to be added in limited quantities to prevent protein
deficiency.
3. The correct answer is B. Individuals with VLCADD
cannot metabolize long-chain fats effectively and
Intralipid is a long-chain fat source. Answer A is incorrect because MCTs provide a source of fat that can be
metabolized to meet caloric needs. Answer C is incorrect because carbohydrates provide an energy source
that can be utilized without fatty acid oxidation. Answer
D is incorrect because cornstarch is a slowly digested
carbohydrate source that can be effective to prevent low
glucose concentrations during fasting.
Chapter 23: Cardiac Disease

1. The correct answer is D. Surgical correction has
emerged as the most efficient method to improve
the nutrition status of these infants. Surgical correction eliminates the cardiac factors contributing to
malnutrition.
2. The correct answer is D. Considering the diversity
of the population and varying degrees of anomalies,
an infant with congenital heart disease may require
energy intakes of 140200 kcal/kg/d body weight to
induce growth.
3. The correct answer is D. The exact etiology for growth
impairment in children with congenital heart disease
remains unclear. Many factors have been identified as
contributing to growth failure in this population.
4. The correct answer is C. The use of a medium-chain
triglyceride enriched diet is based on the understanding
that enterocytes directly absorb MCT into circulation
allowing adequate calories while reducing lymphatic
flow to allow for healing. At least 3% to 4% of fat calories should come from LCT to prevent essential fatty
acid deficiency.
Chapter 24: Renal Disease

1. The correct answer is C. The use of CRRT provides
greater solute clearance and thus electrolytes typically
do not need to be limited and are often supplemented.
Therefore, use of a regular formula as opposed to a lowelectrolyte renal formula is appropriate. Additionally,
enteral products designed for renal patients often are
more concentrated, which can cause GI discomfort.
GI side effects are common in this population and use
of trans-pyloric feeding improves tolerance. Only if
continued tolerance problems or poor gut perfusion is
suspected should PN be considered.
2. The correct answer is D. Although dialysis losses may be
minimal, vitamin B6 intake is often inadequate, likely
due to restriction of high-protein foods to limit excess
intake of phosphorus and potassium. Recent studies
indicate that 25-hydroxyvitamin D may have a role,
in addition to well-known 1,25-(OH)2D, with bone
metabolism and prevention of hyperparathyroidism.
Supplementation to keep serum levels in the appropriate reference range is recommended. Folic acid,
although controversial in its role with homocysteine
reduction and cardiovascular implications, may have a
role with anemia management.
491
3. The correct answer is C. Cardiovascular disease is the

major cause of mortality in patients with CKD. Not
only do CKD patients typically have traditional risk
factors including hypertension, dyslipidemia, and left
ventricular hypertrophy they also have non-traditional
markers or uremic factors that can contribute to CVD
in adult patients. These factors include inflammation,
anemia, fluid overload, proteinuria, abnormal calcium
and phosphorus levels, dyslipidemia, and vascular
injury.
4. The correct answer is A. Recent studies indicate nPCR
is a superior marker of nutrition status in children on
maintenance hemodialysis. In these studies, serum
albumin was a poor indicator of nutrition status. An
nPCR of < 1 g/kg/d was a strong predictor of weight
loss in adolescent patients. However, increased risk of
mortality has been associated with hypoalbuminemia.
Therefore, serum albumin may be used as a nutrition
status marker, but with caution if hypoalbuminemic
factors are present.
Chapter 25: Gastrointestinal Disease

1. The correct answer is D. This patient has Crohns
disease. Diet therapy is effective in the treatment of
Crohns disease. There is no difference in effectiveness
of the polymeric vs elemental diets. A clear liquid diet
is inadequate.
2. The correct answer is A. Patients with inflammatory
bowel disease often have deficits of several nutrients.
This patient has disease of the ileum and is therefore at
greater risk of B12 malabsorption. The combination of
anemia and low MCV are suggestive of iron deficiency.
Both sulphasalazine and methotrexate interfere with
folate metabolism and therefore routine supplementation with folate is recommended. It should be mentioned
that patients with inflammatory bowel disease are also
at risk for bone disease and vitamin D and calcium may
also be considered.
3. The correct answer is C. Currently a strictly glutenfree diet is the sole recommended treatment for celiac
disease and it should be maintained lifelong. (AGA
Institute Medical Position Statement Diagnosis and
Management of Celiac Disease 2006; 131:1977-80).
There is ongoing research to discover alternative treatments including enzyme therapy and immune agents
but as yet none are recommended (Sollid LM, Khosla
C. Future therapeutic options for celiac disease. Nat
Clin Pract Gastroenterol Hepatol. 2005; 2:140145). It
492
should be emphasized that the gluten-free diet should

be continued even after all symptoms have abated.
Chapter 26: Hepatic Disease

1.
2.
3.
4.

The correct answer is E .
Chapter 27: Intestinal Failure

1. The correct answer is C. The small intestine doubles
in length during the last trimester. Therefore, the
remaining length of small bowel has a greater inherent
capacity to increase in length when the bowel resection
occurred earlier in the third trimester.
2. The correct answer is B. Features associated with enteral
autonomy include absence of cholestasis, an intact ilealcecal valve, bowel in continuity, shorter duration of PN,
residual intestinal length > 15 cm, and an intact colon.
Stool number, by itself, is not a predictor.
3. The correct answer is D. The cause of PN-related liver
disease is likely multi-factorial and not related to just
one issue.
4. The correct answer is D. Oral feedings not only enable
the infant to maintain oral feeding skills and decrease
the likelihood of developing oral aversion, but oral feedings will stimulate salivary secretion of hormones such
as epidermal growth factor which is important to the
intestinal adaptive process.
Chapter 28: Pulmonary Disorders

1. The correct answer is C. Acidity in the GI tract may
prevent or retard dissolution of enteric-coated pancreatic enzymes. If activation does not occur in the small
intestine, then it may be difficult for a person with CF
to absorb macro- and micronutrients.
2. The correct answer is B. Blood levels of fat-soluble vitamins should be measured to assure adequacy (vitamins
A, E, D). Prothrombin time is insensitive to vitamin K
deficiency in CF. PIVKA II provides a better indicator
of vitamin K nutrition.
3. The correct answer is A. All risk factors need to be
evaluated. Treatment includes optimizing nutrition,
increasing physical activity, controlling underlying
inflammation, decreased corticosteroid use, and
addressing hormone deficiencies.
4. The correct answer is B. Energy requirements are

increased and are in the range of 125 to 150 kcal/kg/d.
Vitamin A supplementation is important and is often
used in the intensive care unit to prevent BPD. Vitamin
E supplementation is not helpful. These patients also
have large insensible water losses and need extra fluid,
which results in opening of the patent ductus arteriosus
and further stress on the lungs. Fluid restriction often
results in inadequate nutrition intake. Calcium status is
poor due to decreased intake and increased losses due to
diuretics. Adequate intakes of calcium and phosphorus,
protein (33.5 g/kg/d), and antioxidants (copper, zinc,
and manganese) are required, and it is important to
avoid excessive carbohydrate intake because it can
impact pulmonary function.
Chapter 29: Organ Transplantation

1. The correct answer is C. Immunosuppressive therapy
after transplant can exacerbate or cause problems with
hyperglycemia, renal insufficiency, electrolyte and fluid
provision, and hyperlipidemia. Moreover, tacrolimus
has been shown to cause hyperkalemia and hypomagnesemia. All of these imbalances may necessitate a
change in nutrition therapy. Close nutrition monitoring
is essential.
2. The correct answer is D. The use of corticosteroids after
renal transplant can result in hyperglycemia, hyperlipidemia, and obesity. Biochemical testing should include
a lipid profile and glucose levels. A healthy diet including
unsaturated fats and exercise as tolerated should be
encouraged in an effort to prevent these complications.
3. The correct answer is B. Children with cystic fibrosis and
pancreatic insufficiency will continue to have pancreatic
disease after lung transplantation. Therefore, pancreatic
enzyme supplementation with meals and snacks will
need to continue. In general, a semi-elemental enteral
formula should be provided if kilocalorie requirements
cannot be met with oral intake alone. Parenteral nutrition may be needed if neither enteral nor oral intake is
sufficient.
Chapter 30: Oncology, Hematopoietic Transplant,

andSurvivorship
1. The correct answer is A. Methotrexate leads to the
development of mucositis which severely compromises
oral intake.
2. The correct answer is B. Weight gain, ascites, hyperbilirubinemia, hepatomegaly, and increased transaminases
are all symptoms of the development of SOS. Nutrition

management includes fluid and sodium restriction of
the diet, EN, or PN solution.
3. The correct answer is D. EN through the use of
feeding tubes is often discouraged among the pediatric
hematopoietic transplant population because of the need
for frequent tube replacement as a result of vomiting, the
risk of bleeding in the presence of thrombocytopenia
and pancytopenia with mucositis, dislodgement of the
feeding tube, the presence of delayed gastric emptying,
and malabsorption of nutrients.
4. The correct answer is D (increase or decrease the
absorption of other drugs).
5. The correct answer is D. All of the above can contribute
to osteoporosis in the cancer survivor.
Chapter 31: Trauma and Burns

