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© Filodiritto Editore – Proceedings

PROCEEDINGS
OF THE

6th CONGRESS OF THE


ULTRASOUND SOCIETY IN
OBSTETRICS
AND GYNECOLOGY
***************************************************************************

34th FETUS AS A PATIENT


INTERNATIONAL CONGRESS
(Bucharest, Romania, 16-19 May 2018)

Editors
Radu Vladareanu, Claudiu Marginean
Simona Vladareanu

FILODIRITTO
INTERNATIONAL PROCEEDINGS
© Filodiritto Editore – Proceedings

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INDEX

Foreword 16

Ultrasound Signs of Fetal Infection with Congenital Cytomegalovirus 17


BADIU Diana, COSTEA Ovidiu Daniel, SERBANESCU Lucian,
HANGAN L. Tony

Uterine Scar Ultrasound Evaluation in Making the Choice Of Child Delivery –


A Literature Review 23
BALALAU Denisa Oana, BALALAU Cristian, OLARU Octavian Gabriel,
STANESCU Anca Daniela

Correlations Between Disorders of the Prosencephalic Development and


Anatomopathological Examination 28
BĂNACU Mihail, CĂLIN Florin Daniel, GHEORGHIU Diana, PACU Irina,
POPESCU Ina, CĂLIN Alina, MATEI Alexandra, ROȘU George-Alexandru,
POPESCU Mihail, SOCEA Bogdan

Diagnosis and Management of Cases with Antepartum Fetal Demise 33


BERNAD Elena, MOZA Andreea, CRAINA Marius, RADULESCU Crina

Limits of the Legal Liability of the Physician in Diagnosis and Management


of the Cases with Placenta Acretta 37
BERNAD Elena, ONOFRIESCU Mircea, NICOLA George

Aspects Regarding Legal Liability of the Physician in Fetal Ultrasonography 41


PAUN Silviu, BERNAD Elena, ONOFRIESCU Mircea, VLĂDĂREANU Radu

Ultrasound Assessment of the Umbilical Cord Knot 46


BERNAD Elena, MOZA Andreea, BERNAD I. Sandor

Hepatic Artery emodynamics in IUGR Fetuses vs. Macrosomic Fetuses


with Diabetic Mothers 51
BOȚ Mihaela, VLĂDĂREANU Radu, PETCA Aida, BURNEI-RUSU Anca,
ZVÂNCĂ Mona

The Diagnosis of the Degree of Severity of the Anterior Perineal Compartment


Prolapse: Parallels Between Clinical Examination and Ultrasonography 58
BOȚ Mihaela, VLĂDĂREANU Radu, BORISLAVSCHI Andreea,
PETCA Razvan, PETCA Aida

The Severe form of Preeclampsia. Particular Situations, Clinical and Therapeutic


Implications 62
BRAILA Anca Daniela, BRAILA Miha, VIRCAN Elena, VELEA Rodica,
NEACSU Adrian

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Fetal Biophysical Profile in Prolonged Pregnancy 67


BRAILA Anca Daniela, BRAILA Mihai, VELEA Rodica, NEACSU Adrian

New Ultrasonographic Markers in Correlation with Serological Factors –


Prognostic Factors in the First Trimester of Pregnancy 70
BUCURI Carmen Elena, CIORTEA Răzvan, DICULESCU Doru,
MALUTAN Andrei Mihai, OANCEA Mihaela Daniela,
NICULA Renata Lacramioara, MOCAN-HOGNOGI Radu, RADA Maria Patricia,
MIHU Dan

Cesarean Scar Ectopic Pregnancy: A Case Report 76


BURNEI-RUSU Anca, CRISTEA Carmen, BOT Mihaela, ZAMFIRESCU Vlad,
VLADAREANU Radu

A Case Report of Both Abnormally Adherent and Complete Placenta Praevia:


A Successful Management Via Conservative Surgery 82
CALO Ioana, BOBEI Tina, DIACONESCU Denise,
CONSTANTINESCU Camelia

Peripartum Infection in the Caesarean Section Delivery 87


CAPROS Hristiana, MIHALCEAN Luminița, SIRITANU Irina,
BURNUSUS Constantin, BOLOGAN Ion, BOLOGAN Ludmila

Antepartum and Postpartum Evaluation of Fetal Obstructive Uropathy 93


CHICEA Radu, CHICEA Anca, NIȚĂ Paula, OGNEAN Maria Livia

Imaging Correlation Between Ultrasound and Nuclear Magnetic Resonance


Examination in the Diagnosis of Myelomeningocele 98
CHICEA Radu, CHICEA Anca, NIȚĂ Paula, OGNEAN Maria Livia

Clinical and Paraclinical Features of Anemia in Early Infancy 104


CHINCEŞAN Mihaela, MĂRGINEAN Cristina Oana, GRAMA Alina,
CÂMPEAN Ioana, DINCĂ Andreea

Fetal Ovarian Cyst: Prenatal Diagnosis – A Case Report 113


CHIRIAC Daniela Veronica, COPOTOIU Larisa, TUTA-SAS Ioana,
PETRE Izabella, CRAINA Marius

The Characteristics and Severity of Psychological Distress after Abortion 118


HOGEA Lavinia Maria

Pregnancy Induced Hypertention as an Indication for C-Section 123


ERDELEAN Izabela, SERBAN Denis

Prenatal Diagnosis of Cloacal Malformation – A Case Report 129


ERDELEAN Dragos, SERBAN Denis, COPOTOIU Larisa, TUTA-SAS Ioana

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Face to Face with the Fetus 134


CIORTEA Răzvan, DICULESCU Doru, MĂLUȚAN Andrei, OANCEA Mihaela,
MOCAN-HOGNOGI Radu, BĂLTOAICA Răzvan, BUCURI Carmen, RADA Maria,
DUDEA Marina, BERCEANU Costin, MIHU Dan

Inhaled Analgesia During Labor – A Systematic Review 140


COSTIN Adrian, DRAGOMIR Ramona, SPĂTARU Gina, DOBRESCU Cătălin,
FÎRŢĂ Anca, BĂNCEANU Gabriel

Etiopathogenic Considerations of Preeclampsia in Southeastern Romania 144


STUPARU-CRETU Mariana, BUSILA Camelia, CARAMAN Liliana

Romanian Prenatal Care: Certainties and Controversies 150


POP Daria Maria, NICULA Renata Lacrimioara, FLORESCU Fulga,
TODEA Cezarin, MOCAN-HOGNOGI Radu Florin, DICULESCU Doru,
MIHU Dan

Ultrasound Evaluation and Management of Adnexal Masses During Pregnancy 155


DICULESCU Doru, MIHU Dan, FLORESCU Fulga, CIORTEA Răzvan,
MĂLUȚAN Andrei, OANCEA Mihaela, BUCURI Carmen, IUHAS Cristian

Congenitally Corrected Transposition of the Great Vessels – Case Presentation 161


DICULESCU Doru, POIENAR Alexandra Andreea, BALTOAICA Razvan,
PORUMB Ciprian Gheorghe, BLAGA Ligia, MIHU Dan

Preoperative Risk Assessment of Malignancy in Ovarian Tumors


and Correlation with Histopathological Outcome 167
DIJMARESCU Lorena, VRABIE Sidonia, MANOLEA Magdalena,
NOVAC Marius, ILIESCU Dominic, TUDORACHE Stefania, CAMEN Ioana

Ultrasound Manifestations in Gestational Diabetes 172


DRAGOI Vlad, CERCEL Roxana, LEPADAT Cosmin, HORHOIANU Irina Adriana,
NEDELCU Silvia, ICHIM Mircea, MUNTEANU Diana, EDDAN-VISAN Lucica,
GRIGORIU Corina

Feasibility of a Novel Ultrasonographic Evaluation of the


Cerebral Ventricular System in the First Trimester 176
DRĂGUȘIN Roxana-Cristina, ȘOROP-FLOREA Maria, PĂTRU Ciprian-Laurențiu,
ZORILĂ Lucian, MARINAȘ Cristian, DINU Marina, CERNEA Nicolae
TUDORACHE Ștefania, ILIESCU Dominic Gabriel

Detection of Conotruncal Anomalies in the First Trimester, Using an Optimized


Morphological Protocol 183
ȘOROP-FLOREA Maria, DRAGUȘIN Roxana Cristina, PATRU Ciprian-Laurențiu,
ȘOROP Virgiliu Bogdan, ZORILĂ George Lucian, MARINAȘ Cristian,
DINU MARINA, NOVAC Marius, CARA Monica, TUDORACHE Ștefania,
CERNEA Nicolae, ILIESCU Dominic-Gabriel

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Congenital Acute Leukemia Diagnosed at a Fetus with Down Syndrome


Echographic Particulars 189
GARDESCU Marie Jeanne, MUNTEANU Andreea, BACESCU Lucia,
CONCI Stelian, EDU Antoine

Etiopathogenic, Clinical, Imagistic and Histopathological Aspects Regarding


the Involvement of Urinary Infection in Premature Birth with Hypotrophic Fetuses 193
GHEORGHE Ioan Ovidiu, RACA Nicolae

Does the Romanian Population Give the Necessary Importance for


Obstetric Ultrasound Examination and Pregnancy Follow-Up? 199
GHEORGHIU Diana Claudia, SOCEA Bogdan, CONSTANTIN Vlad Denis,
GHEORGHIU Nicolae, CĂLIN Florin Daniel, DAVIȚOIU Bogdan Andrei,
ROȘU George-Alexandru, MATEI Alexandra, VIEZUINĂ Roxana

The Role of Theoretical Ultrasound Training in Improving


the Estimated Fetal Weight 205
GRAMA Ovidiu, GLIGA Marius, VOIDĂZAN Septimiu

Cesarean Sectiona and Hernia Repair: A Merged Intervention 211


GRIGORIU Corina, HORHOIANU Irina Adriana, DRAGOI Vlad,
LUTIC Catalin, GRIGORIU Mihai

Bacterial Strains Isolated from Post-Surgical Infections Diagnosed in


an Obstetrics Department in Timișoara 214
HÂNCU Iasmina, ILINCA Laurențiu, GOLDIȘ Anca, HUDAC Rareș,
GHEORGHE Cosmin, HORHAT Delia, BAGIU Iulia, DRAGOMIR Tiberiu,
DIACONU Mircea, KRASTA Anca, NITU Razvan, DRAGOMIR Adriana

The Low Birth Weight Infant – Cause and Effect 221


HASMASANU Monica Gabriela, IGHIAN Ioana Daria, MATYAS Melinda,
ZAHARIE Gabriela Corina

Congenitally Corrected Transposition of the Great Arteries –


An Apparently “Benign” Condition 228
HERGHELEGIU Catalin Gabriel, CIUTACU Laura Andreea,
FETECAU Andreea Catalina, IOAN Raluca Gabriela, NEACSU Adrian,
OPRESCU Daniela Nuti

Pregnancy after Ovarian Cancer – Case Report 232


HERGHELEGIU Catalin Gabriel, CARBUNARU Ana Elena,
MOLDOVEANU Amira, FETECAU Andreea Catalina, IOAN Raluca Gabriela,
OPRESCU Daniela Nuti

The Diagnostic Power of Ultrasound in Postmenopausal Bleeding 235


HERGHELEGIU Catalin Gabriel, CIUTACU Laura Andreea,
COROCEA Karina, IONASCU Adrian Bradut, IOAN Raluca Gabriela

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Ultrasound Diagnosis of Haemorrhagic Syndrome in the Second Half


of Pregnancy 239
SERBAN Oana, IOAN Raluca Gabriela

Prenatal Detection of Limb-Body Wall Defects and Amniotic Bands Syndrome 243
ILIESCU Dominic-Gabriel, CERNEA Nicolae, TUDORACHE Ştefania,
ȘOROP-FLOREA Maria, DRĂGUŞIN Roxana-Cristina,
MARINAȘ Marius-Cristian, CĂPITĂNESCU Răzvan-Grigoraş,
MOFLEANU Andra, DIJMĂRESCU Lorena, MANOLEA Maria-Magdalena,
PĂTRU Ciprian-Laurenţiu, TĂNASIE Delia-Roxana, ZORILĂ George-Lucian

Fetal Heart: Early Diagnosis Versus Follow-Up 250


ILIESCU Dominic-Gabriel, CERNEA Nicolae, TUDORACHE Ștefania,
ȘOROP-FLOREA Maria, DRAGUȘIN Roxana Cristina, ZORILĂ George Lucian,
ȘOROP Virgiliu Bogdan, DRĂGOESCU Alice, CARA Monica-Laura

Definitive Diagnosis of Major Central Nervous System Abnormalities –


More than a Challenge 256
ILIESCU Dominic-Gabriel, TUDORACHE Stefania,
DRĂGUȘIN Roxana Cristina, MANOLEA Maria Magdalena, VRABIE Sidonia,
Lorena Anda DIJMARESCU, ZORILA Lucian George

Low Birth Weight: Third Trimester Fetal Biometry Assessment


Versus Actual Birth Weight 261
IONESCU Cringu, MATEI Alexandra, GHEORGHIU Diana, BANACU Mihai,
POPESCU Ina, IONESCU Andra, VIEZUINA Roxana, CALIN Dan

The Heart Which “Looks Different” 268


KOVACS Tunde, NEMETI Georgiana, STAMATIAN Florin

Selective Intrauterine Growth Restriction in Twins 275


MANOLEA Maria Magdalena, VRABIE Sidonia Cătălina,
SĂNDULESCU Sidonia Maria, NOVAC Liliana, NEAMȚU Simona,
DIJMĂRESCU Lorena

Fetal Heterotaxia – A Diagnosis with Multiple Possibilities 279


MĂRGINEAN Claudiu, GOZAR Liliana, TOGĂNEL Rodica,
MUNTEAN Iolanda, MĂRGINEAN Cristina Oana, SĂSĂRAN Vlăduț Bogdan

Type 1 Autoimmune Hepatitis, a Rare Condition in Children – A Case Report


and a Review of the Literature 285
MĂRGINEAN Cristina Oana, MĂRGINEAN Claudiu,
SĂSĂRAN Vlăduț Ștefănuț, MĂRGINEAN Maria Oana,
ARMEAN Iulia, RĂCHITĂ Anca, MELIȚ Lorena Elena

Interrelation of Amniotic Fluid Volume with Parameters of Blood Flow


Dopplerometry in Labor 291
MIHALCEAN Luminita, CAPROS Hristiana, SURGUCI Mihai

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Applications of Elastography in Cervical Pathology 296


MIHU Dan, DICULESCU Doru, MĂLUȚAN Andrei, IUHAS Cristian,
OANCEA Mihaela, BUCURI Carmen, DUDEA Marina, CIORTEA Răzvan

Agenesis of the Corpus Callosum 301


MITRACHE Dana, PANTEA Manuela, ANGELESCU-COPTIL Claudiu,
EL GHAZI Ghita

Integrated System for Monitoring People with Diabetes.


Monitoring of Pregnant Women 306
ŞTEFAN Bogdan, COSTACHE Ştefania-Bianca, CRIŞAN-VIDA Mihaela,
STOICU-TIVADAR Lăcrămioara, MITRACHE Dana

Meningitis During Pregnancy 312


MITRACHE Dana, MOZA Andreea, BURLICA Sorin

Evaluation of the Umbilical Cord Insertion 316


BERNAD I. Sandor, MOZA Andreea, MITRACHE Dana

Anatomopathological Diagnostic Possibilities in Perinatal Infection 321


STOICESCU Silvia-Maria, BIZINICHI Mădălina, IONESCU Mioara,
CHIRCULESCU Raluca, MOHORA Ramona

Bilateral Ovarian Neoplasia with Negative Roma Score: A Case Report 325
MOISEI Cristina, LESNIC Anca, SIMA Romina-Maria,
STĂNESCU Anca-Daniela

Hypoechoic Abdominal Mass: Case Report 331


MOISEI Cristina, LESNIC Anca, SIMA Romina-Maria,
BĂLĂLĂU Denisa-Oana

Management of a Case with Anencephaly 335


MOZA Andreea, BRISAN Cosmin, VRINCEANU Luminita

Diagnosis and Management in Placenta Praevia Accreta 340


MOZA Andreea, BERNAD Elena, PANTEA Stelian

Sonographic Evaluation of the Umbilical Cord Vessel Number 345


BERNAD Elena, MOZA Andreea

Umbilical Cord Sonographic and Numerical Investigation 349


BERNAD I. Sandor, MOZA Andreea, BERNAD Elena

Extreme Preterm Delivery Under 32 Weeks. Which is the Best Approach? 353
MUREȘAN Daniel, STAICU Adelina, ROTAR Ioana Cristina, NASTASE Diana,
BONDOR Cosmina, ZAHARIE Gabriela

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Possibilities and Limitations of First Trimester Fetal Heart


Ultrasound Examination 360
MUREȘAN Daniel, ROTAR Ioana Cristina, MĂRGINEANU Claudiu,
TUDORACHE Ștefania, MIHU Dan, SCHITCU Cristina, ZAHARIE Gabriela

Vaginal Microbiome Analysis: Clinical Applications 367


URSU Ramona Gabriela, IANCU Luminița Smaranda

Rare Case of Mechanical Dystocia by Previa Ovarian Cyst – Case Report 373
NOUR Corina Madalina, CRISTUREAN Constantin Viorel, CARDON Iuliana,
TICA Vlad

The Importance of the Prenatal Detection of Umbilical Cord Abnormalities for


Antenatal and Intrapartum Management 379
NOVAC Liliana, DIJMĂRESCU Anda Lorena, MANOLEA Maria Magdalena,
VRABIE Sidonia Cătălina, TUDORACHE Stefania, ILIESCU Dominic Gabriel,
TUDOR Adriana, STOENESCU Manuela, NOVAC Marius Bogdan

Doppler Change in Middle Cerebral Artery and Umbilical Artery – Predictor


for Perinatal Outcome in Intrauterine Growth-Restricted Fetuses 385
NOVAC Maria Violeta, TUDORACHE Stefania, ILIESCU Dominic Gabriel,
MANOLEA Maria Magdalena, DIJMARESCU Lorena Anda, VRABIE Sidonia,
ȘOROP-FLOREA Maria, ALEXANDRU Dragos, TABACU Carmen,
GHEONEA Ioana Andreea, NOVAC Marius

Role of Pre-Natal Diagnosis of Congenital Heart Defects – Case Study 391


OANCEA Mihaela, BLAGA Ligia, BALTOAICA Razvan, CIORTEA Razvan,
BUCURI Carmen, DICULESCU Doru, VIDRA Camelia,
POIENAR Alexandra-Andreea, MIHU Dan

Pulmonary Ultrasound in the Differential Diagnosis of Acute Neonatal


Respiratory Failure – Case Report 397
OGNEAN Maria Livia, ZGARCEA Corina, BOANTA Oana, GROSU Florin,
COTARLA Viorela, CHICEA Radu

Maternal Thrombophilia – Risk Factor for Fetal Cerebral Hemorrhage? 403


OGNEAN Maria Livia, ZGÂRCEA Corina Laura2, DUMITRA Raluca Elena,
BOANTĂ Oana, CHICEA Radu

Accuracy of Tumor Size Measurements During Mammography and


Breast Ultrasonography in Breast Cancer Patients 409
OPREA Adela-Luciana, GEORGESCU Rareș, IONESCU Paul,
MĂRGINEAN Claudiu

Necrotizing Fasciitis of the Thoracolumbar Posterior Area (Type 1)


in a Newborn 417
OSAKWE Henry, CRISAN Carmen, DUMITRA Simona, TRAILESCU Maria,
PAVEL Adrian, PAVEL Nicoleta, CRISAN Adrian

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Management of Prenatally Diagnosed Foetal Goitre 423


PANAITESCU Anca-Maria

Differential Diagnosis of Body Stalk Anomaly and Limb-Body Wall Complex


by Ultrasound in the First Trimester of Pregnancy 427
PANAITESCU Anca-Maria

Chronic Hypertension in Pregnancy and the Risk of Superimposed Preeclampsia 431


PANAITESCU Anca-Maria

Congenital Heart Defects in Down Syndrome 435


MITREA Geta, PATRICIU Mihaela, STEFANESCU Bogdan

Hydranencephaly: Clinical and Paraclinical Considerations Based on


Two Presenting Cases 439
MITREA Geta, PATRICIU Mihaela, STEFANESCU Bogdan

Optimization of the First Trimester Ultrasound Scan for Detection of


Fetal Structural Abnormalities 444
PĂTRU Ciprian Laurențiu, TUDORACHE Ștefania, ȘOROP-FLOREA Maria,
DRAGUȘIN Roxana Cristina, ZORILĂ Lucian George, STOICA Alin,
CRISTIAN Marinaș Marius, LAURA Cara Monica, CERNEA Nicolae,
ILIESCU Dominic Gabriel

Case Report: Prematur Newborn 35 Weeks of Gestation with


Posterior Urethral Valve 452
PAUL Corina, NODITI Georgeta, PETRE Isabela, ENATESCU Ileana,
DIMA Mirabela, VELEA PUIU Iulian, IACOB Daniela, IACOB RADU Emil

Morphological Heterogeneity of Hypoplastic Left Heart Syndrome –


Major Impact in the Therapeutic Strategy 457
LACATUSU Adrian, GOLGOT Ioana, PAUL Corina, LASCU Ana, BRISAN Laura

Succesful Outcome of Pregnancy in a Woman with Uncorrected Tetralogy of Fallot 463


LASCU Ana, PAUL Corina, MITRACHE Dana, LACATUSU Adrian,
BRISAN Cosmin, VRINCEANU Luminita

Pregnancy with Occipital Encephalocel – Case Report 467


PAUL Corina, LASCU Ana, MITRACHE Dana, MOZA Andreea,
BRISAN Laura, LACATUSU Adrian

Chromosome 5p deletion in a fetus with Dandy-Walker malformation 471


PETCA Aida, ZVÂNCĂ Mona, MĂRU Nicoleta, PETCA Răzvan-Cosmin,
VEDUȚA Alina, BOȚ Mihaela

The Role of Ultrasound in Diagnosis and Management in


Renal Colic During Pregnancy 478
PETCA Răzvan-Cosmin, POPESCU Răzvan-Ionuț, MEHEDINȚU Claudia,
BOȚ Mihaela, VEDUȚA Alina, PETCA Aida

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Role of Transvaginal Ultrasound in the Assessment of Cervical Cancer 485


PIRTEA Laurențiu, BALINT Oana, SECOȘAN Cristina, SAS Ioan,
GRIGORAȘ Dorin

The Importance of Ultrasound Assessment in Predicting Recurrence after


Transvaginal Sling Procedures 491
PIRTEA Laurentiu, ILINA Razvan, SECOSAN Cristina, BALINT Oana,
SAS Ioan, GRIGORAS Dorin

Ultrasound Assessment of Tape Position Following Suburethral Sling Procedures 495


PIRTEA Laurențiu, BALINT Oana, SECOȘAN Cristina, SAS Ioan,
GRIGORAȘ Dorin

Unusual Outcome of Twin Pregnancies after IVF 499


PLES Liana, SIMA Romina-Marina, RAHIMIAN Hadi, VYTOULKAS Andreas,
STANESCU Anca Daniela

Fetal Legal Statute in Romanian Law 504


PLES Liana, SIMA Romina-Marina, POENARU Mircea Octavian,
OLARU Octavian-Gabriel

Ultrasound Evaluation of Endometrum in Fibroids Treated with Ulipristal Acetat 509


PLEȘ Liana, SIMA Romina-Marina, SGARBURĂ Zorela Adriana,
BĂLĂLĂU Denisa-Oana, CARP Delia, RÎCU Anca

Prognosis of Non Syndromic Fetal Diaphragmatic Hernia 514


POENARU Mircea Octavian, BRAICU Flavia, VALCEA Ionut
STERIE Ionut Emil, STANESCU Anca Daniela

Ultrasound Diagnosis of Aortic Arch Anomalies – Literature Review


and Case Report 520
POENARU Mircea Octavian, BRAICU Flavia, STERIE Ionut,
VALCEA Ionut, PLES Liana

A Severe Case of Immunisation to the Rhesus D Antigen in the XXIst Century 526
POPESCU Ina, GHEORGHIU Diana, BANACU Mihail, ROBOTIN Carmen,
MATEI Alexandra, IONESCU Andra, DAN Adelina, POPESCU Mihail,
PACU Irina, SOCEA Bogdan

Fetal Left Femoral Hypoplasia Associated with Left Fibular Agenesis


– A Rare Case 531
POSTOLACHE Iulia, SURDU Monica, NICULESCU Costin,
IZVORANU Silvia, STERIU Liliana, MOCANU Diana, TICA Vlad Iustin

Late Diagnosis of Hydrocephalic Fetus. A Case Report and Ethical Dilemmas 535
POSTOLACHE Iulia, SURDU Monica, NICULESCU Costin,
IZVORANU Silvia, STERIU Liliana, MOCANU Diana

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Prenatal Diagnosis of Isolated Lissencephaly: Case Studies and


Literature Review 540
SERGHEI Puiu, CAROLINA Tambala

The Effectiveness of Passive Cooling Methods in Neonates with Severe Perinatal


Asphyxia in Maternities with Limited Resources 546
RADULESCU Luiza, NASTASE Leonard, MOHORA Ramona,
STOICESCU Silvia

The Moment for Extracting Intrauterine Growth Restricted Preterms,


a Beneficial Materno-Fetal Factor 552
STOICESCU Silvia, NASTASE Leonard, MOHORA Ramona,
RADULESCU Luiza

Late Detection of Fetal Congenital Heart Defects – Counseling and


Management Issues – Case Report 557
RÎCU Anca, VÂLCEA Ionuţ, POENARU Mircea-Octavian, CARP Delia,
SIMA Romina Marina

Congenital High Airways Obstruction Syndrome – Diagnosis Principles 563


RUICAN Dan, STOICA Alin, SÂRBU Mirela, NOVAC Marius,
ŞOROP-FLOREA Maria, DRĂGUŞIN Roxana-Cristina, ZORILĂ Lucian-George,
CĂPITĂNESCU Răzvan-Grigoraş, PĂTRU Ciprian-Laurenţiu, CERNEA Nicolae,
TUDORACHE Ştefania, ILIESCU Dominic-Gabriel

Prevalence and Antimicrobial Resistance Pattern of Escherichia Coli


Isolates from Postpartum-Urinary Tract Infections 567
RUS Maria, CIRLEA Natalia, KRASTA Anca, TAMAS Alina,
IONESCU Constantin, DIACONU Mircea, NITU Razvan, DRAGOMIR Tiberiu,
HORHAT Delia

Omega-3 Supplementation During Pregnancy to Prevent Different Obstetrical


Complication: Systematic Review of Literature 572
SANDULESCU Sidonia Maria, VICOL Ramona Mircea,
MANOLEA Magdalena, PATRASCU Anca, VELISCU Andreea

An Interesting Case of Placental Abruption 578


SERBANESCU Lucian, COSTEA Daniel Ovidiu

A Brief Review of the Aetiological Factors Involved in Placental Abruption 582


SERBANESCU Lucian, COSTEA Daniel Ovidiu

Hemorrhage in the Placenta Previa – Risk Factors and Prognosis 585


SOCOLOV Razvan, HALICIU Ana, POPOVICI Diana, AKAD Mona,
ADAM Ana, SOCOLOV Demetra

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Detection of Conotruncal Anomalies in the First Trimester, Using an Optimized


Morphological Protocol 590
ȘOROP-FLOREA Maria, DRAGUȘIN Roxana Cristina, PATRU Ciprian-Laurențiu,
ȘOROP Virgiliu Bogdan, ZORILĂ George Lucian, MARINAȘ Cristian,
DINU Marina, NOVAC Marius, CARA Monica, TUDORACHE Ștefania,
CERNEA Nicolae, ILIESCU Dominic-Gabriel

Echographic Significance of Retroplacental Hematoma Detection 597


STĀNICA Cātālina Diana, BOBEI Tina

Antepartum Haemorrhage in Placental Pathology in Third Trimester


of Pregnancy 601
STĀNICA Cātālina Diana, BOBEI Tina

Transvaginal Ultrasound. Significance in the Diagnosis


of Endometrial Bleeding 605
STĀNICA Cātālina Diana, BOBEI Tina

Utrasound Aspects in Uterine Tumour Pathology 609


STĀNICA Cātālina Diana, BOBEI Tina

Fibular Hemimelia – Case Report and Review of the Literature 613


ȘTEFĂNESCU Bogdan Ioan, MITREA Geta

Polycystic Ovaries and the Polycystic Ovary Syndrome 617


STELEA Lavinia, PETRE Izabella, RAPCEA Raluca, NEAMTU Radu,
CRAINA Marius

Syphillis in Pregnancy 621


STERIU Liliana, NICULESCU Costin, IZVORANU Silvia, PENCIU Roxana,
MOCANU Diana, POSTOLACHE Iulia

On Thin Ice: Counselling in Minor Congenital Anomalies 625


TUDORACHE Stefania, DRAGUSIN Roxana, ILIESCU Dominic Gabriel,
SOROP-FLOREA Maria, DINU Marina, MARINAS Cristian,
TANASE Florentina, STOICA Alin

Abnormal Placenta 631


CEAUȘESCU Andreea, DINU Marina, DRAGUȘIN Roxana,
TUDORACHE Ștefania

Genetic Diagnosis and Counselling Challenges in Prenatal Life 638


DOCEA Andreea, DINU Marina, ILIESCU Dominic Gabriel,
TUDORACHE Stefania

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Counselling in Minor Fetal Abnormalities – Large First Trimester Choroid


Plexus Cyst, Persistent Left Superior Vena Cava and Single Umbilical Artery
in Vanishing Twin Syndrome – A Case Report 644
NAGY Rodica Daniela, ILIESCU Dominic Gabriel, PATRU Ciprian Laurentiu,
DRAGUSIN Roxana, TUDORACHE Stefania

Changes in Markers of Ovarian Reserve and Doppler Velocimetry after


Laparoscopic Surgery 650
VARLAS Valentin, IONESCU Oana, BOSTAN Georgiana

The Degree of Correlation Between Prenatal Ultrasonography and


Fetal Autopsy Findings – A Retrospective Study 659
VARLAS Valentin, BOSTAN Georgiana

Urinary Tract Anomalies – Prenatal Diagnosis and Prognosis 668


VARLAS Valentin, BOSTAN Georgiana, DRAGOȘ Georgescu

Thyroid Ultrasound – Between Endocrinology and Gynaecology 675


VASILIU Cristina, CARSOTE Mara, VALEA Ana, ALBU Simona Elena

Thyroid Nodules on Female Patients of Reproductive Age –


The Importance of Ultrasound 680
VASILIU Cristina, ALBU Simona Elena, GHEMIGIAN Adina, VALEA Ana,
CARSOTE Mara2

Thyroid Ultrasound on Patients Within 5th Decade of Life 686


VASILIU Cristina, ALBU Simona Elena, GHEMIGIAN Adina, VALEA Ana,
CARSOTE Mara

Breast Ultrasound on Young Patient with Mastodynia 692


VASILIU Cristina, ALBU Simona Elena, GHEMIGIAN Adina, VALEA Ana,
CARSOTE Mara

Training in Fetal Echocardiography – The Development of a


Multidisciplinary Approach in Prenatal Imaging 698
VEDUTA Alina, DUTA Simona, PETCA Razvan, PETCA Aida

Cystic Cerebral Lesions in Newborn Infants Diagnosable


by Ultrasound Examination 703
BLAGA Ligia, OANCEA Mihaela, VIDRA Camelia, FUFEZAN Otilia,
MURESAN Marta, HASMASANU Monica, MATYAS Melinda,
DICULESCU Doru

Does Romanian Pregnant Teenage Girls Find First and Second Trimester
Ultrasound Exams and Follow Up Important? 709
VIEZUINĂ Roxana, SOCEA Bogdan, CONSTANTIN Vlad Denis,
GHEORGHIU Nicolae, CĂLIN Florin Daniel, DAVIȚOIU Bogdan Andrei,
ROȘU George-Alexandru, AL AZAWI Alla, GHEORGHIU Diana Claudia

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Are there Cesarean Section Indications Without Ultrasound Exam Nowadays? 715
VIEZUINĂ Roxana, SOCEA Bogdan, CONSTANTIN Vlad-Denis,
GHEORGHIU Nicolae, CĂLIN Florin Daniel, DAVITOIU Bogdan Andrei,
ROȘU George, MATEI Alexandra, GHEORGHIU Diana Claudia

Specific Long-Term Complications After a C-Section 721


VINTEA Alexandra, DRAGOMIR Ramona, DRAGAN Ioana,
DRAGODAN Anda Viviana, BĂNCEANU Gabriel

Ultrasound Endometrial Changes in Perimenopause and Menopausal Transition 725


VOINEA Bogdan, VELEA Rodica, LUNGULESCU C.

Premature Placental Abruption.Ultrasound Aspects 729


VOINEA Bogdan, VELEA Rodica, LUNGULESCU C.

Perinatal Outcome of Intra-Versus Retroplacental Hematomas 732


VRABIE Sidonia Cătălina, NOVAC Liliana, DIJMĂRESCU Anda Lorena,
MANOLEA Maria Magdalena, SANDULESCU Sidonia, ILIESCU Dominic,
NOVAC Marius

Perspective of the Prematures Infants Below 28 Weeks of Gestation 738


ZAHARIE Gabriela, HASMASANU Monica, OBADA Veronica,
MURESAN Daniel, BLAGA Ligia, ZAHARIE Alexandru Teodor,
DRUGAN Tudor, BOIA Marioara, ROTAR Ioana, MATYAS Melinda

Distal Arthrogryposis in Newborns with Turner Syndrome 744


ZAHARIE Gabriela, MURESAN Daniel, MICLEA Diana,
HASMASANU Monica, MATYAS Melinda

Prevalence and Early Outcome of Congenital Heart Disease 750


MATYAS Melinda, KARI Orsolya, OBADA Veronica,
HASMASANU Monica, BLAGA Ligia, ZAHARIE Gabriela

Prenatal Diagnosis of Kabuki Syndrome 757


ZVANCA Mona Elena, PETCA Aida, BOȚ Mihaela,
MUNTEANU Alexandra, NEDELEA Florina Mihaela

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FOREWORD

During the last 30 years the ultrasound has completely changed the prenatal and
gynecological diagnosis. Its implications in the clinical practice of obstetrics and gynecology
and the use of more and more performing ultrasound machines, have been materialized
throughout time in numerous ultrasound meetings and publications.

The 6th Congress of the Ultrasound Society in Obstetrics and Gynecology took place in
Bucharest together with the 34th “Fetus as a Patient” International Society Congress.
Expanding on three days, the meetings reunited around 800 participants and over 100 invited
speakers from country and abroad. This outstanding event has been dedicated to the study of
all aspects of perinatal biology, physiology, screening, diagnosis, management and ethics,
with the goal of continuous quality improvement in the care of maternal, fetal and neonatal
patients. The pre-selection of the uploaded scientific papers led to a number of 213 oral
presentations and 91 e-posters. These papers gathered the work of a generation of
sonographers in obstetrics and gynecology from Romania.

The representative papers of this congress were proposed for publishing in this volume.
We selected a number of 134 papers that we are sure the reader will find to be significant
and to bring important scientific information, consistent in all topics related to ultrasound in
obstetrics and gynecology and in the field of perinatal medicine.

Editors:
Prof. Radu Vlădăreanu Prof. Claudiu Mărginean Prof. Simona Vlădăreanu

Bucharest, 2018

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Ultrasound Signs of Fetal Infection with Congenital


Cytomegalovirus
BADIU Diana1, COSTEA Ovidiu Daniel1, SERBANESCU Lucian,
HANGAN L. Tony1
1Faculty of Medicine, “Ovidius” University of Constanta, (ROMANIA)
Both authors have an equall contributions and should be considered first author
Email: [email protected]

Abstract

Congenital cytomegalovirus (CMV) during pregnancy could determinate fetal anomalies.


Non-immunized women are predisposing to CMV infection. Although the diagnosis of
CMV is made on immunological tests, sometimes ultrasonography signs occur: hydrops,
hydrocephalus, intracranial calcifications, microcephaly, intrauterine growth retardation, etc.
We present herein the main ultrasonographic signs in fetuses with congenital CMV
infection.

Keywords: viral infection, cytomegalovirus, fetus, ultrasound, hydrops, diagnosis

Introduction

Congenital cytomegalovirus (CMV) infection represent the main infection in many


countries, having an incidence of approximately 2.2% in live births [1].
After primary infection of the mother, it was noted an 50% intrauterine infection, and only
10% of neonates presente symptoms at birth [2].
In contrary, the asymptomatic neonates develop different disorders especially sensorineural
hearing loss [3]. Reactivation of the virus do not involve seriouse consequences, having only
minor disorders [4].
Only a small number of CMV infections are prenatally diagnosed and this could be due to
limited experience until present which will lead to a hard decision concerning the integration
of women in prenatal diagnostic programs [4].
From the theoretical point of view, only the pregnant women which have already CMV
infection should be enrolled in such programs and in the cases where seroconversion is not
able to be detected, the diagnosis will remain uncertain [5, 6], in which the investigation of
the thyroid function should be made, having a crucial role in the development of a healthy
baby [7].
In symptomatic cases, ultrasound examination can be very helpfull in order to identify
growth abnormalities which could suggest the presence of the infection. Other types of
infection should be eliminated, as they can cause digestive symptoms, as in case of billiary
pathology – mor efrequent in pregnant women [8].
It was showed that the placenta inflammation could further interfere with hormone
production process leading to structural abnormalities of the fetuses [9] especially in epileptic
women [10] or by in vitro fertilization evaluation or treatment [11, 12]. Another in vitro study
showed the benefit role of magnesium in the inhibition of spontaneous myometrial
contractility [13].

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The abnormalities could vary and can be detected as echogenic bowel, intrauterine growth
restriction, ventriculomegaly, brain calcification or amniotic fluid volume [14].
The ultrasound features are not consider to be specific for CMV infection and ony one
third of infected fetuses will show ultrasound disorders. Although without a higher
application, the presence of an ultrasound abnormalities in pregnant women confirm the
existence of CMV infection [14].
Besides neurologic disorders, hematologic aspects could also be detected like
thrombocytopenia, hyperbilirubinemia and hepatosplenomegaly [15].
We report here the implication of main ultrasonographic signs of CMV infection from fetal
status.

Congenital CMV transmission and risk factors

It was observed that the transmission of fetal CMV in primary maternal infection during
first half of pregnancy is much higher than those infection from the second half of pregnancy
(i.e. non-primary infection) [16, 17].
It was seen a 14.2-52.4% transmission from mother to the fetus of primary infection and
only 1.1-1.7% of non-primary infection [18]. In this respect, non-primary infection contribute
to more cases of CMV disease [19].
Usually, congenital CMV could results in different complications like preterm birth or
preeclampsia leading to fetal or neonatal death [20, 21].
Most symptomatic infected newborns present unilateral or bilateral sensorineural hearing
loss, optic atrophy, strabismus, microcephaly or mental disabilities [17, 22]. The
asymptomatic CMV infected neonated will present long-term sequelae, which could be easy
recognised until five years old [23, 24]. The disorders of the CMV infection acts usually by
clinical injury of the fetuses based on different features [24]. Whatsoever, many studies
sustain the fact that fetal disorders result more from an indirect way based on placental
dysfunction [25].
Therefore, congenital CMV infection come to represent the main non-genetic disorder of
congenital malformations in many countries [26]. Although causing important effects on the
infected fetuses, it becomes less recognized among pregnant women, fathers, obstetricians
and paediatricians and many other practitioners [27].

Diagnosis of maternal CMV infection

Using sometimes only serological tests in order to detect CMV-specific immunoglobulin G


(IgG) antibody may confirm primary CMV infection [28]. In respect with the IgG
seronegatively results of the test, the sample should be collected prior to conception or at the
earliest visit at physician. Whithout confirmation of such tests, CMV-specific IgM antibody
could be detected which will indicate a maternal CMV infection [28].
Normally, reactive CMV IgM antibodies could be detected only after primary or non-
primary infections. The antibodies could persist for a long period of time after primary
infection [25, 26].
In such cases, the reactive CMV IgM antibodies should be used as a supplimentary tests in
order to achieved the maturity of IgG antibodies [28].
Drosse and contributors [29] showed in one study made on 19 fetuses with CMV infection,
that using the ultrasonography it were discovered only five with central nervous features like
hydrocephalus and microcephaly. From this five cases, one was aborted, three were died at
birth and the last one had hearing loss.

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Other authors using ultrasonography found three cases of congenital CMV infection based
on small cerebellum, moderate ventriculomegaly including severe distorsion of the
cerebelium [30].
One study achieved on eight fetuses showed an periventricular echogenicity. This could be
due to different calcifications transependymal resorbtion of the cerebelium [31].

Prenatal detection of fetal CMV infection

In the management of CMV infected fetuses detection, the evaluation and informative
couseling becomes important [32].
Many abnormal fetal structures have been discovered in CMV infected fetuses during
ultrasonography which include: hydrops, hydrocephalus, intracranial calcifications,
microcephaly, intrauterine growth retardation, including the influence of maternal weight on
first trimester biochemical markers concentrations [33, 34]. Therefore, ultrasound represents
an intensive technique in detecting CMV infection, although the major signs could be seen
only in the late pregnancy [35]. In the same context, the absence of specific ultrasound CMV
infection, do not exclude the presence of the virus, considering the fact that only third from
asymptomatic CMV infected fetuses will develop much later such abnormalities [26].
It was noted also that ultrasonography could detect only severely affected cases which
consist of higher anomalies and more small features could be missed. In the same manner, if a
normal anatomic structures could be observed, it cannot provide a sigurance concerning a
normal fetuses [36].
In the case where the diagnosis of CMV infection become the main issue, a series of
ultrasonographyc images should be achives every 2 to 4 weeks which could have a higher
impact of the fetuses structures.
Diagnosis by amniocentesis is not reccomended, at present, due to the possible side effects
[37].