1. The correct answer is C. Solid organ injuries are
common in the child due to the exposure of the liver
and spleen in the upper abdomen. Unless there is
hemodynamic instability, these rarely require operative intervention and can be managed with physical
limitations. Nutrition support generally consists of
resumption of an age-appropriate diet with caloric
supplementation, when caloric intake is inadequate.
2. The correct answer is D. While the extent of pancreatic trauma is quite variable, it is often accompanied
by chemical pancreatitis and ileus. When resection
occurs, it is usually over the neck of the pancreas and
leaves sufficient endocrine tissue for normal glucose
control, but may impact exocrine function as evidenced
by steatorrhea.
3. The correct answer is B. While the concept of immunonutrition is appealing in this population of patients,
randomized clinical studies have failed to show
benefit.
4. The correct answer is A. TBSA remains a predictor
of mortality. In children, age under 4 years, inhalation injury combined with a TBSA injury of > 30%
defines the highest mortality risk group. It is not clearly
proportional to the extent of the stress response, which
is mediated by multiple additional factors. Estimates of
energy needs based on TBSA are consistently inaccurate in their targets.
Chapter 32: Surgery

1. The correct answer is D. The initiation of enteral feedings is the most effective intervention to stimulate
493
hepatobiliary secretions and lead to resolution of

cholestasis. Excessive lipid and carbohydrate calories
are considered provocateurs of cholestasis. Cycling of
PN has been touted to reduce cholestasis.
2. The correct answer is D. Persistent bilious drainage from
the stomach implies distal obstruction. The exception to
this rule is congenital duodenal atresia due to congenital dilation and incompetence of the pyloric channel.
Despite evacuation of duodenal content in a prograde
manner there may be some retrograde flow into the
stomach. Contrast extravasation in esophageal atresia
should initially be managed with continued NPO to
allow the leak to seal without exogenous contamination
of the mediastinum. Passage of a transpyloric feeding
tube would require excessive manipulation. Abdominal distention with lack of stoma output is indicative of
ileus or intestinal obstruction.
3. The correct answer is A. Advancement of enteral feedings is safe when there is no evidence of diarrhea or
malabsorption. Reducing substances < 1/2% and fecal
pH > 7 are indicative of appropriate absorption. Mucoid
stools are a nonspecific finding that only becomes
concerning if they contain gross blood. Increased
frequency of bowel movements is a generic indicator for
feeding intolerance; however, consideration must also
be given to the quantity and nature of the stool. Small
smears should not be considered as bowel movements
whereas large-volume watery output is of concern.
4. The correct answer is A. The hallmark of gastroschisis
is that in the majority of patients there is intestinal
wall edema and serositis resulting in the inability to
determine whether there is continuity or an atresia
present. This is further compounded by the fact that
this intestine returns to normal morphology over a
variable period of time that ranges from 4 to 10 weeks.
The intestine in omphalocele is normal other than its
covered extra-abdominal location. In the absence of
other disorders, these infants tolerate enteral feedings promptly. Hirschsprungs disease patients have
impaired motility but once diagnosed either undergo
primary reconstruction or diverting colostomy and
therefore should have no extended dependence on total
parenteral nutrition. The intestine in congenital malrotation is functionally normal although there may be
some delayed gastric emptying associated with Ladds
bands. If midgut volvulus occurs the patient is at risk
for loss of the entire midgut intestine.
494
Chapter 33: Assessment of Nutrition Status by Age

andDetermining Nutrient Needs
1. The correct answer is D. Components of a detailed
nutrition assessment include anthropometric measurements with comparison to reference standards, a
detailed diet history, laboratory monitoring, and physical examination.
2. The correct answer is C. Rickets and vitamin D deficiency continue to be a concern in the United States and
other Western countries due to exclusively breastfed
infants and decreased sun exposure. As a result, on
October 13, 2008, the American Academy of Pedia
trics issued updated guidelines for vitamin D intake for
infants, children, and adolescents to prevent vitamin
D deficiency and the incidence of rickets. These new
recommendations report a daily intake of 400 International Units of vitamin D for all infants, children, and
adolescents starting from the first few days of life.
3. The correct answer is D. Depleted levels of Hgb and
Hct, along with spoon-shaped nails, may be an indication of iron deficiency anemia.
Chapter 34: Parenteral and Enteral Nutrition Support:

Determining the Best Way to Feed
1. The correct answer is E. All of the above are common
behavioral strategies to address picky eating. A divided
plate helps children to feel more in control, because
they dont want the non-preferred foods touching
the preferred foods. Offering a new food with preferred
foods encourages a child to try the new food, but keeps
the situation from being overwhelming. Family mealtimes are an opportunity for caregivers and siblings to
model healthy, positive mealtime behaviors.
2. The correct answer is A. A height at the 25th percentile
is within normal growth parameters. It is not normal for
a toddler to have no weight gain for an extended period
of time. A decrease of 2 weight channels and taking
longer than 4 hours to eat in a day are both considered
criteria for supplemental nutrition support in children.
3. The correct answer is D. Children with CF have
increased calorie needs. If they are unable to maintain
a good weight with oral intake alone, then the next step
is to provide nutrition supplements. Parenteral Nutrition is not indicated if the child is able to digest/absorb
food. Tube feedings may be needed in the future to
supplement oral intake, if the initiation of oral nutrition
supplements does not produce the desired results.
Chapter 35: Implementation of the Plan

1. The correct answer is B as the expected need for the
CVC is short term.
2. The correct answer is B as there is no waste and minimal
risk of contamination during the procedure.
3. The correct answer is Bbolus feed during the day
after being offered food and nighttime drip feedings.
Chapter 36: Evaluation and Monitoring of Pediatric

Patients Receiving Specialized Nutrition Support
1. False. There are many goals in addition to weight that
may be identified for a patient such as wound healing,
increased energy, improved protein stores, etc.
2. True. Decreasing the rate and extending the time of
infusion may improve the symptoms.
3. True, evaluating the GIR in addition to calorie content will
help determine if PN is contributing to hyperglycemia.
4. False. Higher concentrations of amino acids and dextrose
can improve calcium and phosphorus solubility.
5. False. Copper and manganese are excreted via the
biliary system and these levels should be monitored
periodically in patients with cholestasis receiving PN.
Chapter 37: Ethical Issues in the Provision of Nutrition

2. The correct answer is E.
Index
Page numbers followed by f or t indicate figures or tables, respectively.
A
Abdominal injuries, 381382
Absorption
of carbohydrates, 20
of fats, 26
of minerals, 4647
of proteins, 3334
of vitamins, 57
Academy of Breastfeeding Medicine,
121
Acanthosis nigricans, 154
Acute kidney injury (AKI)
classification
postrenal, 257
prerenal, 257
renal, 257
defined, 269
electrolyte and fluid restrictions,
270
neonatal issues, 271272
nutrition assessment, 270
Adolescents
acne treatment, 78
calcium requirements, 413
dietary habits, 412
protein requirements, 40
Adrenal glands, injury to, 381
Alagille syndrome, 304, 305
Allergy testing, 216

Aluminum
in antacids, 49
infant formula content, 273
toxicity, 268, 273
American Academy of Pediatric
Dentistry (AAPD), 414
American Academy of Pediatrics
(AAP)
breastfeeding policy, 120
dietary calcium needs, 413
hydration guidance, 181t
American College of Sports
Medicine
hydration guidance, 181t
American Dietetic Association
(ADA)
breast milk guidelines, 124
pediatric obesity, 170
American Institute for Cancer
Research Recommendations for
Cancer Prevention, 364
American Psychiatric Association,
205
Amino acid(s)
classification, 38t
conditionally essential, 35t, 3637
essential, 35t
in fetal development, 106
metabolism
role of kidney, 39
role of liver, 3839
and nitrogen balance, 35
non-essential, 35t
placental concentrations, 106
urea cycle, 3738
Amylase
in pancreatic trauma, 381
Anaphylaxis, 214t, 215216
Anemia, 413
in transplant recipients, 343
Animal models
fetal origins of disease, 110
glucocorticoid exposure, 114
iron-deficient diets, 113
nutrient-restricted diets, 112113
of dietary manipulation, 112113
uterine artery ligation, 114
Anorexia nervosa, 205
diagnostic criteria, 205f
diet-induced thermogenesis, 206
energy requirements, 206
in childhood, 205
liver disease and, 303
physical presentation, 205
zinc deficiency, 207
495
496
INDEX
Anthropometric measurements
body mass index-for-age, 146, 415,
415t
head circumference, 144t, 145, 415
length/height, 144145, 414415
parental stature, 415
using knee height, 415
using length board, 414
using standiometer, 414415
using tibial length, 415
mid-arm circumference, 415416
triceps skinfold, 415416
percentiles, 421t
upper arm circumference
percentiles, 420t
weight, 414
method for obtaining, 144, 414
Appetite
control, 4
cultural aspect, 3
development during infancy, 4
hypothalamus role, 4
nutrient intake and, 34
phases
cephalic, 4
gastric, 4
intestinal, 4
programming of, 113
Arachidonic acid (ARA)
in infant formulas, 135136
Arginine
hyperammonemia and, 37
Asthma, 333
B
Baby Friendly Hospital Initiative
(BFHI), 121
Ballard score, 409410, 410t
Bartters syndrome, 277
Bifidobacteria lactus, 137
Bifidobacterium bifidum, 120
Bile acid malabsorption, 316
Binge-eating disorder
Biotin
absorption, 6970
biochemistry, 69
deficiency state, 70
dietary reference intake, 58t
excretion, 6970
metabolism, 6970
physiology, 69
source, 69
supplementation, 70
Bloodstream infections, 317, 449,
470
Body mass index (BMI)
developmental delay and, 195
in growth assessment, 146
Body mass index-for-age, 415, 415t
Breast milk
adding infant formula to, 138
in chronic kidney disease, 273
cytomegalovirus in, 125
fortification, 122123, 122t
hang time, 124
hind milk, 122123
intestinal adaptation and, 313314
labeling, 124
maternal medications and, 125
preterm, 122, 122t
pumping, 122
safety, 124125
storage, 124, 124t
in tube feedings, 124
Breastfeeding
advocacy of, 120
appetite development
exposure to taste, 4
benefits of, 120121, 121t
dyad management, 121
effect on later obesity, 111
infant growth and, 123124
steps for successful, 121t
Bronchopulmonary dysplasia (BPD),
332333
Bulimia nervosa
physical presentation, 205206
Russells sign, 205
zinc deficiency, 207
Burn(s)
inhalation injury, 383
pediatric vs adult, 383
total body surface area, 383
Burn patient
hyperalbuminemia, 384
hyperglycemia in, 384
nutrition support, 384
pediatric, 383
postpyloric feeding, 384
resting energy expenditure, 384
C
Calcium
absorption, 4849
body content, 45, 48
deficiency, 47, 49
deposits in kidney, 276
excess intake, adverse effects, 50
excretion, 49
homeostasis, 49
medication interactions, 50
physiological functions, 48
requirements, 413
sources, 47t, 48
Campylobacter, 346t
Canadian Pediatric Society, 120
Cancer
Childrens Oncology Group
LongTerm Follow-Up
Guidelines for Survivors, 362
complementary and alternative
medicine, 354
disease outcome, 353
gastrointestinal supportive care
medications
acid-blockers, 368369
antiemetics, 369
antihistamines, 371
appetite stimulants, 371372
atypical antipsychotics, 371
cannabinoids, 371
glucocorticoids, 370
motility agents, 368
pheothiazines, 370
malnutrition in, 349350
mucositis medications, 372373
nutrition aspects
metabolic, 351
INDEX
physiological, 351
psychological, 351
nutrition assessment, 352353,
352t
nutrition intervention, 365f,
366t367t
overview, 349
survivors
gastrointestinal problems,
362363
heart health, 363364
osteoporosis, 363
treatment
complications, 354
tolerance, 353
chemotherapy, 350351
radiation therapy, 350, 350t
surgery, 350
Cancer cachexia, 351, 351t
Candida esophagitis, 315
Carbohydrate(s)
absorption, 20
as energy source, 17
classification, 17
complex, 17
digestion
lactose, 1719
starch, 19
malabsorption, 20
disorders, 20t
metabolism, 20
in sports nutrition, 179180, 180t
starches
oligosaccharides, 17
polysaccharides, 17
storage, 17
sugars
disaccharides, 17
monosaccharides, 17
Cardiovascular disease (CVD)
in chronic kidney disease, 268, 269
lipid management and, 268
in pediatric patients, 252254
risk factors, 162, 268
Celiac disease, 287289
at-risk groups, 288t
symptoms, 288t
Centers for Disease Control and

Prevention (CDC)
breast milk guidelines, 124
Epi-Info nutrition calculator, 146
food allergies statistics, 214
growth charts, 143, 411, 416,
423f430f
Central diabetes insipidus, 229
Cerebral palsy
abnormal energy expenditure, 193
inappropriate dietary intake and,
192
oral motor dysfunction, 192
Child abuse, 381
Cholestasis, 439
Cholesterol, 162, 253t
Cholestyramine, 315
Choline
absorption, 7071
biochemistry, 70
metabolism, 7071
physiology, 70
sources, 70
supplementation, 71
Chyle loss, 294
Chylothorax, 252
Chylous ascites, 341
Chyme, 12
Colon injury, 382
Complementary and alternative
medicine (CAM)
in cancer treatment, 354
drug interactions, 194
Congenital heart disease
acyanotic, 247, 247t
cyanotic, 247, 247t
Fontan procedure, 251
growth impairment, 248249,
248t
malnutrition, 248
nutrition management, 250
bolus tube feeds, 250
postsurgical complications
chylothorax, 252
feeding difficulties, 251
nutrition management, 251252
protein-losing enteropathy, 251
497
Congenital posterior urethral valves,

256
Constipation, 296
Continuous feedings, 454
Continuous renal replacement
therapy (CRRT)
caloric needs, 270
defined, 270
enteral nutrition and, 270
Copper, in Wilsons disease, 306
Cornstarch, 306
Cows milk
phosphorus content, 51
protein allergy, 222
Creatinine clearance, 257
Critically ill patient
hyperglycemia in, 227228
nutrition needs, 378379
Cyclic vomiting syndrome, 296
Cysteine
as parenteral nutrition additive,
442
intake requirements, 36
Cystic fibrosis
clinical features, 324t
diagnosis, 324t
eating behaviors in, 330331
fat-soluble vitamin requirements,
326, 327t
gastroesophageal reflux, 332
gastrointestinal complications, 332
lung transplantation, 332
nutrition-related complications
cystic fibrosis related diabetes,
331332
osteoporosis, 331
pancreatic insufficiency in, 324
pathophysiology, 323324
sodium chloride supplementation,
328
transplant complications
distal intestinal obstruction
syndrome, 345
zinc loss in, 328
Cystic fibrosis-related diabetes
(CFRD), 227, 229, 324, 331332
Cystine stones, 274
Cystinuria, 276
498
INDEX
D
D-lactic acidosis,
in intestinal failure, 316
Dental caries, 414
Dentition, 45
by age of eruption, 5t
Depression, 205
Developmental delay
abnormal energy expenditure, 193
clinical features, 193
determining dietary energy needs,
197t
inappropriate dietary intake, 192
micronutrient deficiencies,
193194
nutrient loss, 193
nutrition assessment
diagnostic studies, 196
growth and anthropometric
measurements, 195
growth history, 194
meal observation, 196
medical history, 194
medications, 194
physical examination, 195
review of systems, 194
social history, 194195
nutrition problems
growth failure, 192
osteopenia, 194
overweight, 192
pathophysiology of, 192
prevalence of, 192
undernutrition, 192
nutrition support
behavioral modification, 197
enteral tube feeding, 197198
feeding intolerance, 199
formula administration, 198
nutrition requirements,
196197
positioning and oral feeding,
197
oral motor dysfunction, 192193
z scores, 192, 193
Developmental origins of health and
disease (DOHaD), 112, 115
animal models, 112114
fetal salvage hypothesis, 112
future health implications, 115