Consideration about the therapy in pregnancy

Although the diagnosis of the fetuses with CMV virus infection has been known much
development, the therapy is still lacking. Some new therapies have been showed desired
results like CMV hyperimmun globulin (HIG) in pregnant women. Some studies have been
tried to show the implication of micro-ribonucleic acid or smoking as biomarkers in
pregnancy related disorders [38-43] to be further integrated as usually tests in hospitals [44].
In respect to the infection caused on the fetuses, the immunoglobulin could helping in
reducing the placental disorders and maybe by reducing the cytochine mediate cellular
response [45], being more a consequences of oxidative stress [46].
This therapy could only be achived after the CMV fetal infection was confirmed or the
amniotic liquid is consisted of CMV. In the case when the mother is not tested by
amniocenthesis or the maternal IgG is reduced, the therapy should be monthly considered
until delivery [45]. In the case when maternal IgG antibodies are higher than 50%, the HIG
treatment should be not implemented [47].
On the other hand, fetuses with CMV infection could be oral treated using Valaciclovir (8g
per day) [48]. The same administration of oral Ganciclovir was reported by other studies [49].
However, the application of this therapy remain to be enrolled in controlled trials for better
outcomes highlighted until present especially for nosocomial rotaviral gastroenteritis or
Clostrium difficile in children which presented more severe symptoms [50, 51]. Many things
still remains to be cleared up in terms of epidemiology, pathogenesis and risk factors and the
creation of an software was showed to improve the diagnostic sensitivity [52, 53].

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Therefore, many authors have showed that the application of both therapies should be
better achieved during pregnancy than before pregnancy, considering the fact that women in
pregnancy are more motivated than non-pregnant women [54].

6.Conclusions

CMV infection showed to have a higher prevalence especially in the fetuses, leading to
mental disorders and hear loss. Routine serological tests of all pregnancy is not
reccommended, only in the women with influenza-like disease. In the case that maternal
CMV infection has been detected, fetal disorders could be easily detected by ultrasonography.
The serological test together with the ultrasonographic images could help clinicians in
guiding the pregnant women infected with CMV and further deciding the future of the
pregnancy.

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52. Bohiltea, RE., Curstoiu, MM., Ionescu, CA., Niculescu-Mizil, E., Vladareanu, AM., Voican, I.,
Dimitriu, M., Turcan, N. (2017). Primary myelofibrosis and pregnancy outcomes after low molecular-
weight heparin administration. A case report and literature review. Medicine 96(46), e8735. WOS:
000417630400083.
53. Bohiltea, RE., Turcan, G., Cirstoiu, MM., Ionescu, C., Nemescu, D., Turcan, N., Vladareanu, R. (2017).
Clinical implementation of ultrasound gynecological examination report (software REGU) based on
international consensuses of tumor study groups. 5th Romanian Congress of the Romanian Society of
Ultrasound in Obstetrics and Gynecology, Targu-Mures, Romania. Edited by: Vladareanu S, Marginean
C, Vladareanu R, pp. 99-104. WOS: 000406419700015.
54. Adler, SP., Nigro, G., Pereira, L. (2007). Recent advances in the prevention and treatment of congenital
cytomegalovirus infections. Semin Perinatol 31, pp. 10-18.

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Uterine Scar Ultrasound Evaluation in Making the Choice of


Child Delivery – A Literature Review

BALALAU Denisa Oana1,2, BALALAU Cristian1,3, OLARU Octavian Gabriel1,2,


STANESCU Anca Daniela1,2
1 University of Medicine and Pharmacy Carol Davila, Bucarest, (ROMANIA)
2 Saint John Hospital, Bucur Maternity, Bucarest, (ROMANIA)
3 Saint Pantelimon Emergency Hospital, Bucarest, (ROMANIA)

Email: [email protected]

Abstract

Introduction
C-section worldwide is the first place as frequence between surgical interventions of
obstetrics and gynecology discipline. The number of cesarean operations is on the rise, along
with advancing surgical techniques, intensive care and neonatology, with the progress of the
pharmaceutical industry and suture materials. Vaginal delivery on uterus with scar tissue after
C-section has become increasingly rare, although countless studies have shown a low rate of
uterine rupture.
C-section indication in case of uterine scar tissue should occur after taking into account
several maternal and fetal risk factors. The main maternal risk factor in the case of a pregnant
uterus with previous scar from another C-section is the imminent uterine rupture, whose
prophylaxis can be achieved by serial ultrasound evaluations during pregnancy.

Purpose
The paper proposes a parallelism between studies that indicate vaginal birth on the scar
tissue after cesarean surgery and those that advocate repetitive cesareans.

Material and method


Ultrasonographic evaluation of uterine scar after C-section by tracking several parameters
on a regular basis: thickness, continuity, contour, shape, homogenity.
For the ultrasonographic evaluation, multiple methods have been used, such as: 2D, 3D,
and Color Doppler ultrasound, anamnestic and clinical data.

Results
In the reviewed studies the opinions on the thickness of C-section scar were varied. The
study by Asakura et al., was based on the ultrasound measurement of the lower uterine
segment as a predictor factor for uterine dehiscence, establishing a “cutt-off” of 1.6 mm. More
recent studies such as Basic et al., define uterine scar as a quality scar if the thickness is
3.5mm or more and if its shape is triangular, while Nilanchali Sigh et al. found an increased
rate of uterine scar dehiscence where the thickness was less than 3 mm between 24-28 weeks,
and less than 2 mm over 36 weeks of gestation.

Conclusions
The status of uterine scar after 36th week gestation is the decisive factor in choosing the
way of birth and the operative moment. Ultrasound assessments of uterine scar after 24 weeks

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of gestation were most often performed, with the highest accuracy in assessing the quality of
uterine scar.
Keywords: C-section, uterine scar, vaginal delivery

Introduction

C-section worldwide is the first place as frequence between surgical interventions of


obstetrics and gynecology discipline. The number of cesarean operations is on the rise, along
with advancing surgical techniques, intensive care and neonatology, with the progress of the
pharmaceutical industry and suture materials. Vaginal delivery on uterus with scar tissue after
C-section has become increasingly rare, although countless studies have shown a low rate of
uterine rupture.
C-section indication in case of uterine scar tissue should occur after taking into account
several maternal and fetal risk factors. The main maternal risk factor in the case of a pregnant
uterus with previous scar from another C-section is the imminent uterine rupture [1, 2], whose
prophylaxis can be achieved by serial ultrasound evaluations during pregnancy, along with
monitoring lesions associated with high-grade displasia in pregnancy [3].
In the past the indication for cesarean birth was put only for the pelvic dystocia.
Although there are numerous studies showing a low rate of uterine rupture following
vaginal delivery after cesarean operation (0.2-0.7%), a large number of obstetricians went for
a second caesarean to reduce any maternal risk or fetal. This led to the global increase in the
number of successful births (decreasing the incidence of complications during labor or birth)
and the decrease in vaginal births after a previous cesarean delivery.
Performing the cesarean operation requires a multidisciplinary medical collaboration
(gynecologist, anesthetist, neonatologist), and in the postoperative period there is an increased
risk of complications, especially infections if the patient presented prematurely broken
amniotic membranes.

Purpose

The paper proposes a parallelism between studies that indicate vaginal birth on the scar
tissue after cesarean surgery and those that advocate repetitive cesareans.

Material and method

Ultrasonographic evaluation of uterine scar after C-section is made by examining the


patient with a transabdominal probe with a frequency between 3 MHz and 10 MHz or an
intravaginal probe with a frequency between 5 MHz and 20 MHz in order to track several
parameters on a regular basis: thickness, continuity, contour, shape, homogenity.
For the ultrasonographic evaluation, multiple methods have been used, such as: 2D, 3D,
and Color Doppler ultrasound, anamnestic and clinical data.
2D ultrasound is currently considered the main method of imaging assessment of
anatomical structures in obstetrics. This is a standard method that produces images made up
of a series of thin slides. 3D ultrasound is considered a more advanced technology that is used
only in special cases. 3D technology offers multiple opportunities for evaluating structures so
far only provided by computed tomography and magnetic resonance imaging.
Color Doppler is a semi-quantitative method that is now widely accepted and is the
standard of the most modern ultrasound devices. It has a great advantage in that it localizes
and quantifies the blood flow and is important for rapid orientation and finding the
pathological flow area.

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In the past, the evaluation of uterine scar was subjectively estimated by palpation and
bimanual inspection of the lower uterine segment. This term, lower uterine segment (LUS)
was introduced by Bandl in 1875 and 30 years later Aschoff described the borderline between
the lower uterine segment and the uterine body as ostium internum anatomicum and below the
cervix as ostium internum histologicum.
This paper evaluated multiple criteria for inclusion in the study, concluding that the most
important and relevant were:
1. the choice of pregnant women who had previously had a caesarean section with an
unlimited number of vaginal births;
2. females with segmento-transversal hysterectomy;
3. pregnant women with cranial or pelvic presentation up to 2500gr;
4. women up to 40 years of age;
5. monofetal pregnancies without fetal abnormalities;
6. pregnancies greater than 35 weeks of gestation;
7. pregnant women who agreed to participate in the study.

The exclusion criteria from the study are:


1. absolute indications for caesarean section (pelvic dystocia, maternal health problems
that contraindicate vaginal birth, etc.);
2. multiparae with only vaginal births in antecedents;
3. patients who have previously undergone surgery on the uterus for other medical
reasons or a scar of unknown etiology or uterine malformations;
4. pregnant women, with macrosomes, malformed fetus or still birth;
5. dystocic presentations;
6. multiple gestation pregnancy;
7. women aged over 40;
8. gestation age of less than 35 weeks;
9. previous anterior “T” histerotomy.

Results

The most recent studies based on the results of lower uterine segment (LUS) scarring,
concluded that the risk of rupture is dependent on LUS thinning measured at 37 weeks of
pregnancy.
The particularity of the lower uterine segment is given by the thin layer of muscle and poor
vascularization, which makes it a good place for incision. The scar area after a cesarean
delivery raises a risk of rupture of the lower uterine segment, and its condition can be assessed
by appropriate precautions and intrapartum intensive control, which reduces the risk of tearing
during labour and ensures successful vaginal delivery [4, 5].
In the reviewed studies the opinions on the thickness of C-section scar were varied. The
study by Asakura et al., was based on the ultrasound measurement of the lower uterine
segment as a predictor factor for uterine dehiscence, establishing a “cutt-off” of 1.6 mm [6].
More recent studies such as Basic et al., define uterine scar as a quality scar if the
thickness is 3.5mm or more and if its shape is triangular [7], while Nilanchali Sigh et al.,
found an increased rate of uterine scar dehiscence where the thickness was less than 3 mm
between 24-28 weeks, and less than 2 mm over 36 weeks of gestation [8].
Mazurek-Kantor et al., reported that the maximum scar thickness was 4 mm, including in
measurements both the thickness of the bladder wall and the amniotic membranes [9].
Rozenberg et al., reported that the lower uterine segment was significantly higher among
women who previously had Caesarean section after a 4.5±1.4 mm than among women

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undergoing elective cesarean (3.8 mm±1.5 mm). It was observed that the risk of uterine
dehiscence was directly related to the lower uterine segmentation ultrasonographically
measured at 37 weeks of gestation and claims that labor can be allowed if the scar thickness at
37 weeks is greater than 3.5 mm [10].
Another study (Lebedev et al.,) analyzed ultrasonographically the uterine myometrium and
determined the following criteria: vaginal delivery is recommended after a previous cesarean
delivery if the lower uterine segment is V-shaped, with minimum thickness 3-4 mm and
continuous contour of the lower uterine segment, along with homogeneous structure without
or with small areas of increased ecogeneity. Vaginal birth is contraindicated if the lower
uterine segment has the shape of a balloon, or the thickness is less than 3 mm, or there is
discontinuity of the uterine structures, and the areas with increased ecogeneity prevail in the
scar area [11].

Conclusions

The status of uterine scar after 36th week gestation is the decisive factor in choosing the
way of birth and the operative moment. Ultrasound assessments of uterine scar after 24 weeks
of gestation were most often performed, with the highest accuracy in assessing the quality of
uterine scar.
A longer time interval after a caesarean section offers more scar quality attributes. Modern
ultrasound assessment methods of the lower uterine segment should be part of the usual
pregnancy tracking practice to make a meaningful assessment of uterine scars possible and to
make the right decision in choosing the way to delivery.
The lower uterine segment thickness in cesarean delivery patients decreased from 6.8 mm
± 2.3 mm to 19 weeks of gestation to 2.1 mm ± 0.7 mm at 39 weeks of gestation.
Measurement of the thickness of uterine scarring in the third trimester is more relevant
than measurements in previous quarters.
Measuring the thickness of uterine scarring through the transvaginal probe is more
effective than the transabdominal probe because it allows a better delimitation of the adjacent
structures (bladder, amniotic membranes).

REFERENCES

1. Bălălău, DO., Sima, RM., Bacalbașa, N., Pleș, L., Stănescu, AD. (2016). Emergency peripartum
hysterectomy, physical and mental consequences: a 6-year study. J Mind Med Sci.; 3(1): pp. 65-70
2. Bălălău, DO., Bacalbașa, N, Stănescu, AD. (2017). Cesarean scar defects and placental abnormalities; a
3 year survey study. J Mind Med Sci.; 4(2): 156-162. DOI: 10.22543/7674.42.P156162.
3. Bălălău, DO., Sima, RM., Bacalbașa, N., Banu, P., Bălălău, C., Pleș, L., Stănescu, AD., (2017). High-
grade cervical dysplasia in pregnancy – psychological and medical challenges. J Mind Med Sci.; 4(1):
24-30. DOI: 10.22543/7674.41.P2430.
4. Pleș, L., Sima, RM., Moisei, C., Moga, MA., Dracea, LA., (2017). Abnormal Ultrasound Appearance of
the Amniotic Membranes-diagnostic and significance:a pictorial essay. Medical Ultrasonography;
19(2): pp. 211-215.
5. Poalelungi, CV., Ples, L., Hudita, D., Ceausu, I., (2018). Risk factors and clinical follow-up of patients
with preterm births in a tertiary referral maternity unit in Bucharest, Romania.J Pak Med Assoc; 68(4),
pp. 559-564.
6. Asakura, H., Nakai, A., Ishikawa, G., Suzuki, S., Araki, T. (2000). Prediction of Uterine Dehiscence by
Measuring Lower Uterine Segment Thickness Prior to the Onset of Labor. Journal of Nippon Medical
School. 67. 352-356. 10.1272/jnms.67.352.
7. Basic, E., Basic-Cetkovic, V., Kozaric, H., Rama, A., (2012) Ultrasound evaluation of uterine scar after
cesarean section. Acta Informatica Medica.; 20(3): pp. 149-153. doi:10.5455/aim.2012.20.149-153.
8. Singh, N., Tripathi., R, Mala, YM., Dixit, R., (2015). Scar thickness measurement by transvaginal
sonography in late second trimester and third trimester in pregnant patients with previous cesarean

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section: does sequential change in scar thickness with gestational age correlate with mode of delivery?
Journal of Ultrasound.;18(2):173-178. doi:10.1007/s40477-014-0116-3.
9. Mazurek-Kantor, J., Kietlinska, Z., Spiewankiewicz, B., (1993).Relationship of uterine scar strength to
pre-labor ultrasound appearance. Med Sci Monit.;4: p. 797.
10. Rozenberg, P., Goffinet, F., Philippe, HJ., et al., (1996). Ultrasonographic measurement of lower
uterine segment to assess risk of defects of scarred uterus. Lancet.;347:281. doi: 10.1016/S0140-
6736(96)90464-X.
11. Lebedev, VA., Strizhakov, AN., Zhelnezov, BI., (1991). Echographic and morphological parallels in
the evaluation of the condition of the uterine scar., Akush Ginekol.;8: pp. 44-49.

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Correlations Between Disorders of the Prosencephalic


Development and Anatomopathological Examination

BĂNACU Mihail1,2, CĂLIN Florin Daniel1,2, GHEORGHIU Diana1,


PACU Irina1,2, POPESCU Ina1,2, CĂLIN Alina3, MATEI Alexandra1,
ROȘU George-Alexandru1, POPESCU Mihail4, SOCEA Bogdan2
1 Department of Obstetrics and Gynecology, “Sf Pantelimon” Clinical Emergency Hospital, Pantelimon Blvd, no 340-342,
021661, Bucharest (ROMANIA)
2 Carol Davila University of Medicine and Pharmacy, Dionisie Lupu St, no 37, 020021, Bucharest (ROMANIA)
3 Faculty of Medicine and Pharmacy – “Dunarea de Jos” University, Al. I. Cuza Street, no 35, 800010, Galati (ROMANIA)
4 Department of Obstetrics and Gynecology, Ramnicu Sarat Municipal Hospital, Nicola Bălcescu Street, no 2, Ramnicu Sarat

(ROMANIA)
5 “Bucur” Maternity, “Sf Ioan” Clinical Emergency Hospital, Între Gârle Street, no 10, 040294, Bucharest (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Holoprosencephaly (HPE) represents a complex malformation of the forebrain, determined


by the absence or incomplete cleavage of the prosencephalon. HPE has four subtypes: alobar
holoprosencephaly, semilobar holoprosencephaly, lobar holoprosencephaly, and a middle
interhemispheric fusion variant (syntelencephaly). Since both the forebrain and midface arise
from the prechordal mesoderm, majority of patients with HPE also manifest craniofacial
abnormalities. Prenatal ultrasound can be used to detect the facial abnormalities that are seen
with severe HPE within the first trimester; however, milder forms of the condition may go
unnoticed. We present a series of seven cases collected over a period of eight years in three
Hospitals in Romania. From 2008 to 2016 we performed a multicenter observational
retrospective study and we included all fetuses with ultrasound diagnosis of
holoprosencephaly.
We investigated the following parameters: fetal age at diagnostic, anatomical brain
characteristics for each type of HPE, CNS and face anomalies comparing clinical and
anatomic pathology findings.
Features of HPE identified postmortem – non cleavage of the thalamus (4 cases), non-
cleavage of the hemispheres (4 cases). One case of MIH variant of HPE diagnosed antenatally
by MRI that resulted in stillbirth 6 days postpartum also associated septo-optic-dysplasia
diagnosed after necropsy by optic nerve hypoplasia and pituitary abnormalities.
The presence or absence of the fused anterior horns is the most useful ultrasound parameter
in the differential diagnosis of prosencephalic brain anomalies – all fetuses with fused anterior
horns have HPE. It is important to recognize that HPE is a rare disorder, and most clinicians
will only encounter a few affected cases. In order to fully understand the clinical features of
this disorder, clinicians must continue to collaborate with researchers studying the condition.
Keywords: Holoprosencephaly, Anatomical pathology, Necropsy, Ultrasound diagnosis prosencephalic disorders

Introduction

Abnormal ventral induction may result in disorders of formation, cleavage, and midline
development of prosencephalic structures [1]. Holoprosencephaly (HPE) represents a
complex malformation of the forebrain, determined by the absence or incomplete cleavage of

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the prosencephalon (forebrain) during the 4th week of embryogenesis. It is the most common
brain malformation with an incidence of 1:250 during embryogenesis and 1:16,000 among
live births.
It seems that the lower the gestational age is, the higher the prevalence, this observation
being explained by the high intrauterine mortality of fetuses with HPE, probably due to the
associated genetic and structural defects frequently present [2, 3].
HPE has four subtypes: alobar holoprosencephaly, semilobar holoprosencephaly, lobar
holoprosencephaly, and a middle interhemispheric fusion variant (syntelencephaly) [4, 5].
Alobar holoprosencephaly is the most severe form, and as the name implies, there is no
separation of the cerebral hemispheres [4]. In semilobar holoprosencephaly, the cerebral
hemispheres separate posteriorly, however are fused anteriorly [6, 7]. Lobar
holoprosencephaly is characterized by almost complete separation of the cerebral hemispheres
[4, 6].
Syntelencephaly results from failure of separation of posterior frontal and parietal lobes
[4].
Since both the forebrain and midface arise from the prechordal mesoderm, majority of
fetuses with HPE also manifest craniofacial abnormalities such as microcephaly,
ethmocephaly, cebocephaly, proboscis, anophthalmia, cyclopia, microphthalmia,
synophthalmia, cleft lip and palate, flat nose, absent nasal bridge-leading to a so called
“holoprosencephaly sequence” [1, 6, 8]. This brain-face correlation was also made by William
DeMyer while studding a group of patients with holoprosencephaly, in the end concluding
that “The face predicts the brain”. [8, 9]
The exact cause of HPE is hard to identify as this pathology seems to have a multifactorial
etiology: teratogen exposure, genetic abnormalities and syndromic association. Syndromic
association of HPE includes, but is not limited to Smith-Lemli-Opitz syndrome, Genoa
syndrome, Meckel-Gruber syndrome, Lambotte syndrome, Steinfeld syndrome and Aicardi
syndrome [10]. Maternal diabetes is considered the most important risk factor, potentially
increasing the risk 200-fold [11, 12]. Other risk factors include: alcohol, cigarette smoking,
salicylates, retinoic acid, cytomegalovirus infection [3, 13]. The life quality of neonates with
HPE is influenced by the severity of cerebral and facial anomalies [14]. The presence of
gestational trophoblastic disease in the history of the patient was suspected to increase the risk
of HPE but it was not confirmed [15].
Different imaging modalities can be used to diagnose HPE depending on the severity of the
condition. Prenatal ultrasound can be used to detect the facial abnormalities that are seen
with severe HPE within the first trimester; however, milder forms of the condition may go
unnoticed [16, 17]. During the first trimester ultrasound scan, the most severe anomalies can
be diagnosticated (alobar and semilobar holoprosencephaly) [17, 18]. Lobar
holoprosencephaly cannot be diagnosed in the first or early second trimester since its most
consistent feature – absence of the cavum septi pellucidi – cannot be imaged reliably until at
least 18 postmenstrual weeks. For this reason, this anomaly is usually diagnosed during the
second trimester anomaly scan (performed between 18 and 21 gestation weeks), when we can
identify also cardiac anomalies [19]. Ideally, pregnancies at increased risk of fetal CNS
anomalies and those with suspicious findings on a basic examination should undergo fetal
neurosonography performed by clinicians with expertise in this area [18]. Fetal magnetic
resonance imaging has been used to provide better characterization of the more subtle
malformations during the third trimester of pregnancy [20]. In infants with suspected HPE,
neuroimaging criteria have been established for the assessment of HPE [20]. The imaging
modality of choice is high-resolution magnetic resonance imaging scans, which include thin-
section image sequences in three orthogonal planes (axial, sagittal, and coronal) [19, 20].

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Imaging is important for diagnosis and case management because the severity of the brain
malformation generally correlates with the degree of neurologic problems and life
expectancy. Macrocephaly or microcephaly can influence the counseling of such fetuses. [21]
The diagnosis of alobar HPE in the first and second trimester can rise the option of
termination of pregnancy [22]. Etiologic diagnosis of central nervous system abnormalities
can be done by prenatal or postnatal karyotype and testing for known gene mutations [23].
The classification is based on MRI findings or autopsy findings if one is requested [9, 20].

Methods

We present a series of seven cases collected over a period of 8 years in two tertiary
University Hospitals in Romania, “St Pantelimon” Clinical Emergency Hospital and “Bucur”
Maternity, and one secondary maternity care unit – Ramnicu Sarat Municipal Hospital, with
relevant ultrasound images for each type of HPE. Data were collected from medical files.
From 2008 to 2016 we performed a multicenter observational retrospective study and we
included all fetuses with ultrasound diagnosis of holoprosencephaly. We included the live
births of fetuses >24 weeks gestation and stillbirths >28 weeks excluding abortions and
stillbirths of <28 weeks. We investigated the following parameters: fetal age at diagnostic,
anatomical brain characteristics for each type of HPE, CNS and face anomalies comparing
clinical and anatomopathological findings. As the study was retrospective ethical approval
was obtained from Ethics Comitee.
Prenatal documentation was made using, fetal ultrasound exams in medical files, made on
GE Voluson 730 Pro, Voluson 730 Expert and E8 ultrasound machines and also fetal MRI
performed on a 1.5 Tesla machine was used in 2 cases to better evaluate the brain. Postnatal
confirmation was made using transfontanellar ultrasound and/or MRI (1.5 Tesla) studies in
the few cases that survived or by necropsy. Also data about the clinical evaluation of the
newborns that survived was collected. Genetic counseling and genetic testing (amniocentesis
or biopsy of the chorionic villi) was offered to all cases, but the cost of the test had to be
supported by the parents so less than half of them opted for these investigations.

Results

Our retrospective, observational, multicenter, study consists of a series of 7 cases of HPE


collected from two tertiary University Hospitals and one secondary maternity care unit in the
last 8 years (2010-2018). The fetal age at diagnosis was between 25 to 37 weeks. The
ultrasound diagnostic of HPE was made at a mean fetal age of 28 weeks, with 5 cases
discovered in the second trimester and 2 cases in the third trimester. Out of the total of 7 cases
of HPE reviewed, 1 (14.28%) was diagnosed with alobar HPE, 1 (14.28%) with semilobar
HPE, 3 (42.85%) with lobar HPE and 2 (28.57%) with MIH variant HPE. The mean age of
the mothers was 28.85 years, varying between 18 and 40 years old, also no relevant medical
history or exposure to teratogens was found in any case. Hydrocephaly is one of the most
common medical and management problems in newborns with HPE – from our case series
one newborn was diagnosed with this condition after birth and needed cerebrospinal fluid
(CSF) shunt placed for treatment.
The newborn was diagnosed antenatally with alobar HPE and a large dorsal cyst and after
birth the high intracranial pressure made the diagnosis of hydrocephaly. Motor feeding
dysfunction was also present in almost all cases (6 of 7 cases-85.71%) and all of them needed
a gastrostomy tube for feeding to reduce the risk of choking and acute aspiration pneumonitis.
Besides motor dysfunction cleft palate and lip were found in 2 cases (28.57%) of alobar
HPE also contributing to feeding problems. Motor impairment was common to some extent in

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all our newborns diagnosed with HPE. Lobar HPE and MIH were associated with little to no
motor impairment (5 cases-71.42%). One case of alobar HPE was diagnosed with dystonia of
the upper extremities and truncal hypotonia. One case with semilobar HPE was diagnosed
with cerebral palsy and presented limb rigidity and abnormal truncal posture. Five of the total
newborns resulted in neonatal demise al 0 days to 1 month of life. These patients all had a
common frontal ventricle and callosal and midline malformations. Other features of HPE
were identified postmortem – non cleavage of the thalamus (4 cases), non-cleavage of the
hemispheres (4 cases).
One infant diagnosed with alobar HPE presented severe intrauterine growth restriction
with autopsy that showed absent septum pellucidum, microcephaly, migrational abnormality.
Another fetal demise was due to cerebral herniation due to severe ventriculomegaly – after
necropsy absence fused thalami, ventriculomegaly and facial dimorphism were noted
confirming the antenatal diagnosis of alobar HPE. One case of MIH variant of HPE diagnosed
antenatally by MRI that resulted in stillbirth 6 days postpartum also associated septo-optic-
dysplasia diagnosed after necropsy by optic nerve hypoplasia and pituitary abnormalities. The
other suspected case of MIH variant had an autopsy postmortem after 1day revealing complex
brain malformations: agenesis of the corpus callosum, communicationg lateral ventricles in
their middle portion with normal posterior fossa; pathological confirmation of MIH variant
could not be obtained due to severe autolisys. Karyotype analysis was available in only six
patients and was normal in three, trisomy 13 was found in two and triploidy in one patient.
The patient with triploidy had additional malformations including an open neural tube
defect, a complex cardiac anomaly and cleft lip and palate.

Conclusions

Prosencephalic brain development is a complex malformation commonly associated with


facial anomalies. First line diagnosis of HPE is achieved using ultrasound examination,
completed by MRI in case of subtler variants of HPE. The presence or absence of the fused
anterior horns is the most useful ultrasound parameter in the differential diagnosis of
prosencephalic brain anomalies – all fetuses with fused anterior horns have HPE.

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development. Prenat. Diagn. 29: pp. 340-354. doi:10.1002/pd.2208
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9. Şorop-Florea, M, Ciurea, RN, Ioana, M, Stepan, AE, Stoica, GA, Tănase, F, Comănescu, MC, Novac,
MB, Drăgan, I, Pătru, CL, Drăguşin, RC, Zorilă, GL, Cărbunaru, OM, Oprescu, ND, Ceauşu, I,
Vlădăreanu, S, Tudorache, Ş, Iliescu DG. The importance of perinatal autopsy. Review of the literature
and series of cases. (2017) Rom J Morphol Embryol. 58(2): 323-337. ISSN 1220-0522.
10. Tudorache, Ş, Iliescu, DG, Turcu, A, Florea, M, Dragusin, R, Novac, L, Cernea, N. First Trimester
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11. Winter, TC, Kennedy, AM, Woodward, PJ. Holoprosencephaly: A Survey of the Entity, with
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Diagnosis and Management of Cases with Antepartum Fetal


Demise
BERNAD Elena1,2, MOZA Andreea1,3, CRAINA Marius1,2, RADULESCU Crina4
1 The University of Medicine and Pharmacy Victor Babes Timisoara, Department of Obstetrics and Gynecology (ROMANIA)
2 “Pius Brinzeu” Emergency Clinic County Hospital Timisoara, IInd Department of Obstetrics and Gynecology, Timisoara
(ROMANIA)
3 The University of Medicine and Pharmacy Victor Babes Timisoara, Department of Functional Sciences (ROMANIA)
4 Scoala Nationala de Studii Politice si Administrative (ROMANIA)

Emails: [email protected], [email protected], [email protected]

Abstract

Intrauterine fetal death can cause severe distress to the mother and the family. Often times,
the truth is very difficult to accept and most of the times the family tries to find someone to
blame.
Some cases can end with a malpractice trial. We present the case of a 42 years old patient
secundipara with 33 weeks weeks pregnancy known with chronic hypertension and
gestational diabetes that was sent to our clinic from a lower unit maternity for ruptured
membranes. The admission ultrasound examination established intrauterine fetal death. The
patient went into labour and gave birth to a 2300g masculin fetus with the one minutes Apgar
Score of 0. Several hour after giving birth the patient requested her discharge against medical
advice.
One year later both maternities were called to trial, and requested all evidence especially
video and fetal Doppler that prooved fetal viability.
Guidelines empahsize the role of live 2D ultrasound of the fetal heart and Doppler
ultrasound of the fetal aorta in diagnosing this condition, as well as showing and explaining
the patient and family the results, but make no refrence on the importance of video recording
of the data or saving the data on the ultrasound machine. For some time now the obstetrical
field becomes more and more a target for malpractise trials, so new pinned protocoles should
be made, with inclusion of the specific law in order to raise the awareness about the legal
aspects of intrauterine fetal death.
Keywords: intrauterine fetal demise, pregnancy, ultrasound, hypertension, gestational diabetes

Introduction

Intrauterine fetal death can cause severe distress to the mother and family. Legally
speaking a fetus with no signs of life is declared either fetal death or abortion in respect with
the gestational age or wheight of the baby. Worldwide this limit varies: 20 weeks of grestation
in USA and Australia, 22 weeks gestation United Kingdom [1].
In Romania, according to Law Order no 359 of 4th of March 2012, if the mother expulses a
fetus with no sign of live before 28 weeks it is declared an abortion. If the expulsion takes
place after 28 week’s it declared birth [2].
Despite the fact that the rate of intrauterine fetal death have decreased with 19% in the last
10 years, the number of fetal deaths declared per day is quite high (in 2015, globally
approximately 7178 intrauterine fetal deaths were declared); 90% percent of then occurring in
low income societies [3]. According to Takita (2018) the causes of intrauterine fetal have

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changed in the recent years. Although the prevalence of death related fetal abnormalities has
decreased, cases of intrauterine fetal demise associated to umbilical cord anomalies has risen
[4, 5]. Despite autopsies the prevalence of unexplained fetal death ranges from 30 to 60% [6,
7].

Case presentation

We present the case of 42 years old, 33 weeks getstation gravida II, para II, konwn with
essential hypertension (controlled with 250 mg of Dopegyt 3 times per day) and gestational
diabetes (treated with diet) that was reffered to our hospital from a secondary unit hospital
(located 90 kilometers away) for premature rupture of membranes. She arrived at our hospital
by her personal automobile. According to the papers from the secondary maternity unit, she
had a 33 weeks pregnancy with a life fetus. A 10 minutes cardiotocogram revealed a normal
fetal heart rate with normal variability and no contractions.
At the admission the patient was anxious, afebrile, hemodinamically stable, blood
preassure 160/85 mmHg, pulse 70 beats per minute. Besides amniotic fluid leakeg, she had no
other complaints.
At the inspection the patient’s uterus was 10 centimeters below the xifoid. The speculum
exam identified a closed cervix, however the pooling sign was positive. The palpation
revealed a normal uterine tonus and no contractions. The fetus was in a cefalic presentation.
On palpation the fetal movements could not be detected and the atending doctor could not
detect any fetal heart beat with the stetoscope.
Ultrasound examination confirmed the absence of fetal heart movements. Doppler
examination was not made. The live ultrasound was shown to the pacient and details were
given about the steps in management of the situations.
The patient was admited with the diangosis of 33 weeks pregnancy. Intrauterine fetal
death.
Laboratory tests were taken and antibiotherapy was intistuted. She continued the treatment
for hypertension. Nifedipine was associated due to lack of responding to Dopegyt. Laboratory
tests show leukocitosis (15/103/microl) with granulocitosis 85% and elevated blood sugar
(124g/l).
Blood clothing tests were in normal range. Soon after admission labor began and the next
day she gave birth to a masculin fetus of 2300g, one minute Apgar Score of 0. Cervial culture
swabs were negative. The imediate postpartum evolution was favorable, the patient left the
hospital several hours after giving birth against medical advise.
A year later both hospitals were called in a legal trial in which the judge requested all
medical papers that diagnosed fetal viability/ fetal death.
This case brings up the following issues:
- Why the patient was sent with her own car?
- Why wasn’t an ambulance requested?
- Why wasn’t the ultrasound saved on electronic disk?
- Why wasn’t the diagnosis of intrauterine fetal death confirmed in Doppler mode?
Histopatological exam of the newborn and the placenta were not relevant.
In this kind of circumstances both criminal and civil proceedings could be initiated in order
to punish the medical personnel and to obtain financial compensations for material damages
and for moral damages (usually large amounts due to the impossibility of an objective
assessment) [8].

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Discussions

In Romania there are no official medical recommandations as far as the diagnosis and
management of intrauterine fetal death is concerned.
The medical attended usually susupects intrauterine fetal death if the mother claims
reduced or absent fetal movements. However most of the times the fetus is in his sleep cycle
that usually last between 20 to 40 minutes, in rare cases up to 90 minutes [9]. Althrough a live
fetus, a mother’s perception of active fetal movement can be altered in different situations
[10]:
- the mother’s position (sitting and standing is associated with decreased perception of
fetal movement);
- the location of the placenta, mostly anterior placenta;
- maternal sedative drugg administration;
- maternal smoking;
- maternal elevated blood sugar;
- fetal spinal lie;
- decreased amniotic fluid;
- fetal malformation;
- fetal neutromuscular disorders.
Often times, intrauterine fetal death turns out to be a rutine sonographical event, the mother
stating that she feels fetal kicks. Either way confirming intrauterine fetal death is made only
with the aid of the real time ultrasound, with direct visualization of the fetal cord [11]. In poor
visibility conditions (obesity, abdominal scars, oligoamnios), the color Doppler mode of the
heart and the ombilical cord vessels should be made for an acurate diagnosis. Signs of late
fetal death are the Spalding sign (overlapping of skull bones), edema of the soft tissue, gross
distorsion of fetal anatomy.
RCOG recommends against diagnosing intrauterine fetal death with obstetrical
stethoscope, fetal Doppler and cardiotocography, because fetal heart beats can be mistaken for
maternal heart beats [11]. In this case, the diagnosis of intrauterine fetal death was made
ultrasononographically, both parents were informed. Also the ultrasound results were written
in the medical adminssion papers. However, there is no recording of the ultrasound because of
force of habit. In this situation the medical practitioner did not consider the need of using
Doppler in diagnosis.
The cause of intrauterine fetal death vary. According to MBRRACE if the mother is over
40 she has a 2.4 Odds Ration of intrauterine demise. In case of diabetes the Odds Ratio is 2.5.
In respect with hipertension the Odds Ratio was 4.1 [12, 13]. The cumulative Odds Rate of
intrauterine fetal death is quite high in this patient’s case-9. Because of her associated
pathology, prematurity and ruptured membranes the pregnancy should be considereded a high
risk one, and special attention should be paid in management of this cases. The fetal and
maternal wellbeing were analized at the secondary maternal unit, however, 60 minutes later
fetal demise was diagnosed. In this situation transporting the patient with an ambulance would
have been more proper, however the reason why the woman came with her personal car is
unknown. Althrough the literature recognises cardiotocography to be the best methos of
assurance of fetal wellbeing, studies show that a reactive CTG has a failure rate of 1.9 per
1000 brith in predicting fetal wellbeing [14].

Conclusions

Intrauterine fetal death is in itself a great source of distress for the practitioner and a much
greater source of malpractice trials. Guidelines empahsize the role of live 2D ultrasound of the

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heart and Doppler ultrasound of the fetal aorta in diagnosing this condition, as well as
showing the patient and family the results, but make no refrence on the importance of video
recording of the data, or saving the data on the ultrasound machine. For some time now the
obstetrical field becomes more and more a target for malpractise trials, so new pinned
protocoles should be made, with inclusion of the specific law in order to raise the awareness
about the legal aspects of the matter.

REFERENCES

1. Kowaleski, J., (2008). National Center for Health Statistics; Hyattsville, MD: 1997. State definitions
and reporting requirements for live births, fetal deaths, and induced terminations of pregnancy (1997
revision). Birth Summary Tables, England and Wales. Office for National Statistics. 2010. Birth
statistics 2008. Series FM1 No. 37.
2. Ordinul Nr. 359 din 04.04.2012 privind criteriile de înregistrare şi declarare a nou-născutului.
3. http://www.who.int/maternal_child_adolescent/epidemiology/stillbirth/en/
4. Takita, H., Hasegawa, J., Nakamura, M. (2018). Causes of intrauterine fetal death are changing in
recent years Causes of intrauterine fetal death are changing in recent years J Perinat Med. 26;46(1), pp.
97-101.
5. Bernad, S.I., Bosioc, A.I., Bernad, E.S., Craina, M.L., (2015). Helical type coronary bypass graft
performance: Experimental investigations, Bio-Medical Materials and Engineering, 26(s1), pp. 477-
486.
6. Man, J.C., Hutchinson, A.E., (2008). Heazell Stillbirth and intrauterine fetal death: factors affecting
determination of cause of death at autopsy. Ultrasound in Obsetetrics and Gynecology, 48(5) pp. 566-
573.
7. Bernad, S.I., Totorean, A., Bosioc, A., Crainic, N., Hudrea, C., Bernad E.S. (2015). Fluid mechanics in
stented arterial model, International Conference of Computational Methods in Sciences and Engineering
2015 (ICCMSE 2015), AIP Conf. Proc., vol. 1702, 080008-1-080008-4.
8. Nanu, A., Georgescu, D., Bulgaru, D., Berteanu, M., Radulescu, C., (2012). Using the International
Classification of Functioning, Disability and Health in assessing moral damages – Romanian Journal of
Legal Medicine, 20(1), pp. 77-82.
9. Patrick, J.,Campbell, K.,Carmichael, L., Natale, R., Richardson, B., (1982). Patterns of gross fetal body
movements over 24-hour observation intervals during the last 10 weeks of pregnancy. Am J Obstet
Gynecol, 142, pp. 363-71.
10. RCOG Green top guideline 57: Reduced Fetal Movement, Royal College of Obstetrician and
Gynaecologist, 2011.
11. Late Intrauterine Fetal Death and Stillbirth , Green-Top Guideline No. 55, October 2010, Royal College
of Obstetricians &Gynaecologists.
12. Zetterstro, K., Lindeberg, N., Hansonb, U., (2008). The association of maternal chronic hypertension
with perinatal death in male and female offspring: a record linkage study of 866 188 women.
International Journal of Obstetrics & Gynaecology, 115(11).
13. Bernad, S.I., Bosioc, A., Bernad, E.S., Craina, M.L., (2014). Comparison between experimentally
measured flow patterns for straight and helical type graft, Bio-Medical Materials and Engineering,
Volume 24(1), pp. 853-860.
14. Freeman, R.K., Anderson, G., Dorchester, W.A., (19982). Prospective multiinstitutional study of
antepartum fetal heart rate monitoring. I. Risk of perinatal mortality and morbidity according to
antepartum fetal heart rate test results. Am J Obstet Gynecol, 143, pp. 771-7.

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Limits of the Legal Liability of the Physician in Diagnosis and


Management of the Cases with Placenta Acretta

BERNAD Elena1, ONOFRIESCU Mircea2, NICOLA George3


1 IIIrd Discipline of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Faculty of Medicine, “Victor
Babes” University of Medicine and Pharmacy from Timisoara (ROMANIA)
2 Discipline of Obstetrics and Gynecology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy

Iasi (ROMANIA)
3 Discipline of Legal Liability Elements and Malpractice, 14 th Department, Faculty of Medicine, “Carol Davila” University

of Medicine and Pharmacy, Bucharest (ROMANIA)


Emails: [email protected], [email protected], [email protected]

Abstract

We present the case of a 29 weeks pregnant patient, whoom due to ultrasonographically


suspicion of invasive placenta MRI was recommended. The patient came to the emergency
department with moderate persistent vaginal bleeding. Urgent delivery of the baby was
decided.
Caesarian section was performed by a complex medical team. The uterine incision was
made at the level of the uterine fundus in order to avoid bleeding that can appear in placental
incision.
Caesarian section was followed by total hysterectomy in the same operatory moment. The
evolution was favorable both for the mother and the newborn. The article presents legal
aspects asociated to juridic responsability of the practitioner at the time of following up the
pregnancy, the time of admission and hospitalisation and after discharging the patient.
Keywords: placenta accreta, ultrasound, legal liability

Introduction

Pathologic adherent placenta, called placenta accreta althrough a rare pathology it has its
importance due to the possible hemoragic complications [1]. The incidence of invasive
placenta depends on geographical area from 0.22% in China [2], to 0.9% in Israel [3],
however worldwide, the estimated incidence of adherent placenta is 1.7 in 10000 births.
Imagistic examinations have the most reability in raising the suspicion of placenta accreta.
Ultrasonography can identify sugestive changes for invasion. Magnetic resonance imaging
is standard investigation recommended in cases where invasive placenta is suspected [4, 5].
Whenever placenta accreta is considered, it is mandatory to organise a multidisciplinary
medical team and to plan the date of the delivery in order to low the rates of maternal and
fetal morbidity and mortality [6, 7]. The objective of this article is to present legal aspects
associated to the practitioner’s juridic responsability in the diagnosis and management of
cases with diagnosis or suspected with placenta accreta.