premature infant, early
programming, 112
research needs, 116
thrifty phenotype hypothesis,
112
Diabetes mellitus
cystic fibrosis related, 227
glucose control
in healthy children, 228
on enteral nutrition, 229
on parenteral nutrition,
228229
type 1, 226227
type 2, 227
Diarrhea, 291292, 291t
Diet-induced thermogenesis (DIT),
206
Dietary manipulation
animal models
low-protein, 113
programmed hypertension, 113
severe food restriction, 113
Dietary reference intakes (DRIs)
during pregnancy, 108t
for minerals, 46t
in neurologically impaired
children, 197t
for vitamins, 58t, 75t
Diets, 169176
Atkins Diet, 172
Dean Ornish Diet, 173
Eat Right for Your Type, 174
for children
balanced macronutrient
lowkilocalorie, 174
Food Guide Pyramid, 175
multidisciplinary programs
Kidshape, 175
SHAPEDOWN, 175
Traffic Light Diet, 174175
French Women Dont Get Fat Diet,
171172
Pritikin Diet, 173
South Beach Diet, 172
Suzanne Somers Diet, 173
types
behavioral weight-loss plans,
171172
commercial meal/snack
replacements, 173174
food group guides/exchange
systems, 173
food timing/meals and snacks
combinations, 173
food-focused weight loss plans,
172
reduced macronutrient content
plans, 172173
WeightWatchers, 173174
Digestion
carbohydrates, 17
fats, 25
motor activity factors
caloric density, 13
consistency, 13
nutrient content,13
osmolarity, 13
physiology of, 12
proteins, 3233
small bowel motility, 12-13
Distal intestinal obstruction
syndrome, 324, 345
Docosahexaenoic acid (DHA),
135136
Drug-nutrient interactions, 466467
Duodenal hematoma, 381382
Duodenal injuries, 381382
Duodenal perforation, 381382
Dutch famine, 114115
Dyslipidemia, 268
Dysphagia, 8
E
Eating disorder(s)
anthropometric monitoring,
208209
classification of, 205
etiology, 206
laboratory tests for, 207t
meal-planning guidelines, 208
oral nutrition, 208
prevalence, 204
Eating disorder not otherwise
specified, 206f
Egg allergy, 233, 463
Electrolyte(s)
assessment, 90, 90t
INDEX
dosing guidelines, 440t

in parenteral nutrition, 440
in renal disease, 267
Energy
requirements
in acute kidney injury, 271
in anorexia nervosa, 206
in binge-eating disorder, 206
in burn patient, 383384
in cancer patient, 367t
in chronic kidney disease, 263,
277t
in congenital heart disease, 249
in cystic fibrosis, 325-326
in eating-disordered patient,
206
in hematopoietic stem cell
transplant patient, 356, 356t
in liver disease, 307
in premature infant, 410
Enteral nutrition
aspiration precautions, 457
bolus feedings, 454, 455
in bronchopulmonary dysplasia,
436
in cancer patients, 353354
in congenital heart disease, 250,
436
combination feedings, 454, 455
continuous feedings, 454, 455
in continuous renal replacement
therapy, 270
in critically ill patients, 435
in cystic fibrosis, 436
in developmental delay, 197198
in diabetes mellitus
choice of formula, 229
insulin administration, 229
evaluation and monitoring
anthropometric measurements,
462t
formula tolerance, 461
laboratory values, 462, 462t
oral feeding, 462
parameters, 462t
revision of plan, 463
feeding advancement, 454455
feeding pumps, 455456
feeding tolerance assessment, 457

in food allergies, 223
for eating-disordered patients
bolus feedings, 208
formula type, 208
manipulative behaviors, 208
route of feeding, 208
formula
hang time, 455
preparation, 455
transplant recipients, 358
indications for, 436t
intake and output, 457
in intestinal failure/short bowel
syndrome, 313314
in renal disease, 435
medication administration,
457458
nursing care, 456
reflux, 456457
residuals, 456
route of administration, 435436
route selection, 451452
safety issues, 455456
site care, 456
transplant recipients
intestine, 340341
kidney, 342343
liver, 341
lung, 344
tube flushing, 456
tube placement, 453
verification methods, 453454
tube securement, 456
tube weaning, 458, 458t
types of tubes
gastrojejunostomy, 453
gastrostomy, 453
jejunostomy, 453
nasogastric tube, 452453
orogastric, 453
when to use, 433434
Enterobacter sakazakaii, 123, 124,
137
Eosinophilic esophagitis, 222223
Eosinophilic gastroenteritis,
296-297, 297t
499
Epi-Info nutrition calculator, 146

Escherichia coli, 346t
Essential fatty acid deficiency
(EFDA)
infant formulas and, 135
Ethics
case studies, 483484
childhood obesity, 483
clinical care as team approach, 485
in feeding disorders, 483
in intensive care environment, 481
models
educators, 479
good shepherds, 478479
liberators, 479
natural vs. medical nutrition
provision, 479
nutrition goals determination,
479480
overview, 477
palliative care, 482
special needs, infants and toddlers,
482
truth-telling, 478
values ascribed to feeding,
480481
Extrauterine growth retardation, 116
F
Failure to thrive, 145, 286
Familial hypercholesterolemia (FH),
163
Fat(s)
absorption, 26
adipose tissue, 24
classification, 23f
digestion, 25
in eating disorders, 207
fuel for preterm infant, 27
functions, 24f
in sports nutrition, 181
trans, 23
triglycerides, 22
Fatty acid(s)
essential, 2324
500
INDEX
long chain, 23
medium chain, 23
monounsaturated, 2223
oxidation, 2627
polyunsaturated, 23
Vitamin E intake, 23
saturated, 22, 23f
short chain, 23
synthesis, 26
Feeding difficulties
aspiration, 193
nutrient losses, 193
solid foods, 4
Feeding disorders
ethical considerations, 483
etiology of, 443
evaluation and treatment,
443444
nutrition intervention, 445t
posttransplant
liver, 342
treating, 443t
Feeding teams, 89, 442443, 444,
444f
Female Athlete Triad, 185t
Fenton fetal-infant growth chart,
422f
Fetal development
epigenetic changes, 107
glucose supply, 106
growth,
effect of calcium, 108
effect of iron, 108
effect of protein, 107108
effect of vitamin E, 108109
folic acid and, 108
vitamin B12, 108
hypothalamic-pituitary-adrenal
(HPA) axis, 107, 109110
insulin-responsive tissues, 106
intrauterine insults, 107
liver, 106
macronutrients in
amino acids, 106
glucose, 106
maternal nutrition and
calcium, 108
folic acid, 108
iron, 108
macronutrients, 107108
vitamin B12, 108
vitamin E, 108109
metabolic mediators
cortisol, 106
insulin, 106
insulin-like growth factors, 106
prenatal stress, impact of, 109110
substrate metabolism, 106
Fetal origins of adult disease,
110111
Fluid(s)
body distribution, 8788, 88t
deficit calculation, 89
imbalance, 90
maintenance, 412, 412t
regulation, 8889
requirements
transplantation patient, 357
Holliday-Segar Formula, 89t
syndrome, 314
in kidney transplant, 269,
pediatric, 8990
Fluoride
drinking water levels, 414t
requirements, in adolescents, 414
supplementation, 414, 414t
topical, 414
Folate, 6566
absorption, 6566
biochemistry, 65
excretion, 6566
metabolism, 6566
physiology, 65
source, 65
supplementation, 66
Folic acid, 108, 264
Food Allergen and Consumer
Protection Act (FALCPA), 221
Food allergens
alternative substitutes, 219t
cross-contamination, 221
hidden, 221, 222t
mandatory food labeling, 221