Case presentation

The paper is a case study. We present a 31 years-old gravida, which was admitted with the
following diagnosis in the IInd Department of Obstetrics and Gynecology of the “Pius
Brânzeu” Emergency Clinical County Hospital Timisoara, Romania: IVth gestation IInd parity;

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29 weeks gestation pregnancy with live fetus;. Central placenta praevia with metrorrhagia;
Labour; Uterine scar due to previos c-section; Suspicion of placenta accreta on ultrasound
with recommandation for magnetic resonance imaging to confirm diagnosis.
After admission the patient was investigated in order to deliver the baby. Caesarian section
was decided for the indication: central placenta praevia with persistent moderate
metrorrhagia; risk of uterine rupture at a gravida in labor.
A transvers histerotomy was performed at the level of the anterior uterine wall between the
uterine horns, in order to avoid the massive bleeding that can occur in cases of placental
incision.
After extraction of the newborn, decollation of the placenta was partial due its adherence to
the myometrium. Because hemorrhage from the placenta could not be managed, hemostatic
histeroraphy was performed, followed by total hysterectomy. Postoperative evolution was
favorable for the mother and the newborn.

Results and Discussions

Often times diagnosing placenta accreta can be difficult due to invasion in an area more
difficult to visualised, or because of a changed uterine anatomy due to anterior surgery. In this
case the patient had a uterine scar due to a previous caesarian section. It is important to taking
into consideration the imagistic limitations in diagnosing placenta accreta and also aspect
associated with the management of such a case [8, 9]. As far as the best imagistic method of
diagnosing placenta acreta, meta-analyses reported sensitivity of 90.7% for ultrasound and
94.4% for MRI, and a specificity of 96.9% for ultrasound and 84% for MRI.
There are several ultrasound signs that can appear in invasive placenta: loss of
retroplacental sonolucent zone; irregular retroplacental sonolucent zone; thinning or
disruption of the hyperechoic serosa, focal masses invading the bladder, multiple irregular
lacunae in the placental substance that determine the moth-eaten or Swiss cheese appearance,
hypervascularity of the serosa, crossing vessels form placenta to serosa however none of them
are pathognomonic [10].
According to Comstock an increasing number of lacunae is the most predictive sign in the
diagnosis of placenta accreta (sensitivity 79%, positive predictive value 92%) [11]. MRI is
complementary to ultrasound as it can asses more accurately the level of invasion in the
uterine wall as well as in the soft pelvic tissue, however Bret (2018) warns about the use of
MRI when evaluating the placenta as it can change the diagnosis and often is an incorrect one
[12, 13].
After the diagnosis or suspicion of placenta accreta is done, the practitioner must give
information on all the risks: severe vaginal bleeding with transfusion, damage of the bladder,
hysterectomy, severe clotting disabilities to intravascular disseminated coagulopathy,
maternal death, premature birth, neonatal death. After explaining the risks the patient signed
the informed consent.
The patient must be informed about the cesaean section and about the possibility to be
neccesary the histerectomy. The decision is taken by the surgical team. The decision must be
endorsed by the chief of the department. For the clinical solution of the described situation a
medical team consisting of 2 surgeons specialists, a scrub nurse, an anaesthetist, a
neonatologists each with a nurse and the material resources necessary for the medical
intervention are needed.
• What happens if the available human and/or material resources are not available and
there is no option to carry the patient in a timely manner to a center that has all the
necessary resources?

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• What are the doctor’s options? Can he try to perform a complex surgical intervention
under these conditions? Is it ethical? Is it legal?
Two bioethical principles determine the right action in this situation, namely the principle
of non-harm and the principle of benefit.
The legislator takes over the conclusions of bioethics and turns them into legal norms
imposed on practitioners by force of state constraint [14].
The principle of non-harm (“do not harm”) regains the concepts applied in the following
legal provisions relating to the field investigated: medical staff is civilly liable for damages in
the exercise of the profession and when it exceeds the limits of its competence. Given the
existence of associated conditions, each of these conditions should be
supervised/diagnosed/treated by the doctor in that area of expertise/competence. It is therefore
obvious that doctors are not allowed to carry out medical acts that do not fit into the specialty
they hold.
The principle of benefit (“doing good”) is the source of the legislation providing for an
exception to the above mentioned rule, reserved for emergency situations in which the
medical staff with the necessary competence for the patient’s situation is not available. In this
situation, the doctor may intervene even outside his sphere of competence, but it is necessary
to have evidence of the fact that there is no medical personnel available who is competent to
perform a medical act; this proof is to be done through acts issued by the legal representative
of the healthcare provider, capable of certifying the existing staff at the place of delivery of
the medical act committed outside the limits of competence and the generator of harm.
According to the law [15], “medical staff are civilly liable for damages in the exercise of
their profession and when they exceed the limits of their competence, except in cases of
emergency in which medical personnel with the necessary competence are not available”.
In the above described situation it is clear that the doctor will be able to intervene even
with the overcoming of the competence held within the specialty, the necessary legal
conditions being met. Any other justification of overcoming competence (e.g. intervention for
the benefit of the patient according to the physician’s opinion, without an emergency
situation, imminent risk, and the impossibility of providing medical assistance by a specialist
with the necessary expertise) is a violation of the medical law which could result in the civil
liability of the physician [16].
A possible conclusion that the accused doctor has exceeded the professional limit of
his/her own specialty has an additional negative consequence, namely the non-operation of
the doctor’s professional liability insurance contract because the exceeding of the limits of
competence is a cause of exclusion in the insurance contracts.
The insurer will not pay damages to cover material damage and especially moral damages,
the amount of which may be considerable considering the impossibility of objectively
measuring them [17].

Conclusions

Antepartum diagnosis of placenta accreta can be very difficult. In situations where placenta
accreta is suspicioned a prompt medical intervention is mandatory.
A national guide of diagnosis and management is imperios not only for improving the
medical practice but also to avoid malpraxis situations.

REFERENCES

1. Héquet, D., Ricbourg, A., Sebbag, D., Rossignol, M., Lubrano, S., Barranger, E., (2013). Placenta
accreta: screening, management and complications. Gynecol Obstet Fertil. 41(1), pp. 31-7.

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2. Fan, D., Li, S., Wu, S., et al., (2017). Prevalence of abnormally invasive placenta among deliveries in
mainland China A PRISMA-compliant Systematic Review and Meta-analysis, 96(16), pp. 63-66.
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11. Comstock, C.H., Love, J.J. Jr, Bronsteen, R.A., et al., (2004). Sonographic detection of placenta accreta
in the second and third trimesters of pregnancy. Am J Obstet Gynecol 190, pp. 1135-40.
12. Einerson, B.D., Rodriguez, C.E., Kennedy, A.M., (2017). Magnetic resonance imaging is often
misleading when used as an adjunct to ultrasound in the management of placenta accreta spectrum
disorders. Presented at the Society for Maternal-Fetal Medicine meeting, Las Vegas, NV, Jan, pp. 23-
27.
13. Bernad, E., Pantea, S., Boglut, A., Duta, C., Bernad, S.I., Petre, I., (2016). Investigation of Chorionic
Artery Bifurcation Using Micro Vascular Casting Model, Revista de Chimie, 67(2), pp. 339-343.
14. Nanu, A., Bulgaru-Iliescu, D., Rotaru, T.S., Oprea, L., (2015). The Gap between Bioethics Principlism
and Judicial Responsibility: How Social Sciences Can Help Romanian Law – Revista de cercetare si
interventie sociala, 49, pp. 216-228.
15. Law 95/2006 regarding health reforms, as subsequently amended and supplemented, art. 653, alin (4).
16. Pițuru, S., Vlădăreanu, S., Păun, S., Nanu, A., (2015). Malpractice and professional liability of medical
personnel – Farmacia, 63(2), pp. 318-324.
17. Nanu, A., Georgescu, D., Bulgaru, D., Berteanu, M., Radulescu, C., (2012). Using the International
Classification of Functioning, Disability and Health in assessing moral damages – Romanian Journal of
Legal Medicine, 20(1), pp. 77-82.

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Aspects Regarding Legal Liability of the Physician in Fetal


Ultrasonography

PAUN Silviu1, BERNAD Elena2, ONOFRIESCU Mircea3, VLĂDĂREANU Radu4


1 Discipline of Legal Liability Elements and Malpractice, 14th Department, Faculty of Medicine, “Carol Davila” University
of Medicine and Pharmacy, Bucharest (ROMANIA)
2 IIIrd Discipline of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Faculty of Medicine, “Victor

Babes” University of Medicine and Pharmacy from Timisoara (ROMANIA)


3 Discipline of Obstetrics and Gynecology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy

Iasi (ROMANIA)
4 Discipline of Obstetrisc-Gynecology and Neonatology, 13 th Department, Faculty of Medicine, “Carol Davila” University of

Medicine and Pharmacy, Bucharest (ROMANIA)


Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Introduction
The antenatal ultrasound screening of structural and chromosomal fetal malformations is
an important component of the prenatal care process. Early detection of malformations allows
the couple, together with the treating physician, in deciding to terminate the pregnancy within
legal limits. Informing the patient and the family about the situation should be done with
particular attention to the emotional impact, however, insisting on describing the possible
evolution of the case over time with all possible implications is mandatory.

Methodology
The case study includes a patient who was referred to the Ist Department of Obstetrics and
Gynecology of the “Pius Branzeu” Emergency Clinical Hospital Timişoara, being sent
urgently from a lower-grade maternity hospital for chronic fetal distress, severe
oligohydramnios. To analyze the legal implications, appropriate legal texts and relevant cases
settled by the Romanian courts were studied.

Results
After the assessment of the patient, emergency delivery through caesarian section was
decided. A live fetus with a focal point of the right foot attached directly to the base was
extracted. Ultrasound examination did not detect the malformation during pregnancy. The
postoperative progression was favorable for both the mother and the fetus. The analysis of
possible legal implications reveals ways to bring legal liability to medical staff.

Conclusions
The ultrasound failure of malformation is likely to cause consequences regarding attracting
the legal responsibility of the physician who has monitored the evolution of the pregnancy.
However, some conditions remove the legal liability of the medical staff.
Keywords: fetal malformation, phocomelia, ultrasound, legal liability

Introduction

Phocomelia is a rare birth defect that involves malformations of the arms or/and legs [1]. It
can be inherited as part of a genetic syndrome such as Roberts syndrome [2] or can be present

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isolate such as the presence of the lower limb phocomielia [3]. Phocomelia can also be caused
by maternal exposure to certain drugs (such as thalidomide) during pregnancy [4].
Ultrasound screening performs prenatal detection of the congenital malformations. The
results can be sometimes false positive [5] or can be misdiagnosed as anomalies [6]. Telling
the patient and the family of a suspected malformation is a source of stress for parents, and
setting a wrong ultrasound diagnosis can lead to expensive and sometimes iatrogenic medical
interventions [7, 8].

Methodology

The paper is a case study. We present a 24 years-old gravida, which has the following
diagnosis at the moment of admission in the Ist Department of Obstetrics and Gynecology of
the “Pius Branzeu” Emergency Clinical County Hospital Timisoara, Romania: primipara,
primigesta, with a singleton 40 weeks pregnancy, life fetus in pelvic presentation, intact
amniotic membranes, severe oligoamnios, chronic fetal distress, early labour. After
admission, the patient was investigated to deliver the fetus. It was decided to end the birth by
cesarean section for indications primipara with a fetus in pelvic presentation, severe
oligoamnios. Lack of amniotic fluid made the emergency ultrasound very difficult. No
apparent malformations were described [9].
The newborn had 2600 grams, and the one minute Apgar Score was 5.
At the extraction of the fetus was revealed the presence of the isolated lower limb
phocomelia – the right foot was attached directly to the trunk, with the absence of the thigh
and leg. Nor the obstetrical or family history of the patient was significant. The patient denied
taking drugs or radiation exposure during pregnancy. She had only 2 obstetrical consults with
this pregnancy, one at 6 weeks and one in the third trimester. The patient and her husband
received the news relatively easily, invoking religious reasons [10]. The ultrasound did not
detect the malformation during pregnancy. The postoperative progression was favorable for
both the mother and the fetus.
To identify the legal implications in our case study, the following methods have been
applied: the descriptive method, the observation method, and the documents analysis method.
These allowed us to reach a very accurate presentation of the legal framework applicable to
the case study and to investigate the legal liability of the medical staff further.

Results and Discussions

When a doctor makes a mistake, he or she must repair the damage incumbent to his/her
patient. According to the legal definition “malpractice is the professional misconduct which
occurs while rendering a medical or pharmaceutical service, which results in injury to a
patient, thus resulting in the civil liability of medical personnel and the provider of medical,
sanitary and pharmaceutical products and services” [11]. According to the legal definition of
malpractice, the existence of misconduct in the medical behavior should be proved, as well as
the existence of damage or injury incurred by a patient through such medical misconduct. It is
also necessary to be able to prove causality between the injury or damage incurred by the
patient and the act performed by the defendant.
Therefore, to analyze this case from a legal point of view, we have to take into account the
following elements:
A. Was there an illegal act?
B. Was there an injury?
C. Was there a causal link between the illicit deed and the injury?

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A. Was there an illegal act?


The illegal act is generally defined as a breach of the rules of conduct imposed by the law
or local habits. This means that medical malpractice can be analyzed from two points of view:
a legal approach (breach of the medical law) and a scientific approach (breach of the medical
guidelines endorsed by any responsible body of opinion in the relevant specialty) [12].
These legal regulations transpose modern bioethics principles into rules imposed to the
medical practice by coercion [13]. Failure to detect a malformation using an ultrasound
investigation is a medical error (breach of the medical guidelines endorsed by any responsible
body of opinion in the relevant specialty)?
An expert should look into whether a physician’s fault causes the failure or whether it has
occurred independently from a medical mistake.
Medicine has not advanced far enough to detect all the existing fetal malformations. A
multicenter European study (the Eurofetus Project) based on a mass screening program that
studied the effectiveness of ultrasound in the detection of fetal malformations identified that
the overall detection rate had a sensitivity of 61% [14]. In these circumstances the doctor's
responsibility is removed.
For further analysis purpose, let’s assume that the medical error occurred, the physician did
not notice a malformation that any other physician in his place would have spotted.

B. Is there an injury?
In the case presented above, there may be several complainants, namely: newborn, mother
and father.
As far as the newborn is concerned, there are specific malformations. In the case of
parents, the damage can be represented by the cost of treatment of the child (pecuniary
damages) and mental suffering (moral damages). The courts subjectively assess the moral
damages in the absence of an objective measurement instrument assumed by the legislator.
The are some indications that a tool developed by the World Health Organization for
measuring health and disability at both individual and population levels (The International
Classification of Functioning, Disability, and Health) could be used for assessing the moral
damages in the future [15].

C. Is there a causal link between the fault and the injury?


The physician’s misconduct has not determined fetal malformations. Even if the doctor has
mistaken and did not notice these malformations, he did not cause them. Under these
conditions, the doctor’s responsibility is excluded.
About the harm to parents, it can be argued that malformation could have provided parents
with other options, including termination of pregnancy. For this to be possible, however, it
was necessary and mandatory for the ultrasound examination to be performed at the age of
pregnancy allowing it to be detected and no more than 14 weeks. This malformation did not
endanger the life of the mother or the fetus; therefore it was not a therapeutical indication of
abortion [16].
After 14 weeks of age, even if the doctor mistakenly didn’t detect the malformation, the
damage would have been produced anyway by birth, any other conduct on the part of the
physician being excluded (interruption of pregnancy over the age of 14 weeks without
therapeutic indication in this sense it is a crime).
In our case, the ultrasound investigations were performed after 14 weeks, and the fetal
malformation was not a curable one.
In conclusion, there is no causal link between the physician's mistake and the injury to the
newborn nor the parents. This conclusion is consistent with court decisions in similar cases in
Romania [17].

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Therefore, even in the scenario where the physician's mistake can be demonstrated, it will
not be civilly liable for the cumulative fulfillment of the three conditions described above.

Conclusions

Ultrasonography is not a safe diagnostic method, and there are conditions in which the
diagnosis cannot be accurately determined. The detection rates of the structural anomalies
dependent on the equipment settings and the sonographer experience and vary according to
the organ system being examined. For the analysis of the legal implications in the described
case, the applicable legal texts and relevant cases settled by the Romanian courts were
studied.

REFERENCES
1. Bermejo-Sánchez, E., Cuevas, L., Amar, E., Bianca, S., Bianchi, F., Botto, L.D, Canfield, M.A.,
Castilla, E.E., Clementi, M., Cocchi, G., Landau, D., Leoncini, E., Li, Z., Lowry, R.B., Mastroiacovo,
P., Mutchinick, O.M., Rissmann, A., Ritvanen, A., Scarano, G., Siffel, C., Szabova, E., Martínez-Frías,
M.L., (2011). Phocomelia: a worldwide descriptive epidemiologic study in a large series of cases from
the International Clearinghouse for Birth Defects Surveillance and Research, an overview of the
literature. Am J Med Genet C Semin Med Genet, 2011, 157C(4), pp. 305-320.
2. Goh, E.S., Li, C., Horsburgh, S., Kasai, Y., Kolomietz. E., Morel, C.F., (2010). The Roberts
syndrome/SC phocomelia spectrum-a case report of an adult with a review of the literature. Am J Med
Genet A, 152A, pp. 1-478.
3. Priyanka, B., Akhil, B., Shitalmala D., (2012). Isolated Lower Limb Phocomelia – a Rare Limb
Malformation. Iran J Pediatr, 22(3), pp. 432-433.
4. Vargesson, N., (2015). Thalidomide‐induced teratogenesis: History and mechanisms. Birth Defects Res
C Embryo Today, 105(2), pp. 140-156.
5. Debost-Legrand, A., Laurichesse-Delmas, H., Francannet, C., Perthus, I., Lémery, D., Gallot, D.,
Vendittelli, F., (2014). False positive morphologic diagnoses at the anomaly scan: marginal or real
problem, a population-based cohort study. BMC Pregnancy Childbirth, 14, p. 112.
6. Bernad, S.I., Bernad, E.S., Barbat, T., Barbu, D., Albulescu, V., (2010). Assessment of the placental
blood flow in the developing and growth-restricted fetus, Proceedings of the 22nd European Congress of
Perinatal Medicine, Granada, Spain, May 26-29, pp. 127-130.
7. Ermito, S., Dinatale, A., Carrara, S., Cavaliere, A., Imbruglia, L., Recupero, S., (2009). Prenatal
diagnosis of limb abnormalities: the role of fetal ultrasonography J Prenat Med, 3(2), pp. 18-22.
8. Petre, I., Bernad, E., Muresan, A., Bordianu, A., Bernad, S.I., Bacean, O., Folescu, R., Milulescu, A.,
Pantea, S., (2015). Choriocarcinoma developed in a tubal pregnancy – a case report, Rom J Morphol
Embryol, 56(2 Suppl), pp. 871-874.
9. Bernad, E.S., Craina, M., Tudor, A., Bernad, S.I., (2012). Perinatal outcome associated with nuchal
umbilical cord, Clinical and Experimental Obstetrics & Gynecology, 39(4), pp. 494-497.
10. Enatescu, V.R., Enatescu, I., Craina, M., Gluhovschi, A., Papava, I., Romosan, R., Marian, C., Oprea,
A., Bernad, E., (2014). State and trait anxiety as a psychopathological phenomenon correlated with
postpartum depression in a Romanian sample: a pilot study, Journal of Psychosomatic Obstetrics and
Gynecology, 35(2), pp. 55-61.
11. Law 95/2006 regarding health reforms, as subsequently amended and supplemented, art. 653, paragraph
1, letter b)
12. Pițuru, S., Vlădăreanu, S., Păun, S., Nanu, A., (2015). Malpractice and professional liability of medical
personnel – Farmacia, 63(2), pp. 318-324.
13. Nanu, A., Bulgaru-Iliescu, D., Rotaru, T.S., Oprea, L., (2015). The Gap between Bioethics Principlism
and Judicial Responsibility: How Social Sciences Can Help Romanian Law – Revista de cercetare si
interventie sociala, 49, pp. 216-228.
14. Levi, S., (2003). Mass screening for fetal malformations: the Eurofetus study. Ultrasound Obstet
Gynecol, 22, pp. 555-558.
15. Nanu, A., Georgescu, D., Bulgaru, D., Berteanu, M., Radulescu, C., (2012). Using the International
Classification of Functioning, Disability, and Health in assessing moral damages, Romanian Journal of
Legal Medicine, 20(1), pp. 77-82.

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16. Octavian, O.G., Ionescu, A.C., Lesnic, A., Filipescu, G.A., Ples, L., (2018). Ethical and medico-legal
aspects of the therapeutic abortion – our experience. Romanian Journal of Legal Medicine, 26(1), pp.
82-85.
17. Civil sentence no. 2891, 2012, Law Court Iasi, Romania.

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Ultrasound Assessment of the Umbilical Cord Knot

BERNAD Elena1, MOZA Andreea2, BERNAD I. Sandor3


1 The University of Medicine and Pharmacy Victor Babes Timisoara (ROMANIA)
2 “Pius Brinzeu” Emergency Clinic County Hospital Timisoara, IInd Department of Obstetrics and Gynecology, Timisoara
(ROMANIA)
3 Romanian Academy – Timişoara Branch, Centre for Fundamental and Advanced Technical Research (ROMANIA)

Emails: [email protected], [email protected], [email protected]

Abstract

Umbilical cords have a complex geometrical structure. In this complex structure, umbilical
arteries are longer than the umbilical vein. Umbilical arteries are wrapped around each other
and wrapped vein, so finally, the umbilical cord forms a triple helix. In the medical practices,
the physicians use the word knot for two different structures, namely, for the called “false
knot” and for the “true knot”. Of the 84 women with singleton pregnancies who gave birth at
our Department during the study period, 5 (1.19%) experienced true umbilical cord knot.
Measured umbilical cords were significantly longer in cases of cord knot (mean 74.3±10.2 vs.
53.4±10.8 cm – regular umbilical cord). True knot was present in 5 cases (5.95%) and the
false knot in 1 cases (1.19%) in the study group. From the results presented in this study, we
can conclude that the risk factors associated with true umbilical cord knot formation are: the
cord length, multiparous women, hypertension, obesity, diabetes and fetal activity.
Keywords: ultrasonography, umbilical cord knot, risk factor, pregnancy

Introduction

The primary function of the umbilical cord is to carry blood and oxygen to the fetus. In the
pregnant human females, the umbilical cord is typically composed of two arteries and one
vein [1].
The vein is twisted around the arteries, and the arteries are twisted within the cords to form
a triple helix. The length of the umbilical cord at birth (38 weeks) is 57±12cm [2].
Umbilical cords have a complex geometrical structure. In this complex structure, umbilical
arteries are longer than the umbilical vein. Umbilical arteries are wrapped around each other
and wrapped vein, so finally, the umbilical cord forms a triple helix. Umbilical cords can be
either left-handed, right-handed, straight or with mixed helicity [3].
In the medical practices, the physicians use the word knot for two different structures,
namely [4, 5]: for the called “false knot” and for the “true knot”. The frequencies of the true-
knots formation during the gestation is around of 1% of all pregnancies [4-7].
If a true knot is detected, further fetal surveillance is required both by fetal
cardiotocography and Doppler flow velocity [8]. The literature mentioned that detection of an
umbilical cord knot is not an indication for delivery unless is it associated with evidence of
compromise of the fetal circulation. The presence of the umbilical cord are associated with an
increased risk of change of the umbilical cord hemodynamic pattern, and therefore, the
literature suggests a targeted sonographic examination of the last signs of the presence of the
pathological hemodynamic [9-10].

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This study aimed to determine the association between the true umbilical cord knot and the
adverse pregnancy outcomes among the cases where the true knot was detected using
ultrasound technique [11-13].

Patients and method

This study was conducted in the Department of Obstetrics and Gynecology of the County
Emergency Hospital Timisoara, Romania. This study used data for May 2012, to December
2012. After vaginal or cesarean deliveries, the placenta and umbilical cord were checked
clinically and measured (insertion of the umbilical cord, weight of placenta and length of the
umbilical cord). Gestational age was defined based on the date of the last menstrual period,
and by ultrasound, if there was a disparity of more than three days on the first-trimester
measurement or 7 days on the second-trimester measurement.

Fig. 1. A) A longitudinal scan of an umbilical cord knot. B) and C) The true knot measurement after delivery

Results

In this study conducted in the Department of Obstetrics and Gynecology of the County
Emergency Hospital Timisoara Romania, were included 84 pregnant women who delivered in
our department from May 2011 to December 2011.

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Fig. 2. A) gray-scale ultrasound evaluation of the umbilical cord shows the presence of the cord knot; B) and C)
Macroscopic images of the true knot after delivery (normo-coiled umbilical cord).

Of the 84 women with singleton pregnancies who gave birth at our Department during the
study period, 5 (1.19%) experienced true umbilical cord knot. Measured umbilical cords were
significantly longer in cases of cord knot (mean 74.3±10.2 vs. 53.4±10.8 cm – regular
umbilical cord). True knot (Figure 1 and 2) was present in 5 cases (5.95%) and the false knot
in 1 cases (1.19%) in the study group. Average birth weight for the true knot group is 3025
(values between 1825g-4075g), and for the false knot group, the average birth weight was
2775±0g (Table 1 and Figure 3).

Discussions

Several studies, related about adverse pregnancy and delivery outcomes such as
intrauterine fetal death [14-17], cord accidents [18, 19], higher risk of cesarean delivery and
low Apgar score at 1 minute [3, 20-21].

Table 1. Umbilical knot type characteristics


NVD CD Birth weight
Knot type Cases Corg length [cm]
[cases] [cases] [g]
true knot 5 4 1 3025±1081 74.3 ± 10.2
false knot 1 1 0 2775±0 58.4±0
NVD – normal vaginal delivery
CD – cesarean delivery

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Fig. 3. Umbilical cord knot distribution in normal and cesarean delivery.

Conclusions

From the results presented in this study, we can conclude that the risk factors associated
with true umbilical cord knot formation are: the cord length, multiparous women,
hypertension, obesity, diabetes and fetal activity.
Also, the study can conclude the presence of a higher incidence of umbilical cord knot
among the male fetuses.

Acknowledgment
For S.I. Bernad this work was partially supported by the CFATR/LHC 2016-2020 research
programme. For Elena Bernad this work was supported by the grant of the Romanian National
Authority for Scientific Research and Innovation, CNCS/CCCDI–UEFISCDI, project number
PN-III-P2-2.1-PED-2016-0293, within PNCDI III.

REFERENCES

1. Malpas, P., Symonds, A. M., (1966). Observations on the structure of the human umbilical cord.
Surgery Gynec. Obstet 123, pp. 746-750.
2. Ente, G., Penzer, P.H., (1991). The umbilical cord: normal parameters. J. Roy.Soc. Health, August, pp.
138-140.
3. 50. Fletcher, S. (1993). Chirality in the umbilical cord. Brit. J. Obstet. Gynec., 100, pp. 234-236.
4. Joura, E.A., Zeiler, H., Sator, M.O., (1998). Epidemiologie und klinische wertigkeit von echten
nabelschnurknotten. Wien. Klin. Wochenschr 110, pp. 232-235.
5. Sornes T., (2000). Umbilical cord knots. Acta Obstet. Gynecol, Scand. 79, pp. 157-159.
6. Hershkovitz, R., Silberstein, T., Sheiner, E., Shoham-Vardi, I., Holcberg, G., Katz, M., Mazor, M.,
(2001). Risk factors associated with true knots of the umbilical cord. Eur. J. Obstet. Gynecol. Reprod.
Biol. 98, pp. 36-39.
7. Airas, U., Heinonen, S. (2002). Clinical significance of true umbilical knots: A population-based
analysis. American J. Perinatology, 19, pp. 127-132.
8. Ulm, M.R., Obwegeser, R., Ulm, B., Deutinger, J. (1998). An undetected reason for severe fetal growth
retardation. Eur J Ultrasound, 8, pp. 213-217.
9. Jones, I. (1998). A truly knotted cord. Aust N Z J Obstet Gynaecol, 38, pp. 98-99.
10. Sherer, D.M., Dalloul, M., Zigalo, A., Bitton, C., Dabiri, L., Abulafia, O. (2005). Power Doppler and 3
dimensional sonographic of multiple separate true knots of the umbilical cord. J Ultrasound Med 24, pp.
1321-1323.

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11. Bernad, S.I., Bernad, E.S., Barbat, T., Barbu, D., Albulescu, V., (2010). Assessment of the placental
blood flow in the typically developing and growth-restricted fetus. Proceedings of the 22nd European
Congress of Perinatal Medicine, May 26-29, 2010, Granada, Spain Advances in perinatal medicine, pp.
127-130
12. Bernad, S.I., Bernad, E.S., Barbat, T., Barbu, D., Albulescu, V., (2010). Assesment of the placental
blood flow in the developing and growth-restricted fetus, Proceedings of the 12th European Congress of
Perinatal Medicine, Granada, Spain, May 26-29, pp. 127-130.
13. Vida, M.M., Lupse, O.S., Stoicu-Tivadar, L., Bernad, E., (2012). Flexible Solution for Interoperable
Cloud Healthcare Systems. Proceedings of the 24 th Medical Informatics in Europe Conference (MIE),
Aug 26-29, 2012, Pisa, Italy. QUALITY OF LIFE THROUGH QUALITY OF INFORMATION, Book
Series Title: Studies in Health Technology and Informatics, Volume: 180, pp. 280-284, DOI:
10.3233/978-1-61499-101-4-280.
14. Räisänen, S., Georgiadis, L., Harju, M., Keski-Nisula, L., Heinonen, S., (2013). True umbilical cord
knot and obstetric outcome. International Journal of Gynecology and Obstetrics 122, pp. 18-21.
15. Aibar, L., Puertas, A., Valverde, M., Carrillo, M.P., Montoya, F., (2012). Fetal sex and perinatal
outcomes. J Perinat Med 40(3), pp. 271-276.
16. Oron, T., Sheiner, E., Shoham-Vardi, I., Mazor, M., Katz, M., Hallak, M., (2001). Risk factors for
antepartum fetal death. J Reprod Med 46(9), pp. 825-30.
17. Toivonen, S., Heinonen, S., Anttila, M., Kosma, V.M., Saarikoski S., (2002). Reproductive risk factors,
Doppler findings, and outcome of affected births in placental abruption: a population-based analysis.
Am J Perinatol 19(8), pp. 451-60.
18. Bernad, S.I., Bosioc, A.I., Bernad, E.S., Craina, M.L., (2015). Helical type coronary bypass graft
performance: Experimental investigations, Bio-Medical Materials, and Engineering, 26(s1), pp. 477-
486.
19. Petre, I., Barjica, D., Duta, C., Boglut, A., Bernad, E., Craina, M., Bolintineanu, S., Pantea, S., Radu,
D., Ionita, I., (2016). Sclerotherapy for Varicose Veins, Materiale Plastice, 53(4), pp: 765-766.
20. Papinniemi, M., Keski-Nisula, L., Heinonen, S., (2007). Placental ratio and risk of velamentous
umbilical cord insertion are increased in women with placenta previa. AmJ Perinatol, 24(6), pp. 353-
357.
21. Ionita, I., Grigorita, L., Miloicov, C.B., Petre, I., Bernad, E., Craina, M., Diaconu, M., Citu, C., Radu,
F., Oros, D., Boglut, A., Furau, G., Enatescu, V., (2016). The Role of Thrombophilia in Pregnancy,
Revista de Chimie, 67(12), pp. 2643-2647.

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Hepatic Artery Emodynamics in IUGR Fetuses Vs. Macrosomic


Fetuses with Diabetic Mothers

BOȚ Mihaela1, VLĂDĂREANU Radu1, PETCA Aida1, BURNEI-RUSU Anca1,


ZVÂNCĂ Mona1
1Elias Emergency Hospital Bucharest, Department of Obstetrics-Gynecology and Neonatology, University of Medicine and
Pharmacy Carol Davila, Bucharest, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

The fetal liver, being a large, well-vascularized organ, easily to visualise via ultrasound
examination, has been of great interest and has so far benefited from a series of velocimetric
measurements, such as the hepatic artery. Doppler velocimetry measurements of fetal hepatic
artery in intrauterine growth restriction fetuses showed the installation of the adaptive
mechanism of circulatory redistribution both in the case of the hepatic artery, and at the level
of the middle cerebral artery in the case of a decrease in the umbilical flow. This mechanism
represents the process of vasodilatation in these vessels (implicitly, the increase in blood
flow), coupled with the increase of the shunting degree through the ductus venosus, thus
ensuring an adequate intake of blood to the heart, brain and the hepatic tissue (noble tissues).
This pattern of intrahepatic hemodynamics is called hepatic buffer response and seems to
work from intrauterine life, under conditions of chronic hypoxemia within IUGR. This kind of
response is not seen in cases of fetal macrosomia, complicated with gestational diabetes
mellitus.
Keywords: hepatic artery, hepatic buffer response, IUGR, ductus venosus, mean cerebral artery, umbilical artery, fetal
macrosomia

Introduction

Ultrasound assessment of fetal liver during pregnancy has been of great interest since the
beginning of detailed anatomical examination of the fetus. Being a large organ, relatively
easily to visualize via the ultrasound technique, while having an important metabolic function
and a rich vascularization, the fetal liver has benefited from multiple attempts to standardize
the measurement criteria for Doppler velocimetry, such as the flows through the hepatic
artery.
The mechanisms that control intrahepatic circulation in physiological situations are closely
related to umbilical, placental and cardiac function. Thus, the key element, the essential
outlet, is the ductus venosus (1). During the second half of pregnancy, under physiological
conditions, about 30% of the umbilical venous flow shunts through the ductus venosus
towards systemic circulation, particularly towards the brain. After 30 weeks of gestation, this
ratio is reduced to 20%, the remaining 70-80% being intra-hepatically distributed (1).
During hypoxemia, there is an increased vasoconstriction in the portal circulation (2, 3)
and a less increased one in the ductus venosus (4, 5), by adrenergic stimulation. This will lead
to a redistribution of an even greater supply of blood (6) to the cardio-cerebral circulation
under sympathetic stimulation (7, 8). Many factors combine in varying degrees and
proportions to adjust the proper supply of oxygenated blood to different organs, according to

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priorities (1). The increase of the shunting degree through the ductus venosus provides a more
or less adequate blood supply to the heart and brain, a situation that is often maintained for
long periods of time.
It is obvious that in these conditions, the liver, an organ which is of uppermost priority,
will be hypoxic, state which can disrupt its long-term development.
IUGR refers to a suboptimal fetal growth/below the potential of a fetus under normal
conditions and which is caused by a cause of chronic fetal distress (9). The use of Doppler
ultrasonography in assessing the fetal circulation, the fetal cardiac activity and fetal
biophysical profile examinations have improved the defining framework of IUGR. The
adjusting of the fetal circulation is a phenomenon triggered by hypoxemia with the aim to
preserve the function of vital organs. The increased cardiac output determined by the
increased fetal heart rate fails to compensate for the fetal needs in such situations. Therefore,
the distribution of oxygenated blood is preferentially directed towards the heart and brain.
This redistribution or “centralization” phenomenon has both an arterial and a venous
component (10). Maternal conditions that can lead to IUGR are: pregnancy-induced
hypertension/preeclampsia complicated by IUGR in approximately 30-40% of cases (11, 12),
diabetes mellitus complicated by IUGR in 10-20% of cases irrespective of the glycemic level,
respiratory, cardiac and hematological disorders.
Similarly, the intrauterine environment may be compromised by smoking (13,14) and
drug/toxic substance use (15). These factors frequently lead to asymmetric IUGR, with
different effects on fetal development (16).
Fetal macrosomia/Large for gestational age (LGA) refers to a birth weight greater than the
th
90 percentile for gestational age or a weight greater than 4000g and occurs in 15-45% of
gestational diabetes mellitus cases. It is common in all diabetes classes, suggesting that it
could rather be the effect of metabolic disorders in the last trimester of pregnancy (17). Fetal
Doppler velocimetry does not detect changes in the parameters to be measured in conditions
of uncomplicated gestational diabetes mellitus (18).

Aim

This is a prospective study conducted in the Department of Obstetrics and Gynecology of


Elias University Emergency Hospital Bucharest, during a period of 36 months, from
December 2010 until November 2013, within POSDRU 107/1.5/S/82839 research project.
The research had two distinct stages. One stage was to establish a standardized technique
for measuring the peak systolic velocity and the pulsatility index in the fetal hepatic artery in
the second and third trimesters and the reference intervals (19). The second stage aimed to test
the hypothesis that the hepatic arterial buffer response operates prenatally, in the fetal liver
(20), in certain situations such as intrauterine growth restriction and gestational diabetes
mellitus (21, 22).

Materials and method

The study population was divided into two different lots. Lot 1 included 38 pregnant
women with intrauterine growth restriction (with/without pregnancy-induced
hypertension/preeclampsia), while Lot 2 included 9 pregnant women with gestational diabetes
mellitus. The measured variables for both study groups were: maternal demographic
characteristics (maternal enrollment age, BMI, parity and smoking rate) and newborn data
such as fetal weight at birth, the 5th minute Apgar score and the exact gestational age at birth.
The pregnant women were examined three times during the second and third trimesters of
pregnancy (21-23 weeks of gestation, 26-28 weeks and 31-33 weeks). During the

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examination, we assessed the pulsatility index in the fetal hepatic artery (HA-PI) – Fig. 1, the
middle cerebral artery (MCA-PI), and in the umbilical artery (UA-PI) and the fetal biometry.

Regarding the HA-PI values of Lot 1 and 2, we had the following findings:
- They were compared to normal values of normoponderal fetuses, singleton
pregnancies, without any associated pathologies (19). For the latter cases, HA-PI
values increase directly in proportion to gestational age and fetal weight, which is
explained by the increase of the vascular calibre and do not correlate with the flows
measured in MCA and UA, suggesting that these flows evolve according to an
individual pattern in fetuses with normal umbilical flow (19).
- We analysed the influence of the variables to be investigated on PI-HA.

Fig. 1. Normal Doppler flow in the fetal hepatic artery during the first ultrasound, 21-23 weeks of gestation
(21 weeks + 3 days)

Fig. 2. Normal Doppler flow in the fetal hepatic artery during the ultrasound at 31-33 weeks of gestation
(31 weeks + 4 days)

Results

In normoponderal fetuses, HA-PI increases progressively, directly related to gestational


age and fetal weight measured in percentiles (19).
Lot 1 – 38 cases of IUGR fetuses (pregnant women with/without pregnancy-induced
hypertension/pre-eclampsia). The age of pregnant women ranged between 23 and 42 years,
with an average of 34.13 years (deviation standard 4.44). In terms of BMI (23.24), subjects
were between 19.29 and 44.98, with an average of 28.1 (being considered overweight, as they
ranged from 25-29.99).
Analysing and centralizing the distribution of the group of fetuses with IUGR according to
HA-PI values within the same chart, for all 3 assessments – at 21-23 weeks of gestation, 26-
28 weeks and 31-33 weeks – we noticed that the HA-PI values for the ultrasound performed

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in the 21-23 week of gestation were greater than the 10th percentile corresponding to the
gestational age. At the following two ultrasound assessments, at 26-28 weeks of gestation and
31-33 weeks, they showed a progressive evolution mostly below the 10th percentile
corresponding to gestational age (abnormal Doppler flow) – Fig. 3.

Fig. 3. Abnormal Doppler flow in the fetal hepatic artery during the first ultrasound, 21 to 23 weeks of gestation
(23 weeks + 1 day)

Using the Mann-Whitney test, we also compared the HA-PI values for IUGR fetuses and
for the ones with normal weight. We found statistically high significant differences (p <0.001)
at all 3 ultrasound examinations between the two groups, always the pulsatility index in the
hepatic artery being higher in fetuses with a normal weight compared to IUGR fetuses.
In order to evaluate the relationship between HA-PI and MCA-PI and between HA-PI and
UA-PI – simultaneously performed measurements – at each of the three ultrasound
examinations for IUGR fetuses we used the Pearson correlation coefficient r. During the first
examination for the IUGR fetuses, at 21-23 weeks of gestation, we found only one
statistically significant correlation (p <0.05), namely the connection between HA-PI and
MCA-PI values. The relationship is inversely proportional – the higher HA-PI is, the lower
MCA-IP is – r = -0.428.

Lot 2 – 9 pregnancies complicated with gestational diabetes mellitus. We performed


the nonparametric Mann-Whitney test in order to identify possible differences in Doppler
flows in the hepatic artery in fetal macrosomia cases originated from pregnancies complicated
with gestational diabetes mellitus. There were found no significant differences between HA-
PI values in the fetuses with macrosomia as opposed to the normoponderal ones (19) - p
Mann-Whitney = 0.002 <0.05.

Discussions and conclusions

To sum up, regarding the results obtained by statistical analysis of the IUGR fetuses in an
attempt to test the hypothesis that the hepatic artery buffer response operates prenatally, we
found that:
➢ The intrauterine growth restriction installed progressively after 26-28 weeks of
gestation, most frequently after the 30th week, in line with the literature (25, 26, 27).
➢ UA Doppler blood flows (UA-PI increase) changed from the nomogram, thus
demonstrating the degree of placental dysfunction with decreased umbilical flow,
correlated with the evolution of fetal weight towards growth restriction (28, 29).
➢ At the same time as the UA-PI increased and the umbilical flow decreased, we found
the pulsatility index in the middle cerebral artery (MCA-PI) decreasing compared to

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the nomogram, thus demonstrating the phenomenon of centralizing and circulatory


redistribution with vasodilatation at the cerebral level for protective purposes (30,
31,32).
➢ In parallel with the decrease of MCA-PI (33, 34) we found the decrease of HA-PI,
suggesting the installation of the adaptive mechanism of circulatory redistribution (35)
also in the hepatic artery, in case of umbilical flow decrease. This mechanism is
basically the process of hepatic artery vasodilatation and, implicitly, of the increase of
blood flow through this vessel, in conditions of drastic decrease of blood supply
through the portal vein, corroborated with the increase of the shunting degree through
the ductus venosus (36, 37). In so doing, an adequate supply of blood reaches the heart
and brain. This model of intrahepatic hemodynamic regulation is called the
hepatic buffer response (20) and appears to function from intrauterine life, under
conditions of chronic hypoxemia in IUGR fetuses, although the hepatic artery has a
relatively modest contribution to hepatic vasculature (38, 39, 40, 41). This adaptive
process reflects the extremely important role of the liver, a multifunctional organ
within the fetal body. However, by identifying a single statistically significant
correlation, namely the relationship between the HA-PI and MCA-PI values, at only
21-23 weeks of gestation in fetuses with IUGR, we have found that these circulatory
prioritizations take place for the purpose of sparing the fetal liver vasculature, but
only at an early stage of fetal compromise.

Similar data were obtained in the lot with fetal macrosomia, but the mechanisms need to be
studied thoroughly because the low prevalence of the studied pathology prevented us from
getting statistically significant results. I must mention that in this case we are not talking
about an adaptive mechanism of the hepatic artery, the excessive fetal growth not being the
result of an increased blood flow through the hepatic artery and an increased hepatic
anabolism, but the result of the metabolic disorders caused by maternal gestational diabetes
mellitus.
I was aware of the theoretical limitations when I approached the subject, but I considered
that additional data on the Doppler ultrasound assessment of the fetal hepatic artery would be
of great practical value for future pregnancies with a decreased umbilical flow. Only the
future will give us an answer to the question: “Is the liver of the fetus the fourth preferential
organ?” (42).

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27. Figueras F, Gardosi J. Intrauterine growth restriction: newconcepts in antenatal surveillance, diagnosis,
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Diagnosis of the Degree of Severity of the Anterior Perineal


Compartment Prolapse: Parallels Between Clinical Examination
and Ultrasonography

BOȚ Mihaela1, VLĂDĂREANU Radu1, BORISLAVSCHI Andreea1,


PETCA Razvan2, PETCA Aida1
1 Elias University Hospital, Obstetrics & Gynecology and Neonatology Department, University of Medicine and Pharmacy
“Carol Davila”, Bucharest, (ROMANIA)
2 Burghele Clinical Hospital, Bucharest, University of Medicine and Pharmacy “Carol Davila”, Bucharest, (ROMANIA)

Email: [email protected]

Abstract

The cystocele’s degree of severity is most often established by clinical examination. An


accurate classification is essential in selecting the optimal treatment, as in the case of mild and
moderate forms of cystoceles, conservative treatment is recommended, whereas the severe
form of cystocele warrants the surgical reconstruction of the pelvic floor. The simple clinical
examination is not sufficient in choosing the optimal treatment for each case. Diagnosis by
imaging is more reproducible than diagnosis by clinical examination, thus it became an
essential tool in the protocol of diagnosis. Due to its non-invasive characteristic, high
availability and low cost, the translabial or transperineal ultrasonography is wide spread. The
diagnosis of the cystocele’s degree of severity by transperineal ultrasonography is decisive in
electing treatment and avoiding surgical intervention, however it runs a greater risk of
subjectivity.

Article

The cystocele is defined by the International Continence Society as the prolapse of the
anterior vaginal wall such that urethrovesical junction (a point 3 cm proximal to the external
urinary meatus) is less than 3 cm above the plane of the hymen [1], [2].
Pelvic floor weakness and organ prolapse is relatively common condition in middle aged
and elderly parous women who present with: pain, pressure, urinary and fecal incontinence
[3], [4], constipation, urinary retention, that can have a significant impact on quality of life
[5].
From the clinical point of view, the anterior perineal compartiment prolapse clasifies in 3
degrees: mild, moderate and severe. A correct classification is essential in selecting the
optimal treatment, as in the case of mild and moderate forms of cystoceles, conservative
treatment by inserting a pessary ring is recommended, whereas the severe form of cystocele
needs the surgical reconstruction of the pelvic floor. Therefore, physicians have realized that
clinical assessment alone is a not enough for electing the optimal treatment for each case. The
recurrence after pelvic reconstructive surgery is common [6], the problem is poor diagnosis,
not poor treatment (the best procedure in the hands of a highly competent surgeon will be a
failure if performed on the misdiagnosed patient). Diagnosis by imaging is more reproducible
than diagnosis by palpation, thus it became an essential tool in the protocol of diagnosis [7],
[8], [9].
History. Starting with the 1980s, due to the increasing availability of ultrasonography, the
women urinary incontinence methods of examination include transabdominal, transperineal,

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transvaginal and transrectal ultrasonography. Due to its non-invasive character, high


availability, low cost, the use of translabial or transperineal ultrasonography is wide spread
[10].
Transperineal ultrasonography. The traditional classification proposed by Green [11] on
cystocele [12], [13], [14] it’s based on measuring the uretrovesical angle (the angle between
the proximal urethra and trigonal surface of the bladder si the degree of urethral rotation):
• Type I – open retrovesical angle (≥140°) and urethral rotation <45°
• Type II – open retrovesical angle (≥140°) and urethral rotation between 45° and 120°
= cystourethrocele:
o Stress urinary incontinence
• Type III – intact retrovesical angle (<140°):
o Genital prolaps symptomatology and voiding dysfunction
By the clinical point of view, the type III cistocele differentiates from the type II
(cystourethrocele) by identifying a groove made by the bladder neck on the anterior vaginal
wall (suggesting an intact retrovesical angle).
Ultrasonography is done with the patient in lithotomy position, with both hips flexed and
slightly abducted or in standing position – Fig. 1. Voiding the bladder is preferable. The
transducer is placed against the perineum in the midsagittal position and at the maximal
Valsalva maneuver can be identified the descent of the neck bladder, the degree of
retrovesical angle and the urethral rotation to detect the degree and Green type of the
cystocele.

Fig. 1. Transducer placement for translabial/perineal ultrasound – longitudinal and transversal view
(author’s personal collection)

Fig. 2. Voluminous cystocele (type III) – author’s personal collection

The transperineal ultrasonography diagnostic of the degree of severity of cystocele is


decisive in selecting the treatment and avoiding the surgical intervention, however it runs a
greater risk of subjectivity.

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There are studies who use in the ultrasonographyc diagnostic a reference line crossing the
inferoposterior margin of the symphysis pubis [16] (fixed in one point) or the midpubic line
[17] – >Fig. 2.
Ultrasonographic classification together with clinical examination of cystocele using as
reference line the midpubic line (bony fixed structure) measure the position of the inferior
point of the bladder during rest and in Valsalva maneuver:
• Group I – in Valsalva maneuver: the lowing point at more than 1 cm above the
midpubic line which clinical is degree 0 sau 1 (should not be considered prolapse);
• Group II – the lowest end is 1 cm above midpubic line and in clinical examination
may be seen and maybe also felt by coughing patients; they can be framed as anterior
perineal compartiment prolapse;
• Group III – above the midpubic line. At the clinical examination, it is identified the
voluminous cystocele, the patients detect the prolaps when coughing, a reason to refer
to the uro-gyneclologist specialist doctor.
In terms of this classification, the surgical intervention being mainly based on the restricted
mobility of the bladder, group I does not require surgical intervention, while group III
definitely requires, and group II might require.
For the most part the cystocele’s degree of severity is easily determined by clinical
examination, but in some cases in which an extensive genital prolapse may prevent the precise
diagnosis of cystocele or its degree, or even the accurate Green classification between grade II
and III (etiologies with different functional implications), which indicates the corelation with
ultrasonography [18, 19, 20].

REFERENCES

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and pelvic floor dysfunction: an imaging panel and practical approach, ultrasound. Obstet Gynecol
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3. Berceanu C, Bratila E, Cirstoiu MM, Bot M, Berceanu S, Ciortea R, Petca A, Bohiltea R, Paitici S,
Mehedintu C. Clinical Assessment in Bowel Dysfunction Associated with Pelvic Organ Prolapse. 2017.
PROCEEDINGS OF THE 14TH NATIONAL CONGRESS OF UROGYNECOLOGY AND THE
NATIONAL CONFERENCE OF THE ROMANIAN ASSOCIATION FOR THE STUDY OF PAIN;
pp. 48-53 ISBN:978-88-95922-98-0.
4. Boț Mihaela, Vlădăreanu Radu, Vlădăreanu Simona, Zvâncă Mona,
Petca Aida – Stress urinary
incontinence (SUI) due to causes other than parturition. Proceeding for the 13th national congress of
urogynecology, UROGYN 2016, FiLOdiritto editore, pp. 56-62, ISBN 978-88-95922-78-2.
5. Mocuta, D; Popovici, LR; Dumitriu, AS; Burlibasa, L; Ionescu, CA, Sfeatcu, R. METALURGIA
INTERNATIONAL Volume: 14; pp. 62-64 Published: 2009. Accession Number:
WOS:000272155900013.
6. Song Y, Wang X-J, Chen Y-S, Hua K-Q. Management of Urinary Incontinence before and after Total
Pelvic Reconstruction for Advanced Pelvic Organ Prolapse with and without Incontinence. Chinese
Medical Journal. 2018; 131(5): pp. 553-558. doi:10.4103/0366-6999.226057.
7. Bot M, Burnei-Rusu A, Mitran M, Bohiltea R, Nastasia S, Coroleuca C, Vladareanu R. Aspects of
Ultrasound Imaging in the Genital Prolapse.2017. 5 th Romanian congress of the Romanian Society of
Ultrasound in Obstetrics and Gynecology. ISBN: 978-88-95922-95-9.
8. Berceanu C, Cirstoiu MM, Berceanu S, Ciortea R, Bot M, Gheonea IA. Ultrasound Evaluation of the
Posterior Perineal Compartment. 2017. 5 TH ROMANIAN CONGRESS OF THE ROMANIAN
SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY; pp. 67-72. ISBN:978-88-
95922-88-1.

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9. Ples L, Sima RM, Stanescu AD, Poenaru MO, Moga M. Transperineal Ultrasound Role for Pelvic Floor
Dysfunction Evaluation. 2016. 13TH NATIONAL CONGRESS OF UROGYNECOLOGY (UROGYN
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Dysfunction and Pelvic Surgery in the Elderly. Springer, New York, NY. Online ISBN 978-1-4939-
6554-0.
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15. Bot M, Ichim M, Oprescu C, Mehedintu C, Berceanu C, Zvanca M, Petca A. The Role of Transperineal
Ultrasound in the Assessment of the Modern Surgical Treatment Efficiency in Stress Urinary
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UROGYNECOLOGY AND THE NATIONAL CONFERENCE OF THE ROMANIAN
ASSOCIATION FOR THE STUDY OF PAIN; pp. 69-73. ISBN:978-88-95922-98-0.
16. Dietz. Pelvic floor ultrasound: a review. Am J Obstet Gynecol 2010.
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by Transperineal Ultrasonography”. Journal of Evolution of Medical and Dental Sciences 2014; Vol. 3,
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The Severe Form of Preeclampsia. Particular Situations, Clinical


and Therapeutic Implications

BRAILA Anca Daniela1, BRAILA Mihai1, VIRCAN Elena2, RODICA Velea1,


NEACSU Adrian3
1 University of Medicine and Pharmacy of Craiova, Department of Obstetrics and Gynaecology, (ROMANIA)
2 Allergology and Clinical Immunology, Fundeni Clinical Institute, Bucharest (ROMANIA)
3 University of Medicine and Pharmacy Carol Davila,Bucharest (ROMANIA)

Email: [email protected]

Abstract

Gestational hypertension is a decisive factor in the triggering of some severe


complications: eclampsia, retro placental hematoma, HELLP syndrome, intrauterine growth
restriction, prematurity, intra uterus fetal death. Those 6 clinical cases shown are the layout of
the gestational hypertension, complications of the severe forms of preeclampsia. These cases
have not been attended in the region, not investigated, probably with organic deficiencies, of
which detection should have been made preconceptionally or previously in the gestation.
Through its paternal component, the gestation represents a provocation for the transplant
heterology because of the antigen-antibody immuno-genetic conflict. For that reason, the fetal
annexes can be called “a gestational biological transitory system”.
The objective of the study consists in the importance of the ultrasound study and multi
vascular arterial Doppler at the pregnancies with hypertension and restriction of intrauterine
growth, in the reduction of the morbidity and the prenatal mortality. The results to these cases
are satisfactory regarding the maternal vital prognosis and infaust according the fetal
prognosis (fetal mortality in the cases of placentary apoplexy and HELLP syndrome). The
ultrasound study and multi vascular arterial Doppler has a predictive value for the gestational
hypertension and intrauterine growth restriction, in the reduction of the morbidity and
perinatal mortality.
Keywords: preeclampsia, multi vascular Doppler, fetal and maternal prognosis

Introduction

In the developed countries, 16% of the causes of maternal mortality are due to
hypertensive troubles [1]. Gestational hypertension occupies the first step among the factors
that determine the maternal mortality, followed by hemorrhage 13%, abortion 8%, and sepsis
2%. USA report 12.3% cases of maternal mortality due to preeclampsia or eclampsia [2], and
France a rate of 10% of maternal mortality [3]. More of the half of these deaths due to
pregnancy hypertension could have been prevented [4].
Gestational hypertension is a decisive factor in the triggering of some severe
complications:
eclampsy, retro placental hematoma, HELLP syndrome, intrauterine growth restriction,
prematurity, intra uterus fetal death.
Pregnant woman that register a growth of their systolic pressure with 30 mmHg or of the
diastolic with 15 mmHg must be close monitored because they can develop eclamptic
convulsions even at values of the blood pressure under 140/90 mmHg [5]. One sudden rise of

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the mean arterial pressure appeared late in the pregnancy can cause risks similar to
preeclampsia even if the blood pressure is under 140/90 mmHg [6, 7].
In the arterial gestational hypertension the trophoblastic invasion is incomplete, the spiral
arterioles staying in the intramyometrial territory. At the trophoblast-decidua level we see an
immuno-genetic conflict with antagonistic substance flowing over the vascular walls.
Through the trophoblast and through the platelets vasoconstrictor substances (thromboxane
A2, angiotensin II) are liberated and the vascular endothelium release antiagregants and
vasodilatory substances (PG E2, PG I2, nitric oxide). In the preeclampsia takes place the
lowering of the intermediary metabolism of the PG I2 (6 keto prostaglandin F1 α) in the
maternal serum, placenta and umbilical veins. There have been found alterations of the
endotelium from the umbilical artery at the mothers with severe PE. It associated with a
severe microangiopathic hemolysis feed by the fragmentation of the blood cells with anemia,
trombocytopenia, the increase of the fibronectin (explained by the endothelial deteriorations),
decrease of the antitrombina III (presence of trombs), decrease of α 2 antiplasmin ( which
explains the fibrinolisis) [8, 9].
All these initial present phenomena in the utero placental territory, are expanding all over
the body through a phenomenon of capillary endotheliosis, affecting the maternal and fetal
vital prognosis [10].
The inadequate trophoblastic invasion of the spiral arterioles determines the diminished
placental perfusion, and upstream a heightened resistance of the uterine arterioles.
The increase of the velocimetry in the uterine arteries in the first two trimesters of
pregnancy constitutes a predictive test for severe preeclampsia [11, 12].
The object of the study consists in the importance of the ultrasound study and the arterial
multivascular Doppler at the gestational hypertension in reducing perinatal morbidity and
mortality.

Materials and Methods

We have studied 6 cases of severe preeclampsia (PE), complicated forms, unattended in


the territory, some in primiparous parturients under 18 years old, others at big multiparous
over 30 years old, admitted and solved in the last 5 years in the Obstetrical Clinic,
SCJUCraiova.
We interned as an emergency 3 very young parturients, primiparous, aged between 16-18
years old, with blood pressure between 160/110 mmHg-210/120 mmHg; in their cases the
hipotensive treatment was started since they were first admitted in the Unit of Receiving
Emergencies.
Also, we admitted and applied the emergency management therapeutic for 2 cases of retro
placental hematoma at multiparous parturients, over 30 years old with dead infants. One case
-XII G V P, pregnancy 37 gestational weeks, was with cranial presentation, dead infant,
cervico-vaginal bleeding, blood pressure 190/120 mmHg. It was a patient aged 32 years old.
The second case – XV G VI P, pregnancy 39 gestational weeks with cranial presentation,
dead infant, cervical vaginal bleeding, blood pressure 180/120 mmHg. The patient was 34
years old.
The last case was a 24 years old patient, admitted as an emergency with diagnosis: IG IP,
pregnancy 36 gestational weeks, cranial presentation, PE (TA 180/110 mmHg), dead fetus,
haemoperitoneum.

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Results Discussion

At the 3 young primiparous patients, with blood pressure between 160/110 mmHg-210/120
mmHg the Doppler velocimetry has been performed in the uterine artery, in the umbilical
artery and in the cerebral medium artery.
The Doppler velocimetry in the uterine artery showed: the increase of the impedance both
in the systole, as especially in the diastole, the increase S/D, of IR>0.5 and of IP, the presence
of the protodiastolic incisures.
The Doppler velocimetry in the umbilical artery showed the decrease on the end-diastolic
component or the absence of the diastolic flux with the increase of the S/D, IR>0.6 and
IP>0.92.
The Doppler velocimetry in the medium cerebral artery showed relatively normal values at
2 patients and the increase of the diastole with decrease of S/D<4, IR<0.7 and IP<1.75 at one
pregnant woman.
The evolution of those 3 patients was toward a neural-convulsive syndrome and an
eclamptic coma.
The labor evolved correspondingly, the patients arriving in 2-3 hours to complete
dilatation, the cranium profoundly engaged, the fetal heart beats present, rhythmic. In the
operating bloc, under hypotension treatment and intravenous Diazepam, having the required
local conditions, in the presence of the anesthetist and of the obstetrical team, according to the
protocol, the infants were extracted through application of forceps Naegele.
The state of the infants at birth was good, with Apgar between 6-8, two infants of female
sex, one infant of male sex. The 3 mothers left the hospital with good general health, with the
specific recommendations in the territory.
In the 2 cases of retro placental hematoma at multiparous patients, aged over 30 years old,
dead infants, the patients were transported as an emergency to the operating bloc, being
diagnosed with severe form of gestational hypertension, uterus-placental apoplexy. In
emergency the fetuses were extracted through cesarean operation, total hysterectomy with
bilateral anexectomy, transfusions of blood and plasma iso-group, iso-Rh. They had good post
operatory evolution and they have been discharged 7-9 days later, surgically healed.
The 24 years old patient interned as an emergency with diagnosis: IG IP, pregnancy 36
gestational weeks, cranial presence, preeclampsia (blood pressure 180/110 mmHg), dead
infant and haemoperitoneum, it has been intervened surgically with a multidisciplinary team
(general surgeon). It has been performed a median pubo-xifoid incision, segmental-transversal
histerotomy extracting one dead infant of 2400g, female sex. Intraoperatory we found a
rupture of hepatic capsule, the right lob with appreciable haemoperitoneum. As a matter of
necessity the bleeding liver was buffered with 4 fields with physiological serum above the
liver region and 4 fields under the liver region. Provisional abdominal closure in anatomical
planes. 48 hours later the surgical team intervened again, they extracted the compressive
fields of hemostasis, they performed the control of the liver, they fixed the sponges of
tachocomb on the diaphragmatic surface of the right lobe, with definitive abdominal closure
with draining on the flanks with polietilene tubes. She was discharged 14 days later,
surgically healed. At 2 successive controls, at one month and 3 months, patient presented with
good general health, psychically balanced with the normal question of her future maternity.
These cases were not attended in the teritory, not investigated, probably with organic tares,
whose detection should have been made preconceptionally or early into gestation. Those 6
clinical cases exposes are the privilege of the gestational hypertension, complications of the
severe forms of preeclampsia [13, 14].

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Through the paternal component, the gestation constitutes a challenge for the transplant
heterology due to the immuno-genetic antigen-antibody conflict. That is why, the fetal
annexes can be called “gestational transitory biological system”.
The compromise of the uterus-placental circulation is obvious only in pregnant women that
develop severe form of preeclampsia. The amplitude of the abnormal velocity in the uterine
arteries is correlated with the severity of the fetal affectation [15, 16]. The presence of the
diastolic “notch” on the Doppler image of the uterine artery has a predictive value in the
restriction of the intrauterine fetal growth, but not in preeclampsia [17].

Conclusions

The result of these cases is satisfactory according to the vital maternal prognosis and
infauste according to the fetal prognosis (fetal mortality in the 2 cases of AUP and HELLP
syndrome).
The ultrasound study and multi vascular arterial Doppler has a predictive value for the
gestational hypertension and intrauterine growth restriction, in the reduction of the morbidity
and perinatal mortality.

REFERENCES

1. Khan KS, Wojdyla D, Say L (2006). WHO analysis of causes of maternal death: a systematic review.
Lancet 367, p. 1066.
2. Berg CJ, Callaghan WM, Swerson C (2010). Pregnancy-related mortality in the United States, 1998 to
2006. Obstet Gynecol 116(6), p. 1302.
3. Saucedo M, Deneux-Tharaux C, Bouvier-Colle MH (2013). Ten years of confidential inquiries into
maternal death in France, 1998-2007. Obstet Gynecol 122(4), p. 752.
4. Berg CJ, Harper MA, Atkinson SM (2005). Preventability of pregnancy-related deaths. Obstet Gynecol
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5. Alexander JM, McIntire DD, Leveno KJ (2006). Selective magnesium sulphate prophilaxis for the
prevention of eclampsia in women with gestational hypertension. Obstet Gynecol 108, p. 826.
6. Macdonald-Wallis C, Laulor DA, Fraser A (2012). Blood pressure change in normotensive, gestational
hypertensive, preeclamptic, and essential hypertensive pregnancies. Hypertension 59(6), p. 1241.
7. Vollaard E, Zeeman G, Alexander JA (2007). “Delta eclampsia” – a hypertensive encephalopathy of
pregnancy in “normotensive” women. Abstract No. 479, Am J Obstet Gynecol 197(6 Suppl): S140.
8. Braila AD, Marinov Krastev B, Mihai-Zamfir E, Caraveteanu DC, Nawaf Al Krayem, Braila M, Velea
R, Neacsu A (2017). Uteroplacental apoplexy associated with invasive cervical neoplasm, RJME 58(4),
pp. 1465-1470.
9. Brăila AD, Gluhovschi A, Neacșu A, Lungulescu C, Brăila M, Cotoi BV, Goganau A (2018). Placental
abruption. etiopathogenic aspects, diagnostic and therapeutic implications, RJME 59(1)
10. Braila AD, Fortofoiu C, Zamfir E, Velea R, Braila M (2017). Eclampsia and epilepsy. differential
diagnosis. associated diagnosis, Congress of the Romanian-German Society of Obstetrics-Gynecology,
Filodiritto Editore – Proceedings, pp. 84-87.
11. Gebb J, Einstein F, Merkatz IR (2009a). First trimester 3D power Doppler of the intervillous space in
patiens with decreased PAPP-A levels and increased uterine artery pulsatility index. Abstract No 279.
Presented at the 29th Annual Meeting of the Society for Maternal-Fetal Medicine, January 26-31.
12. Gebb J, Landsberger E, Merkatz I (2009b). First trimester uterine artery Doppler, PAPP-A and 3D
power Doppler of the intervillous space in patiens at risk for preeclampsia. Abstract No 251. Presented
at the 29th Annual Meeting of the Society for Maternal-Fetal Medicine, January 26-31.
13. Braila AD, Braila M, Alkrayem Nawaf, Goganau A (2017) Uterine haemostasis in puerperality by
radical and conservative surgical procedures, Congress of the Romanian-German Society of Obstetrics-
Gynecology, Filodiritto Editore – Proceedings, pp. 81-83.
14. Braila M, Neacsu A, Velea R, Braila AD (2017). Caesarian section and the forceps use -5 year study in
Craiova SCJU maternity section, Congress of the Romanian-German Society of Obstetrics-Gynecology,
Filodiritto Editore – Proceedings, pp. 91-94.
15. Groom KM, North RA, Stone PR (2009). Patterns of change in uterine artery Doppler studies between
20 and 24 weeks of gestation and pregnancy outcomes. Obstet Gynecol 113(2), p. 332.

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16. Ghidini A, Locatelli A: Monitoring of fetal well-being (2008). Role of uterine artery Doppler. Semin
Perinatol 32, p. 258.
17. American College of Obstetrcians and Gynecologists (2013a). Fetal growth restriction, Practice Bulletin
No. 134.

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Fetal Biophysical Profile in Prolonged Pregnancy

BRAILA Anca Daniela1, BRAILA Mihai1, VELEA Rodica1, NEACSU Adrian2


1University of Medicine and Pharmacy of Craiova, Department of Obstetrics and Gynaecology, (ROMANIA)
2University of Medicine and Pharmacy Carol Davila, Bucharest (ROMANIA)
Email: [email protected]

Abstract

The fetal biophysical profile is an important ultrasonic exploration for the evaluation of the
intrauterine state of the newborn, in the decision to end the gestation and to choose the way of
birth. The fetal tests performed antepartum differentiate the healthy newborn from those with
fetal distress. The role of the evaluation of the biophysical profile is important, as much for
the prevention of the morbidity and the perinatal mortality, the prevention of the long term
neurological and motor sequels, as well as for the observation of the pregnant woman with
high risk.
The research that has been made had for objective to estimate the signification of the
prognosis of the profile and the biophysical fetal score in prolonged pregnancy.
In the studied prolonged pregnancies, we observed 3 pathognomonic syndromes:
hypermaturisation of the fetus, senescence of the fetal annexes and chronic fetal distress.
The management of the birth is based on the interpretation of the biophysical fetal score in
the clinical context, which pinpoints the gestational age, the maternal and obstetrical factors.
The interpretation of each biophysical fetal profile must be done in the clinical context of
each case. A modified biophysical fetal score needs a periodic reevaluation, having for
objective the minimization of the risk of intrauterine death and of perinatal morbidity.
We are in favor of the active therapeutic conduct, the ultrasound through the biophysical
fetal score can evaluate the state of the newborn in uterus and together with the Doppler
vascular study, it gives information that allows the intervention when is it the right moment.
Keywords: biophysical fetal score, fetal distress, morbidity, perinatal mortality

Introduction

The profile and the biophysical fetal score are important ultrasonic explorations for the
evaluation of the intrauterine state of the infant, for the decision of the termination of the
gestation and the choosing of the way of birth. The rate of the births through cesarean section
for dystocia and fetal distress has been significantly high in prolonged pregnancy, the
convulsion and neonatal deaths incidence doubled in 42 weeks [1, 2, 3]. The birth at 38 weeks
has the lowest perinatal mortality risk [4].
The fetal tests performed before differentiate the healthy fetuses of those with fetal
distress.
There have been reported high frequent cerebral paralysis in premature newborns [5],
lower levels of IQ at children born over 42 gestational weeks [6], but it was not signaled the
association of autism with prolonged pregnancy [7].
The role of the evaluation of the biophysical fetal score is major, as well for the prevention
of the morbidity and perinatal mortality, prevention of long term neurological and motor
sequels, as well as for the monitoring of the pregnant woman with high risk.

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The perinatal mortality rate grows after exceeding the probable date of birth, according to
studies performed in Sweden, US and Denmark [8, 9, 10].
The research had for objective the estimation of the prognostic signification of the profile
and the biophysical fetal score in prolonged pregnancy.

Materials and Methods

There had been investigated 67 prolonged pregnancies, admitted and solved in the
maternity of the Craiova Clinical Hospital of Emergency, between 2016 and 2017.
In order to estimate the gestational age we used: the anamnesis criteria (gestational age
from a chronological point of view corresponded to the real exceeding of the term of the birth
of over 295 days or 42 gestational weeks ), the clinical criteria (high and the lowering of the
uterine lower uterine part, the abdominal circumference, the Pinard measurement palpation,
the Bishop score) that has proved to be insignificant, the ultrasound criteria (fetal profile and
of the fetal annexes, the Manning biophysical fetal score).
The biophysical fetal score Manning followed the parameters: fetal active movements (at
least 3 movements in 30 minutes – 2 points; under 3 movements – 0 points ), fetal tonus (at
least 1 episode of extension-flexion – 2 points; the absence of the episode of extension-flexion
– 0 points), respiratory movements of the thoracic cavity (at least 1 episode of respiration with
the duration of at least 30 seconds in 30 minutes – 2 points; under 30 seconds of respiration in
30 minutes – 0 points), the non stress test (at least 2 accelerations of at least 15 beats/minute
for at least 15 seconds in 30 minutes – 2 points; 0 or 1 acceleration in 30 minutes – 0 points),
the volume of the amniotic liquid (an amniotic liquid bag of 2x2 cm – 2 points; the bag with
amniotic liquid under 2x2 cm or its absence – 0 points).
The biophysical score 10/10 - normal fetus, 8/10 with the normal volume of the amniotic
liquid – normal fetus, non-asphyxiated, we repeat the BFS 2 times a week, 8/10 with low
volume of the amniotic liquid - fetus suspected of fetal chronic asphyxia, birth is
recommended, 6/10 – possible fetal asphyxia, it is repeated after 24 hours; if the score is
maintained 6/10 the obstetrical staff has to decide the way of birth, under 6/10 – birth is
recommended.

Results and Discussion

The birth management is based on the interpretation of the biophysical fetal score in a
clinical context, which pinpoints the gestational age, maternal and obstetrical factors [11, 12,
13].
Of the 67 prolonged studied pregnancies, 46 of the cases (69%) had the gestational age
between 42 weeks and 2 days and 42 weeks and 6 days and 21 cases (31%) were with the
gestational age over 43 weeks.
Out of the 67 prolonged pregnancies, 55 of the pregnant women (82%) had a BFS 8, 8
pregnant women (12%) with BFS fewer than 6.
The finalisation of the gestation, at the 67 pregnant women, has been made through natural
birth in 16 cases (24%) and through cesarean section in 51 cases (76%).
The maternal vital and functional prognosis was good in all of the cases. The fetal
prognosis was good in 56 cases (84%) and in 11 cases (16%) the Apgar score was 5 and 6.
In the prolonged pregnancies studied, we remarked 3 pathognomonic syndromes: the
hypermaturisation of the fetus, the senescence of the fetal annexes, the chronic fetal distress
(16% of the cases).
The post maturity fetal syndrome was described at 10% of the pregnancies between 41 and
43 weeks [14] and the association of the oligoamnios determined by ultrasound with a bag of

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amniotic liquid under 1 cm at 42 weeks [15]. The placental apoptosis was significantly high
between 41 and 42 weeks, in comparison with the weeks 36-39 [16]. More proapoptotic genes
have been over showed in tissular placental fragments in prolonged pregnancies compared to
the term placenta [17].

Conclusions

The interpretation of each biophysical fetal profile must be done in the clinical context of
each case. A modified biophysical fetal score needs a periodic reevaluation, having for
objective the minimization of the risk of intrauterine death and of perinatal morbidity.
We are in favor of the active therapeutic conduct, the ultrasound through the biophysical
fetal score can evaluate the state of the newborn in uterus and together with the Doppler
vascular study, it gives information that allows the intervention when is it the right moment.

REFERENCES

1. Alexander JM, McIntire DD, Leveno KJ. (2000a). Forty weeks and beyond: pregnancy outcomes by
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and the course of labour and delivery. Am J Obstet Gynecol 148, p. 547.
15. Trimmer KJ, Leveno KJ, Peters MT (1990). Observation on the cause of oligohidramnios in prolonged
pregnancy. Am J Obstet Gynecol 163, p. 1900.
16. Smith SC, Baker PN (1999). Placental apoptosis is increased in postterm pregnancies. Br J Obstet
Gynecol 106, p. 861.
17. Toricelli M, Novembri R, Conti N (2012). Correlation with kisspeptin in postterm pregnancy and
apoptosis. Reprod Sci 19(10), p. 1133.

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New Ultrasonographic Markers in Correlation with Serological


Factors-Prognostic Factors in the First Trimester of Pregnancy

BUCURI Carmen Elena1, CIORTEA Răzvan1, DICULESCU Doru1,


MALUTAN Andrei Mihai1, OANCEA Mihaela Daniela1,
NICULA Renata Lacramioara1, MOCAN-HOGNOGI Radu1,
RADA Maria Patricia1, MIHU Dan1
1IInd Department of Obstetrics and Gynecology, University of Medicine and Pharmacy “Iuliu Hațieganu”, Cluj-Napoca
(ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

The incidence of embryonic demise is 25%. Complications of the first trimester pregnancy
are a current health problem. The etiology of embryonic demise is multifactorial, with
chromosomal abnormalities being the most common (40%). Other causes may include: luteal
phase defects, maternal thyroid abnormalities, maternal diabetes, infections, hereditary or
acquired thrombophilia, and exogenous agents. Prenatal monitoring seeks to increase the
effectiveness of screening methods and improve diagnostic methods for first-trimester
pregnancies whose evolutionary potential can be reserved. Initially, the embryo is detected
immediately adjacent to the yolk sac (YS). If the embryo is separated from it, separation is
due to its development. As the cranio-caudal length (CRL) increases, the distance between the
embryo and YS also increases.
For embryos with a CRL of 5 mm or less, there should be no separation of the YS from the
embryo or a very small one (<2 mm). A small distance (considered 3 mm in the literature)
between an embryo and YS with CRL greater than 5 mm is an unfavorable prognostic marker.
Thus, the distance between the embryo and YS (assessed by endovaginal ultrasound) for
embryos with CRL greater than 5 mm was studied and a correlation between this and the
serum level of Human Chorionic Gonadotropin β (beta HCG) was identified, showing a low
level of beta-HCG in patients with an unfavorable pregnancy, respectively, less than 3 mm
between the embryo and YS.
Keywords: ultrasonographic, yolk sac, beta hCg

Introduction

One in four women at some point in her reproductive lifetime lose a pregnancy and the
incidence of early embryonic death is high compared to other complications of early
pregnancy [1].
Ultrasound evaluation is the method of choice for assessing evolutionary prognosis of the
early pregnancy. The purpose of the ultrasound in the first trimester is to ascertain the location
of pregnancy, to determine the pregnancy viability, to establish with precision the gestational
age, to asses the corionicity in case of a multiple pregnancy, to identify the presence of
adnexal or uterine tumors and to diagnosis morphologic abnormalities of the embryo. There
are no prospective data to outline the guidelines for ultrasound diagnosis as accurate as
possible for embryonic demise. The endovaginal ultrasound technique has become a valuable

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tool in the worthy assessment of pregnancy and has helped to establish new elements about its
evolution [2].
The ultrasound diagnosis of the first trimester pregnancy with unfavorable outcome was
based on a variety of elements, represented by absence of YS, lack of identification of the
embryo or its cardiac activity, abnormalities of the gestational sac (GS).
The identification of other prognostic echographic elements has also been required. The
depiction of separation of an embryo with a CRL of 5 mm or less from the YS indicates
development of a yolk stalk and thus a more advanced stage of gestation can be deduced from
the CRL alone. The yolk stalk sign is valuable for assessing pregnancy prognosis and can be
used independently or in combination with other abnormal features [3].
hCG, a major embryonic signal, plays a critical role in the initiation and maintenance of
pregnancy. At the time of implantation, hCG has been shown to be involved in a wide
spectrum of cell targets and biological actions[4, 5]. Synthesized early by the trophoblast,
hCG appeared to influence endometrial receptivity and implantation, promote the
decidualization of human endometrial stromal cells [6], and to possess both direct and indirect
angiogenic properties [7-10].

Material and method

The paper is a case-control prospective analysis which took place at the “Dominic Stanca”,
IInd Clinic of Obstetrics and Gynecology, Cluj Napoca and includes two groups of patients:
170 patients in the first trimester of pregnancy without associated pathology. Patients were
grouped according to the current state of pregnancy – 81 patients with first-trimester
pregnancy in evolution and 89 patients with embryonic demise, both groups with amenorrhea
between 6-11 weeks.
Initially, in the case study, 95 patients with pregnancy that had potentially reserved
evolutive pregnancy were enrolled in the study. Ultrasonographically they had a distance
between YS and embryo less than 3 mm at a gestational age at which separation should
already have taken place.
For 6 of these, the prediction of the ultrasound parameters studied to an unfavorable
evolution was not confirmed. This differentiation was performed by realizing endovaginal
ultrasounds for each patient included in the study to exclude patients with incomplete abortion
or ongoing abortion. Endovaginal ultrasonographic exploration (Voluson 739) was serialized,
performed in dorsal decubitus, with bent knees, in order to evaluate the parameters sought to
identify predicted evolutionary prognostic factors: cranio-caudal length (LCC), SG size, the
YS dimension, and the distance between the lower pole of the embryo and the YS(DYSE).
There were on average 2-3 serial ultrasound examinations, performed at regular intervals
until the final diagnosis of embryonic demise was made.
From each subject enrolled in the study, 20 ml of blood was collected by venipuncture into
anticoagulant-free tubes for beta hCG dosing. Serum obtained by centrifugation was divided
and stored in 600 μl freezing tubes at -30 °C until samples were taken to avoid repeated
freeze-thaw cycles. As a priority of the study, the privacy, privacy and dignity of the person
were respected.
The participation of the patients in the research activities was made only after the informed
consent. Also, the working methodology has been obtained by the Ethics Commission of the
University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca.
Descriptive statistics elements were calculated, data presented using centrality, location
and distribution indicators. The Shapiro-Wilk test was used to test normal distribution. The
variance was tested with the F test. In the case of the normal distribution data, the t (Student)
test was used and in the case of non-uniform distribution values or ranks the non-parametric

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Mann-Whitney (U) test was used for two non-paired samples. For the analysis of three or
more samples the ANOVA test was used for normal distribution data or Kruskal-Wallis
nonparametric test for non-uniform values or ranges. The significance threshold for the tests
used was α=0.05 (5%), 0.01 (1%) or 0.001. The Pearson correlation coefficient (r) was used to
detect the correlation between two continuous quantitative variables with normal (uniform)
distribution. In the case of non-uniform variables, Spearman (ρ) correlation coefficient was
used. Analysis of correlation coefficients was performed using Colton’s rule. The method
used to obtain the mathematical equation of the dependence of a variable of another variable
was polynomial regression.

Results

No statistically significant difference between the two groups (p>0.05) was observed in
statistical analysis of gestational age (Weeks of amenorrhea-WA).

Table 1. Comparative analysis for WA values in studied groups and statistical significance
Indicators Group Media ES Mediane DS Min Max Statistical significance (p)
I 8,49 0,1767 9 1,5900 6 11
WA 0,779
II 8,56 0,1721 9 1,6234 6 11

In the statistical analysis of DYSE values statistically significant differences were observed
between the two groups (p<0.001) in all the WA studied. Thus, it was shown that a distance
of less than 3 mm correlated with an unfavorable prognosis of pregnancy evolution.

Fig. 1. DYSE of the both groups

Fig. 2. beta hCG of the both groups

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Fig. 3. Correlation between beta hCG and DYSE of control group

Fig. 4. Correlation between beta hCG and DYSE of case group

Discussion

The studies in the literature as well as the present study show a correlation between the low
serum hCG level and the unfavorable evolution of the first trimester pregnancy. Although the
role of beta hCG in the first-trimester pathology is extremely well known, this is the first
study in the literature that demonstrated the correlation between an ultrasound parameter,
DYSE and this serum parameter.
In the early embryonic development, the embryo is immediately revealed adjacent to YS.
Separation of the embryo to the YS is due to the development of both this structure and the
embryo. Thus, the distance between the embryo and YS is increased due to the growth of
“yolk stalk”. For embryos with CRLs less than or equal to 5 mm, there must be no separation
of the YS. But in some pregnancies with small embryos, there is a clear separation of the YS.
When the embryo reaches 5 mm, there is a physiological separation between the embryo
and YS due to the development of this structure. Thus, when embryo separation is observed
with a CRL less than 5 mm, without cardiac activity, this aspect is considered an unfavorable
prognostic factor. Also, the absence of separation of the embryo and YS, when the CRL
exceeds 5 mm and the embryo is with cardiac activity, is considered also an unfavorable
prognostic factor. The cut off dimension of 3 mm is the one where the evolutionary prognosis
of the pregnancy in which CRL with cardiac activity exceeding 5 mm and in which no
significant separation of the YS- embryo, is considered to become uncertain [11].
Serum biochemical markers have been used to predict viability alone or in combination
[12, 13]. They have been studied in a variety of populations either defined by clinical
symptoms or by ultrasound findings. Most studies attempting to use hCG have not correlated
levels with ultrasound findings and like this study, none have found a single hCG
measurement to be a useful predictor of viability [14].
A single hCG value, however, can be used as a surrogate marker for gestation using the
concept of an hCG discriminatory zone. An hCG series can help determine if the gestation is

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potentially viable and/or if the trend is expected for a normal growth or spontaneous
resolution [15].
In normal pregnancy hCG levels peak at about 8-10 weeks of pregnancy to a level of
100,000 IU/L and then decline to 40,000 IU/L from 20 weeks until delivery. But there is a
large variation in a “normal” hCG level for any given time in pregnancy [16].
If these results are considered, various ranges of relations are observed between obstetric
and hormonal measurements. Sometimes it is dificult to decide if a pregnancy is healthy by
only using hormonal methods, or only volumetric measurements. Using the relation between
these parameters and combining both volumetric and hormonal measurements, increased
prediction rate may be obtained [17].
The data from the present study shows that DYSE is an ultrasonographic feature that
indicates earlier embryonic demise compared to specific ultrasonographic parameters, which
certainly confirms the absence of pregnancy evolution at a more advanced gestational age
[18].
For higher diagnostic accuracy, it is important that this parameter is correlated with a
serum marker [19, 20]. By this association, the originality of this study is outlined: the
correlation of this ultrasound parameter with an important hormone, which is highly used in
the literature and which is known to have an important role in the first trimester.

Conclusions

DYSE has a high positive predictive value in identifying potentially reserved evolutivity of
pregnancies, demonstrating in this study that a DYSE <3 mm leads to an unfavorable
evolution of pregnancy. Also, correlating this ultrasound parameter with a serologic one,
respectively with the hCG serum level, brings valuable information about pregnancy viability
in the first trimester.
The low serum level of beta hCG is associated with an increased rate of non-viable
embryos.

Aknoledgments
This paper was published under the project no 7690/15.04.2016 funded by “Iuliu
Hatieganu” University of Medicine and Pharmacy, IInd Department of Obstetrics and
Gynecology, Cluj-Napoca, Romania.