Food allergies, 213224
algorithm for evaluation of, 217f
anaphylaxis, 214t, 215216
and other allergic conditions, 215
Centers for Disease Control and
Prevention statistics, 214
clinical assessment, 218
clinical presentation, 215216
common definitions, 214t
cows milk protein allergy, 222
definitions, 213214, 214t
eosinophilic esophagitis, 222223
epidemiology, 214215
food protein-induced enterocolitis
syndrome, 216
immunoglobulin E mechanisms,
213214
laboratory assessment, 218
major allergens, 215
management, 216217
micronutrient supplementation,
221222
milk substitutes, 221
National Health and Nutrition
Examination Survey results,
215
nutrition intervention, 220
nutrition risk, 218t
oral allergy syndrome, 214t, 215
pediatric formulas, 220t
radioallergosorbent test, 216
resources, 220t
skin prick testing, 216
toddler diets, case scenarios, 219t
tolerance, 213
Food and Drug Administration
(FDA)
aluminum content labeling, 442
breast milk safety, 124
regulation of dietary supplements,
46
Food protein-induced enterocolitis
syndrome (FPIES), 216
Food safety, 345
Foodborne pathogens, 346t
INDEX
G
Galactosemia
etiology, 241242
management
acute, 242
chronic, 242
diet, 242t
Gastroesophageal reflux (GER), 286,
332, 390
Gastrointestinal disease
disordered ingestion, 283-284
failure of absorption, 284
failure of digestion, 284
functional disorders, 295-296
increased needs, 284
nutrition assessment, 284-285,
285t
Gastrojejunostomy tube(s), 198, 404,
453
Gastroparesis, 295-296, 295t
Gastrostomy (G) tube
button device, 198t
in esophageal atresia, 393
insertion, 404, 453
PERT supplements, 330
safety issues, 450
Glucocorticoids
effect on fetus, 109110
as preterm delivery treatment, 109
Glucose
as fetal energy source, 106
in trauma response, 378379
Glycogen storage diseases (GSDs),
306
Graft versus host disease, 360361,
361t
Growth
average daily intrauterine weight
gain, 411t
breastfed infants, 123124
chronic kidney disease and,
259260
overview, 143144
of premature infant, 410
Growth assessment
body mass index, 146
failure to thrive (FTT), 145
head circumference, 144t, 145
height (length/stature), 144145,

144t
ideal body weight, 146
percentiles
z score comparisons, 146t
time intervals, 144t
weight, 144, 144t
weight-for-length percentiles, 145
Growth charts
Fenton fetal-infant, 422f
interpreting, 146147
limitations, 147
Lubchenco, 410
National Center for Health
Statistics, Centers for Disease
Control and Prevention, 143,
411, 416, 423f430f
World Health Organization,
143144
Growth hormone (GH) therapy,
260f
Growth velocity, 411t
H
Healthy People 2010, 120
Heart transplantation
biochemical tests, 339t
recipient
dietary modificiation, 344
nutrition requirements, 344
Hematopoietic stem cell
transplantation (HSCT), 354362
complications
bacterial overgrowth, 361
graft versus host disease,
360361, 361t
hemorrhagic cystitis, 362
infections, 361
mucositis, 360, 372373
pancreatic insufficiency, 361
sinusoidal obstruction
syndrome, 362
diet restrictions, 357358
medication side effects, 359t
nutrition support, 358-360
enteral nutrition, 358
oral, 357
procedure, 355
501
recipient
anthropometric assessment,
356
caloric requirements, 356, 356t
fluid requirements, 357
mineral requirements, 357
nutrition evaluation, 355356
protein requirements, 356, 356t
vitamin requirements, 357
Hemodialysis (HD)
in chronic kidney disease,
258259
in hypercalcemia, 97
for hypermagnesemia, 96
phosphorus clearance, 267
Holliday-Segar Formula, 49t
Honey, 139
Human milk, 120124
banked, 123
calcium content, 48
fortification, 122123, 122t
hind milk, 122123
iron content, 123
vitamin D content, 123
Human Milk Banking Association of
North America, 124
Hydration
guidance, 181t
Hydrochloric acid, 32
Hyperalbuminemia
in burn patients, 384
Hyperammonemia
treatment of, 37
Hypercalcemia, 50
Hypercalciuria
kidney stones and, 275
Hypergastinemia, 316
Hyperglycemia
in critically ill patient, 227228
in refeeding syndrome, 209
in organ transplant recipient, 269,
341, 343, 344, 345
in trauma patient, 380
Hyperhomocysteinemia, 264
Hyperkalemia, 341
502
INDEX
Hyperlipidemia, 341, 343

Hypermagnesemia
manifestations, 53
neonatal, 53
Hypermetabolism
in cirrhotic patients, 304305
Hypernatremia
in nephrogenic diabetes insipidus,
277
Hyperphosphatemia, 52
Hypertension
in transplant recipients, 341, 343,
344
Hypervolemia, 89
Hypocalcemia, 49
Hypoglycemia
in young children, 228
Hypokalemia
in refeeding syndrome, 209, 210
Hypomagnesemia
definition, 53
etiology, 53
in refeeding syndrome, 209, 210
in transplant recipients, 341
manifestations
adults, 53
infants, 53
Hypophosphatemia
etiology, 51
in refeeding syndrome, 209
manifestations, 51
Hypothalamic-pituitary-adrenal
(HPA) axis, 107
prenatal programming, 109-110,
110f
Hypothalamus, 4
Hypovolemia, 89
I
Immunoglobulin E (IgE)
mediated allergic diseases,
215216
reaction, 214
Immunosuppressive medications,
344, 345
kidney damage from, 269
side effects, 269
Immunosuppressive therapy
noncompliance with, 346
Inborn errors of metabolism (IEM),
232-242
defined, 232
newborn screening, 233
nutrition management, 233f
symptoms, 233t
Indirect calorimetry, 197t
Infant formula
as breast milk additive, 138
calcium salts, 48
concentrating, 250t
contamination, 124, 137
design of, 129130
forms
liquid concentrate, 137
powder, 137138
ready-to-feed, 137
functional ingredients
arachidonic acid (ARA),
135136
docosahexaenoic acid (DHA),
135136
nucleotides, 136
prebiotics, 136
probiotics, 136137
lactose in, 17
magnesium requirements, 52
manufacturers Web sites, 130t
medium-chain triglyceride, 252t
mixing
increasing caloric
concentration, 138, 138t
modular macronutrients, 138
standard dilution, 138
water, 138
Portagen, 124
regulation, 130
specialized
amino acid based, 134135,
136t, 220, 220t
carbohydrate free, 135, 136t
extensively hydrolyzed protein,

134, 135t
reduced fat/modified fat, 135,
137t
reduced mineral, 135, 137t
types
for symptoms of intolerance,
130, 132t
added rice starch, 132133,
132t
lactose-free, 132, 132t, 220,
220t
partially hydrolyzed
protein,130-131, 132t,
220, 220t
premature discharge, 134, 135t
premature or low birth weight,
133, 134t
soy-based,133, 133t, 220, 220t
standard milk-based, 130, 131t
whey-based, for chronic kidney
disease, 273
Infant(s)
appetite development, 4
complementary foods, 139
feeding problems, 67
feeding skills, 56
hypomagnesemia, 53
iron deficiency, 123
neonatal cholestasis, 305
neophobia, 4
premature
birth weight classification, 410t
calcium requirements, 413
delayed gastric emptying, 13
magnesium overdose, 53
necrotizing enterocolitis, 18
Inflammatory bowel disease,
289291
Inhalation injury, 383
Insensible water loss, 90, 332
Insulin
in enteral nutrition, 229
Intestinal adaptation
role of ileal-cecal valve, 313
surgical procedures
Bianchi procedure, 313
INDEX
longitudinal intestinal
lengthening and tailoring
(LILT), 315
Serial Transverse Enteroplasty
(STEP), 313, 315
Intestinal failure (IF)
causes, 312t
complications
bacterial overgrowth, 316
bile acid malabsorption, 316
D-lactic acidosis, 316
hypergastinemia, 316
nephrolithiasis, 316
rapid intestinal transit, 316
definition, 312
etiology of, 313
management
enteral nutrition, 313314
fluids, 314
general principles, 315316
medications, 314315
parenteral nutrition, 314
nutrition deficiencies, 316
prevalence of, 312
Intestine transplantation, 318, 339t,
340, 341
Intrauterine growth restriction
(IUGR), 106, 410
maternal dietary deficiencies, 107
placental transport insufficiency
and, 106
placental weight, 106
Intravenous fat emulsion (IVFE),
437, 439, 439t
Irritable bowel syndrome, 296
Iron
human milk fortifier, 123
deficiency, 113, 413
fetal growth and, 108
lactoferrin and, 123
requirements
adolescents, 413
premature infants, 413
Iron deficiency anemia, 413
J
Jejunostomy tube, 453
K
Kidney(s)
amino acid metabolism, 39
functions, 257
injury, 381
nephrogenesis, 257
phosphorus homeostatis and, 51
transplantation
biochemical tests
339t
calcium intake, 269
cardiovascular disease and, 269
complications, 343344
fluid intake, 269
recipient
342343, 343t
trauma to, 381
Kidney disease. See also Acute
kidney injury
chronic
effect on growth, 259260
incidence, 256
primary diagnosis, 258t
stages of, 257t, 258
nephrotic syndrome, 274
stages, 257t, 258
Kidney stones. See Renal stones
L
Lactase, 17, 18, 18f
Lacto engineering, 122
Lactobacillus, 120
Lactobacillus GG, 137
Lactoferrin, 123
Lactose, 1719
Lanthanum carbonate, 267
Length board, 414
Leptin
appetite control, 4
food intake and adiposity, 113
liver disease and, 303
Leucine, 35
Lipase
gastric, 25, 32
in pancreatic trauma, 381
503
Lipid disorders, 162167