REFERENCES

1. Elson J, Salim R, Tailor A, et al., (2003). Prediction of early pregnancy viability in the absence of an
ultrasonically detectable embryo. Ultrasound Obstet Gynecol 21, pp. 57-61.
2. Rowling, SE, Langer, JE, Coleman, BG, et al., (1999). Sonography during early pregnancy: dependence
of threshold and discriminatory values on transvaginal transducer frequency. AJR Am J Roentgenol
172, pp. 983-988.
3. Filly, MR, Callen, PW, Yegul, NT, et al., (2010). The Yolk Stalk Sign. J Ultrasound Med 29, pp. 237-
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4. Bourdiec A1, Shao R, Rao CV, et al., (2012). Human chorionic gonadotropin triggers angiogenesis via
the modulation of endometrial stromal cell responsiveness to interleukin 1: a new possible mechanism
underlying embryo implantation. Biol Reprod 87(3), p. 66.
5. Capatina, C; Radian, S; Baciu, I; Ghinea, A; Deciu, D; Dumitrascu, A; Ciubotaru, V; Poiana, C.
Spontaneous conception and term delivery in a woman with uncontrolled acromegaly and
hypogonadotropic hypogonadism. ACTA ENDOCRINOLOGICA-BUCHAREST, Vol: 12, Issue: 4, pp.
481-484, DOI: 10.4183/aeb.2016.481, Published: OCT-DEC 2016.
6. Tang B, Gurpide E. (1993). Direct effect of gonadotropins on decidualization of human endometrial
stroma cells. J Steroid Biochem Mol Biol 47, pp. 115-121.

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7. Zygmunt M, Herr F, Keller-Schoenwetter S, Kunzi-Rapp K, Munstedt K, Rao CV, Lang U, Preissner


KT. (2002). Characterization of human chorionic gonadotropin as a novel angiogenic factor. J Clin
Endocrinol Metab.
8. Zygmunt M, Herr F, Munstedt K, Lang U, Liang OD. (2003). Angiogenesis andvasculogenesis in
pregnancy. Eur J Obstet Gynecol Reprod Biol 110(87), pp. 5290-5296.
9. Islami D, Bischof P, Chardonnens D.(2003). Modulation of placental vascular endothelial growth factor
by leptin and hCG. Mol Hum Reprod 9, pp. 395-398.
10. Filicori M, Fazleabas AT, Huhtaniemi I, Licht P, Rao Ch V, Tesarik J, Zygmunt M. (2005). Novel
concepts of human chorionic gonadotropin: reproductive system interactions and potential in the
management of infertility. Fertil Steril 84, pp. 275-284.
11. Filly MR, Callen PW, Yegul NT, et al., (2010). The yolk stalk sign: evidence of death in small embryos
without heartbeats. J Ultrasound Med 29(2), pp. 237-241.
12. Carabineanu A., Navolan D., Birsasteanu F., Crețu O., Boia M., Craina M., Badiu DL., Ionescu CA.,
Mehedințu C., Vlădăreanu S., Ciohat I., Craciunescu M., Nemescu D. The Effect of Chemical
Compounds from Cigarettes Smoke on First Trimester Biochemical Markers. Revista de Chimie. Vol.
68 No. 10/ 2017, pp. 2122-2124, ISSN:0034-7752.
13. Navolan D*, Vladareanu S*, Ciohat I, Carabineanu A, Craina M, Nemescu D, Birsasteanu B,
Onofriescu A, Boia M, Tepetzikiotis E, Craciunescu M, Birsasteanu F. (2017). Distribution of
Biochemical and Ultrasound Markers Values in the First Trimester Screening Program in Timisoara.
Revista de Chimie. Vol. 68, Issue: 7, pp. 1636-1639, ISSN:0034-7752 *(equal contribution).
14. Karin Lautmann, Mark Cordina, Janine Elson, Jemma Johns, Katharina Schramm-Gajraj,Jackie A. Ross
. (2011). Clinical use of a model to predict the viability of early intrauterine pregnancies when no
embryo is visible on ultrasound. Human Reproduction 26, pp. 2957-2963.
15. Kurt T. Barnhart. (2012). Early pregnancy failure: beware of the pitfalls of modern management.
Fertility and Sterility 98, pp. 1061-1065.
16. Nermin K, AydÂn K, Nilgün Ö. (2012). First trimester volumetric measurements: relation with
hormone levels and fetal heart rate. Arch Gynecol Obstet 286, pp. 365-372.
17. Phipps MG, Hogan JW, Peipert JF, et al., (2000). Progesterone, inhibin, and hCG multiple marker
strategy to differentiate viable from nonviable pregnancies. Obstet Gynecol 95(2), pp. 227-231.
18. Burnei-Rusu, A., Zamfirescu, V., Bot, M., Traistaru, A., Boiangiu, A., Cotman, R., Vladareanu, R.
(2007). Intrauterine Growth Restriction – Predictive Markers in Early Pregnancy. Proceeding paper for
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155-159.
19. Daily CA, Laurent SL, Nunley WC Jr. (1994). The prognostic value of serum progesterone and
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20. Taghavi AH. (2004). Detection of changes of hCG, progesterone and estradiol serum levels in
threatened abortion in the first three months of gestation. Iran J Endocrinol Metab 6, pp. 163-169.

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Cesarean Scar Ectopic Pregnancy: A Case Report

BURNEI-RUSU Anca1, CRISTEA Carmen2, BOT Mihaela3,


ZAMFIRESCU Vlad4, VLADAREANU Radu5
1-4UMF “Carol Davila” Bucharest, Department of Obstetrics & Gynecology & Neonatology, Elias Emergency University
Hospital (ROMANIA)
5 Professor and Chairman, Department of Obstetrics & Gynecology & Neonatology, Elias Emergency University Hospital

(ROMANIA)
Email: [email protected]

Abstract

Scarring uterus, after cesarean section, involves complications at distance and the most
important are the abnormal location of the future pregnancy, more precisely, scar ectopic
pregnancy, placenta previa or abnormally adherent placenta. Therefore, in patients with
scarring uterus, the imaging of the location of pregnancy, placental insertion, and the risk of
abnormal placentation is indicated. We report the case of a 42-year-old woman with a
cesarean birth history (9 years ago), currently with six-week scar ectopic pregnancy. The
ultrasound detected a gestational sac, located intrauterine, at the anterior wall at the isthmic
portion, separated from endometrial cavity in previous caesarean scar, with a corresponding
CRL of six weeks with cardiac activity. Treatment with Methotrexate 60 mg intramuscular
(days 1, 3, 5) associated with calcium folinate 6 mg intramuscular (days 2, 4, 6) was initiated.
Ultrasound exam after treatment detected the embryo without cardiac activity. The BHCG
was down from 9226 mUI/ml to 107 mUI/ML. Conservative medical management was
applied and 9 weeks later with the second period, it was ultrasound certified that the
pregnancy was eliminated.
Keywords: ectopic pregnancy, scarring uterus, cesarean section

Introduction

The scar ectopic pregnancy is an increasingly common pathology, given the increase rate
in cesarean delivery. There is not much information about the natural history of this condition,
but it appears to be the most common occurrence after cesarean surgery. The incidence of
ectopic pregnancy ranges from 1: 1800 to 2216 births, at a rate of 0.15% in women with only
one cesarean in the past and 6.1% in all ectopic pregnancies.[1, 2] It has also been
demonstrated that scar ectopic pregnancy occurred in 52% of cases after one cesarean
surgery, 36% of cases after the first 2 surgeries, and in 12% of cases after 3 or more
cesareans. [3] On average, it was diagnosed at an interval of 6 months to 12 years after the
last surgery, at a gestational age of 5-12 weeks. The mechanism of this pathology is unclear. It
is assumed that scar tissue defects resulting from inadequate healing of previous trauma
caused by caesarean section [4], myomectomy, curettage, abnormal placentation and manual
extraction of the placenta may lead to the appearance of ectopic pregnancy. [5] Different
assisted reproductive technology (ART) procedures [6, 7] seem to influence the risk for
ectopic pregnancy but reproductive health characteristics of the woman carrying the
pregnancy are more likely to be involved in the pathology of scar pregnancy.
Two types of scar ectopic pregnancies have been identified. Type I has implantation in the
previous scar with progression to the cervico-isthmic space or uterine cavity. Type II is

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caused by a deep implantation in scarring defect with infiltrative growth in myometrium and
the uterine serous, which can result in uterine rupture and massive hemorrhage in the first
trimester of pregnancy.
Clinical manifestations can range from totally absent with an accidental breakthrough, to
vaginal bleeding with or without pelvic pain and can lead to uterine rupture and hypovolemic
shock. Clinical studies on cases of scar ectopic pregnancies revealed that 45% of the patients
were asymptomatic, 55% had vaginal bleeding and 7% had abdominal pain. [8, 9]
Ultrasound was the first large scale method of diagnosis ectopic pregnancy with a
sensitivity of 84%. Early diagnosis of this condition is necessary for effective, timely
management. Diagnosis depends on the symptomatology, history of scarring, BHCG level
and transvaginal ultrasound examination. Ultrasound examination can detect: empty uterine
cavity, gestational sac developed in the anterior wall, in the isthmic region, Doppler
examination detects functional trophoblastic circulation, the absence of the integral
myometrium between the bladder and the gestational sac (differential diagnosis with cervico-
isthmic pregnancy). [10, 11, 12]
Regarding the management, there is no universal guide given the low incidence.
Therapeutic conduct is established according to the symptoms, the ultrasound evaluation
and the patient’s desire and must be adapted to each individual. In a stable hemodynamic
patient, local, systemic or both Methotrexate or local potassium chloride and Methotrexate
can be given. It is also possible to practice embolization of uterine arteries or hysteroscopic
evacuation of the pregnancy. In a hemodynamically unstable patient or non-responsive at
medical treatment patient, surgical intervention is performed: laparoscopy, laparotomy,
possible hysterectomy. [13, 14, 15, 16]

Case Report

We report the case of a 42-year-old patient who is hospitalized in the Department of


Obstetrics and Gynecology, Elias Emergency University Hospital for 6 weeks of amenorrhea,
a positive pregnancy test. From the patient’s history, we report a caesarean birth (9 years ago),
total thyroidectomy and cervical conization for high-grade intraepithelial lesion associated
with HPV infection.
The anamnesis, the clinical and paraclinical outcome (Bhcg at admission 9226 mUI/mL),
the ultrasound examination (Fig. 1): transvaginal ultrasound detects the implantation of the
gestational sac within the previous scar, with embryo with cardiac activity and CRL
corresponding to 6 weeks (Fig. 2), lead to the diagnosis 6-week scar ectopic pregnancy and it
was decided to start treatment with Methotrexate 60 mg intramuscular days 1, 3, 5 associated
with calcium folinate 6 mg intramuscular days 2, 4, 6.

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Fig. 1. Scar ectopic pregnancy

Fig. 2. Cardiac activity for scar ectopic pregnancy

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We monitor the patient’s condition and the paraclinical outcome and perform serial TV
ultrasounds. Upon completion of treatment with Methotrexate, the ultrasound detects the
absence of cardiac activity and it is decided to discharge the patient with good overall status
and without vaginal bleeding, waiting for a spontaneous abortion. The patient was informed
of the risk of massive home bleeding for whom she will come at Elias Emergency Room.
The follow up was weekly by ultrasound examination and Bhcg test, which reached 5
mUI/ml at the 6th week after the treatment was finished, simultaneously with the first period.
The subsequent ultrasound of this menstrual period showed a ballooning gestational sac
(Fig. 3).
During the 9th week, with the second period, it was certified by ultrasound that the
pregnancy was eliminated (Fig. 3).

Fig. 3. Image preceding second period shows a ballooning gestational sac

Discussions

There are reports that support the two management options in this pathology, both medical
and surgical. Conservative or medical treatment of Methotrexate, whether or not combined
with uterine artery embolization, minimizes the risk of massive hemorrhage. [17] Not least,
must be taken into account the subsequent outcome after conservative treatment of a cesarean
scar pregnancy such as uterine rupture, placenta accrete, intrauterine growth restriction. [18,
19]
Other studies support surgical approach, even in the absence of hemorrhage, by elective
laparotomy with gestational mass excision. These authors claim that excision of the old scar,
with a new uterine suture, reduces the risk of recurrence. Both medical and ethical
implications should be considered while choosing the treatment plan. [20]

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It is time to consider the measures necessary to prevent the occurrence of cesarean scar
ectopic pregnancy. Regarding the role of single-layer suture versus multi-layer uterine suture
in order to prevent scarring defects, literature is controversial. [21, 22]
Currently no way seems to be completely safe and can’t guarantee uterine integrity.

Conclusions

Cesarean scar ectopic pregnancy is a complex condition with an increasing incidence in


recent years. Early diagnosis and effective management are important to reduce maternal
mortality and morbidity, treatment should be performed in the first trimester to preserve
fertility and prevent recurrence.

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83(12):1167-72.
19. Timing for the delivery of the growth-restricted fetus: a resolvable issue. A Petca, S Vlădăreanu, M
Zvâncă, M Boț, R Vlădăreanu. Proceedings of 49 th Annual Scientific Meeting of the European Society
for Clinical Investigation, 27-30 may, 2015, Cluj Napoca, Printed in July 2015 by Editografica,
European Journal of Clinical Investigation pp. 273-279, ISBN 978-88-7587-719-4.
20. Olaru Gabriel Octavian, Antoniu Crangu Ionescu, Anca Lesnic, George Alexandru Filipescu, Liana
Ples. Ethical and medico-legal aspects of the therapeutic abortion – our experience. Journal of
Romanian Legal Medicine 26(1), pp. 82-85.
21. Toader O, Vintea A, Voichitoiu A, Suciu N, Cirstoiu M, Esanu S, Bohiltea R. HYPERLINK
“http://gineco.eu/index.php/arhiv/74326” Caesarian scar ectopic pregnancy. A case report. Gineco.eu
2017, 13, 47(1), pp. 23-26. HYPERLINK “http://gineco.eu/index.php/arhiv/74326”
DOI:10.18643/gieu.2017.23
22. Ionescu CA, Vlădăreanu S, Brătilă E, Coroleucă CA, Coroleucă CB, Pacu I, Bohîlțea R, Dimitriu M.
Uterine rupture risk assessment with third trimester transvaginal ultrasonography in women with
previous cesarean section. Gineco.eu 2017, 13, 49(3), pp. 97-99. DOI: HYPERLINK
“http://gineco.eu/index.php/arhiv/74343” 10.18643/gieu.2017.97

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A Case Report of Both Abnormally Adherent and Complete


Placenta Praevia: A Successful Management Via Conservative
Surgery

CALO Ioana1, BOBEI Tina1, DIACONESCU Denise1,


CONSTANTINESCU Camelia1,2
1“St. John” Hospital, “Bucur”, Maternity, Bucharest (ROMANIA)
2UMF “Carol Davila”, Bucharest (ROMANIA)
Emails: [email protected], [email protected]

Abstract

Placenta praevia is an obstetric complication that occurs when the placenta attaches to the
lower area of the uterus, covering partially or totally the internal cervical os.
Material and method: We report the diagnosis, evolution and peculiarities of a case from
our clinic with abnormally adherent and complete placenta praevia
Results: We present a case of a 35-year-old woman G3P3 with abnormal placentation
insertion, with a history of two cesarean sections and her last pregnancy with complete
placenta praevia (terminated at 31 weeks of gestation due to vaginal bleeding) was admitted
in our clinic for abdominal pain without spotting. The transvaginal ultrasound showed
insertion of the placenta both on the anterior and posterior wall of the lower segment and
complete coverage of the cervix without sonographic signs of accreta. Due to high obstetrical
risk, the patient was kept hospitalized for further monitoring without presenting vaginal
bleeding. The C-section was scheduled at 38 weeks of gestation. The incision was made
transplacental and a healthy neonate weighing 3500g IA-10 was delivered. The extraction of
the placenta was difficult due to areas of accreta on the posterior wall of the lower segment.
Bleeding was minimal from the area of placental insertion, so the decision of preserving
the uterus was made. Due to an episode of uterine relaxation managed by mechanical
techniques and use of uterotonics with hemodynamic instability (hypotension and
tachycardia) and vaginal bleeding, a Blakemore balloon was inserted and filled with 300 ml of
normal saline. The patient was cared for in intensive care for 3 days with favorable outcome.
Conclusion: The particularity of this case is her history of complete placenta praevia in the
previous pregnancy with the termination for vaginal bleeding by cesarean section and the
current both abnormally adherent and complete placenta praevia in which case, our
experience indicates that the conservative method can be considered an option in the
management of such high obstetrical risk patients.
Keywords: placenta praevia, conservative surgery, cesarean section

Introduction

Placenta praevia is an obstetric complication that occurs when the placenta attaches to the
lower area of the uterus, covering partially or totally the internal cervical os.
The number of caesarean sections increases the risk of placenta praevia so: if a woman has
had one caesarean section she will have an odds ratio for placenta praevia of 4.5. Thus,
making the caesarean section an important risk factor in the incidence of placenta praevia. [1]

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The placental implantation in the lower uterine segment depends on the presence of
scarring or endometrial disruption determined by uterine instrumentation, such as curettage,
placenta praevia, or caesarean section. [2] Due to the development of new vessels and to a
poorly contractile area, when placenta praevia and accrete coexist the risk of severe uterine
bleeding increases. [3]
The management of placenta praevia-accreta includes a scheduled caesarean delivery,
earlier in gestational age and preoperative preparation for cesarean-hysterectomy and
interventions to reduce the risk of massive hemorrhage. [4]
We report the diagnosis, evolution, management and peculiarities of a case from our clinic
with abnormally adherent and complete placenta praevia.

Case report

We present a case of a 35-year-old woman G3P3 with abnormal placentation insertion,


with a history of two cesarean sections and her last pregnancy with complete placenta praevia
(terminated at 31 weeks of gestation due to vaginal bleeding) was admitted in our clinic for
abdominal pain without spotting.
The transvaginal ultrasound showed insertion of the placenta both on the anterior and
posterior wall of the lower segment and complete coverage of the cervix without sonographic
signs of accreta which would normally be: (a) complete loss of the retroplacental sonolucent
zone, (b) focal disruption of hyperechoic bladder mucosa and the presence of an exophytic
placenta invading the bladder, (c) appearance of ‘moth‐eaten’ placental lacunae, (d) thin
retroplacental myometrium <1mm, (e) pattern of diffuse lacunar flow visualized by color
Doppler mapping, (f) multiple vascular lakes with high peak systolic velocity (PSV) and
low‐resistance turbulent flow. [5]
Due to high obstetrical risk, the patient was kept hospitalized for further monitoring
without presenting vaginal bleeding which is unsual in a pacient with complete placenta
praevia. The C-section was scheduled at 38 weeks of gestation.
In the day of the surgery, the necessary obstetric and anesthetic measures were taken
regarding the patient’s increased obstetrical risk. The opening and inspection of the peritoneal
cavity revealed a thin lower uterine segment, with a vivid appearance with vascular loops of
about 3/3 cm.

Fig. 1. Thin lower uterine segment, with a vivid appearance with vascular loops of about 3/3 cm

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Fig. 2. Abnormal adherence area in the posterior wall

The incision was made transplacental and a healthy neonate weighing 3500g IA-10 was
delivered. The extraction of the placenta was difficult and with significant bleeding due to an
abnormal adherence area in the posterior wall which could not be extracted,so we decided to
place a hemostatic suture at the base of the cotyledon rest. Afterwards, bleeding was minimal
from the area of placental insertion, so the decision of preserving the uterus was made.

Fig. 3.

Due to an episode of uterine relaxation managed by mechanical techniques and use of


uterotonics with hemodynamic instability (hypotension and tachycardia) and vaginal
bleeding, a Blakemore balloon was inserted and filled with 300 ml of normal saline.
The patient was cared for in intensive care for 3 days with favorable outcome and the
discharge in the 9th day.

Discussions

Placenta previa classically presents as painless vaginal bleeding in the last trimester as a
consequence of an abnormal placentation near or covering the internal cervical os. Thanks to
modern use of ultrasonography and obstetrical screening, the diagnosis of placenta previa is

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commonly made earlier in pregnancy and can also identify the protrusion of the uterine
surface or placental area into the amniotic cavity. [6]
Most studies report an incidence of placenta previa between 1 in 150 and 1 in 300 patients
(3-6/1000). Abnormal placentation such as placenta accreta, increta, and percreta occurs less
frequently, from 1 in 1600 to 1 in 12,000 patients. [7]
Placenta accreta is often associated with placenta previa.Placenta accreta occurs in
approximately 1 of 2500 deliveries. Among women with placenta previa, the incidence is
nearly 10%. In this high-risk group advanced maternal age and previous cesarean section are
independent risk factors. [8]
In a study comparing the impact of conservative and extirpative strategies for placenta
accreta on maternal morbidity and mortality the conclusion was that leaving the placenta
accreta in situ appears to be a safe alternative to removing the placenta. In our case, we chose
to extract the placenta with leaving in place the small placental area of abnormal adherence
with minimal bleeding. [9]
In a review of 48 case reports concerning the safety and efficacy of conservative
management of abnormal invasive placentation their findings were relevant to our experience
in this case, stating that the conservative management can be effective but should only be
considered in high selected cases where blood loss is minimal and/or fertility can be
preserved. [10]
In todays medicine, doctors are more concerned in trying to establish more conservative
protocols in treating pacients with high obstetrical risks. Our use of a mechanical way of
hemostatis, an intrauterine balloon, is mentioned in a retrospective study regarding the
conservative management in placenta praevia-accreta. In some cases the haemostatis failed
and a hysterectomy was performed. [11] This was not our experience.
The particularity of this case is her history of complete placenta praevia in the previous
pregnancy with the termination for vaginal bleeding by cesarean section in 2016, and the
current both abnormally adherent and complete placenta praevia.
In a study examining the association between cesarean delivery and previa and abruption
in subsequent pregnancies the results showed that the risk of praevia increases with the
number of prior caesarian sections, and with a short interpregnancy period. [12]

Conclusion

We presented the diagnosis, evolution, management and peculiarities of a case from our
clinic with abnormally adherent and complete placenta praevia in a pacient with a complete
placenta praevia in the previous pregnancy and our experience indicates that the conservative
method can be considered an option in the management of such high obstetrical risk patients.

REFERENCES

1. Rao, K.P., Belogolovkin, V., Yankowitz, J., and Spinnato, J.A.(2012) Abnormal placentation: evidence-
based diagnosis and management of placenta previa, placenta accrete, and vasa previa. Obstet Gynecol
Surv. 67: pp. 503-519.
2. Oyelese, Y. and Smulian, J.C. Obstet Gynecol. (2006); 107: pp. 927-941.
3. Palacios-Jaraquemada, José. (2012). Caesarean section in cases of placenta praevia and accreta. Best
practice & research. Clinical obstetrics & gynaecology. 27. 10.1016/j.bpobgyn.2012.10.003.
4. Shih, J. C., Jaraquemada, J. M., Su, Y. N., Shyu, M. K., Lin, C. H., Lin, S. Y. and Lee, C. N. (2009),
Role of three‐dimensional power Doppler in the antenatal diagnosis of placenta accreta: comparison
with gray‐scale and color Doppler techniques. Ultrasound Obstet Gynecol, 33: pp. 193-203.
5. Sawsan Al Obaidly,Asim Kujak (2010), Prenatal diagnosis of morbidly adherent placenta with 2D
ultrasonography, 3D color power Doppler and Magnetic Resonance Imaging.Donald School Journal of
Ultrasound in Obstetrics and Gynecology, April-June 2010; 4(2): pp. 199-204.

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6. Pleș L, Sima RM, Moisei C, Moga MA, Dracea LA.(2017) Abnormal Ultrasound Appearance of the
Amniotic Membranes-diagnostic and significance:a pictorial essay. Medical Ultrasonography 19(2): pp.
211-215.
7. Saleh, H, Glob.libr.women’smed., (ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10121.
8. David A. Miller, MD, Janet A. Chollet, MD, T.Murphy Goodwin, MD (2007), Clinical risk factors for
placenta previa-placenta accreta. American Journal of Obstetrics & Gynecology 10.1016/S0002-
9378(97)70463-0.
9. Gilles Kayem, Céline Davy, François Goffinet, et al., (2004), Conservative Versus Extirpative
Management in Cases of Placenta Accreta. Obstetrics & Gynecology: September 2004 – Volume 104 –
Issue 3 – pp. 531-536.
10. Sarah Timmermans, Arjanneke van Hof, and Johannes Duvekot (2007), Conservative Management of
Abnormally Invasive Placentation. Obstetrical & Gynecological Survey: August 2007 – Volume 62 –
Issue 8 – pp. 529-539.
11. Arduini, M., Epicoco, G., Clerici, G., Bottaccioli, E., Arena, S. and Affronti, G. (2010), B‐Lynch
suture, intrauterine balloon, and endouterine hemostatic suture for the management of postpartum
hemorrhage due to placenta previa accreta. International Journal of Gynecology & Obstetrics, 108: pp.
191-193. doi:10.1016/j.ijgo.2009.10.007.
12. Darios Getahun, Yinka Oyelese, Hamisu Salihu, et al., (2006), Previous Cesarean Delivery and Risks of
Placenta Previa and Placental Abruption. Obstetrics & Gynecology: April 2006 – Volume 107 – Issue 4
– pp. 771-778.

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Peripartum Infection in the Caesarean Section Delivery

CAPROS Hristiana1, MIHALCEAN Luminița1, SIRITANU Irina1,


BURNUSUS Constantin1, BOLOGAN Ion1, BOLOGAN Ludmila2
1 State Medical University of Medicine end Pharmacy «N. Testemitanu», (REPUBLIC OF MOLDOVA)
2 Center for Continuing Medical Education of Medical and Pharmaceutical Staff with Medium Studies (REPUBLIC OF
MOLDOVA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected]

Abstract

We present a clinical study based on cross-sectional observation. The study was performed
at the Municipal Clinical Hospital No. 1, 2014-2015 in the Obstetric sections no.1, no. 2 and
no. 3, and Septic gynaecology section. The study includes 530 women who gave birth by
caesarean section. In order to study the degree of implementation of the institutionalized
standardized clinical protocol “Antibiotic prophylaxis in caesarean section”, we divided the
study into two periods: January-March (236 cases – 44.5%±2.16, MI: 40.3%-48.9%) and
September to November (294 cases – 55.5%±2.16, CI: 51.1%-59.7%). We drew attention to
spesific data: caesarean sectional indications, emergency/planar caesarean operation, time of
delivery, alchidic period, number of vaginal exams, complications during surgery,
administration of antibiotic, time of administration and the number of doses. At the end of the
first year of implementation of the standardized clinical protocol, we noticed a decrease in
septic complications.
Keywords: Antibiotic, caesarean section, septic complications

Introduction

The approached problem is very actual for contemporary obstetrics, as a result of steadily
rising of cesarean surgery. This increase of the percentage of cesarean surgery brings with it
many complications, the most common of which are infectious [1].

Purpose

Highlighting the need of rational use of antibiotic prophylaxis in caesarean section.

Materials and methods

The presented clinical study is based on retrospective and cross-sectional data, performed
at the Clinical Municipal Hospital no. 1 (CMH no. 1), in the obstetrical department no. 1, no.
2 and no. 3 and septic gynecology department. The study includes a group of 530 women who
gave birth by caesarean section. The group was selected based on diagnosis of caesarean
section and includes the total number of caesarean cases performed during the period of study,
corresponding to the low or moderate risk of infections, so the obtained results could be
representative and generalized for the overall general statistics.
In order to achieve all the proposed objectives, we carried out a retrospective analysis of
the case history of the patients who gave birth by caesarian section during the period of

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January – March, 2015 (236 cases). Also, we investigated additionally to the basic analysis,
based on the anamnestic and objective data, 294 case history of patients who have had a
cesarean surgery between september and november 2015 in the perinalogical department of
the CMH no. 1. To study the degree of implementation of the institutionalized standardized
clinical protocol “Antibiotic prophylaxis in cesarean section”, we divided the study into two
periods: January-March (236 cases – 44.5%±2.16, CI: 40.3%-48.9%) and September –
November (294 cases – 55.5%±2.16, CI: 51.1%-59.7%). Dividing the group depending on the
obstetrical department where they were hospitalized and the study period, we note that the
groups consist of: 70 women (13,2%) from obstetrical department no. 1, 98 women (18,49%)
from obstetrical department no.2 and 68 women (12.83%) from obstetrical department no. 3,
who gave birth by caesarean section, between January and March 2015. For the second stage
of the study (September-November), 132 cases (24.9%) were performed surgery in the
obstetrical department no. 1, 74 women (13.96%) in obstetrical department no. 2 and 88
women (16,62%) in the obstetrical department no. 3. The collected data includes: woman’s
age, the term of pregnancy, the evolution of pregnancy, the number of pregnancies and births,
the complicated obstetric anamnesis, gynecological and obstetrical anamnesis, the presence of
the concomitant pathologies. indications for cesarean section, emergency/planned cesarean
surgery, labor time before surgery, the period after amniotic membrane rupture, multiple
vaginal examination, presence of vaginal infections, complications during surgery, antibiotic
administration, administration time and number of antibiotics doses. At the same time, we
used post surgery clinical data like: accusations, temperature, leukocytosis, local status to
highlight early local infectious complications [2].
Selection criteria of the study group:
➢ parturients who gave birth by CS;
➢ low and moderate infection risk;
➢ women who received antibiotic prophylaxis.

Results

The initial lot of 530 parturients was divided in two groups, according to the number of
antibiotic doses administered perioperatively for the prophylaxis of post surgery septical
complications. The first group included 196 (37%±2.1% CI: 32.9%-41.3%) women who
received a single dose of antibiotic. The second group included 334 (63%±2.1%, CI: 58.7%-
67.1%) women, who received two and more perioperative antibiotic doses for prophylaxis
(Fig. 1.).

Fig. 1. Distribution of parturients according to the number of received antibiotic doses

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According to the antibiotic administration time in the first study group, we notice that from
the 196 parturients who received a single dose of antibiotic, in 87 (44.39%±1.61%, CI:
41.4%-48.9%) cases, the antibiotic was administered 15-60 minutes before the skin incision,
but in 109 (55.61%±1.76%, CI: 51.3%-59.3%) cases the doses of antibiotic were given after
the clamping of umbilical cord. In the second group, from the 334 included women, 103
(30.84%±1.72%, CI: 26.2%-33.1%) of them received the first dose of antibiotic pre or
intraoperative, followed by other postoperative doses of antibiotics, the other 231
(69.16±2.15%, HI: 65.3%-72.9%) cases, two or more doses of antibiotics were administrated
only postoperatively.
The parturients age ranged from 17 to 42 years (average 26.7 years ± 4.72 years). Within
the total of 530 cases, 210 (40.0%±2.13%, CI: 35.5%-43.9%) parturients reported a
complicated obstetrical anamnesis. According to the repartition by lots, the Ist lot includes –
79 (40,3% ± 3,42%) parturients, and the IInd lot – 131 (39,22%±2,71%) parturients with the
complicated obstetrical anamnesis. According to the statistical difference, the lots are similar
p>0.05. Study group’s characteristics depending on the type of cesarean surgery.
Of the total of 540 operations, 329 (62.1%±2.11%, CI: 57.8-66.2%) of interventions were
urgently carried out and 201 (37.9%±2.11%, CI: 33.8% 2%) of them were planned cesarean
section.
In correlation with study groups, we note that in the Ist group of the 196 interventions,
38.3%±3.47% (75 operations) were carried out on a planned basis and 61.7%±3.47% (121
interventions) were carried out urgently, compared to second group, where 37.7%±2.65%
(126 interventions) were performed planned and 62.3%±2.65% of them were urgently
operated. According to the veracity of the difference, p> 0.05 – insignificant statistical
difference.
Following the examination of the clinical case history and the instruction sheets of the
parturients included in the study, was shown a wide range of antibiotics at different doses. In
the first group, the use of Cefazolin 1g was recorded in 139 (70.9%±3.24%) cases, also have
been notified: Amoxacillin 1,2g – 12 (6.1%±1.71%) cases, Cefazolin 2g – 28 (14.3%±2.5%)
cases, Cefuroxime 1.5g – 13 (6.6%±1.78%) cases and Ampicillin 1g – 4 (2%±1.01%) cases.
In the second group, the variation and combinations of antibiotics administered two and
several days are very diverse, more frequently were noted: Cefazolin 2g – 51 (15.3%±1.97%)
cases; Cefazolin 1g – 88 (26.3%±2.41%) cases; Cefazolin 2g + Ceftazidine 1g – 26
(7.8%±1.47%) cases; Cefuroxime 1.5g – 42 (12.6%±1.81%) cases; Cefuroxim 0.75g – 31
(9.3%±1.59%) cases; Cefuroxime 0.75g + Metronidazole – 15 (4.5%±1.13%) cases;
Cefazolin 1g + Metronidazole – 23 (6.9%±1.39%) cases; Ceftriaxone 1.5g - 26 (7.8%±1.47%)
cases; Ampicillin 1g - 18 (5.4%±1.24%) cases; Amoxacillin 1.2g - 14 (4.2%±1.1%) cases.
After questioning womens included in the study and studying their case history, in 26
(4.9% ± 1.59%, CI: 2.1-6.5%) cases were found septical complications after cesarian surgery
from the total of 530 cases included in the study. In first study group, which included women
who received a single dose of antibiotic, were registered 9 (4.6%±2.61%) cases of puerperal
infection, of them, respectively 3 (3.4%±0.71%) cases of them received the antibiotic with 15-
60 mines before the skin incision and 6 (5.5%±2.11%) cases of those who received a dose of
antibiotics after umbilical cord clamping. In the second group, 17 (5.1%±2.01%) childwifes
showed signs of puerperal infection, respectively 5 (4.85%±1.71%) cases from the group of
those who received a pre- or intraoperative antibiotic dose and many postoperative antibiotic
doses and 12 (5.2%±2.08%) cases of women that were given several doses of antibiotic after
the surgery.
According to the veracity of the difference, p> 0.05 - insignificant statistical difference.
Clinical signs recorded in postoperative infections.

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The childwifes showed the following signs of septic complications of postoperative


wound:
• wound hyperemia – 26 (4,9%±1.38%, CI: 2,4-6,3%) cases;
• wound suppuration – 22 (4,1%±1.24%, CI: 1,9-5,7%) cases;
• wound’s abscess – 8 (1,5%±0.53%, CI: 0,7-3,1%) cases.
Associatively, we can accentuate, the incidence of other non-specific, identified signs of
puerperal infection:
➢ fever – 66 (12.5%±1.43%, CI: 9,8-15,6%) cases;
➢ chills – 30 (5.7%±1.0%, CI:3,9-8,1%) cases;
➢ leukocytosis – 78 (14.7%±1.54%, CI:11,9-18,1%) cases;
➢ deviation of leukocyte formula to the left – 52 (9.8%±1.29%, CI: 7,5-12,7%) cases.
Analyzing the data presented above, we conclude that for both groups presented the same
signs and symptoms of local postoperative infection are specific and prevalent. The presence
of endometritis was confirmed in 11 (2.07%±1.07%, CI: 1.03-3.9%) cases from total cases,
respectively 4 (2.0%±1.71%) cases of the childwifes included in first group and 7
(2.1%±1.06%) endometritis cases recorded in second group. Thus, out of 9 cases of septic
complications determined in the first group, 7 (3.6%±0.93%) cases of them are postoperative
wound infection and 4 cases of endometritis, 3 women had both postoperative wound
supuration, as well as endometritis. For second group, are characteristic 12 (3.69%±1.9%)
cases of septic complications of the postoperative wound and 7 cases of endometritis, where
two of them showing both wounds supuration and endometritis (Fig. 2).

Fig. 2. Incidence of postcaesarean septic complications

In order to analyze the aspects of the incidence of puerperal infection, we retrospectively


researched the cases of post-partum puerperal infection hospitalized in the septic gynecology
department of CMH no. 1, during two years, 2014-2015.
We noticed that in 2014, from 74 patients hospitalized with postoperative infectious
complications, 35 women had a caesarean section in CMH no. 1, so the rate is
47.29%±1.74%.
During the year of 2015, in the septic gynecology department were 81 patients with
various postcaesarean infections, 31 of them being operated in the CMH no. 1, the rate is
45.7%± 2.09%. (p>0.05)
Reported on the number of caesarean surgeries during the last two years, 2014-2015, the
rate of septic complications admitted in the septic gynecology department of the CMH No. 1,
is insignificant. So, during the last two years, there were 1425 births by caesarean section. In

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2014 it is reported that 2.45%±0.76% of the childwifes were hospitalized in the septic
gynecology department, and in 2015 – 2.17%±1.29% (Fig. 3).

Fig. 3. The relation of postcaesarean infection ratio enrolled in septic gynecology department and the total
number of yearly caesarean

Also, a insignificant decrease, but it is important for demonstrating the effectiveness of


antibiotic prophylaxis with a single dose of antibiotics is equivalent to the administration of
multiple antibiotic doses.
Respectively, we can conclude that the implementation of the standardized clinical
protocol of antibiotic prophylaxis in caesarean does not increase the puerperal infection rate at
the hospital level that also oincide with actual recommendations [3]. Also, we noticed the
decrease in postcaesarean puerperal infection and that the implementation of the institutional
protocol has a positive dynamics.

Conclusions

1. The administration of a single pre-operative prophylactic dose of antibiotic


(cephalosporin: Cefazolin 1g) does not produce a higher rate of puerperal infection
than administration of multiple doses of antibiotics peri or post-operative.
2. The optimal time of antibiotic administration for prophylaxis of puerperal
complications after caesarean section is 15-60 minutes before the incision of the skin.
3. The implementation degree of the Standardized Clinical Protocol “Cesarean Antibiotic
Prophylaxis” in CMH no. 1 is increasing. So, for the period January-March the
implementation rate is 27.6% and double increased in September-November up to
48.3%.
4. At the end of the first year of the implementation of the standardized clinical protocol,
there is an decrease in the puerperal infections for 2015 from 5.08% in the first stage
of the study to 4.76% in the second phase of the study. At the end of the first year of
the implementation of the standardized clinical protocol, there is an decrease in the
puerperal infections for 2015 from 5.08% in the first stage of the study to 4.76% in the
second phase of the study.

REFERENCES

1. American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine. Safe
prevention of the primary cesarean delivery. Obstetric Care Consensus. September 2015.

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2. Centers for Disease Control and Prevention. Births – Method of delivery, 2015.
https://www.cdc.gov/nchs/fastats/delivery.htm
3. World Health Organization. WHO Recommendations for Prevention and Treatment of Maternal
Peripartum Infections. Geneva: WHO Press; 2015. pp. 1-6.

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Antepartum and Postpartum Evaluation of Fetal Obstructive


Uropathy

CHICEA Radu1, CHICEA Anca1, NIȚĂ Paula2, OGNEAN Maria Livia1


1University of Lucian Blaga, Sibiu (ROMANIA)
2Country Emergency Clinical Hospital Sibiu (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Introduction and objectives


The widespread use of fetal morphology ultrasound in the 2nd trimester of pregnancy has
increased the fetal anomaly detection rate. Fetal hydronephrosis is the most common
antepartum detected anomaly. Fetal hydronephrosis is defined as dilation of the kidney pelvis
and calycels.
When hydronephrosis is observed the antenatal ultrasound should document: the level of
amniotic fluid, the bladder filling algorithm, the presence of a contralateral kidney, the
presence of other organ system abnormalities. The aim of the paper is to evaluate the
correlation between in utero ultrasound examination of renal obstructive pathology and
neonatal ultrasound by exposing cases from our clinic at the Sibiu County Emergency Clinical
Hospital.

Methods and Methodology


We aimed to obtain an evidence of pregnancies detected with obstructive renal pathology
during 2016-2017 in the maternal-infant block in the County Emergency Clinical Hospital of
Sibiu. There have been identified 12 pregnant women with fetuses with obstructive pathology.
The patients gave birth in the Obstetrics Gynecology Clinic in Sibiu and the newborns
were taken over by the neonatology team of the County Emergency Clinical Hospital of Sibiu.
On the third day postpartum, a newborn ultrasound was performed. Ultrasound
examination was performed to confirm or refute the suspected diagnosis in utero and
eventually to establish therapeutic behavior where appropriate.

Results
Of the 12 newborns with obstructive uropathy, 8 were diagnosed with
ureterohydronephrosis.
Two of the 8 newborns with ureterohydronephrosis presented bilateral
ureterohydronephrosis.
Three newborns were diagnosed with pielo-ureteral junction syndrome. There was only
one case of megavezic. All cases were confirmed on neonatal ultrasound.

Conclusions and discussion


The antenatal ultrasound examination has good sensitivity and specificity in diagnosis of
urinary obstructive pathology confirmed postnatally.
In obstructive urinary tract pathology, the most common cause in male fetuses is posterior
urethral valve syndrome. The posterior urethral valve syndrome accounts for approximately
50% of cases with classical ultrasonic features. Female fetuses often present more complex,

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morbid pathologies, such as cloacal sinus abnormalities, including microcolon-megacystis


syndrome (the bladder disfunctional in both the bladder and the distal intestine).
Keywords: fetal, ultrasound, hydronephrosis, postpartum

Introduction and objectives

The widespread use of fetal morphology ultrasound in the 2nd trimester of pregnancy has
increased the fetal anomaly detection rate.[1], [2] Fetal hydronephrosis is the most common
antepartum detected anomaly. Fetal hydronephrosis is defined as dilation of the kidney pelvis
and calycels. Most cases of fetal hydronephrosis (79-84%) resolve spontaneously at birth and
are given by the physiological dilatation of the ureter during its development process (urine
production begins before complete ureter canalization, resulting in transient obstruction with
hydronephrosis). Fetal prognosis is directly dependent on anteroposterior diameter and
gestational age at the time of hydronephrosis. [3], [4]
When hydronephrosis is observed, the antenatal ultrasound should document: the level of
amniotic fluid, the bladder filling algorithm, the presence of a contralateral kidney, the
presence of other organ system abnormalities etc. [5]
The most common types of obstructive pathology are transient hydronephrosis,
ureteropelvic junction obstruction, vesicoureteral reflux, ureterovesical junction
obstruction/megaureter.
Urinary obstructive syndromes can result in tubular pathology (salt loss syndrome, renal
acidosis with hyperpotasemia or insipid diabetes) or a significant reduction in nephron
number being one of the main causes of infantile kidney failure. [6]
The degree of severity of in utero and postpartum hydronephrosis is variable, some cases
requiring even postpartum surgery. During the postpartum period, fetal hydronephrosis is
evaluated using ultrasound. The two most common standardized systems for evaluating
hydronephrosis are The Society for Fetal Urology (SFU) grading system and the measurement
of the anteroposterior diameter of the renal pelvis. [7], [8], [9].
First-line imaging modality in confirming hydronephrosis, the degree of obstruction and
the degree of expansion in newborns is ultrasound examination.
All fetuses diagnosed with hydronephrosis in the uterus are subjected to an ultrasound
assessment in the first week of life. Usually this assessment is performed from day 4 of life
because changes occurring in the newborn during the first few days of life may lead to
underestimation of the severity of the hydronephrosis or even to a false negative result. [10],
[11], [12].
However, when there is suspicion of posterior urethral valve syndrome, severe bilateral
hydronephrosis or single kidney, ultrasound examination is required during the first two days
of life. [13]
In the ultrasound evaluation of hydronephrosis in postpartum, the anteroposterior diameter
of the renal pelvis or distal ureter and the thickness of the renal parenchyma should be
followed. Bladder assessment is also required to exclude vesicoureteral abnormalities. [14]
An important contribution to the evaluation of obstructive versus non-obstructive
hydronephrosis is brought by the Doppler examination of the intrarenal renal artery. Also,
three-dimensional renal ultrasound provides more accurate information about the volume of
renal parenchyma. Unilateral or bilateral hydronephrosis usually resolves postpartum
spontaneously. [15]
Transient hydronephrosis has an incidence of 41%-88%. In order to differentiate transient
hydronephrosis from renal obstruction of the ureteropelvic junction, several ultrasound
examinations are required. [16]

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The aim of the paper is to evaluate the correlation between in utero ultrasound examination
of renal obstructive pathology and neonatal ultrasound by exposing cases from our clinic at
the Sibiu County Emergency Clinical Hospital.

Methods and Methodology

We aimed to obtain an evidence of pregnancies detected with obstructive renal pathology


during 2016-2017 in the County Emergency Clinical Hospital Sibiu, Obstetrics Gynecology
Department. There have been identified 12 pregnant women with fetuses with obstructive
pathology. All 12 cases of hydronephrosis were diagnosed in the second and third trimester of
pregnancy and were monitored until birth. The cases were re-evaluated every 4 weeks when
the diagnosis was established in the 2nd trimester of pregnancy and every 2 or 3 weeks when
the pathology was diagnosed in the third trimester of pregnancy. On ultrasound examination,
the following parameters were evaluated: the renal cortical aspect, proximal ureter diameter,
bladder size as well as the anteroposterior diameter of the renal pelvis.
In all cases, an increase in the degree of hydronephrosis was observed with gestational age.
Hydrophoresis was considered when the anteroposterior diameter of the pelvis was greater
than 7 mm as you can see in figure 1.
The patients gave birth in the County Emergency Clinical Hospital Sibiu, Obstetrics
Gynecology Department. Infants were evaluated by ultrasound in the 3rd day of life.
Ultrasound examination was performed to confirm or refute the uterine diagnosis of
obstructive disease. In order to establish the intrauterine diagnosis of obstructive pathology
were evaluated: the renal cortical aspect, proximal ureter diameter, bladder size as well as the
anteroposterior diameter of the renal pelvis. In the postpartum ultrasound examination, the
same criteria as antepartum were followed to determine renal obstruction.

Fig. 1. Ultrasound image of fetal hydronephrosis at 22 week of gestation

Results

All cases were confirmed on neonatal ultrasound. All 12 cases of hydronephrosis were
diagnosed in the second trimester of pregnancy and were monitored by ultrasound until birth.
In all cases it has been observed increased anteroposterior diameter of the pelvis directly
proportional to gestational age. In one case, besides hydronephrosis, megavezica was
observed in the ultrasound examination. In one case, besides fetal hydronephrosis, the
megaureter was also associated. Neonatal ultrasound examination revealed the following:
renal cortical was normal in all 12 cases. The diameter of the proximal portion of the ureter

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was increased in one case. There was only one case in which the bladder size was increased.
All newborns had the anteroposterior diameter of the renal pelvis above normal limits. (Fig.
2)
Of the 12 newborns with obstructive uropathy, 8 were diagnosed with transient
ureterohydronephrosis. Two of the 8 newborns with transient ureterohydronephrosis
presented bilateral ureterohydronephrosis. Three newborns were diagnosed with pielo-ureteral
junction syndrome. There was only one case of megavezic.

Fig. 2. Anteroposterior diameter of the enlarged renal pelvis on day 4 of life

Conclusions and discussion

Ultrasound examination remains the main method of diagnosis and evaluation of fetal
urinary tract malformations as well as postpartum. The antenatal ultrasound examination has
good sensitivity and specificity in diagnosis of urinary obstructive pathology confirmed
postnatally.
Doppler ultrasound provides additional information to guide to a correct diagnosis. A
correct diagnosis is important in order to establish a birth and postnatal behavior. There is the
possibility that in some cases the pregnant woman will be directed to give birth in a medical
center with specialized staff in solving fetal hydronephrosis right after birth.
Most diagnoses have been confirmed postpartum except for those who are hard to establish
even postpartum without following the evolution of the case over time.
In obstructive urinary tract pathology, the most common cause in male fetuses is posterior
urethral valve syndrome. The posterior urethral valve syndrome accounts for approximately
50% of cases with classical ultrasonic features. Female fetuses often present more complex,
morbid pathologies, such as cloacal sinus abnormalities, including microcolon-megacystis
syndrome (the bladder disfunctional in both the bladder and the distal intestine). Fetal
prognosis is unfavorable in both bilateral and obstructive syndromes associated with cystic
renal dysplasia, with renal (glomerular and tubular) dysfunction resulting in severe
oligoamniasis, pulmonary hypoplasia and limb position abnormalities. The abnormal aspect
of renal cortical (defined as the appearance of cortical cysts) shows, according to the
literature, a low sensitivity (0.29) but a good specificity (0.89) for evaluating functional renal
fetal and neonatal prognosis.

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REFERENCES

1. Micu, R, Chicea, A., Bratu, D.G., Nita, P. Nemeti, G. , Chicea, R. (2017) Ultrasound and magnetic
resonance imaging in the prenatal diagnosis of open spina bifida, MedUltrason 2017: 0,1-7
DOI:10.11152/mu-1325
2. Chicea, R., Niță, P., Ţăroi, C., (2017) Complete Corpus Callosum Agenesis, Imagistic Resources in
Establishingthe Diagnosis – Case Report, 5th Romanian Congress of the Romanian-Society-of-
Ultrasound in-Obstetrics-and-Gynecology, Targu Mures, Romania; http://sruog2017.medical-
congresses.ro.
3. Filiz, G., Fatoş, Y., Suat, F., Z. Birsin, Ö., (2012) Evaluation and outcome of antenatal hydronephrosis:
a prospective study., 34(6), pp. 718-721.
4. Dennis, B., (2017) Antenatal Hydronephrosis, https://emedicine.medscape.com/article/1016305-
overview
5. Anthony, C.D.(2006). Antenatal Hydronephrosis: Differential Diagnosis, Evaluation, and Treatment
Options, The Scientific World JOURNAL, vol. 6, pp. 2345-2365, 2006.
https://doi.org/10.1100/tsw.2006.366.
6. Rodriguez, M. M. (2014). Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT). Fetal
and Pediatric Pathology, 33(5-6), pp. 293-320. http://doi.org/10.3109/15513815.2014.959678
7. Fernbach, S.K., Maizels, M., Conway, J.J (1993) Ultrasound grading of hydronephrosis: Introduction to
the system used by the Society for Fetal Urology.Pediatr Radiol2 3 pp. 478-480.
8. Nguyen, H.T., Herndon, C.D., Cooper, C., Gatti, J., Kirsch, A., Kokorowski, P., Lee, R., Perez-
Brayfield, M., Metcalfe, P., Yerkes, E., Cendron, M., Campbell, J.B (2010) The Society for Fetal
Urology consensus statement on the evaluation and management of antenatal hydronephrosis. J Pediatr
Urol 6: pp. 212-231.
9. Sidhu, G., Beyene J, Rosenblum, N.D. (2006) Outcome of isolated antenatal hydronephrosis: A
systematic review and meta-analysis. Pediatr Nephrol 21, pp. 218-224.
10. Wiener, J.S., O’Hara, S.M. (2002) Optimal timing of initial postnatal ultrasonography in newborns with
prenatal hydronephrosis. J Urol.168(4 Pt 2), pp. 1826-1829.
11. Laing, F.C., Burke, V.D., Wing, V.W., Jeffrey, R.B., Hashimoto, B. (1984) Postpartum evaluation of
fetal hydronephrosis: optimal timing for follow-up sonography. Radiology. 1984; 152(4), pp. 23-424.
12. Navolan D*, Vladareanu S*, Ciohat I, Stoian D, Badiu D, Craina M, Tomovici M, Birsasteanu F,
Craciunescu M. A preliminary study over second trimester biochemical markers and their clinical
utility. Revista de Chimie, 2016, vol 67, nr. 6, pp. 12224-1226. ISSN:0034-7752.
13. Nguyen, H.T., Herndon, C.D., Cooper, C., Gatti, J., Kirsch, A., Kokorowski, P., et al., (2010). The
Society for Fetal Urology consensus statement on the evaluation and management of antenatal
hydronephrosis. J Pediatr Urol 6, pp. 212-231.
14. Wiener, J.S., O’Hara, S.M. (2002) Optimal timing of initial postnatal ultrasonography in newborns with
prenatal hydronephrosis. J Urol 168(4 Pt 2), pp. 1826-1829.
15. Riccabona, M., Fritz, G.A., Schollnast, H., Schwarz, T., Deutschmann, M.J., Mache, C.J.(2005)
Hydronephrotic kidney: pediatric three-dimensional US for relative renal size assessment: initial
experience. Radiology.236 pp. 276-283.
16. Choi, Y. H., Cheon, J.-E., Kim, W. S., & Kim, I.-O. (2016). Ultrasonography of hydronephrosis in the
newborn: a practical review. Ultrasonography,35(3), pp. 98-211.

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Imaging Correlation Between Ultrasound and Nuclear Magnetic


Resonance Examination in the Diagnosis of Myelomeningocele

CHICEA Radu1, CHICEA Anca1, NIȚĂ Paula2, OGNEAN Maria Livia1


1University of Lucian Blaga, Sibiu (ROMANIA)
2Country Emergency Clinical Hospital Sibiu (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Introduction and objectives


Myelomeningocele is the most common congenital abnormality of the central nervous
system which is characterized by impaired neuromuscular function. Statistically speaking, this
malformation occurs once in 1000 births, and the neural tube defect can be located anywhere
along the spine.

Methods and Methodology


The paper represents an exposure of imaging from the literature, suggestive for the
diagnosis of myelomeningocel. We also included in the article a serie of two cases from our
experience at the Obstetrics Gynecology Clinic of Sibiu County Emergency Clinical Hospital.
As methods of diagnosis were used the ultrasound examination and nuclear magnetic
resonance. Also nuclear magnetic resonance was used to establish the surgical management.
The first case was presented in the emergency department of our clinic at 36 weeks
gestation for vaginal bleeding easily.

Results
In both cases of myelomeningocel there was a good correlation between ultrasound
examination and MRI scan. The ultrasound diagnosis was confirmed by MRI, and the latter at
birth.

Conclusions and discussion


There is a good correlation between ultrasound imaging and MRI in the evaluation of
myelomeningocel.
Keywords: myelomeningocele, IRM, ultrasound, fetus

Introduction and objectives

Myelomeningocele is the most common congenital abnormality of the central nervous


system which is characterized by impaired neuromuscular function. Statistically speaking, this
malformation occurs once in 1000 births, and the neural tube defect can be located anywhere
along the spine. [1], [2], [3] Evaluation of fetal anomalies in utero is performed by ultrasound
examination. The diagnosis rate of myelomeningocele increased with the spread of routine
fetal morphology ultrasound in the 2nd trimester of pregnancy Although studies conducted in
the past few years show increased sensitivity of two-dimensional ultrasound in the diagnosis
and assessment of bone abnormalities, it should be brought to mind that two-dimensional
ultrasound examination does not have a sensitivity of 100%. [4], [5], [6] The purpose of the

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paper is to expose the correlation between ultrasound and magnetic resonance imaging in the
diagnosis of myelomeningocele.

Methods and Methodology

The paper represents an exposure of imaging from the literature, suggestive for the
diagnosis of myelomeningocel. We also included in the article a serie of two cases from our
experience at the Obstetrics Gynecology Clinic of Sibiu County Emergency Clinical Hospital.
As methods of diagnosis were used the ultrasound examination and nuclear magnetic
resonance. Also nuclear magnetic resonance was used to establish the surgical management.
The technique used in the evaluation of myelomeningocel is the same all over the world.
Typically, the diagnosis of spina bifida established in the second trimester of pregnancy is
based on the presence of indirect signs in the fetal skull, which is much easier to examine than
the entire length of the vertebral column. The indirect cranial signs of myelomening are the
lemon sign and banana sign. Likewise, Chiari malformation type II is often associated with
ventriculomegaly. [7], [8] The sign of certainty in establishing the diagnosis of
myelomeningocel is the visualization of the spinal cord herniation. The current trend is to
establish the diagnosis of myelomeningocele at a lower gestational age – the end of the first
trimester of pregnancy or the beginning of the second trimester of pregnancy. It is intended to
establish the diagnosis of myelomeningocele as early as possible because, when diagnosed
during the first trimester of pregnancy, the couple has the option to terminate the pregnancy.
In this regard, numerous studies were carried out which aimed to introduce measurements
as markers in the early diagnosis of myelomeningocel. [9], [10], [11], [12], [13], [14] Thus,
the diameter of the following structures was studied: cisterna magna, fourth ventricle, the
brainstem, the occipital bone of the brainstem, the roof of the third ventricle and the aqueduct
of Sylvius. Of all these measurements proposed and studied in various papers published in the
literature, the measurements associated with spina bifida in the first trimester of pregnancy are
the anteroposterior diameter of the fourth ventricle and the anteroposterior diameter of the
magna cisterna. More information in the diagnosis and evaluation of myelomeningocele is
given by three-dimensional ultrasound. In the last few years, three-dimensional ultrasound is
flourishing due to increasingly performing software. Three-dimensional ultrasound volumes
are acquired which can be further processed by the examiner.
Although ultrasonography is a diagnostic method accessible and available to anyone, it still
has the disadvantage that it has a low penetration of the ultrasound in obese women,
oligoamnios or bone structures. [15], [16], [17], [18]. Nuclear magnetic resonance imaging
(IRM) has a high degree of tissue penetration and provides specific information about the
examined structure. The MRI evaluation allows accurate visualization of the posterior fossa,
cerebellum and spinal cord.
Surgical treatment of myelomeningocel in utero is established following the MRI
assessment of the cerebral herniation degree. [19], [20], [21].
The first case was presented in the emergency department of our clinic at 36 weeks
gestation for vaginal bleeding easily. The patient has never been to a doctor during pregnancy.
At the ultrasound examination at admission, significant hydrocephalus was observed as can
be seen in Figure 1 and a defect in the lumbar spine as can be seen in Figure 2. Following the
ultrasound, the diagnosis of Arnold Chiari type II malformation was established.

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Fig. 1. Hydrocephaly at 36 weeks of gestation

Fig. 2. Myelomeningocel the lumbar spine at 36 weeks of gestation

No other associated anomalies were found. Following an interdisciplinary consultation


with the neurosurgeon specialist, an MRI examination of the fetus was performed. Following
MRI examination the following were observed: hernia of the cerebellum, bulb and lower part
of the IV ventricle in the cervical canal, as can be seen in Figure 3 and the presence of
myelomeningocele.

Fig. 3. Fetal IRM at 36 weeks of gestation: hernia of the cerebellum, bulb and lower part of the IV ventricle in
the cervical canal

Diagnosis of Chiari malformation type II established by ultrasound was confirmed by


IRM.
The patient gave birth by cesarean. The neural tube defect observed at birth was spread
over a length of 6 cm as shown in Figure 4. Immediately postpartum neonatology and
neurosurgery team took over the newborn and intervened surgically. Figure 5

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Fig. 4. Postpartum appearance of myelomeningocel

Fig. 5. Postoperative image of the newborn operated by myelomeningocel

The second case of myelomeningocel was diagnosed at 26 weeks of gestation. The patient
has been presented to the doctor since the first trimester of pregnancy. There were no
malformations in the ultrasound evaluation at 12 weeks of pregnancy. At the time of the fetal
morphology ultrasound in the second trimester of pregnancy, the patient did not submit for
evaluation.
Instead, the patient was presented at 26 weeks of gestation for ultrasound assessment.
Cerebellum, cisterna magna and lateral ventricle measurements were performed as you can
see in Figure 6.

Fig. 6. Measurements of the cerebellum and cisterna magna

Upon ultrasound examination of the spine we observed the presence of a tumor suggestive
for myelomeningocel. Magnetic resonance imaging was performed and the diagnosis of
myelomeningocele was established. The patient completed the pregnancy and gave birth by
caesarean surgery. At birth, once again, the diagnosis of myelomeningocele confirmed. The
newborn was operated by the neurosurgery team as can be seen from Figure 7.

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Results

In both cases of myelomeningocel there was a good correlation between ultrasound


examination and MRI scan. The ultrasound diagnosis was confirmed by MRI, and the latter at
birth. However, MRI examination has brought extra information regarding the correct staging
of the Arnold Chiari malformation. However, both imaging methods revealed the same thing
with the difference that the MRI examinations were much clearer because of the high degree
of penetration of the tissues.

Conclusions and discussion

There is a good correlation between ultrasound imaging and MRI in the evaluation of
myelomeningocel.
If a few years ago ultrasound was seen as a limited examination of congenital cerebral
anomalies [22], [23], it is now beginning to gain ground in assessing the central nervous
system.
Evolution of software systems makes it possible to highlight brain changes that in the past
could only be highlighted by MRI. The main issue in the MRI evaluation of a case is the
increased costs. Ultrasound examination is accessible to everyone. An advantage of the
ultrasound examination is that through the three-dimensional evaluation, it is possible to
purchase volumes that can be further processed by the examiner. Considering the increased
MRI examination costs and the good correlation between ultrasound and MRI, ultrasound
remains the gold standard in diagnosing myelomeningocel. The MRI evaluation is extremely
useful for neurosurgeons who establish the surgical treatment of myelomeningocelia after
MRI evaluation.
In conclusion, both imaging methods are useful and complementary to each other and none
of them excludes the other.

REFERENCES

1. Noel, A.E., Richard, N. (2014) Advances in evaluating the fetal skeleton, Int J Womens Health.6, pp.
489-500.
2. Szabó, A. (2014) Nasal bone length: prenasal thickness ratio: a strong 2D ultrasound marker for Down
syndrome, Prenat Diagn. 34(12) pp. 1139-1145.
3. Thomas, W., Ralf, L., Rolf, F., Manfred, E. (2002) Three-dimensional sonographic evaluation of the
fetal lumbar spinal canal, J Anat. 200(5), pp. 439-443.
4. Jeffrey, M., Samantha, L. Piper, C., (2015) The utility of ultrasound for the detection of fetal limb
abnormalities – a 20-year single-center experience, Prenat Diagn.; 35(4) pp. 348-353.
5. Zheng, L., Gong, L., Guo, F., Chang, H., Liu, G. (2015), Application research on three-dimensional
ultrasonic skeletal imaging mode in detecting fetal upper jaw bone, Int J Clin Exp Med; 8(8) pp. 12219-
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6. Ashwitha, G., Yashant, A., Karan, M., (2016) Prenatal diagnosis of hypophosphatasia congenita using
ultrasonography, Ultrasonography. 35(1) pp. 83-86.
7. Micu, R, Chicea, A., Bratu, D.G., Nita, P. Nemeti, G., Chicea, R. (2017) Ultrasound and magnetic
resonance imaging in the prenatal diagnosis of open spina bifida, MedUltrason 2017:0,1-7
DOI:10.11152/mu-1325
8. Chicea, R., Niță, P., Ţăroi, C., (2017) Complete Corpus Callosum Agenesis, Imagistic Resources in
Establishingthe Diagnosis – Case Report, 5th Romanian Congress of the Romanian-Society-of-
Ultrasound in-Obstetrics-and-Gynecology, Targu Mures, Romania; http://sruog2017.medical-
congresses.ro
9. Markov, D., Pavlova, E., Atanasova, D., Markov, P., Ivanov, S. (2010), Absent intracranial
translucency-new ultrasound marker for spina bifida at 11-13+6 weeks of gestation, Akush Ginekol
(Sofiia), 49(6) pp. 56-60.

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10. Bahlmann, F. et al., (2015) Cranial and cerebral signs in the diagnosis of spina bifida between 18 and
22 weeks of gestation: a German multicentre study., Prenat Diagn.; 35(3) pp. 228-35. doi:
10.1002/pd.4524. Epub 2015 Feb 4.
11. Lachmann, R., Chaoui, R., Moratalla, J., Picciarelli, G., Nicolaides, K.H. (2011) Posterior brain in
fetuses with open spina bifida at 11 to 13 weeks.Prenat Diagn. 31, pp. 103-6.
12. Orlandi, E., Rossi, C., Perino, A., Cucinella, G., Orlandi, F. (2015) Prospective sonographic detection of
spina bifida at 11-14 weeks and systematic literature review., J Matern Fetal Neonatal Med. 29(14) pp.
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13. Kose, S., Altunyurt, S., Keskinoglu, P. (2017) A prospective study on fetal posterior cranial fossa
assessment for early detection of open spina bifida at 11-13 weeks., Congenit Anom (Kyoto).
14. Kappou, D., Papastefanou, I., Pilalis, A., Kavalakis, I., Kassanos, D., Souka, A.P., (2015) Towards
detecting open spina bifida in the first trimester: the examination of the posterior brain., Fetal Diagn
Ther. 37(4) pp. 294-300.
15. Ples, L., Sima, R.M., Stanescu, A.D., Olaru, O.G. (2017)The Importance of a National Congenital
Anomalies Registry – the Role of the Prenatal Diagnosis. Proceeding paper for the 5 th romanian
congress of the romanian society of ultrasound in obstetrics and gynecology, pp. 505-510.
16. Karl, K., Heling, K.S., Chaoui, R. (2015) Fluid area measurements in the posterior fossa at 11-13 weeks
in normal fetuses and fetuses with open spina bifida., Fetal Diagn Ther. 37(4) pp. 289-93.
17. Liu, M., Liu, Y., Li, Z.H., Yu, D., (2015) Screening for Fetal Spina Bifida Aperta by the Ultrasound and
Intracranial Translucency Examinations at 11-13(+6) Weeks of Gestation., Cell Biochem Biophys.72(2)
pp. 439-41.
18. Robinson, A.J., Ederies, M.A. (2016) Diagnostic imaging of posterior fossa anomalies in the fetus.,
Semin Fetal Neonatal Med. 21(5) pp. 312-20.
19. Orit, A.G. (2010) MR imaging of the fetal brain, Pediatr Radiol. 40(1), pp. 68-81.
20. Nemec, U., Nemec, S.F., Krakow, D., Brugger, P.C., Malinger, G., Graham, J.M., Jr. Jr., Rimoin, D.L.
(2011), Prayer D.The skeleton and musculature on foetal MRI 2, pp. 309-318.
21. Shaode, Y., Rui, Z., Shibin, W., Jiani, Hu., Yaoqin, X. (2013) An edge-directed interpolation method
for fetal spine MR images, Biomed Eng Online 12, p. 102.
22. Vladareanu S, Popescu S, Bot. M, Berceanu C, Bratila E, Coroleuca C. (2017). Ultrasonography
Aspects of Multisystem Organ Involvement and Extracerebral Lesions in Hypoxic-Ischemic
Encephalopathy of the Neonate. Proceeding for 5TH ROMANIAN CONGRESS OF THE ROMANIAN
SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY. pp. 664-669. Filodiritto
Publisher, ISBN: 978-88-95922-88-1.
23. Vladareanu S, Popescu S, Boț M, Berceanu C, Mehedintu C, Coroleuca C. (2017). The Role of Cranial
Ultrasonography in the Evaluation of Neonates with Hypoxic-Ischemic Encephalopathy. Proceeding for
5TH ROMANIAN CONGRESS OF THE ROMANIAN SOCIETY OF ULTRASOUND IN
OBSTETRICS AND GYNECOLOGY. pp. 670-674. Filodiritto Publisher, ISBN: 978-88-95922-88-1.

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Clinical and Paraclinical Features of Anemia in Early Infancy

CHINCEŞAN Mihaela1, MĂRGINEAN Cristina Oana1, GRAMA Alina1,


CÂMPEAN Ioana2, DINCĂ Andreea1
1University of Medicine and Pharmacy Tg-Mures; Department of Pediatrics I (ROMANIA)
2Emergency County Hospital Tg-Mures-Pediatric Clinic (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

Background
Anemia is defined as a decrease in Hemoglobin, Hematocrit or Red Blood Cell (RBC)
counts, the lower limit being set to <2 SD (standard deviations) below the normal range for
age and sex, set for the general population.

Material and methods


We performed an analytical, descriptive, retrospective study, analyzing a group of 129
infants, aged between 2 weeks and 6 months, admitted in the 1st Pediatrics Clinic of Tîrgu
Mureş in 2016, with a diagnosis of Anemia, regardless the underlying etiology.

Results
The prevalence of anemia among small infants from Pediatrics Clinic during the year 2016,
was 33.1% (129 cases out of 428 admissions in small infants). Regarding the etiology, we
observed anemia within infections (57 cases – 44.1%), physiological anemia of the infant (36
cases – 27.9%), nutritional anemia (21 cases – 16.2%), anemia of prematurity (9 cases –
6.9%), Iron deficiency anemia (4 cases – 3.1%), post hemorrhagic anemia (2 cases – 1.5%).
There was no statistically significant association between gender (male/female) and the
predisposition to develop anemia (p=0.93). We did not identified any statistically significant
associations regarding anemia and natural feeding (p=0.086), dairy formula feeding (p=0.070)
or cow’s milk diet (p=0.49). Concerning Anemia within Infections, we found a statistically
significant association with the presence of paleness (p=0.001), refusal to eat (p=0.004),
presence of splenomegaly (p=0.03) or hepatomegaly (p=0.04). It was also observed that the
infant’s physiological anemia was most commonly associated with the presence of jaundice
(p=0.0001).

Conclusions
In Pediatrics, due to its multifactorial etiology and the complexity of short and long-term
effects on neurological development of the children or the immunological status, Anemia
requires a multidisciplinary approach. Any infectious episode within the first months of life
should be a trigger for testing the infant for Anemia in order to recommend Iron supplements
when needed, or to enlarge the investigations if there is an underlying condition suspected.
Keywords: Anemia, Iron deficiency, Infection, small Infancy

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Introduction

Anemia is defined as a decrease in Hemoglobin, Hematocrit or Red Blood Cell (RBC)


counts, the lower limit being set to <2 SD (standard deviations) below the normal range for
age and sex, set for the general population [1].
The first step in establishing the diagnosis of Anemia is to determine whether the damage
relates to a single cell line defect, or to a multiple line dysfunction. Pancytopenia may indicate
the involvement of bone marrow, an immunological disorder, a Connective Tissue Disease, or
an abnormal destruction of cells (Hypersplenism). In addition to a complete history and
physical examination of the patient, diagnostic criteria include a complete blood cells count,
blood smear and Reticulocyte count. In order to determine the etiology, further investigations
are required: serum Iron value, Ferritin, and Transferrin levels (if Iron deficiency anemia is
suspected), Bone Marrow aspiration, serum levels of vitamin B12 and folate, bilirubin,
establishing the possibility of a hemolytic process [1, 2] In certain cases, when no other cause
can be identified, a potential malignant disorder should also be taken into account [3].
In the case of iron-deficiency Anemia, the most frequent cause is a low Iron intake during
periods of growth when there is an increased need. The growth rate is accelerated especially
during the infancy and puberty period, the body of a newborn having an iron content of 75
mg/kg. Thus, in the presence of a low-Iron diet or a blood loss, the preexisting iron deposits at
birth will be exhausted until the age of 6 months (in the full-term newborns), respectively in
3-4 months (in premature infants) [2]. Iron deficiency presents a number of multisystem
complications such as gastrointestinal, central nervous system, cardiovascular, immunological
(increased susceptibility to infections) [2].
Iron deficiency Anemia can either be absolute, when Iron deposits in the body are reduced,
or a functional one, in case of a redistribution of Iron from places of use to storage sites,
mainly in the monocyte-macrophage hepatic system and spleen [4, 5]. Anemia within
Infections is based on a number of physio-pathological processes. The infectious agents will
activate the immune cells by several mechanisms, and Hepcidin plays an important role, by
diverting Iron to the mononuclear-phagocyte system and limiting its flow into circulation [4,
6, 7]. Hepcidin production is stimulated by various factors, one of which being the
lipopolysaccharides contained in the Gram-negative cell wall [6]. A key organ in Anemia
within Infections is the liver – as hepatocytes are the main source of hepcidin synthesis, while
the major site for infection-driven Iron storage is the Kupffer cells [8, 9]. Also, the spleen is
another important site where Iron is retained by macrophages [10, 11]. It seems that the
transport of blood gases (O2 and CO2) is facilitated by Hemoglobin; In addition, Hemoglobin
represents a nitric oxide (NO) buffer system. Therefore, qualitative or quantitative changes
that occur in Hemoglobin activity alter normal respiratory functions. Alveolar macrophages
obtain Iron directly from the erythrocyte metabolism, and their function can be altered in Iron
deficiencies states.
This hypothesis may be the explanation for the association between respiratory tract
infections and Iron deficiency, and consequently with the occurrence of Iron deficiency
anemia [12].

Material and methods

We performed an analytical, descriptive, retrospective study, analyzing a group of 129


patients (infants) aged between 2 weeks and 6 months, admitted in the 1st Pediatrics Clinic of
Tîrgu Mureş between January and December 2016. The study group was selected on the basis
of the following inclusion criteria: the age between 0-6 months, a diagnosis of Anemia,

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regardless of the underlying etiology. The exclusion criteria consisted in incomplete


clinical/paraclinical data, and subjects who did not meet the inclusion criteria listed above.
For the statistical analysis, we used Chi square, Anova and Bonferoni correction statistical
tests (95% confidence interval, p <0.05 is considered statistically significant).

Results

The prevalence of anemia among infants aged 0-6 months who were admitted in Pediatrics
Clinic during the year 2016, was 33.1% (129 cases out of 428 admissions in small infants).
The study group consisted of 129 subjects, including 56 female infants (43.4%) and 73
male infants (56.6%) – “Fig. 1”. The minimum age of patients was 2 weeks and the maximum
age was 6 months, with an average age of 2.5 months. We identified 17 premature babies
(13.1%) and 112 full-term babies (86.8%) – “Fig. 2”.

Fig. 1. Distribution of Patients by gender

Fig. 2. Distribution of Patients by age

Analyzing the birth weight of the patients, an average birth weight of 3030g was found, the
minimum weight being 700g and the maximum weight of 4800g. The average weight of the
patients at the time of admission was 4850g. The distribution of the patients based on current
weight is shown in the “Fig. 3” (corresponding to age and gender weight percentile).

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Fig. 3. Distribution based on actual weight

Among the entire group, 17 premature infants (13.1%) were identified, out of which, 9
cases of anemia were labeled as Anemia of prematurity, the remaining ones being associated
to an infectious syndrome.
Mainly, anemia within infections was associated to Acute Respiratory Infections (52
cases), digestive disorders (12 cases) or other pathologies. Only 18 cases of Anemia were
admitted for anemia symptoms (“Fig. 4”).

Fig. 4. Distribution of the main diagnoses

Thus, 89 cases of anemia (69%), were identified within an infectious context, and 40 cases
(31%) were found in noninfectious patients. Regarding the etiology (“Fig. 5”), the cases were
divided as it follows: anemia within infections (57 cases – 44.1%), physiological anemia of
the infant (36 cases – 27.9%), nutritional anemia (21 cases – 16.2%), anemia of prematurity (9
cases – 6.9%), Iron deficiency anemia (4 cases – 3.1%), post hemorrhagic anemia (2 cases –
1.5%).

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Fig. 5. Types of anemia

Out of all the patients included in the study, 64 (49.6%) were breastfed, 44 (34.1%) were
fed with a formula, 16 mixed alimentation (12.4%), and 5 patients (3.8%) received a
diversified diet.
From a clinical point of view, several signs and symptoms were analyzed: pallor – obvious
in 51 patients (39.5%); refusal to eat – 25 patients (19.4%); irritability V present in 11 patients
(8.5%); failure to thrive – described in 12 patients (9.3%); jaundice was highlighted in 8
patients (6.2%); splenomegaly in 5 patients (3.9%), while hepatomegaly was observed in 8
patients (6.2%). (Table 1)

Table 1. Signs and Symptoms of Anemia


Signs and Symptoms Number of Percentage (%)
patients
paleness 51 39,5
refusal to eat 25 19,4
irritability 11 8,5
failure to thrive 12 9,3
jaundice 8 6,2
splenomegaly 5 3,9
hepatomegaly 8 6,2

Based on the Blood smear results, anemia was classified into: normocytic normochromic
anemia – 57 cases (44.2%) and microcytic hypochromic – 72 cases (55.8%). Other
paraclinical features highlighted: hyperbilirubinaemia – described in 10 patients (7.8%);
presence of inflammatory syndrome – 27 cases (20.9%); hepatic cytolysis – in 42 patients
(2.6%). 74 patients received antibiotic treatment (57.4%), Iron supplements were prescribed
for a group of 35 patients (27.1%); only 5 patients required substitution treatment with blood
transfusion.
Neither nutritional anemia or infancy anemia were found to be associated to an infectious
context (p=0.0001 in both cases). There was no statistically significant association between
gender (male/female) and the predisposition to develop anemia (p=0.93). Regarding the type
of diet and the predisposition to develop anemia, we did not identify any statistically
significant associations: association of anemia – natural feeding (p=0.086); association of
anemia – dairy formula feeding (p=0.070); anemia – diet with cow’s milk (p=0.49).
Concerning Anemia within infections, we found a statistically significant association with
the presence of paleness (p=0.001), refusal to eat (p=0.004), presence of splenomegaly
(p=0.03) or hepatomegaly (p=0.04). Failure to thrive as a clinical manifestation, was
statistically associated with Anemia of prematurity (p=0.002). It was also observed that the
infant’s physiological anemia was most commonly associated with the presence of jaundice

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(p=0.0001). The presence of thrombocytosis was not found to be associated to any type of
anemia (p=0.44).

Discussions

In the neonatal period, all newborns experience a decrease in Hemoglobin concentration.


The transition from a relatively hypoxic environment (in utero) to a relatively hyperoxic
environment with increased tissue oxygenation after birth, leads to a decrease in
Erythropoietin concentration and the occurrence of secondary anemia. In the case of full-term
newborns, a physiological and often asymptomatic anemia occurs at 8-12 weeks of life [13].
In our study, we observed a 33.1% prevalence of anemia in infants up to 6 months of age,
comparable to other studies, where a 20.2% to 65.2% prevalence was reported as follows: a
similar study in Brazil, reveals an incidence of anemia of 20.2% in infants under 6 months of
age [14]. On the other hand, there are studies that describe a much higher incidence of anemia
– 65.2% in infants under the age of 6 months [15]. The variability of the incidence of anemia
in the studied target group (20-65%), results from the socio-economic background of the
patients. Thus, the predisposition to both anemia and poor nutritional status are directly
related to the socio-economic status, to the mother’s dietary habits during pregnancy and also
to the infant’s diet during the first months of life [16, 17]. In addition, several genes have been
proved to influence the nutritional status of the newborn, such as: fat mass and obesity-
associated gene, leptin receptor gene, human peroxisome proliferator-activated receptor
gamma, transforming growth factor-beta 1 [18, 19]. Further on, genetic susceptibility was
proven to influence the child’s nutritional status further on in life [20], leading in some cases
to poor nutritional status associated to anemia.
According to literature data, there is no gender susceptibility in developing anemia [21].
Similarly, in our study, we did not identify any statistically significant difference between
the incidence of anemia in females (43.4%) compared to males (56.6%). The mean age of the
study group was 2.5 months, with a range of 2 weeks and 6 months respectively.
Anemia of prematurity is characterized by an exaggerated, pathological response of
premature baby to the pre/postpartum transition. Anemia of prematurity is a normochromic,
normocytic anemia, often hypo regenerative, described by low erythropoietin levels, despite
an extremely low concentration of Hemoglobin. Nutritional deficiencies (Iron, vitamin B12,
folate), as well as hemorrhage or a short life of red blood cells, may worsen the degree of
anemia. Anemia of prematurity is usually self-limiting and resolves spontaneously in the first
3-6 months of life. In exceptional cases, blood transfusions or Erythropoietin is required [13].
In the current study, most patients were full-term newborns – 112 cases (86.8%), and only
17 were premature (13.1%). It was observed 9 cases of Anemia of prematurity, out of a total
of 17 pre-term patients included in the group. The described cases, were characterized by the
presence of normocytic normochromic anemia, results that correspond to the conclusions of
other specialized studies in the field [13, 14]. As expected, in the anemia of prematurity,
failure to thrive was observed as a distinctive sign. Unlike other studies [14, 15] no
Erythropoietin was required for any patient. Nevertheless, 5 patients were treated with blood
transfusion therapy.
Anemia is a common pathology encountered in infectious context. In many cases it is an
indicator of the duration or activity of the infection. Intra-infectious anemia is a part of the
host response to the infectious process; therefore, it is induced by pro-inflammatory cytokines
[21, 22].
Most infectious patients show a decrease in Hemoglobin within one week from the onset of
the disease similarly to the case described by Meliț et al., of sepsis in an 8-month-old female
infant who present a severely low value of hemoglobin after 5 days from the onset [23]. The

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prevalence of anemia is associated with inflammatory syndrome and fever duration. The
present study revealed an incidence of anemia associated to infection of 44.1%, being the
main type of anemia described. An increased incidence was observed in another similar study,
which reported the incidence of this condition to be 21.4% [12]. This is explained by the high
susceptibility of the under 6 months infants group, both to develop infections and anemia.
Respiratory infections were the main type of anemia-associated infections (52 cases), an
association frequently described also in the literature [24]. In case of Anemia within
Infections, a low Iron value does not always suggest a real Iron deficiency, therefore lab
analysis should be performed outside the infectious context in order to be relevant. In
addition, Ferritin and Hepcidin levels could not be assessed in our study, and therefore, we
could not precisely evaluate the Iron metabolism in order to distinguish Iron deficiency
Anemia of Anemia within Infections. We found different suggestive clinical signs to be
associated with anemia: pallor, food refusal, splenomegaly or hepatomegaly; on the other
hand, in other etiologies, these associations were not found to be significant.
Particular importance is granted to the association between dietary habits and susceptibility
to anemia. The World Health Organization (WHO) recommends exclusive breastfeeding
during the first 6 months of life. However, Iron deficiency is a problem for naturally fed
infants, especially vulnerable populations [4]. In the present study, we identified 21 cases of
nutritional anemia, but we did not find any statistically significant correlations between the
type of diet (natural, milk formula, or diversification) and a relatively higher risk of anemia.
Multipara mothers have an increased risk of developing anemia, which will result in a
reduction of transplacental Iron transfer. Therefore, the newborn presents an additional risk
factor for developing Iron deficiency. Even appropriate for gestational age (AGA) newborns
from anemic mothers, will have low Iron reserves and an increased risk of developing anemia
[25].
Therefore, there is an increased prevalence of anemia among infants and young children,
that can be attributed to the imbalances between intake (reserve) and inadequate Iron needs in
order to meet growth needs. Within the studied group, iron deficiency anemia was identified
only in 4 cases. The value is not suggestive given the small number of cases and the lack of
Iron dosing in some cases.
Although our research was carefully prepared, certain limitations of the study should be
mentioned. First of all, the study included a relatively small number of patients, which
decreases the statistical significance of the conclusions. In addition, we had some technical
limitations: the inability to determine the Ferritin and Hepcidin levels, though they would
have provided more precise data regarding the Iron metabolism, allowing us to divide more
accurate the cases depending on the etiology.

Conclusions

Anemia is a frequent and complex condition, representing a global public health challenge
in nowadays society. In Pediatrics, due to its multifactorial etiology and the complexity of
both short and long-term effects regarding the neurological development of the children or the
immunological status, it requires a multidisciplinary approach. Therefore, it is highly
recommended to perform a screening test to all infants within the first 6 months of life. Any
infectious episode within the first months of life should be a trigger for testing the infant for
anemia in order to recommend Iron supplements when needed, or to enlarge the investigations
if there is an underlying condition suspected.

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in sepsis. Crit Care Med. 1991 May; 19(5): pp. 732-5.
12. Ballin A, Senecky Y, Rubinstein U, Schaefer E, Schaeffert E, Peri R, et al., Anemia associated with
acute infection in children. Isr Med Assoc J IMAJ. 2012 Aug; 14(8): pp. 484-7.
13. Anemia of Prematurity: Background, Etiology, Epidemiology. 2017 Dec 28 [cited 2018 Apr 21];
Available from: https://emedicine.medscape.com/article/978238-overview
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20. Mărginean CO, Mărginean C, Voidăzan S, Meliţ L, Crauciuc A, Duicu C, et al., Correlations Between
Leptin Gene Polymorphisms 223 A/G, 1019 G/A, 492 G/C, 976 C/A, and Anthropometrical and
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21. Dong C, Ge P, Zhang C, Ren X, Fan H, Zhang J, et al., [Effects of different feeding practices at 0-6
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22. Means RT. The anaemia of infection. Baillieres Best Pract Res Clin Haematol. 2000 Jun; 13(2): pp.
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23. Melit Lorena Elena, Marginean Cristina Oana, Georgescu A, Duicu C. Complications of sepsis in
infant. A case report. J Crit Care Med 2393-1809. 2016; 2(2): pp. 96-9.
24. Hussain SQ, Ashraf M, Wani JG, Ahmed J. Low Hemoglobin Level a Risk Factor for Acute Lower
Respiratory Tract Infections (ALRTI) in Children. J Clin Diagn Res JCDR. 2014 Apr; 8(4):PC01-03.
25. Carter RC, Jacobson JL, Burden MJ, Armony-Sivan R, Dodge NC, Angelilli ML, et al., Iron deficiency
anemia and cognitive function in infancy. Pediatrics. 2010 Aug; 126(2):e427-434.