fasting lipid profile interpretation,
164t
genetic
familial hypercholesterolemia,
163
lipoprotein lipase deficiency,
163
nutrition management
antioxidants, 166
dietary cholesterol, 164, 166t
fiber, 165
garlic, 166
monounsaturated fats, 165
omega-3 fatty acids, 166, 166t
plant sterols/stanols, 165166
polyunsaturated fats, 165
saturated fats, 164165, 166t
simple carbohydrates, 165, 166t
soy protein, 166
trans fats, 165, 166t
pharmacologic intervention, 167
physical activity, 166, 166t
polygenic
hypercholesterolemia
(nonfamilial), 163
screening for, 163t
Lipoprotein lipase (LPL) deficiency,
163
Listeria monocytogenes, 346t
Liver
amino acid metabolism, 3839
functions, 302
injuries to, 380381
transplantation
recipient
feeding disorders, 342
growth and development,
342
nutrition requirements, 341
parenteral nutrition, 341,
342t
Liver disease, 302309
anorexia in, 303
fat-soluble vitamin
supplementation, 307308,
308t
504
INDEX
fluid requirements, 308

glycogen storage diseases, 306
malnutrition in
hypermetabolism, 304305
iatrogenic factors, 303304
inadequate dietary intake, 303
malabsorption, 304
non-cholestatic, 305306
nonalcoholic fatty liver disease
(NAFLD), 306
parenteral nutrition and, 308, 317
salt depletion syndrome, 303
Wilsons disease, 306
Lung disease
asthma, 333
bone health and, 334
bronchopulmonary dysplasia,
332333
nutrition recommendations, 334
technology dependent, 333
Lung transplantation
complications, 344345
in cystic fibrosis, 332, 344
M
Magnesium
absorption, 52
deficiency, 53
excess intake, adverse effects, 53
excretion, 52
in infant formulas, 52
metabolism, 5253
physiological function of, 52
renal transport, 52
sources, 52
tissue distribution, 52
Malnutrition
Waterlow criteria, 411, 411t
classification, 145t
Malnutrition, inflammation, and

atherosclerosis syndrome (MIA),
268
Mastication, 45
Meconium ileus, 324
Medium-chain triglyceride(s)
(MCTs)
in chylothorax management, 252
in enteral nutrition, for liver
disease, 308
formulas, 252t
Metabolic bone disease, 263, 470
Metabolic disorders, 149158, 467t
Metabolic syndrome
Acanthosis nigricans, 154
cluster
pediatric population and, 153
in adults, 150151
controversies
cut-points, 151
etiology, 151
risk and treatment, 151
diagnostic criteria, 150t
etiology, 150t
in children, 151153
controversies
cut-points, 152
non-traditional
cardiovascular risk
factors, 152153
puberty, 152
Northern Manhattan Family
Study, 154
overview, 149150
risk factor profile, 153155
Methylmalonic acidemia
etiology, 237, 238f
management
acute, 238
chronic, 238239
Migrating motor complex (MMC),
12
Milk substitutes, 221
nutrition comparison with whole
milk, 221t
Mineral(s), 4555
absorption
intestinal, 46
renal, 46
deficiency states, 4748

dietary requirements, 46
metabolism, 47
serum concentrations, 45
sources, 46
supplements, 46
Minimal change disease, 274
Motility
delayed gastric emptying, 1314
dumping, 14
gastric, 12
intake and motor activity
caloric density, 13
consistency, 13
nutrient content, 13
osmolarity, 13
rapid intestinal transit, 14
slow intestinal transit, 14
small bowel, 1213
in trauma patients, 379
Mucositis, 360, 372373
Munchausen Syndrome by Proxy,
450
Myelomeningocele, 192, 193, 333
N
Nasogastric tube, 329, 452453
Nasojejunal tube, 453
National Cholesterol Education
Program, Adult Treatment Panel
III (NCEP-ATP III)
metabolic syndrome, 150t
recommendations, 155156,
157
risk factor profile, 153155
National Health and Nutrition
Examination Survey
food allergies, 215
National Kidney Foundation, 258
National Kidney Foundation Kidney
Disease Outcomes Quality
Initiative (NKF KDOQI), 257,
266
Necrotizing enterocolitis (NEC)
breast milk and, 121
in premature infants, 18
Neonatal hypermagnesemia, 53
Neonatal cholestasis, 305
INDEX
Neonatal iron storage disease, 305

Nephrocalcinosis, 276, 278
Nephrogenesis, 257
Nephrogenic diabetes insipidus
(NDI), 277278
Nephrolithiasis, 276, 316
defined, 274
risk factors, 274
Nephrotic syndrome, 274
Neural tube defects, 108
Niacin, 6364
absorption, 6364
biochemistry, 63
excretion, 6364
metabolism, 6364
physiology, 63
source, 63
supplementation, 64
Non-cholestatic liver disease,
305306
Non-insulin-dependent diabetes
mellitus, 110111
Nonalcoholic fatty liver disease
(NAFLD), 306
Normalized protein catabolic rate
(nCPR), 258259
Norovirus, 346t
North American Pediatric Renal
Trials and Collaborative Studies
(NAPRTCS), 257
Northern Manhattan Family Study,
154
Nutrition assessment
of adolescents, 412414
biochemical indices, 416417
of children, 411t , 411412
in cancer patients, 352353, 352t
in cystic fibrosis, 325, 325t
in chronic lung disease, 333
in congenital heart disease,
249250, 249t
of full-term infants, 411t, 411412
in gastrointestinal disease,
284285, 285t
in liver disease, 307, 413414
of premature infants
Ballard score, 409410, 410t
classification parameters,
409410
Lubchenco growth chart, 410
physical examination, 417, 417t
pretransplant, 339340
Waterlow criteria
stunting, 411, 411t
wasting, 411, 411t
Nutrition intervention
in cancer patients, 352, 353t
feeding disorders, 445t
Nutrition support
closed head injuries, 380
for cystic fibrosis, 329330
developmental delay, 196199
during trauma, 379
for eating disorders, 208
pancreatic trauma, 381
traumatic brain injury, 380
O
Obesity
breastfeeding, 111
cardiovascular disease, 252254,
268
childhood, 169170
clinical approach, 170
ethical considerations, 483
postnatal weight gain and, 111
in trauma patients, 379, 384385
Oral allergy syndrome, 214t, 215
Oral motor dysfunction, 192193
Organ transplantation
biochemical tests pretransplant,
339t
complications, 343, 346
foodborne illnesses, 345
immunosuppressive therapy, 344,
346
indications for, 338339, 338t
physical examination, 339
quality of life, posttransplant, 346
recipient
anthropometric assessment,
338
dietary modification, 344
505