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Fetal Ovarian Cyst: Prenatal Diagnosis – A Case Report

CHIRIAC Daniela Veronica1, COPOTOIU Larisa1, TUTA-SAS Ioana1,


PETRE Izabella1, CRAINA Marius1
1“V. Babeş” Medicine and Pharmacy University – Obstetrics and Gynecology Department Department, Timisoara,
(ROMANIA)
Email: [email protected]

Abstract

Foetal ovarian cysts are the most commonly diagnosed abdominal tumours in the prenatal
period. They are usually unilateral and diagnosed in the third trimester. Although the
aetiology is still unknown, hormonal stimulation is generally considered to be responsible for
the disease (foetal gonadotropins, maternal oestrogen and placental human chorionic
gonadotropin). The decrease of hormonal stimulation after delivery may lead to spontaneous
resolution of the cyst.
Fetal ovarian cyst often presents complication such as torsion and seems to be an
indication for surgical intervention. The literature presents different management options from
conservative approach such as wait and aggressive approach as intrauterine aspiration or
surgery.
Postnatal symptomatic cysts or cysts with a diameter greater than 5 cm that do not regress
or enlarge should be treated, but uncomplicated asymptomatic cysts less than 5 cm in
diameter should only be observed and reassessed by serial ultrasonography. If they regress
spontaneously, no surgical intervention is necessary independent of their sonographic
findings.

Case report
We have presented the diagnosis and management of a large complex fetal ovarian cyst
diagnosed prenatally. Towards the end of pregnancy the cyst changed its consistency and
increased in size suggesting torsion The patient was delivered by a cesarian section and was
refered to a pediatric surgeon who chose conservative management and followed the case at 2
weeks.
Keywords: Ovarian Cysts, Ultrasonography, Prenatal, Abnormalities

Introduction

Ovarian cysts are the most frequent type of abdominal tumor. The first neonatal ovarian
cyst (NOC) was reported in 1889 as an autopsy finding in a stillborn preterm infant [1, 2].
The incidence of ovarian cysts has been estimated at more than 30% (this estimate is based
on an investigation of stillborns or infants who died within 28 days). Ovarian cyst often
presents complication such as torsion and seems to be an indication for surgical intervention.
A standard guide to management, treatment and follow-up of ovarian cyst is not yet
available. Ovarian cysts are classified with regard to their ultrasonographic features as
“simple” or “complex”, and with regard to their size as “small” or “large” cyst.

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Small cysts are usually asymptomatic and show spontaneous regression within a few
months after birth .Rarely, they are complicated, depending on their size and pedicle length.
The most frequent and frightening complication of simple cysts is torsion of the ovary.
Other complications are intracystic hemorrhage, rupture, dystocia during birth, pressure on
nearby structures such as blood vessels, uterus, intestines and urinary system. If a cyst is
complex from the beginning, there is a probability of ovarian-vascular dysgenesis or of a
neoplasm. Complex cysts generally occur as complications of large cysts. The treatment
modality of NOC, especially of large simple cysts is controversial, while the treatment of
torsioned or complicated cysts is unequivocally surgical and causes the loss of the affected
ovary.
The therapeutic approach must be personalized, targeted in function of the clinical and
imagistic aspects [3-6].

Case report

A 28-years-old primigravida (with LMP= 05.07.2017) was referred to our prenatal center
at 32 weeks of gestation following the ultrasonographic detection of a fetal cystic mass in the
abdomen.
The past medical history and antenatal scans were unremarkable. Ultrasound examination
demonstrated normal anatomy of the bladder, kidneys, liver and intestine in a female foetus.
The cyst measured 6.2/4.7 cm in diameter, had a septum, anechoic content and thin wall
mass located in the lower foetal abdomen; these findings suggesting a simple ovarian cyst.

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(A) Complex ovarian cyst: prenatal sonography at 33 weeks

The patient was informed about the condition and the serial ultrasosnographic scans were
performed every 2 weeks until birth.
The biochemical tests revealed a fasting glucose tolerance test of 178 mg/dl (above the
normal ranges of the one step screening test 74-106 mg/dl).
These findings were followed by the glucose tolerance test, GTT (with 75 one-hour oral
glucose load) and it was revealed:
- The fasting glycemia of 178 mg/dl
- A one-hour oral glucose load glycemia of 190 mg/dl
- A two-hours oral glucose load glycemia of 168 mg/dl.
These findings were consistent with the diagnostic of gestational diabetes and the patient
was referred to be seen in the Diabetes Clinic where a diet control monitoring of the glycemia
was indicated.

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A follow up ultrasound examination was performed in 2 weeks time, at 34 weeks of


gestation and revealed a regression of the abdominal cyst to 4.7cm/3.8 cm and also at 36
weeks of gestation the dimensions of cyst remained at about 4/3.5 cm but at 36 weeks
hidramnios appear (AFI=18 cm).
At 38 weeks of gestation it is noticed an increase in the size of the ovarian cyst to 6,2
cm/4,8 cm, with a change of ultrasound pattern that was consistent with intracystic
hemorrhage. In addition was reavealed the presence of polyhydramnios (with an AFI of 20
cm) [Fig. 3a, b].

Fig. 3(a). Ovarian cyst with intracystic haemorrhage

Fig. 3(b). Ovarian cyst with intracystic haemorrhage

An elective caesarean section is performed at 38 GA with the delivery of a newborn baby


of 3000 g, Apgar=9.
A neonatal scan examination is performed in the first days of life and the ultrasound
findings raise the suspicion of ovarian teratoma (because of the intracystic haemorrhage) and
the need of further assessment for definite diagnostic.The neweborn was reffered on day 5
after delivery to the pediatric surgeon who chose conservative management and followed the
case at 2 weeks when a reduction in cyst size was observed at 4,2 cm.

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An expectant management with a follow up scan performed in week 6 after delivery


reveals (reassuring findings).

Discussion

Ovarian cysts are the most frequent, prenatally diagnosed intra-abdominal cysts. The
etiology of fetal ovarian cysts is still unknown, but hormonal stimulation is generally
considered to be responsible for the disease (fetal gonadotrophins, maternal estrogen and
placental human chorionic gonadotrophin). The association of fetal ovarian cysts with
maternal diabetes or fetal hypothyroidism has been described .In our case, we detected
gestational diabet [7-10].
The differential diagnosis should be made with: mesenteric and urachal cysts, intestinal
duplication anomalies, cystic teratoma, and intestinal obstruction A differential diagnosis
between ovarian cysts and one of these conditions cannot be made with intrauterine
sonography.
Because ovarian cysts are almost always functional and benign tumors, the question of
malignancy is not important in prenatal diagnosis. Also accompanying malformations are
extremely rare. As a result, the question of emergence and nature of any complications, such
as torsion, plays a significant role, as these can be an indication for surgical intervention in
what would otherwise be an instance of an inconspicuous cyst. In addition, polyhydramnios or
ascites (the result of transudation)could appear. Serial ultrasound examinations to detect any
structural change (size, appearance) in the mass or complications (hydramnios, ascites,
torsion). A normal of the gastrointestinal tract, may be present In our case the polihidramnios
appeared at 34 weeks of gestation (AFI was 24 cm) [10, 11].
Bleeding within an ovarian cyst usually arises in connection with torsion. For that reason,
postnatal surgery for all fetal ovarian cysts which are complex, has been recommended. If the
cyst did not induce the symptoms, no intervention was necessary, because the cyst regressed
spontaneously. We observed spontaneous resolution in our case at 6 weeks after deliveryin.
Aspiration of the cyst to by ultrasonic guided reduce its size (and so that one can
investigate its contents) can be performed prenatally. However, the value of cyst aspiration is
a point of controversy.There is a small risk of infection of the amniotic cavity and premature
labor.

Psychological counselling

The patient received counseling in order to reduce the level of anxiety and emotional
distress and to prevent depression [12-14].
Cognitive restructuring techniques, breathing and relaxation control techniques
(autogenous training Schultz) were applied.
During therapy, the patients completed a personal diary in which they described daily
personal experiences, results of exercises and themes [15, 16].

Conclusion

In summary, an ovarian cyst is not a life-threatening condition, so that further diagnostic


procedures can be carried out in the first few days of life. It is natural that postnatal
symptomatic cysts demand intervention. Postnatally asymptomatic fetal ovarian cysts smaller
than 5 cm in diameter, even exceeding 5 cm at initial diagnosis, with tendency to regress
should be closely monitored pre- and postnatally until spontaneous resolution. If they regress

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spontaneously, no surgical intervention is necessary independent of their sonographic


appearances.

REFERENCES

1. Crombleholme T.M., Craigo S.D., Garmel S., D’Alton M.E. (1997). Fetal ovarian cyst decompression
to prevent torsion. J Pediatr Surg 32: pp. 1447-1449.
2. Sandler M.A., Smith S.J., Pope S.G., Madrazo B.L. (1985). Prenatal diagnosis of septated ovarian cysts.
J Clin Ultrasound 13: pp. 55-57.
3. Andreescu N.I., Nussbaum L.A., Hogea L.M., Grădinaru R.C., Muntean C., Ștefănescu R., Puiu M.
(2016). Antipsychotic Treatment Emergent Adverse Events in Correlation with the Pharmacogenetic
Testing and Drug Interactions in Children and Adolescents with Schizophrenia and Bipolar Disorder.
Farmacia 64(5): pp. 736-744.
4. Nussbaum L.A., Andreescu N.I., Hogea L.M., Muntean C., Stefanescu R., Puiu M. (2016).
Pharmacological and Clinical Aspects of Efficacy, Safety and Tolerability of Atypical Antipsychotic
Medication in Child and Adolescent Patients with Schizophrenia and Bipolar Disorders. Farmacia
64(6): pp. 868-875.
5. Nussbaum L.A., Hogea L.M., Andrescu N.I., Grădinaru R.C., Puiu M., Todica A. (2016). The
Prognostic and Clinical Significance of Neuroimagistic and Neurobiological Vulnerability Markers in
Correlation with the Molecular Pharmacogenetic Testing in Psychoses and Ultra High-Risk Categories.
Rom J Morphol Embryol 57(3): pp. 959-967.
6. Nussbaum L.A., Ogodescu A., Hogea L.M., Nussbaum L., Zetu I. (2017). Risk Factors and Resilience
in the Offspring of Psychotic Parents. Review of Research and Social Intervention 56: pp. 114-122.
7. Micoara N.C., Mladin D., Morariu S.I. (2017). Biomarkers in Diagnosing Preeclampsia and Their
Correlation with Blood Pressure 68(10): pp. 2448-2451.
8. Popovici D.C., Ionita I., Ionita C. (2017). Statistical Hierarchy of Diagnostic Criteria for Chronic
Myeloid Leukemia, Revista de Chimie 68(10): pp. 2463-2466.
9. Mioc M., Avram S., Tomescu A.B. (2017). Docking Study of 3-mercapto-1, 2, 4-triazole Derivatives as
Inhibitors for VEGFR and EGFR, Revista de Chimie 68(3): pp. 500-503.
10. Hogea L.M., Tuta Sas I., Poroch V., Nussbaum L.A., SAS I., Serban D., Erdelean D., Folescu R.,
Zamfir C.L., Bredicean C.A., Simu M.A. (2018). Comparative study using progesterone and Gynipral –
Hexoprenaline Sulphate, with effects in postpone preterm birth, Chimia vol. 69(4): pp. 934-937.
11. Milulescu A., Dorneanu, F., Iacob, D., Stoian, D., Petre, I., Chiriac, V.D., Margan, R., Ionita, I., Marti,
D., Moleriu, L.C., Procalcitonina – Diagnostic Marker In Neonatal Sepsis, Mat. Plast., 2017, 54(4).
12. Hogea L.M., Hogea B.G., Nussbaum L.A., Chiriac V.D., Grigoras M.L., Andor B.C., Levai C.M.,
Bredicean A.C. (2017). Health-related quality of life in patients with hallux valgus. Rom. J. Morphol.
Embryol, 2017, 58(1): p. 175.
13. Hogea L.M., Nussbaum L.A., Chiriac D.V., Ageu L.S., Andreescu N.I., Grigoras M.L., Folescu R.,
Bredicean A.C., Puiu M., Rosca E.C.I., Simu M.A., Levai C.M. (2017). Integrative clinic-biological,
pharmacogenetic, neuroimagistic neuroendocrinological and psychological correlations in depressive
and anxiety disorders. Rom. J. Morphol.Embryol 58(3): p. 767.
14. Nussbaum L.A., Hogea L.M., Chiriac D.V., Grigoras M.L., Folescu R., Bredicean A.C., Rosca E.C.I.,
Muncan B., Nussbaum L.M., Simu M.A., Levai C.M. (2017). The effect of neurobiological changes in
the brain of children with schizophrenia, ultra high-risk for psychosis and epilepsy: clinical correlations
with EEG and Rom. J. Morphol. Embryol 58(4): p. 1435.
15. Nussbaum L.A, Hogea L.M., Calina D., Andreescu N., Gradinaru R., Stefanescu R., Puiu M. (2017).
Modern treatment approaches in psychoses. Pharmacogenetic, neuroimagistic and clinical implications,
Farmacia vol. 65(1): pp. 75-81.
16. Chiriac D.V., Hogea L.M., Bredicean A.C., Rednic R., Nussbaum L.A., Hogea G.B., Grigoras M.L.
(2017). A rare case of Meckel-Gruber syndrome Rom. J. Morphol. Embryol 58(3):1023.

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The Characteristics and Severity of Psychological Distress after


Abortion

HOGEA Lavinia Maria1


1“V. Babeş” Medicine and Pharmacy University - Psychology Department, Timisoara, (ROMANIA)
Email: [email protected]

Abstract

The purpose of this work is to analyze the type and seriousness of emotional distress that
women have after a miscarriage, compared to a control group with interrupted pregnancies on
request. 50 women, divided into equal groups (50% with abortion on request, 50%
miscarriage due to other causes) were included in the study. The questionnaires that were used
were: Profile of Affective Distress (PDA) and Perinatal Grief Scale.
The results reveal statistically significant differences in the short-term emotional reactions
between the two groups of participants.
Keywords: distress, post-traumatic stress, abortion

Introduction

Reproduction fulfills several goals and ambitions, which have little in common with being
a parent, but play a role in reinforcement of parental identity and improvement of self-esteem.
By understanding how a pregnancy is oriented towards the enrichment of self value, we can
appreciate better the number of depressive consequences that follow a perinatal loss.
Psychologically rather than spiritually, a pregnancy allows a woman to feel a complete
woman [1-3]. The desire to have children is present since childhood. Later, when these goals
to do not become a reality due to various causes, the women experiences the humiliating
inability to feel a complete woman.
The future mother faces the dire result of death when she expects it the least. Her own
mortality wakes up, and sometimes the thought of her own death scares her [4-6].
There are a lot of normal reactions following a miscarriage, such as: constant lack of value,
deep guilt, anger against injustice, sense of emptiness and fragmentation, but also
psychosomatic symptoms [7-10]. All these can be better understood as a result of
overwhelming wounds of self esteem, rather than a suffering caused by the death of the baby.
The whole therapeutic and psychotherapeutic approach must be personalized and carefully
adapted [11-13].

Material and methods

The study had 50 women who suffered from a perinatal miscarriage, between 15 and 35
years old. Two groups were formed: 25 women who asked for abortion and another lot of 25
women who had a miscarriage.
For data gathering, we used the following scales: Profile of Affective Distress (PDA) and
Perinatal Grief scale.

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Among the subjects that participated in the study were frequent the abortions due to
medical causes, among which we mention: uterine disorder, fetus that stopped growing,
intrauterine fetal death, and fetal malformations in different stages of pregnancy.
The results of the examinations led to the decision to terminate the pregnancy. Labour was
induced by using medical abortion procedures that include surgical techniques, induced by
drugs.
The statistical estimation was done using the decision criterion of the statistical tests:
p0,05 – insignificant differences; p0,05 – significant differences; p0,01 – very significant
differences; p0,001 – extremely significant differences.

Results and discusions

Statistical analysis of data revealed a statistically significant difference between the two
groups in terms of affective distress for all measured scales (p=.000; p<.001). The mean of the
participants in the second group being higher than that of the first group, indicating a relevant
tendency for the women in the first group to experience a strong affective disorder [Table 1].

Table 1. Mean score, standard deviations and student t-Test for PDA scales
Mean SD
Term Preterm Term Preterm student t
Variable N delivery delivery delivery delivery Test

PDA 25 106.86 222.86 16.19 51.91 t(58)= -11.683


p = .000 *
Funct. negative 25 6.33 13.96 2.08 3.718 t(58)= -9.802
Emotions/depression p = .000 *
Dysfunct.negative emotions 25 9.00 26.40 1.43 8.33 t(58)= -11.266
depression p = .000 *
Funct. negative 25 8.33 24.76 2.66 4.68 t(58)= -16.704
Emotions/anxiety p = .000 *
Dysfunct.negative 25 7.66 24.86 2.39 4.73 t(58)= -17.737
emotions/anxiety p = .000 *
Funct.negative emotions 25 17.33 46.43 4.86 9.95 t(58)= -14.290
depression/anxiety p = .000 *
Dysfunct.negative 25 16.66 51.23 3.83 9.41 t(58)= -18.261
emotion depression/anxiety p = .000 *
Positive emotions 25 44.00 50.00 3.80 6.39 t(58)= -4.416
p = .000 *
p = .000; *p<.001

From the analysis of the results obtained after completing the PAD-questionnaire, it is
observed that the level of general affective distress and the level of scales for the evaluation of
functional negative emotions, dysfunctional negative emotions sadness/depression,
worry/anxiety is significantly lower in women with abortion on request, they present low
intensity distress, compared to a higher level (p<.001) in women with miscarriage,
experiencing functional/dysfunctional negative emotions with higher frequency and intensity.
On the other hand, the level of positive emotions is also significantly higher in women who
loss the pregnancy compared to those with women abortion on request (p<.001) [14-18].
Statistical analysis of the data reveals a significant difference between the two groups in
terms of loss-related pain for all measured scales (p=.000; p<.001), the average of the
participants in the miscarriage group being higher than abortion on request group, indicating a

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relevant tendency in women with loss of pregnancy to feel pain, sadness and acute distress
[Table 2].

Table 2. Mean score, standard deviations and student –t Test for Grief scale
M SD
Abortion on Miscarriage Abortion on Miscarriage Student t
Variable N request request Test
Grief 30 54.13 118.10 14.06 17.02 t(58)=-15.862
p = .000 *
Activ 30 17.16 41.46 4.99 5.16 t(58)=-18.533
Grief p = .000 *

Acut distress 30 18.50 39.46 4.56 7.14 t(58)=-13.544


p = .000 *
Coping 30 18.53 37.30 4.80 5.96 t(58)=-13.426
p = .000*
p = .000; *p<.001

These findings suggest that by reducing stress and psychological distress and through
improving social support, it may be possible to enhance the quality of life of these patients
[19-23].

Conclusions

The complications present during the development of the fetus, and the need to terminate
the pregnancy represent a difficult situation for the future mother to manage. The results
obtained during the data processing prove that the patients that suffered a miscarriage
experience higher emotional distress.

REFERENCES

1. Broen A.N., Moum T., Bödtker A.S., Ekeberg Ö. (2004). Psychological Impact on Women of
Miscarriage Versus Induced Abortion: A 2-Year Follow-up Study. Psychosomatic Medicine 66(2): pp.
265-271.
2. Farren J., Jalmbrant M., Ameye L., Joash K., Mitchell-Jones N., Tapp S., Timmerman D., Bourne T.
(2016). Post-traumatic stress, anxiety and depression following miscarriage or ectopic pregnancy: a
prospective cohort study. BMJ Open. 6(11):011864.
3. Kersting A., Wagner, B. (2012). Complicated grief after perinatal loss. Dialogues in Clinical
Neuroscience 14(2).
4. Milulescu A., Dorneanu F., Iacob D., Stoian D., Petre I., Chiriac V.D., Margan R., Ionita I., Marti D.,
Moleriu L.C. (2017). Procalcitonina – Diagnostic Marker In Neonatal Sepsis, Mat. Plast 54(4).
5. Mioc M., Avram S., Tomescu A.B. (2017). Docking Study of 3-mercapto-1,2,4-triazole Derivatives as
Inhibitors for VEGFR and EGFR, Revista de Chimie 68(3): pp. 500-503.
6. Micoara N.C., Mladin D., Morariu S.I. (2017). Biomarkers in Diagnosing Preeclampsia and Their
Correlation with Blood Pressure 68(10): pp. 2448-2451.
7. Chiriac D.V., Hogea L.M., Bredicean A.C., Rednic R., Nussbaum L.A., Hogea G.B., Grigoras M.L.
(2017). A rare case of Meckel-Gruber syndrome Rom. J. Morphol. Embryol 58(3):1023.
8. Andreescu N., Nussbaum L., Hogea L.M., Grădinaru R., Muntean C., Ștefănescu R., Puiu M. (2016).
Antipsychotic Treatment Emergent Adverse Events in Correlation with the Pharmacogenetic Testing
and Drug Interactions in Children and Adolescents with Schizophrenia and Bipolar Disorder. Farmacia,
64(5), pp. 736-744.
9. Hogea L.M., Tuta Sas I., Poroch V., Nussbaum L.A., SAS I., Serban D., Erdelean D., Folescu R.,
Zamfir C.L., Bredicean C.A., Simu M.A. (2018). Comparative study using progesterone and Gynipral –
Hexoprenaline Sulphate, with effects in postpone preterm birth, Chimia vol. 69(4): pp. 934-937.

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10. Hogea L.M., Hogea B.G., Nussbaum L.A., Chiriac V.D., Grigoras M.L., Andor B.C., Levai C.M.,
Bredicean A.C. (2017). Health-Related Quality Of Life In Patients With Hallux Valgus, Rom J
Morphol Embryol, 58(1), pp. 175-179.
11. Nussbaum L.A., Hogea L.M., Andreescu N.I., Grădinaru R.C., Puiu M., Todica A. (2016). The
Prognostic and Clinical Significance of Neuroimagistic and Neurobiological Vulnerability Markers in
Correlation with the Molecular Pharmacogenetic Testing in Psychoses and Ultra High-Risk Categories,
Rom J Morphol Embryol, 57(3), pp. 959-967.
12. Nussbaum L., Gradinaru R., Andreescu N., Dumitrascu V., Tudor A., Suciu L., Stefanescu R., Puiu M.
(2014). The Response to Atypical Antipsychotic Drugs in Correlation with the CYP2D6 Genotype:
Clinical Implications and Perspectives, Farmacia, 62(6), pp. 1191-1201.
13. Nussbaum L., Hogea L.M., Călina D., Andreescu N., Grădinaru R., Ștefănescu R., Puiu M. (2017).
Modern Treatment Approaches in Psychoses. Pharmacogenetic, Neuroimagistic and Clinical
Implications, Farmacia, 65(1), pp. 75-81.
14. Nussbaum L.A., Dumitrascu V., Tudor A., Gradinaru R., Andreescu N., Puiu M. (2014). Molecular
Study of Weight Gain Related to Atypical Antipsychotics: Clinical Implications of the CYP2D6
Genotype, Rom J Morphol Embryol, 55(3), pp. 877-884.
15. Nussbaum, L., Andreescu, N., Hogea, L.M., Muntean, C., Ștefănescu, R., Puiu, M. (2016).
Pharmacological and Clinical Aspects of Efficacy, Safety and Tolerability of Atypical Antipsychotic
Medication in Child and Adolescent Patients with Schizophrenia and Bipolar Disorders, Farmacia,
64(6), pp. 868-875.
16. Nussbaum L.A., Ogodescu A., Hogea L.M., Nussbaum L., Zetu I. (2017). Risk Factors and Resilience
in the Offspring of Psychotic Parents. Rev Cercet Interv So, 56 (1), pp. 114-122.
17. Popa, Z., Chiriac V.D., Cobec I.M., Lungeanu D., Craina M., Bernad E., Ionita I., Moleriu R.D., Iacob
D., Petre I. (2017). HPV Cervical Cancer Screening. An Analysis Over HPV Markers Between
Worldwide Statistics and Romanian Reality. Rev Chim. 68(10), pp. 2459-2462.
18. Popovici Calamar D., Ionita I., Ionita C., Marinita A., Moleriu R.D., Ionita H., Iacob D., Chiriac V.D.,
Petre I. (2017). Statistical Hierarchy of Diagnostic Criteria for Chronic Myeloid Leukemia. Rev Chim.
68(10), pp. 2463-2466.
19. Stevanovic D., Bagheri Z., Atilola O., Vostanis P., Stupar D., Moreira P., Franic T., Davidovic N.,
Knez R., Niksic A., Dodig-Curkovic K., Avicenna M., Multazam Noor I., Nussbaum L., Deljkovic A.,
Aziz Thabet A., Petrov P., Ubalde D., Monteiro L.A., Ribas R. (2016). Cross-cultural Measurement
Invariance of the Revised Child Anxiety and Depression Scale Across 11 World-Wide Societies,
Epidemiology and Psychiatric Sciences, pp. 1-11, DOI: 10.1017/S204579601600038X, ISSN 2045-
7979.
20. Hogea L.M., Nussbaum L.A., Chiriac D.V. (2017). Integrative Clinico-Biological, Pharmacogenetic,
Neuroimagistic, Neuroendocrinological And Psychological Correlations In Depressive And Anxiety
Disorders, Romanian Journal Of Morphology And Embryology, 58(3): pp. 767-775.
21. Hogea L.M., Hogea B.G., Nussbaum L.A., Chiriac V.D., Grigoras M.L., Andor B.C., Levai C.M.,
Bredicean A.C. (2017). Health-related quality of life in patients with hallux valgus. Rom. J. Morphol.
Embryol, 2017, 58(1):175.
22. Nussbaum L.A., Hogea L.M., Chiriac D.V., Grigoras M.L., Folescu R., Bredicean A.C., Rosca E.C.I.,
Muncan B., Nussbaum L.M., Simu M.A., Levai C.M. (2017). The effect of neurobiological changes in
the brain of children with schizophrenia, ultra high-risk for psychosis and epilepsy: clinical correlations
with EEG and Rom. J. Morphol. Embryol 58(4):1435.
23. Toedter L., Lasker N.J., Janssen H.J.E.M. (2001). International comparison of studies using the
Perinatal grief scale: A decade of research on pregnancy loss. Death Studies.

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Pregnancy Induced Hypertention as an Indication for C-Section

ERDELEAN Izabela1, SERBAN Denis1


1“V. Babeş” Medicine and Pharmacy University – Obstetrics and Gynecology Department Timisoara (ROMANIA)
Email: [email protected]

Abstract

The aim of the study is finding the risk factors that contributed to pregnancy induced
hypertension, by doing that, we can avoid or prevent them, thus, preventing these women
from developing a fatal complication. 62 cases of pregnancy induced hypertension were
included, in which 36 cases of them had a C-section (58% of the total cases), while the
remaining 27 cases (41,9%) had a vaginal delivery. Gravidas are between the ages of 18 and
43 years, all of them of the romanin nationality. Personal history, family history, lab analysis,
pregnancy history and previous out comes symptoms, risk factors, management, diagnoses,
and baby status all were collected and carefully analyze.
Birth remains only curative treatement of this disease, due to the previous fact, pregnancy
induced hypertension is considered as an indication for section, when vaginal birth is not
possible, thus C-section in lots of cases is considered the only treatement for these patients,
leading, to the fact that pregnancy-induced hypertension remains an important cause of
maternal-fetal mortality and morbidity.
Keywords: pregnancy, hypertension, C-section, preeclampsia

Introduction

Species are constantly diverging and creating entirely new lineage. Giving birth and being
born, brings us into the essence of creation.
Pregnancy-induced hypertension, with its sub-categories (gestational hypertension,
preeclampsia, eclampsia, Pre-eclampsia superimposed on chronic hypertension) is one of the
major complication that can occur during pregnancy. A hypertensive pregnancy disorder
complicates and effects approx. 2-3% of all pregnancies, about 10-15% of all pregnancy
women will end-up on the operating table to deliver the baby with a cesarean section surgery
[1-3].
Hypertension during pregnancy affects both mother and fetus. What are the causes, is it
possible to prevent it, why it leads to a C-section and how to avoid it. All and some more
issues I’ll discuss in my research thesis and hopefully find answers and some solution [4-6].

Materials and methods

62 cases of pregnancy induced hypertension were included, in which 36 cases of them had
a C-section (58% of the total cases), while the remaining 27 cases (41,9%) had a vaginal
delivery.
Gravidas are between the ages of 18 and 43 years, all of them of the romanin nationality.
The study took place in the period between, the October 2015 until October 2016, all the
cases were diagnosed and treated in the emergency clinic of Municipal Hospital, Timisoara,
obstetrics and gynecology department. Personal history, family history, lab analysis,

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pregnancy history and previous out comes symptoms, risk factors, management, diagnoses,
and baby status all were collected and carefully analyze.
In this observational study, no intervention was made, rather only “observation” and
assessment of the risk factors, of developing hypertension during pregnancy and the
relationship between pregnancy induced hypertension and delivering by a C-section. Three
types of observational studies exist: cohort studies, case-control studies and cross-sectional
studies. Cohort studies and case-control studies were both used in this study.

Results

The patients were classified into two groups depending on how the baby was delivered:
through a vaginal delivery or a cesarean section. The first group includes the patients who had
a C section (60%), the mean age was 33 years old and the second group includes patients who
had a vaginal delivery (40%), mean age was 31 years old. Old age is a risk factor for more
complicated pregnancy by hypertension, preeclampsia, eclampsia and HELLP syndrome.
The highest blood pressure values were doucomented in the severe preeclampsia category,
which lead to the conclusion that the higher the blood pressure value is, the more likely for
the women to develop a more severe form of pregnancy induced hypertension. A normal
blood pressure is systolic – 120 mmHg and diastolic 80 mmHg.

Fig. 1. Indication for C-section

Among all the diseases that might lead to C-section, 8 were documented in this study, of
all the women suffering from pregnancy inducet hypertension, 73% gravidas had the C-
section due to thr actual pregnancy induced hypertension. Severe preeclampsia composed
45% for C-section, and mild preeclampsia 19% of the total C-section indication.

Fig. 2. Gravidas classification according to their BMI

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Being overweight or obese is not a must to develop hypertension or eclampsia or


preeclampsia during pregnancy, but it is a risk factor, and it does complicate the pregnancy. In
all of the tree categories, women who had a BMI more that 25 (normal) composed a decent
percentage of the total women.

Fig. 3. Mean value of proteinuria in patients with positive proteinuria in each category

Acordin to the results optained from the previos graph, the severity of proteinuria
corresponds with severity of the ecclampsia the more severe the hypertension and the
symptoms of preeclampsia the higher the rate of proteinuria. Higher values of proteinuria are
present in more complicated pregnancies, thus these women have poorer outcomes.

Fig. 4. Mean gestational age (weeks) for alive and dead babies delivered by C-section

The babies in the second group- the alive babies were delivered closer to term while the
babies in the first group-dead babies were way before term. Thus, supporting the theory,
stating that due to the related prematurity, the shorter the term of pregnancy, the greater the
risks of mortality and morbidity for the baby.

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Fig. 5. Mean gestational age for babies delivered by C-section in each maternal category

The obtained values for hypertensive women and for women with mild preeclampsia
where almost identical, with a difference of 0,6 weeks more for babies born to mothers with
mild preeclampsia, while in the case of severe preeclampsia the babies were born way more
too immature comparing to the others two categories with a mean gestational age of 33,6.

Fig. 6. Weight of the fetus at birth

A low birth weight can be caused either by a preterm birth or if the infant being small for
gestational age, or a combination of both. Intrauterin growth restriction can be mainly caused
be hypertension during pregnancy. Macrosomia is a term used for babies who were born large
for gestational age, the main cause is diabetes in the mothers during pregnancy. In addition,
obesity before pregnancy, or a higher increase in weight than normal due pregnancy is another
two common causes for macrosomia in babies.

Discussion

Highest blood pressure values belong to gravidas diagnosed with severe preeclampsia,
represented by a mean of value of 163/103 mmHg, followed by blood pressure value of
156/97,6 mmHg, recorded in women with gestational hypertension, while the blood pressure
mean value of gravidas diagnosed with mild preeclampsia was 150,5/97 mmHg [7].

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55% of the total gravidas diagnosed with preeclampsia had a vaginal delivery, while the
remaining 45% had C-section. In gestational hypertension, 38% of the gravidas had a C-
section, and the other 62% had a vaginal delivery.
The biggest percentage for C-section indication, were 45%, owing that to severe
preeclampsia, mild preeclampsia composed 19% of the total indication for C-section and 9%
of the indication are due to gestational hypertension.
Gravidas were classified according to their BMI as follows: [2, 8] mild preeclampsia, 50%
normal weight, 17% overweight, 17% underweight and 16% obese [7, 9-11]. Severe
preeclampsia: 53% had a normal weight, 27% of them were overweight, none of them were
obese, and 20% were underweight [6], gestational hypertension: 40% obese, 20% were
underweight, 20% were overweight, and 20% had a normal weight [12-14].
Gravidas with mild preeclampsia had a mean value of proteinuria of 1,65 the lowest mean
value of proteinuria of 1,65 the lowest mean value of proteinuria was in patients with
gestational hypertension, while the highest value of mean proteinuria was in patients with
severe preeclampsia. Mean gestational age for deceased babies was 27,5. And mean
gestational age for alive babies was 36 weeks.
Babies born to mothers with mild preeclampsia had a mean of 37 weeks of GA, with
severe preeclampsia is 33,6 weeks and with gestational hypertensive mothers is 36,4 [2-7].

Psychological counseling

The patients received counseling during 14 sessions of group therapy in order to reduce the
level of anxiety and emotional distress and to prevent depression [15, 16]. If needed, when
prescribing medication, the pharmacological intervention should be personalized and
carefully chosen in function of the pharmacogenetical and psychological profile of the
patients, in order to prevent potential adverse events and for improved life quality [17-19].
Cognitive restructuring techniques, breathing and relaxation control techniques
(autogenous training Schultz) were applied [20-22]. During therapy, the patients completed a
personal diary in which they described daily personal experiences, results of exercises and
themes.

Conclusion

Unfortunately, birth remains only curative treatement of this disease, due to the previous
fact, pregnancy induced hypertension is considered as an indication for section, when vaginal
birth is not possible, thus C-section in lots of cases is considered the only treatement for these
patients, leading, to the fact that pregnancy-induced hypertension remains an important cause
of maternal-fetal mortality and morbidity.

REFERENCES

1. Elwood M. (2007). Critical Appraisal Of Epidemiological Studies And Clinical Trial. 3rd Ed Oxford
University Press, Oxford, pp.1-570.
2. Pregnancy Labor And Birth. Women’s Health. 2010 (27).
3. Chiriac D.V., Hogea L.M., Bredicean A.C., Rednic R., Nussbaum L.A., Hogea G.B., Grigoras M.L.
(2017). A rare case of Meckel–Gruber syndrome Rom. J. Morphol. Embryol 58(3):1023.
4. Milulescu A., Dorneanu F., Iacob D., Stoian D., Petre I., Chiriac V.D., Margan R., Ionita I., Marti D.,
Moleriu L.C. (2017). Procalcitonina – Diagnostic Marker In Neonatal Sepsis, Mat. Plast 54(4).
5. Hogea L.M., Tuta Sas I., Poroch V., Nussbaum L.A., SAS I., Serban D., Erdelean D., Folescu R.,
Zamfir C.L., Bredicean C.A., Simu M.A. (2018). Comparative study using progesterone and Gynipral –
Hexoprenaline Sulphate, with effects in postpone preterm birth, Chimia vol. 69(4): pp. 934-937.

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6. Molina G., Weiser T.G. (2015). Raltionship Between Cesarean Delivery Rate and Maternal and
Neonatal Mortality, JAMA 314(21): pp. 2263-70.
7. Lauwers J., Swisher A. (2010). Counseling The Nursing Mother: A Lactation Consultant’s Guide.
Jones&Barlett Publishers, p. 274.
8. Magee L.A. (2008). Diagnosis, Evaluation and Management of The Hypertensive Disorder of
Pregnancy. Journal of Obstetrics and Gynecology Canada 30:S1-S48.
9. Micoara N.C., Mladin D., Morariu S.I. (2017). Biomarkers in Diagnosing Preeclampsia and Their
Correlation with Blood Pressure 68(10): pp. 2448-2451.
10. Popa Z., Chiriac V.D., Cobec I.M. (2017). HPV Cervical Cancer Screening. An Analysis Over HPV
Markers Between Worldwide Statistics and Romanian Reality. Revista de Chimie 68(10): pp. 2459-
2462.
11. Popovici D.C., Ionita I., Ionita C. (2017). Statistical Hierarchy of Diagnostic Criteria for Chronic
Myeloid Leukemia, Revista de Chimie 68(10): pp. 2463-2466.
12. Mioc M., Avram S., Tomescu A.B. (2017). Docking Study of 3-mercapto-1, 2, 4-triazole Derivatives as
Inhibitors for VEGFR and EGFR, Revista de Chimie 68(3): pp. 500-503.
13. Sibai B.M. (2005). Diagnosis, Prevention and Management of Eclampsia. Obstet Gynecol, 105: p. 402.
14. Walker AP. (1998). The practice of genetic counseling. In Baker DL. A guide to genetic counseling,
Wiley & Sons, Inc. Publication, New York.
15. Hogea L.M., Nussbaum L.A., Chiriac D.V., Ageu L.S., Andreescu N.I., Grigoras M.L., Folescu R.,
Bredicean A.C., Puiu M., Rosca E.C.I., Simu M.A., Levai C.M. (2017). Integrative clinic-biological,
pharmacogenetic, neuroimagistic neuroendocrinological and psychological correlations in depressive
and anxiety disorders. Rom. J. Morphol.Embryol 58(3):767.
16. Hogea L.M., Hogea B.G., Nussbaum L.A., Chiriac V.D., Grigoras M.L., Andor B.C., Levai C.M.,
Bredicean A.C. (2017). Health-related quality of life in patients with hallux valgus. Rom. J. Morphol.
Embryol, 2017, 58(1):175.
17. Nussbaum L.A., Hogea L.M., Chiriac D.V., Grigoras M.L., Folescu R., Bredicean A.C., Rosca E.C.I.,
Muncan B., Nussbaum L.M., Simu M.A., Levai C.M. (2017). The effect of neurobiological changes in
the brain of children with schizophrenia, ultra high-risk for psychosis and epilepsy: clinical correlations
with EEG and Rom. J. Morphol. Embryol 58(4):1435.
18. Nussbaum L.A, Hogea L.M., Calina D., Andreescu N., Gradinaru R., Stefanescu R., Puiu M. (2017).
Modern treatment approaches in psychoses. Pharmacogenetic, neuroimagistic and clinical implications,
Farmacia vol. 65(1): pp. 75-81.
19. Nussbaum LA, Ogodescu A, Hogea LM, Nussbaum L, Zetu I. (2017). Risk Factors and Resilience in
the Offspring of Psychotic Parents. Review of Research and Social Intervention. 2017; 56: pp. 114-122.
20. Nussbaum L, Andreescu N, Hogea LM, Muntean C, Stefanescu R, Puiu M. Pharmacological and
Clinical Aspects of Efficacy, Safety and Tolerability of Atypical Antipsychotic Medication in Child and
Adolescent Patients with Schizophrenia and Bipolar Disorders. Farmacia, 2016, 64(6): pp. 868-875.
21. Andreescu N, Nussbaum L, Hogea LM, Grădinaru RC, Muntean C, Ștefănescu R, Puiu M.
Antipsychotic Treatment Emergent Adverse Events in Correlation with the Pharmacogenetic Testing
and Drug Interactions in Children and Adolescents with Schizophrenia and Bipolar Disorder. Farmacia,
2016, 64(5): pp. 736-744.
22. Nussbaum LA, Hogea LM, Andreescu NI, Grădinaru RC, Puiu M, Todica A. The Prognostic and
Clinical Significance of Neuroimagistic and Neurobiological Vulnerability Markers in Correlation with
the Molecular Pharmacogenetic Testing in Psychoses and Ultra High-Risk Categories. Rom J Morphol
Embryol, 2016, 57(3): pp. 959-967.

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Prenatal Diagnosis of Cloacal Malformation – A Case Report

ERDELEAN Dragos1, SERBAN Denis1, COPOTOIU Larisa1, TUTA-SAS Ioana1


1Department of Obstetrics-Gynecology I, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, (ROMANIA)
Email: [email protected]

Abstract

Cloacal malformation is an extremely rare fetal pathological condition. It affects


predominantly females, with prevalence of 1:50,000 birth. Prenatal ultrsonography usually
reveals: a cystic mass in the lower abdomen, ambiguous genitalia, oligohydramnios and a
single ombilical artery. Here, we report a rare case of 19 weeks of gestation with
characteristic ultrasound features of cloacal malformation (cystic pelvic mass,
oligohydramnios and ambiguous genitalia).
Keywords: cloacal malformation, ambiguous genitalia oligohydramnios

Introduction

The cloacal malformation is an extremely rare fetal pathological condition defined by a


confluence or coming together of the urinary tract, vagina and rectum to form a single
common channel that opens on the perineum. It is common channel that is refered to as a
cloaca. The discovery of cystic mass in the lower abdomen during the first trimester may
indicate a diagnosis of cloacal malformation [1-3]. It predominantly affects females, with
prevalence of 1 in 50,000 birth.

Case report

A 33 year old secundigravida underwent routine antenatal ultrasound at 19 weeks


gestation.

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The ultrasound showed a single live fetus with a biparietal diameter and femur length
corresponding to 19 weeks gestation “Fig. 1”. A hypoechoic cystic mass was seen in the
lower abdomen “Fig. 4 a, b” and bilateral hydronephrosis (Fig 3). The dimension of the pelvic
mass was about 3 cm. The amniotic fluid was reduced (AFI was 6 cm.) and fetal sex could not
be determined “ambiguous genitalia – Fig 2”. The patient had not been exposed to any
teratogenic agent during pregnancy and her history was unremarkable. The first child that was
born 2 years ago, was normal. Cloacal dysgenesis was suspected on the basis of the
ultrasound features (cystic pelvic mass, oligohydramnios and ambiguous genitalia). After we
consulted the parents we decided to determine the fetal karyotype through amniocentesis. The
result was normal (female karyotype-46 xx).