340341, 342343, 344
survival rates, 346
Ornithine transcarbamylase
deficiency
etiology, 239
management
acute, 239
chronic, 240
urea cycle, 239f
Orogastric tube, 453
Osteopenia, 46, 194, 442
Osteoporosis
and cystic fibrosis, 331
in pediatric cancer patients, 363
in transplant recipients, 344, 345
P
Pancreas
fetal, 106
injury to, 381, 385
Pancreatic enzyme replacement
therapy (PERT), 330
posttransplant, 344
Pancreatic insufficiency, 292293,
292t
Pancreatic pseudocyst, 381
Pancreatitis, 293294
Panhypopituitarism, 230
Pantothenic acid
absorption, 69
biochemistry, 69
excretion, 69
metabolism, 69
physiology, 69
source, 69
supplementation, 69
Parenteral nutrition
access, 437
additives
carnitine, 441442
cysteine, 442
cysteine hydrochloride salt, 36
heparin, 441
aluminum in, 442
amino acid solutions, 37
506
INDEX
in anorexia nervosa, 437

in cancer, 354
central parenteral nutrition, 433
central venous lines, 437
cholestasis, 389390, 439
complications, 442
metabolic bone disease, 470
in congenital heart disease,
250251, 437
in diabetes mellitus, 228
choice of dextrose solution, 228
insulin infusion, 228229
in eating-disorders, 208
egg allergy, 233
electrolyte dosing guidelines, 440t
evaluation and monitoring
blood urea nitrogen level, 463
calcium solubility, 465t
calcium-phosphorus
precipitation, 465, 465t
form, 472f
formulation integrity, 464465
infusion-related incidents, 463
macronutrient tolerance,
463464
parameters, 464t
phosphorus solubility, 465t
total nutrient admixtures,
464465, 465t, 466t
volume tolerance, 463
for food allergic patient, 223224
gastrointestinal conditions, 436
transplant, 358
indicators for, 437
initiation and advancement of,
440t
syndrome, 314
intradialytic, 274
intravenous catheters
central venous catheter, 449
peripherally inserted central
catheter, 449
intravenous fat emulsion, 437, 439,
439t
laboratory tracking sheet, 473f
limits, 471t
macronutrients
amino acids, 437439, 438t
carbohydrates, 437
magnesium overdose, 53
medications
compatability of, 467
drug-nutrient interactions,
466467, 467t
nursing care, 451, 452t
peripheral, 433, 449
in premature infants, 410,
436437
safety issues
bloodstream infections, 317,
450, 470
prevention of, 451t
Munchausen Syndrome by Proxy,
450
site care, 450
chlorhexidine gluconate, 450
Guidelines for the Prevention
of Intravascular
Cather Infections
recommendations, 450
total nutrient admixtures
advantages and disadvantages,
466t
factors affecting stability, 465t
in trauma, 379
trace elements
chromium, 441, 441t
copper, 440, 441t
manganese, 441, 441t
selenium, 441, 441t
zinc, 440, 441t
in transplantation
intestine, 340341
liver, 341, 342t
vitamins, 441t
when to use, 433434
Pelvic injury, 382
Pepsinogen, 3233
Peptide, 32, 32t
Peripheral blood stem cell
transplantation (PBSCT).
See Hematopoietic stem cell
transplantation (HSCT)
Peripheral parenteral nutrition

(PPN), 433, 437, 449
Peripherally inserted central catheter
(PICC), 449
Peristalsis, 12
Peritoneal dialysis (PD), 259
Phenylalanine, 35
Phenylketonuria (PKU)
etiology, 234, 234f
low-phe formula calculation, 235f
management
acute, 234235
chronic, 235
maternal, 234
meal plan for, 236t
recommended nutrient intakes,
235t
supplementation
cofactors, 237
large neutral amino acids, 237
tyrosine requirement in, 37
Phosphorus
absorption, 51
binding medications, 51
biochemistry, 50
deficiency, 51
effect on calcium, 49
excess intake, adverse effects,
5152
excretion, 51
glomerular filtration rate and, 51
human milk content, 51
intake from soft drinks, 50
kidney as regulator as, 51
management, in chronic kidney
disease, 266267
physiological function of, 50
serum concentration, 50
sources, 5051
tissue distribution, 50
Phosphorus binders, 267
Placental transport insufficiency, 106
Prebiotics 136
Pregnancy
dietary reference intakes, 108t
epigenetic changes, 107
intergenerational effects, 114115
INDEX
intrauterine growth restriction,

106
intrauterine insults, 107
maternal nutrition effect on fetus,
107109
nutrition physiology, 105107
recommended daily nutrient
intakes, 108t
Primary hyperoxaluria, 278
Probiotics, 136137
Protein catabolic rate (PCR), 258
Protein(s)
absorption, 3334
digestion, 3233
effect on fetal growth, 107108
ontogeny and gastrointestinal
tract, 3132
requirements
in acute kidney injury, 271
in chronic kidney disease, 263,
277t
in continuous renal replacement
therapy, 270
transplant patient, 356, 356t
in sports nutrition, 180181,
180t
in transplant recipients, 340,
344
Protein-losing enteropathy (PLE),
251
Pulmonary disorders, 323334
Purine, in uric acid stones, 276
R
Refeeding syndrome
definition, 209
hyperglycemia, 209
hypokalemia, 209, 210
hypomagnesemia, 209, 210
hypophosphatemia, 209
incidence of, 209
preventing, 210211, 210t
treatment, 210211, 210t
Renal failure
creatinine clearance, 257
nutrition management, 277t
oxalosis, 278
Renal stones
2,8-dihydroxyadenine calculi, 276
calcium-based, 275276
cystine stones, 274
cystinuria, 276
infection stones, 276
nutrition management, 275t
in pediatric patients, 275
struvite calculi, 274, 276
uric acid, 274, 276
xanthine stones, 276
Renal tubular acidosis, 276277
Renal tubular disorders
Bartters syndrome, 277
nephrogenic diabetes insipidus,
277278
renal tubular acidosis, 276277
Resting energy expenditure (REE)
in developmentally delayed child,
193
in trauma patients, 379
equation, 412, 412t
Rett syndrome, 192, 193
Riboflavin, 6263
absorption, 6263
biochemistry, 62
excretion, 6263
metabolism, 6263
physiology, 62
source, 62
supplementation, 63
Rickets, 46, 413
S
Salmonella, 346t
Seatbelt injury, 381, 382
Serial transverse enteroplasty
(STEP), 313, 315
Serum albumin, 262
Sevelamer carbonate, 267
507
Short bowel syndrome (SBS), 312

Shwachman-Diamond syndrome,
304
Sinusoidal obstruction syndrome
(SOS), 359
Sirolimus, 269, 343
Skeleton
as mineral reservoir, 4546
growth, 46
injuries to, 382
Skin prick testing, 216
Small intestine
injuries, 382
motility, 1213
Sodium
absorption, 91
balance, 91
deficiency, in cholestatic liver
disease, 303
losses, 91, 182
management, in chronic kidney
disease, 265
physiological effects, 91
serum level
normal, 91
Spastic hemiplegia, 192
Spastic quadriplegia, 192
Specialized nutrition support (SNS)
chemistry profiles, 468
evaluation and monitoring of,
460473
laboratory values, 467, 471t, 473f
liver function tests, 468
nutrition-related laboratory tests,
468
physical data, 462t, 467468
reassessment of plan, 466, 466f
Spinal cord trauma, 380
Spleen injury, 380
Sports nutrition
at bedtime, 183
carbohydrates, 179180
practical application, 180, 180t
challenges, 183, 185t
fat, 180t, 181
practical application, 180t, 181
Female Athlete Triad, 185t
fueling for competition, 184t
hydration, 181182, 181t
508
INDEX
practical application, 182

hyponatremia, 182
minerals, 182
overview, 178179
protein, 180181
practical application, 180t, 181
recovery nutrition, 183
resources, 183, 186t
timing to sport, 182183, 184t
vitamins, 182
Standiometer, 414415
Starvation pathophysiology, 209
Stomach
and food intake, 12
injury to, 381
motility, 12
Stool, monitoring, 461, 462t
Stunting, 411, 411t
Surgery
airway disorders, 400401
anorectal malformations, 397
biliary atresia, 399400
choledochal cyst, 400
colon atresia, 396
congenital diaphragmatic hernia,
399
congenital heart disease, 251252
distal intestinal obstruction,
395396
duodenal atresia, 394395
esophageal atresia, 393394
gastroschisis, 397399
Hirschsprungs disease, 396397
intestinal malrotation, 402
intestinal perforation, 402
meconium ileus, 396
midgut volvulus, 402
necrotizing enterocolitis, 401402
neonatal, 388389
neurosurgical disorders, 400
nutrient considerations, 387388
omphalocele, 397
orthopedic disorders, 400
proximal intestinal obstruction,
393
pyloric stenosis, 402403
thoracic disorders, 400
urologic disorders, 400
Swallowing
esophageal phase, 5
oral phase, 5
pharyngeal phase, 5
Syndrome of inappropriate
antidiuretic hormone (SIADH),
89, 380
T
Tacrolimus, 53, 269, 341, 345
magnesium deficiency and, 53
Thiamin, 6162
absorption, 61
biochemistry, 61
excretion, 61
metabolism, 61
physiology, 61
source, 61
supplementation, 62
toxicity, 78
Thoracic injuries, 382
Toddler(s)
feeding problems, 78
feeding skills, 7
formula, 139, 140t
Total body water (TBW), 87, 88t
Total nutrient admixtures (TNAs),
464465, 465t, 466t
Trans-fatty acids, 23
Transsulfuration pathway, 36
Trauma
adrenal hemorrhage, 381
age-related injuries, 379
anatomical classification, 379
blunt abdominal, 380381
hollow visceral injuries,
381382
solid visceral injuries, 380381
brain injury, 380
child abuse, 381
childhood, 379
clinical examples, 384385
closed head injuries, 380
duodenal injuries, 381382
extremity injury, 382
facial, 382
hyperglycemia and, 380
metabolic response, 378379

obesity and, 384385
pancreatic, 381
pelvic injury, 382
physiological response, 378379
renal, 381
small intestine and colon injuries,
382
spinal cord injury, 380
syndrome of inappropriate
antidiuretic hormone (SIADH)
in, 380
thoracic injuries, 382
traumatic brain injury, 380
Traumatic brain injury, 380
Triglyceride(s)
defined, 22
Tube feeding. See Enteral nutrition
Tumor necrosis factor (TNF)
Type IIa Na/phosphate
cotransporter (Npt2a) protein, 51
Tyrosine
intake requirements, 37
N-acetyl-tyrosine (NAT), 37
phenylketonuria and, 37
U
U.S. Department of Agriculture,
Food Safety and Inspection
Service, 345
Umbilical cord blood transplantation
(UCBT). See Hematopoietic stem
cell transplantation (HSCT)
United Nations International
Childrens Fund (UNICEF), 121
Baby Friendly Hospital Initiative,
121
Urea cycle, 38f, 239f
Uric acid stones, 274, 276
Urinary extravasation, 381
V
Vascular access device (VAD), 449
blood sample techniques, 450t
Very long chain acyl-CoA
dehydrogenase deficiency
(VLCADD)
etiology, 240
INDEX
fatty acid oxidation and, 240f

management
acute, 240
chronic, 241
Video feeding study, 340
Vitamin(s)
allergen-free, 222, 222t
fat-soluble, 7486
water soluble, 5671
Vitamin A
absorption, 7677
biochemistry, 76
deficiency, 7778
metabolism, 7677
physiology, 76
sources, 76
toxicity, 78
Vitamin B1. See Thiamin
Vitamin B2 . See Riboflavin
Vitamin B3. See Niacin
Vitamin B5. See Pantothenic acid
Vitamin B6
absorption, 6465
biochemistry, 64
excretion, 6465
metabolism, 6465
physiology, 64
source, 64
supplementation, 65
Vitamin B7. See Biotin
Vitamin B9. See Folate
Vitamin B12
absorption, 6667
biochemistry, 66
excretion, 6667
metabolism, 6667
physiology, 66
source, 66
supplementation, 67
Vitamin C
absorption, 68
biochemistry, 6768

excretion, 68
metabolism, 68
physiology, 6768
source, 68
supplementation, 69
Vitamin D
absorption, 7980
biochemistry, 7879
in chronic kidney disease,
263264, 266
in cystic fibrosis-specific
multivitamins, 328, 327t
deficiency, 80, 413-414
metabolism, 7980
physiology, 7879
sources, 79
toxicity, 80
Vitamin E
absorption, 8182
biochemistry, 81
deficiency, 82
metabolism, 8182
physiology, 81
sources, 81
toxicity, 8283
Vitamin K
absorption, 83
biochemistry, 83
deficiency, 8384
metabolism, 83
physiology, 81
sources, 83
toxicity, 84
W
Wasting, 411, 411t
Wilsons disease, 306
509
Winkler, Marion, 3
breastfeeding, 120, 129
growth charts, 143144
malnutrition classification, 145t
metabolic syndrome, 150t
resting energy expenditure
equation, 412, 412t
X
Xanthine stones, 276
Z
z scores
in developmental delay, 192, 193
percentile comparisons, 146t
Zinc
multivitamins, 327t, 328

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The A.S.P.E.N.

Pediatric Nutrition Support

AMERICAN SOCIETY FOR PARENTERAL AND ENTERAL NUTRITION

Copyright 2010. American Society for Parenteral and Enteral Nutrition.

7. Water-Soluble Essential Micronutrients. . . . . . . . . . . . . . 56

9. Fluids and Electrolytes. . . . . . . . . . . . . . . . . . . . . . . . . . . 87

2.Gross Digestion Principles: Gastric Grinding

3. Carbohydrates: Changes with Development. . . . . . . . . . . 17

10. Nutrition and Early Development. . . . . . . . . . . . . . . . . 105

5.Protein Digestion, Absorption, and Metabolism. . . . . . . . 31

Russell J. Merritt, MD, PhD, FAAP

11. Human Milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

12. Infant Formulas and Complementary Feeding. . . . . . . 129

13. Growth Assessment and Monitoring . . . . . . . . . . . . . . 143

14. Obesity and Metabolic Disorders. . . . . . . . . . . . . . . . . 149

15. Lipid Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162

16. Use of Fad and Popular Diets. . . . . . . . . . . . . . . . . . . . 169

17. Sports Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

19. Eating Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204

20. Food Allergies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213

21. Diabetes Mellitus and Other Endocrine Disorders. . . . 226

22. Inborn Errors of Metabolism . . . . . . . . . . . . . . . . . . . . 232

23. Cardiac Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247

24. Renal Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256

25. Gastrointestinal Disease. . . . . . . . . . . . . . . . . . . . . . . 283

26. Hepatic Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302

27. Intestinal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311

30.Oncology, Hematopoietic Transplant,

31. Trauma and Burns . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378

32. Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387

34.Parenteral and Enteral Nutrition Support:

35. Implementation of the Plan. . . . . . . . . . . . . . . . . . . . . 448

36.Evaluation and Monitoring of Pediatric Patients

37. Ethical Issues in the Provision of Nutrition . . . . . . . . . 477

Robert H. Squires, Jr., MD

28. Pulmonary Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . 323

29. Organ Transplantation. . . . . . . . . . . . . . . . . . . . . . . . . 337

Test Your Knowledge Answers. . . . . . . . . . . . . . . . . . . . . . . . 487

Janice Antino, RD, MS, CNSD, CSP

Anupama Chawla, MD, CNSP, DCH (UK)

Michelle Battista, BS, PhD Candidate

Catherine Christie, PhD, RD

Wendy Cruse, MMSc, RD, CNSD

Kelly Green-Corkins, MS, RD, CNSD

Neelam Katyal, MS, RD, LDN

Allison Mallowe, RD, LDN

Goldie Markowitz, MSN, CRNP

Barbara Marriage, PhD, RD

Winston Koo, MBBS, FACN, CNS

Maria Mascarenhas, MBBS

Kathleen J. Motil, MD, PhD

Judith C. Rodriguez, PhD, RD

Christina L. Nelms, MS, RD, CSP, CNSC, LD

Ricardo Rueda, MD, PhD

Andrea Nepa, MS, RD, CSP, LDN

May Saba, PharmD, BCNSP

Liesje Nieman Carney, RD, CNSD, LDN

Nancy Sacks, MS, RD, LDN

Robert H. Squires, Jr., MD

Letitia Warren, RD, CSP

2.Gross Digestion Principles: Gastric Grinding

5.Protein Digestion, Absorption, and Metabolism. . . . . . . . 31

30.Oncology, Hematopoietic Transplant,

34.Parenteral and Enteral Nutrition Support:

36.Evaluation and Monitoring of Pediatric Patients