Fig. 1. DBP and HC corresponding at 19 weeks Fig. 2. Ambiguous genitalia


of gestation

The parents were informed of the poor chance of survival. Poor prognostic features
included severe oligohydramnios and pulmonary hypoplasia. They have decided and we
advice termination of pregnancy with the signed consent of the mother. Labor was induced by
using Prostaglandin E2.
A fetus weighing 300 kg with an protuberant abdomen, imperforate anus and ambiguous
genitalia was delivered. Gross examination revealed a smooth perineum, without patent
urethral, vaginal and anal openings (Fig. 3, 4).

Fig. 4(a). Abdominal cystic mass in the Fig. 5. Ambiguous genitalia


lower abdomen

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Fig. 4(b)

Discussions

Cloacal dysgenesis is a lethal malformation with a highly variable presentation. It is


characterized by direct communication between the gastrointestinal, urinary, and genital
structures, resulting in a single perineal opening. Prenatal diagnosis of cloacal anomaly is
often difficult because of highly variable imaging features. Cloacal dysgenesis is considered
when severe anorectal atresia occurs in association with a common cavity for the hindgut and
urogenital sinus. The primary malformation includes a smooth perineum, with the absence of
labioscrotal development and absence of anal, genital, and urinary orifices. The mean
gestational age at diagnosis is 27 weeks (19-33 weeks), but many cases are diagnosed only in
the third trimester or after birth [4-7]. Antenatal ultrasound features include: abdominopelvic
cystic structure, oligohydramnios, nonvisualized or poorly visualized bladder and ambiguous
genitalia, cystic or dysplastic kidney, and hydronephrosis [8-12]. The prognosis for a fetus
with cloacal dysgenesis is poor. Poor prognostic features include severe oligohydramnios,
pulmonary hypoplasia. Oligohydramnios may also develop as a consequence of urinary tract
obstruction, and may lead to pulmonary hypoplasia if it occurs before 24 weeks of gestation,
like in our case. The differential diagnosis of this lesion includes bowel atresia, megacystis-
microcolon-intestinal hypoperistalsis syndrome, and obstructive uropathy [13-15].
The attitude must take, with great attention, into account, all the present comorbidities,
associated pathologies, the medical and family history and the heredo-collateral antecedents
[16, 17].

Psychological counselling

Antenatal diagnosis now permits parental counseling and postnatal management [18-20].
Extensive parental counseling regarding the significant anatomic anomalies that constitute
the complex is appropriate in conjunction with psychological support [21-23].

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Conclusions

In summary, in cloacal malformation the ultrasound diagnosis is sometimes difficult.


Cloacal malformation, should be considered in the different diagnosis of a midline, cystic,
abdominopelvic mass in a female fetus.
In this case the presence of an abdominal cyst in the central region of the fetal pelvis
increased the suspicios of a cloacal anomaly, wich was confirmed during the postnatal period.

REFERENCES

1. Hayashi S., Sago H., Kashima K. (2005). Prenatal diagnosis of fetal hydrometrocolpos secondary to a
cloacal anomaly by magnetic resonance imaging. Ultrasound Obstet Gynecol 26(5): pp. 577-579.
2. Qureshi F., Jacques S.M., YaronY., Kramer R.L., Evans M.I., Johnson M.P. (1998). Prenatal diagnosis
of cloacal dysgenesis sequence: Differential diagnosis from other forms of fetal obstructive uropathy.
Fetal Diagn Ther 3: pp. 69-74.
3. Rios L.T.M., Junior E.A., Nardozza L.M.M. (2012). Prenatal Diagnosis and Postnatal Ultrasound
Findings of Cloacal Anomaly: A Case Report. Case reports in pediatrics
http://dx.doi.org/10.1155/2012/969860.
4. Anthony A. (2007). Congenital Urologic Anomalies. Im. Schrier RW. Diseases of the Kidney and
Urinary Tract. Lippincott Williams &Wilkins Philadelphia, pp. 594-596.
5. Odibo A.O., Turner G.W., Borgida A.F., Rodis J.F., Campbell W.A. (1997). Late prenatal ultrasound
features of hydrometrocolpos secondary to a cloacal anomaly: Case report and review of the literature.
Ultrasound Obstet. Gynecol 9: pp. 419-21.
6. Chiriac D.V., Hogea L.M., Bredicean A.C., Rednic R., Nussbaum L.A., Hogea G.B., Grigoras M.L.
(2017). A rare case of Meckel-Gruber syndrome Rom. J. Morphol. Embryol 58(3): p. 1023.
7. Milulescu A., Dorneanu F., Iacob D., Stoian D., Petre I., Chiriac V.D., Margan R., Ionita I., Marti D.,
Moleriu L.C. (2017). Procalcitonina – Diagnostic Marker In Neonatal Sepsis, Mat. Plast 54(4).
8. Hogea L.M., Tuta Sas I., Poroch V., Nussbaum L.A., SAS I., Serban D., Erdelean D., Folescu R.,
Zamfir C.L., Bredicean C.A., Simu M.A. (2018). Comparative study using progesterone and Gynipral –
Hexoprenaline Sulphate, with effects in postpone preterm birth, Chimia vol. 69(4): pp. 934-937.
9. Cilento B.G.-Jr, Benacerraf B.R., Mandell J. (1994). Prenatal diagnosis of cloacal malformation.
Urology 43: pp. 386-8.
10. Zaccara A., Gatti C., Silveri M., Rivosecchi M., Bilancioni E., Spina V. (1999). Persistent cloaca: Are
we ready for a correct prenatal diagnosis? Urology 54: p. 367.
11. Qureshi F., Jacques S.M., Yaron Y., Kramer R.L., Evans M.I., Johnson M.P. (1998). Prenatal diagnosis
of cloacal dysgenesis sequence: Differential diagnosis forms of fetal obstructive uropathy. Fetal
DiagnTher 13: pp. 69-74.
12. Micoara N.C., Mladin D., Morariu S.I. (2017). Biomarkers in Diagnosing Preeclampsia and Their
Correlation with Blood Pressure 68(10): pp. 2448-2451.
13. Popa Z., Chiriac V.D., Cobec I.M. (2017). HPV Cervical Cancer Screening. An Analysis Over HPV
Markers Between Worldwide Statistics and Romanian Reality. Revista de Chimie 68(10): pp. 2459-
2462.
14. Popovici D.C., Ionita I., Ionita C. (2017). Statistical Hierarchy of Diagnostic Criteria for Chronic
Myeloid Leukemia, Revista de Chimie 68(10): pp. 2463-2466.
15. Mioc M., Avram S., Tomescu A.B. (2017). Docking Study of 3-mercapto-1,2,4-triazole Derivatives as
Inhibitors for VEGFR and EGFR, Revista de Chimie 68(3): pp. 500-503.
16. Andreescu NI, Nussbaum LA, Hogea LM, Grădinaru RC, Muntean C, Ștefănescu R, Puiu M.
Antipsychotic Treatment Emergent Adverse Events in Correlation with the Pharmacogenetic Testing
and Drug Interactions in Children and Adolescents with Schizophrenia and Bipolar Disorder. Farmacia,
2016, 64(5): pp. 736-744.
17. Nussbaum L.A., Andreescu N.I., Hogea L.M., Muntean C., Stefanescu R., Puiu M. (2016).
Pharmacological and Clinical Aspects of Efficacy, Safety and Tolerability of Atypical Antipsychotic
Medication in Child and Adolescent Patients with Schizophrenia and Bipolar Disorders. Farmacia
64(6): pp. 868-875.
18. Nussbaum L.A., Hogea L.M., Andrescu N.I., Grădinaru R.C., Puiu M., Todica A. (2016). The
Prognostic and Clinical Significance of Neuroimagistic and Neurobiological Vulnerability Markers in
Correlation with the Molecular Pharmacogenetic Testing in Psychoses and Ultra High-Risk Categories.
Rom J Morphol Embryol 57(3): pp. 959-967.

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19. Nussbaum L.A., Ogodescu A., Hogea L.M., Nussbaum L., Zetu I. (2017). Risk Factors and Resilience
in the Offspring of Psychotic Parents. Review of Research and Social Intervention 56: pp. 114-122.
20. Hogea L.M., Hogea B.G., Nussbaum L.A., Chiriac V.D., Grigoras M.L., Andor B.C., Levai C.M.,
Bredicean A.C. (2017). Health-related quality of life in patients with hallux valgus. Rom. J. Morphol.
Embryol, 2017, 58(1): p. 175.
21. Hogea L.M., Nussbaum L.A., Chiriac D.V., Ageu L.S., Andreescu N.I., Grigoras M.L., Folescu R.,
Bredicean A.C., Puiu M., Rosca E.C.I., Simu M.A., Levai C.M. (2017). Integrative clinic-biological,
pharmacogenetic, neuroimagistic neuroendocrinological and psychological correlations in depressive
and anxiety disorders. Rom. J. Morphol.Embryol 58(3): p. 767.
22. Nussbaum L.A., Hogea L.M., Chiriac D.V., Grigoras M.L., Folescu R., Bredicean A.C., Rosca E.C.I.,
Muncan B., Nussbaum L.M., Simu M.A., Levai C.M. (2017). The effect of neurobiological changes in
the brain of children with schizophrenia, ultra high-risk for psychosis and epilepsy: clinical correlations
with EEG and Rom. J. Morphol. Embryol 58(4):1435.
23. Nussbaum L.A, Hogea L.M., Calina D., Andreescu N., Gradinaru R., Stefanescu R., Puiu M. (2017).
Modern treatment approaches in psychoses. Pharmacogenetic, neuroimagistic and clinical implications,
Farmacia vol. 65(1): pp. 75-81.

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Face to Face with the Fetus

CIORTEA Răzvan1, DICULESCU Doru1, MĂLUȚAN Andrei1,


OANCEA Mihaela1, MOCAN-HOGNOGI Radu1, BĂLTOAICA Răzvan1,
BUCURI Carmen1, RADA Maria1, DUDEA Marina1, BERCEANU Costin2,
MIHU Dan1
1 Department of Obstetrics and Gynecology, “IuliuHaţieganu” University of Medicine and Pharmacy, Cluj-Napoca,
(ROMANIA)
2 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected], [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected]

Abstract

The face is an essential part of human interactions, hence facial abnormalities have an
important impact in terms of emotional responses to them. Apart from the psychological
issues, facial defects are often associated with other abnormalities, and may be the starting
point in finding chromosomal diseases or more complex genetic syndromes. This has practical
consequences with regard to invasive tests (chorionic villus sampling, amniocentesis), and
genetic counselling.
The detection of facial anomalies is of great value, notably in isolated cases, as the couple
then have time to understand and accept the pathology, and additionally, they can be
counseled by paediatric/plastic surgeons in the matter of treatment options and long-term
prognosis for the baby. Therefore, ultrasound evaluation represents the first step in depiction
of facial abnormalities, and implies a good understanding of 2D/3D techniques in order to
make a precise diagnosis.
In standard 2D ultrasound, scanning of the fetal face is particularly carried out in 3 planes
(coronal, transverse, and sagittal), and each plane provides information about the fetal face
(anatomy, position, biometry). However, all the acquired data must be correlated with the
gestational age. Further information about the nature of the defect may be obtained by using
3D ultrasound (tomographic ultrasound imaging (TUI), surface randering), and live scanning
using 4D probes.
Keywords: ultrasound, fetal face, diagnosis, abnormalities

Fetal face represents a permanent concern of ultrasound examination because, using this
method, an important number of abnormalities can be identified. Some of these defects are
isolated, but there is a significant percentage associated with different syndromes.
The sonographic approach of fetal face implies scanning in 3 planes – coronal, axial, and
sagittal. A true midsagittal view will allow assessment of the forehead, nasal bone, alignment
of the maxilla and mandible, and can ascertain the presence of facial clefting and facial
tumours (Fig. 1.). The coronal plane will allow assessment of the orbits, lens of the eyes, lips,
chin, nostrils, and it is useful in detecting conditions such as micrognathia, premaxillary
protrusion, frontal bossing, proboscis, facial tumours (Fig. 2.). The axial transverse plane will
assess orbits, orbital diameters, upper lip, maxilla, tongue, and mandible (Fig. 3.).
The present article aims to give a succinct summary of the relevant aspects of the fetal
face, involving both the normal and abnormal – eyes, nose, ears, tongue, mouth, profile, and

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facial angles. Targeted examination for ocular abnormalities can be done in each trimester,
but the first analysis of the eyes and orbits should be arranged during the first trimester
assessment for chromosomal abnormalities. Furthermore, a normal appearance of the eyes in
the first trimester can constitute a landmark in evaluating this part of the fetal face during the
second and third trimesters. Regarding the development of the eyes, these structures are first
positioned on either side of the head. The angle between the imaginary lines passing through
the optical axes of each eye is 180 degrees, and decreases to 71 degrees. [1]

Fig. 1. Midsagittal view


Fig. 2. Coronal view

Fig. 3. Axial view (maxilla) Fig. 4. Axial view (mandible)

Demonstration of the orbits should reveal that both of them are of equal size. There are
charts available for orbital measurements (orbital diameter, interorbital distance, binocular
distance), but as a rule of thumb the interorbital distance is approximately equal to the orbital
diameter. (Fig. 5, 6.)

Fig. 5. Orbits and lens of the eyes (first trimester) Fig. 6. Binocular distance

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Ocular abnormalities
Hypotelorism – the orbits are too close together (interorbital distance and/or binocular
distance below the 5th centile); hypotelorism may be the only finding associated with
holoprosencephaly and may be very mild; there are some chromosomal abnormalities which
can be associated with hypotelorism. [2]
Hypertelorism – the orbits are too far apart (interorbital distance above the 95th centile). [3]
Microphthalmia is a rare condition in which the orbital diameter is below the 5th centile.
This finding can be associated with chromosomal disease, infections, and maternal
alcoholism. [4]
Anophthalmia is caused by failure of formation of the optic pit and optic outgrowths from
the forebrain resulting in absence of the lens, optic nerves, and chiasma. Sonographically, the
diagnosis can be rather difficult. [5]
Congenital cataracts can have 3 sonographic appearances: the normal lens is completely
hyperechoic; double ring appearance; central hyperechoic area within the lens. [6]

Tumorile orbitale şi periorbitale


Dacrocystocoeles are cysts of the lacrimal duct, typically located inferomedially to the
orbit, and are completely transonic.[4]
Retinoblastoma is a malignant tumour that rapidly develops from the neuroepithelial cells
of the retina. The sonographic appearance is that of a solid mass with heterogeneous
echogenicity.
The tumour can obstruct the orbit, and can affect the brain due to its fast pace of
development. [7]

The nose
Assessment of the nasal bone requires a true midline sagittal view. The mojority of authors
recommend that evaluation, in the first trimester, should only focus on the presence or
absence of the nasal bone (Fig. 7.). However, in the second trimester, the measurement of
nasal bone lenght is carried out from the tip to the synostosis of nasal bones (Fig. 1.).

Fig. 7. Nasal bone (first trimester)

A comparison of two populations, Caucasian and African, suggests that are some
differences regarding the nasal bone in utero. In African population, the absence of nasal bone
may not be considered a marker for chromosomal abnormalities [8]. 3D volumetric
acquisitions may offer additional information in the analysis of the nasal bone.
The ear has a complex embryology, and can be seen on 3D ultrasound starting from 9/10
weeks of gestation. Ultrasound evaluation should establish the presence of both ears, ear lobe
morphology, and the relationship to the temporal bone to exclude low-set ears. Anomalies of
the fetal ear can be associated with complex syndromes. In the second trimester, the outer rim
of the ear (helix) can be identified, with the upper part at the level of the parietal suture. Ear

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length is measured in coronal view as the maximum distance between the superior and the
inferior aspect of the ear. A small ear (below the 5th centile) has been shown to be associated
with aneuploidies (80%). [9]

In a transverse axial plane perpendicular to the long axis of the neck just above the level of
the mandible, the tongue appears as an ovoid echogenic structure bordered laterally by the
echogenic mandibular rim, and posteriorly by the hypoechoic pharynx. In the 3rd trimester, it
is more difficult to assess the tongue due to its active movements.
Technique of measurement of fetal tongue and nomograms have been established in cases
of microglossia and macroglossia [10]. Before the nomograms were assented, in utero
diagnosis of macroglossia was made subjectively by visualization of tongue beyond the
alveolar ridge.
Macroglossia is commonly associated with: chromosomal abnormalities, Beckwith-
Wiedemann Syndrome, congenital hypothyroidism, metabolic storage disorders.
Macroglossia can be best visualized on sagittal view, more often in the 2nd and 3rd trimesters.

The profile view should form a smooth curve running from forehead, nose, lips, and
maxilla to mandible (chin). Superior facial angle is measured on the facial profile as the angle
between the vertical section of the frontal bone and nasal bones. An angle of more than 130
degrees describes a flat profile [11]. In addition, an unduly flat profile raises the possibility of
chromosomal disease. In the mid-sagittal plane, prenasal thickness is the shortest distance
between the anterior edge of the lowest part of the frontal bone and the facial skin anteriorly.
The cutoff for prenasal thickness is 6 mm [12]. Inferior facial angle is measured as the
angle between the line perpendicular to the vertical part of the forehead, drawn at the level of
the synostosis of nasal bones and another line joining the tip of mentum to the more
protrusive lip (Fig. 9.). This angle is used in the assessment of retrognathia [13].

Fig. 8. Superior facial angle Fig. 9. Inferior facial angle

The structures of the mouth can be visualized starting from the 1st trimester using
transvaginal scanning. Analysis of maxilla and mandible is essential in delineation of facial
abnormalities. In the axial plane, the width of maxilla and mandible is measured along a line
perpendicular to the sagittal axis at 10 mm from the anterior interosseous border (Fig. 10,
11.).
Subjective finding of prominent upper lip and receding chin in the mid-sagittal view of the
face can be due to micrognathia (short mandible) or retrognathia (backward displacement of
the mandible). Severe micrognathia is associated with polyhydramnios due to glossoptosis
[14].

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Fig. 10. Measurement of maxilla Fig. 11. Measurement of mandible

Assessing the palate can be difficult using only 2D ultrasound, because of the bone
structures which can cause shadow cones (Fig. 12.). Hence, to improve the diagnostic
accuracy one can use 3D ultrasound (TUI) (Fig. 13.).

Fig. 12. Shadow cone Fig.13. TUI

Facial clefting

Using a coronal plane, the hallmark of cleft lip is the demonstration of a vertical transonic
area within the lip. Scanning in the transverse plane will show the defect in the alveolar ridge
in addition to the cleft in the lip. Bilateral cleft lip and/or palate will demonstrate, in a sagittal
plane, the presence of premaxillary protrusion.
In the event of unilateral cleft lip and/or palate karyotyping may show an abnormality in
5% of cases, which will increase to 15% for cases with bilateral clefts [15]. Associated
structural anomalies are seen in 11% of cases for unilateral clefts, and in 20% of cases for
bilateral clefts [16]. There is a high incidence of cardiac abnormalities among fetuses with
facial clefts.

REFERENCES

1. Whitehead MT, Vezina G. (2016). Normal Developmental Globe Morphology on Fetal MR Imaging.
AJNR Am J Neuroradiol 37(9), pp. 1733-1737.
2. Sukonpan K, Phupong V. (2008). Fetal ocular distance in normal pregnancies. J Med Assoc Thai 91(9),
pp. 1318-1322.
3. Roth P, Roth A, Clerc-Bertin F, Sommerhalder J, Maillet R. (1999). Prenatal ultrasonic measurements
of the eye and the interorbital distance.J Gynecol Obstet Biol Reprod 28(4), pp. 343-351.
4. Ionescu C, Dimitriu M, Poenaru E, Viezuina R, Furau CG. (2017). Fetal-Maternal toxicology: fetal
somatic consequences of noxious habits in pregnant women. Rom J Leg Med 25, pp. 82-88.

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5. Wong HS, Parker S, Tait J, Pringle KC.(2008). Antenatal diagnosis of anophthalmia by three-
dimensional ultrasound: a novel application of the reverse face view. Ultrasound Obstet Gynecol. 32(1),
pp. 103-105.
6. Trkova M, Hynek M, Dudakova L, Becvarova V, Hlozanek M, Raskova D, Vincent AL, Liskova P
(2016). Early detection of bilateral cataracts in utero may represent a manifestation of severe congenital
disease. Am J Med Genet A 170(7), pp. 1843-1848.
7. Paquette LB, Miller D, Jackson HA, Lee T, Randolph L, Murphree AL, Panigrahy A.(2012). In utero
detection of retinoblastoma with fetal magnetic resonance and ultrasound: initial experience. AJP Rep
2(1), pp. 55-62.
8. Collado F, Bombard A, Li V, Julliard K, Aptekar L, Weiner Z. (2005). Ethnic variation of fetal nasal
bone length between 11-14 weeks’ gestation.Prenat Diagn. 25(8), pp. 690-692.
9. Wei J, Ran S, Yang Z, Lin Y, Tang J, Ran H. (2014). Prenatal ultrasound screening for external ear
abnormality in the fetuses.Biomed Res Int2014:357564.
10. Ronin-Walknowska E, Samborska M, Płonka T. (2006). Anomalies of the tongue in the fetus and
neonate. Ann Acad Med Stetin 52 Suppl 3, pp. 7-11.
11. Vos FI, Bakker M, de Jong-Pleij EA, Ribbert LS, Tromp E, Bilardo CM. (2015) Is 3D technique
superior to 2D in Down syndrome screening? Evaluation of six second and third trimester fetal profile
markers.Prenat Diagn 35(3), pp. 207-213.
12. Levaillant JM, Touboul C, Sinico M, Vergnaud A, Serero S, Druart L, Blondeau JR, Abd Alsamad I,
Haddad B, Gérard-Blanluet M. (2005). Prenatal forehead edema in 4p- deletion: the “Greek warrior
helmet” profile revisited.Prenat Diagn 25(12), pp. 1150-1155.
13. Captier G, Faure JM, Bäumler M, Canovas F, Demattei C, Daures JP. (2011).Prenatal assessment of the
antero-posterior jaw relationship in human fetuses: from anatomical to ultrasound cephalometric
analysis.Cleft Palate Craniofac J 48(4), pp. 465-472.
14. Zellner EG, Reid RR, Steinbacher DM (2017). The Pierre Robin Mandible is Hypoplastic and
Morphologically Abnormal. J Craniofac Surg 28(8), pp. 1946-1949.
15. Kim DW, Chung SW, Jung HD, Jung YS. (2015) Prenatal ultrasonographic diagnosis of cleft lip with
or without cleft palate; pitfalls and considerations.Maxillofac Plast Reconstr Surg. 37(1), pp.22-24.
16. Destree A, Fourneau C, Dugauquier C, Rombout S, Sartenaer D, Gillerot Y. (2005) Prenatal diagnosis
of trisomy 6 mosaicism. Prenat Diagn 25(5), pp. 354-357.

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Inhaled Analgesia During Labor – A Systematic Review

COSTIN Adrian1, DRAGOMIR Ramona1, SPĂTARU Gina1,


DOBRESCU Cătălin1, FÎRŢĂ Anca1, BĂNCEANU Gabriel2
1 Department of Obstetrics and Gynecology, Polizu Hospital, National Institute for Mother and Child Health
“Alessandrescu-Rusescu” (ROMANIA)
2 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy “Carol Davila” (ROMANIA)

Email: [email protected]

Abstract

During the process of childbirth women experience one of the most severe pain. This pain
has many causes, and during the last years, a multitude of studies were realized in order to
find appropriate methods to manage it. We can divide the methods used to relieve the pain
during labor, into pharmacological and non-pharmacological methods. Our study will focus
on the pharmacological ones, especially on the inhaled analgesia, which offers new
perspectives and directions regarding the health care during labor.
Currently there is a huge evolution in the field of labor analgesia, from ether and
chloroform, which were used in the 19th century, to a comprehensive programe for labor pain
management available nowadays.
There are many agents that have been tested for inhaled analgesia, substances such as
sevoflurane, isoflurane and enflurane, and the most studied one, nitrous oxide (Entonox).
In the present research we will try to analyze the studies conducted until now, regarding
inhaled analgesia during labor, and to summarize the effects, the benefits and the downfalls of
it.
Keywords: inhaled analgesia, labor analgesia, labor pain, nitrous oxid, entonox, sevoflurane

Introduction

According to the American Society of Anesthesiology (ASA) “in the absence of medical
contraindication, maternal request is sufficient medical indication for pain relief during labor”
(statement on pain relief during labor, Oct 17, 2007) [1].
The pain felt by the women during labor is described as one of the worst pain in life. It’s
important to make continuous efforts to search and find methods to make this pain a little
more comfortable. Inhaled analgesia seems to be a safe and effective choice regarding the first
stages of labor [2, 3].
The start of childbirth analgesia was in 1847, when ether was administrated by Dr. J.Y.
Simpson to a woman in labor, and later chloroform was administered by John Snow to
Britain’s Queen, Victoria, during the birth of her eight child, Prince Leopold. After that, many
other substances began being used, such as nitrous oxide, isoflurane, enflurane, desflurane
and sevoflurane. An important moment was the approval of Entonox use by Central Midwives
Board in 1965.
An ideal obstetric analgesic should respect a few criteria as: it should attenuate maternal
anxiety, fatigue and deliver health, they shouldn’t cross the placental barrier in order to have
minimal effects on mother or fetus health, they should be easy to administer with minimal
monitoring and easily reversible if necessary [1].

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Methods

A review of the literature was performed regarding inhaled analgesia, its effects, benefits
and disadvantages. The strategy implied using key words such as inhaled analgesia, labor
analgesia, labor pain, nitrous oxid, Entonox, sevoflurane, with articles selection, narrative
description of the obtained data and citation of the studied articles.

Results

The most administrated agent for inhaled analgesia during labor is Entonox. Volatile
anaesthetic agents have been tried in the recent years such as sevoflurane (Sevox), isoflurane
and enflurane.
Entonox used 50% nitrous oxide in oxygen provides analgesia within 20-30 seconds of
inhalation with a maximum effect after about 45 second [4].
A systemic review of the use of Entonox in labor concluded that Entonox is not such a
potent analgesic. The Obstetric Anaesthesia Association, UK (2005) guidelines states that
Entonox is being phased out from the UK in view of the poor analgesic efficacy and
environmental pollution [5]. Though other studies suggest beneficial effects on parturients if
the method of inhalation is properly followed. Entonox inhalation is a good method in cases
where neuroaxial techniques are not practiced, and in parturients with short labor [6].
The American College of Nurse-Midwives (ACNM) states that “Research has supported
the reasonable efficacy, safety, and unique and beneficial qualities of N2O as an analgesic for
labor and its use as a widely accepted component of quality maternity care” (2011) [7].
Many countries, for example Canada, Sweden, Australia, Finland and the United Kingdom
use a blend of 50% oxygen and 50% nitrous oxide to treat pain during labor.
Using nitrous oxide for labor analgesia has many advantages. According to Rooks, “nitrous
oxide labor analgia is safe for the mother, fetus, and neonate and can be made safe for
caregivers.
It is simple to administer, does not interfere with the release and function of endogenous
oxytocin, and has no adverse effects on the normal physiology and progress of labor” [6].
Another advantage is represented by the fact that it can be self-administered, so the woman
can choose how much to use, when to stop it and it allows the use of another method of pain
relief if needed, because its easy way to stop and its effects disappear within a few minutes
[8].
The use of nitrous oxide can also have risks, sedation, dizziness, nausea and vomiting can
occur. Other risks can appear if the dose used is above 50% concentration [9]. A study
showed a dose dependent association between intrapartum exposure to nitrous oxide and a
later addiction to amphetamines later in life when the mother used 100% nitrous oxide [6].
When prolonged exposure to very high doses of nitrous oxide happens, fertility problems
may appear, as has been shown in animal studies.
A study realized at Polizu Maternity, Romania, during 2016-2017 regarding the utilization
of Entonox as labor analgesia concluded that from a total of 111 patients, 55,85% reported a
decrease in perception with 2 points on pain scale, 24,32% reported a reduction with 3-4
points and for 9% of the patients, the pain did not modify [10]. Side effects as nausea and
vomiting appeared after approximatively 30 minutes of administration [11].
Sevoflurane is a volatile inhalational agent commonly used during general anaesthesia.
Sevoflurane can be a well suited inhalational agent for labor analgesia because of its short
onset and offset of action [12]. It also can be administered as patient-controlled inhalation
analgesia.

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In a study conducted by Toscano in 2003 regarding Sevoflurane analgesia in obstetrics, it


was shown that sevoflurane can be effective for the treatment of labor pain. This was the first
study on the use of sevoflurane at sub-anesthetic doses during labor and delivery. The
research included fifty parturients, that breathed a mixture of 2-3% sevoflurane, oxygen and
air before each uterine contraction began. The women examined the quality of analgesia by
using a visual analogue scale (0-10) before the inhalation of sevoflurane and after each uterine
contraction. All patients, but one were satisfied, with a mean visual analogue score before and
after sevoflurane administration of 8,7+/-1,1 and 3,3+/-1,5, respectively [13].
Another study compared the use of Entonox and Sevoflurane at a concentration of 0.8%
for labor analgesia in 32 healthy parturients. They concluded that self-administered
sevoflurane at subanaesthetic concentration (0.8%) can provide useful pain relief during the
first stage of labor, and to a greater extent than Entonox [14, 15]. Although greater sedative
effects were experienced with sevoflurane, it was preferred to Entonox. Nausea and vomiting
were more common in Entonox group.
In 1984, McGuiness conducted a study regarding enflurane as an analgesic in labor. The
analgesic efficacy of enflurane 1% in air was compared with Entonox in 20 cases of women
during the first stage of labor. Pain scores were significantly lower with enflurane compared
to Entonox, though drowsiness scores were higher [16].
The effects of self-administered isoflurane in labor were also compared with the ones from
Entonox. Their analgesic effects were compared in the first stage of labor in 32 consenting
women. Linear analogue pain scores were significantly lower with isoflurane than with
Entonox, bur scores for drowsiness were higher for isoflurane [17].
According to Cochrane Collaboration “ women in labor who need pain relief should not
only have access to invasive methods such as an epidural, which may have considerable side
effects, but other means of pain relief as well” [18].
Researchers at the Cochrane Collaboration reviewed 26 separate studies that involved
nearly three thousand women. They concluded that inhaled pain medications were effective,
easy to administer and provided pain relief within minutes [18]. Another advantage is that
they are less invasive than other pain relief methods, like epidurals and nerve blocks.

Conclusions

Moir stated in 1979, in the British Journal of Anaesthesiology, “Delivery of the infant into
the arms of a conscious and pain-free mother is one of the most exciting and rewarding
moments in medicine”.
The pain felt by the mother during labor it a severe one, but its intensity is variable,
depending on maternal and fetal factors. Many psychosocial factors are as well implied in this
process [19].
It’ s difficult to design studies that evaluate the efficacy of the labor analgesia techniques.
Randomized control studies that assign patients to a group that offers no analgesia in order
to study the efficacy of a particular technique are not ethical.
Until now, the studies concluded that Entonox and sevoflurane are well suited to be
administered during labor, with a proven pain relief.
It’s important to find new ways to asses the efficacy of the analgetic agents. Future
research is needed in this field in order minimize the pain during labor, so that nothing can
shadow the joy of giving birth.

Author contribution
All authors contributed equally to the design and the writing of this research.

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REFERENCES

1. Michael Wee – Analgesia in labour: inhalational and parenteral, Anaesthesia & Intensive Care
Medicine, Vol 8 Issue 7, July 2007, pp. 276-278
2. Findley I, Chamberlain G. (1999) – ABC of labor care. Relief of pain. BMJ. 318 pp .927-930.
3. Coping with pain in labour – non-epidural - Intrapartum Care: Care of Healthy Women and Their
Babies During Childbirth, National Institute for Health and Care Excellence (UK); 2014 Dec.
4. Rosen MA. – Nitrous oxide for relief of labor pain: A systematic review. Am J Obstet Gynecol.
2002;186:S110-26.
5. Yentis SM. – The use of Entonox for labour pain should be abandoned. Proposer. Int J Obstet Anesth
2001; 10; pp. 25-29.
6. Rooks, J.P (2011) – Safety and risks of nitrous oxide labor analgesia: A review. Journal of Midwifery &
Women’s Health, 56 (6)
7. American College of Nurse Midwives. (2011). – Nitrous oxide for labor analgesia.
8. Likis FE, Andrews JC, Collins MR, (2014) et al., – Nitrous oxide for the management of labor pain: a
systematic review. Anesth Analg. 118 pp.153.
9. Collado V, Nicolas E, Faulks D, Hennequin M. (Sep. 2007) – A review of the safety of 50% nitrous
oxide/oxygen in conscious sedation. Expert Opin Drug Saf. 6(5) pp. 559-71.
10. Oana Toader, Alexandra Vintea, N Suciu, A Voichițoiu – Modern methods for dealing with pain during
labor-inhalator analgesia with nitrous oxide. Proceedings of the 13th Conference of the Romanian-
German Society of Obstetrics and Gynecology, 14-16 September 2017. Filodiritto Editore-Proceedings,
pp. 289-292, ISBN 978-88-95922-95-9.
11. Toader Oana, Vintea Alexandra, Suciu Nicolae, Voichițoiu Andrei – Techniques of analgesia during
labour. – Proceedings of the National Conference of the Romanian Association for the Study of Pain,
26-27 October 2017. Filodiritto Editore-Proceedings, pp. 629-632, ISBN 978-88-95922-98-0.
12. Patel SS, Goa KL. – Sevoflurane. A review of its pharmacodynamic and pharmacokinetic properties
and its clinical use in general anaesthesia. Drugs 1996; 51: pp. 658-700.
13. Toscano, C. Pancaro, S. Giovannoni, G. Minelli, C. Baldi, G. Guerrieri, J. A. Crowhurst,a V. A. Peduto
- Sevoflurane analgesia in obstetrics: a pilot study, International Journal of Obstetric Anesthesia (2003)
12, pp. 79-82, doi:10.1016/S0959-289X(02)00195-4.
14. S. T. Yeo, A. Holdcroft, S. M. Yentis, A. Stewart and P. Bassett – Analgesia with sevoflurane during
labour: II. Sevoflurane compared with Entonox for labour analgesia, British Journal of Anaesthesia 98
(1): pp. 110-15 (2007) doi:10.1093/bja/ael327.
15. Yeo ST, Holdcroft A, Yentis SM, Stewart A. – Analgesia with sevoflurane during labour: I.
Determination of the optimum concentration. Br J Anaesth 2007; 98: pp. 105-9.
16. McGuiness C, Rosen M. – Enflurane as an analgesic in labour. Anaesthesia 1984; 39: pp. 24-6.
17. McLeod DD, Ramayya GP, Tunstall ME – Self-administered isoflurane in labour. Anaesthesia 1985;
40: pp. 424-6.
18. Jones L, Othman M, Dowswell T, Alfirevic Z, Gates S, Newburn M, Jordan S, Lavender T, Neilson JP
– Pain management for women in labour: an overview of systematic reviews. Cochrane Database of
Systematic Reviews 2012, Issue 3. Art. No.: CD009234.
19. Caton D, Corry MP, Frigoletto FD, Hopkins DP, Lieberman E, Mayberry L, Rooks JP, Rosenfield A,
Sakala C, Simkin P, Young D – The nature and management of labor pain; Executive summary. Am J
Obstet Gynecol 2002; 186: s1-15.

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Etiopathogenic Considerations of Preeclampsia in Southeastern


Romania

STUPARU-CRETU Mariana1,2, BUSILA Camelia2,3, CARAMAN Liliana1,2


1 Clinical Obstetrics and Gynecology Hospital “Buna Vestire”, Galati,(ROMANIA)
2 Medical-Pharmaceutical Research Center,Faculty of Medicine and Pharmacy, University “Dunarea de Jos” of Galati
(ROMANIA)
3 Emergency Clinical Hospital for Children “Sfantul Apostol Ioan”, Galati, (ROMANIA)

Emails: [email protected], [email protected]

Abstract

As a human specific pathology, the last trimester pregnancy-related disease has a multitude
of etiological factors, with placental, maternal or fetal origin. Preeclampsia is mainly defined
by the association between hypertension and proteinuria, edema is often considered as
common to pregnancy. PE is recognized as a cause of premature birth, delay in intrauterine
fetal growth, even for the death of the mother or fetus, so it is necessary to recognize early
signs of diagnosis.
The study is retrospective over a three-year period. Gestosis cases have been analyzed in
pregnant women over 20 weeks of pregnancy age, admitted to the Obstetrics-Gynecology
Hospital “Buna Vestire” Galati, Romania. The incidence of preeclampsia was reduced, with
over 60% being healthy nulliparous women, with a maximum frequency in the age group of
31-35 years. Only 7% of pregnant women have developed severe complications, but quarter
of the fetuses had IUGR and almost 5% of the newborns were admitted of the Neonatal
Intensive Care Unit. Proper disease management is required to prevent PE recurrent forms. A
good communication between patient and health care provider is the key to recognize the
early signs of diagnosis and also the successful management of preeclampsia.
Keywords: preeclampsia, etiopathogenity, statistical correlation

Introduction

As a human specific pathology, the last trimester pregnancy-related disease has a multitude
of etiological factors, with placental, maternal or fetal origin [1]. Preeclamsia (PE) is included
in hypertensive disorders of pregnancy [2] and defines a condition occurring during
pregnancy evolution after 20 weeks.
With a frequency in the world up to 10%, is describe to 25% in United States during the
past 20 years [3]. PE and eclampsia is still an important cause of perinatal mortality and
morbidity, also with seriously complication for fetus or newborn. The severity of
preeclampsia is correlated with maternal end-organ dysfunctions. On the other hand, fetal
manifestation may occur with the maternal manifestatios or in absence of this [4].
The classic definition of preeclampsia includes new increases in systolic blood pressure
(SBP) over 140 mmHg or a diastolic blood pressure (DBP) above 90 mmHg, persisting at two
measurements in four hours and proteinuria of ˃ 0,3g /24 hours. In the absence of proteinuria,
one of the following anomalies is considered: trombocytopenia, impaired liver or kidney
function, pulmonary edema or cerebral or visual disturbances [1]. Edema is often considered
as common to pregnancy, so has been eliminated for diagnostic use in the latest American
College of Obstetricians and Gynecologists (AGOG) guide, in 2013 years [3], [5]. A severe

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forme of PE include a systolic BP ≥ 160 mmHg or a dyastolic BP ≥ 110 mmm Hg, a number
of plateletes ≤ 100 000/μL impaired liver and renal function, visual or cerebral disturbances
[3], [5].
The mechanisms involved in preeclampsia is not yet clare, the last researches included
vascular epithelial dysfunction, vascular spasm and ischemia [4] with inflammatory blood
markers expression, such as CRP [6]. The risk factors describes in clinical studies includes
preexisting hypertension or renal disfunction, previous PE or eclampsia, Diabetes mellitus,
nulliparity, highy BMI, antiphospholipid antibody syndrome, age more 35 years and molar
pregnancy. Although preeclampsia is supposed to be a self-limited disease that resolves with
the delivery of fetus and placenta, some studies have shown that this endothelial dysfunction
can last for a long time after the PE episode. [7]
The clinical manifestation result from microangiopathy of target organs, including the
placenta, the brain, liver and kidney. Signs and symptoms of PE include high values of blood
pressure, proteinuria, edema, headaches, epigastic pain and visual disturbances [4].
Serious complications can be avoided by administreting the antihypertensive medication or
inducing the premature delivery [2]. Intensive maternal and fetal monitoring will identify
early clinical signs of the disease and avoidance of intrauterine growth restriction often
associated with PE. Gestational hypertension which is diagnosed postpartum, is treated as
chronic hypertension and requires additional investigations. Moreover, women who had
recurrent forms of preeclampsia were more likely to have hypertension and other
cardiovascular disease later in life [7], [8].

Material and Methods

The study is retrospective over a three-year period: 2012-2015. Hypertensive gestosis cases
have been analyzed in pregnant women over 20 weeks of age, admitted to the Obstetrics-
Gynecology Hospital “Buna Vestire” Galati, of Southeastern Romania.
Of the 5345 total births, 130 were diagnosed with preeclampsia. At these, the frequencies
and correlations between the following variables were studied: Patient age, Gestational age,
Area of origin, date of Pregnancy monitoring, Parity, PE Diagnosis moment, Body Mass
Index (BMI), Type of birth, Diastolic Blood pressure, PE forms, Edema and Ponderal curve,
Proteinuria value (g/24h), Hemoglobine value (mg/dL), C-Reactive Proteine (CRP)
value(mg/L), Birth timing, Type of delivery, Hospitalization rates, Maternal complications,
Fetal complications.
The statistics results have been processed using the Analysis ToolPak in Microsoft Excel
2010, Minitab 18 (Minitab® 18) and Unscramble X program (Camo, Norway).

Results

The statistical results obtained are analyzed in the context of the clinical data and the
definitions accepted by the international specialized guidelines.
The Microsoft Excel 2010 programs offers the possibility to obtaining differents graphs
with frequency of the analyzed variables. The following data was obtained.
The incidence of preeclampsia was reduced (2.4%), with 63,84% being healthy nulliparous
women and 23,8% beigh multiparous; 55,38% of cases were from rural areas, with a
maximum frequency in the age group of 31-35 years and 20% of them did not correctly
follow the medical program visits during pregnancy. Less than 10% of cases were
normoponderal, 59,3% of pregnant women were obese, correlated positively with the severity
of the manifestations.

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Compared to AGOG data, the peak PE frequency occurs in obese women, over 35 years,
and does not take parity into account [3].
Only 7% of the studied cases have developed severe maternal complication: 3,1% abrubtio
placenta, 2,3% HELLP syndrome (hemolysis, elevated liver enzymes and low platelet count)
and 1,53% vascular disseminated coagulation (DIC). In addition, 9,23% from cases have had
oligoamnios and placental ischemia. Of all newborns, over 50% had a normal birth weight
and 10.7% had less than 2000 g with a favorable progression. Fetal complications occurred in
a significant percentage of cases: 26,15% cases with IUGR and 3 were declared intrauterine
death.
Comparative, in a 2013 study, 6,9% of PE cases had abruptio placenta, 4,2% HELLP
syndrome, 5,6% DIC and 12,3% renal impairment [9].
Birth occurred via caesarean section for 57,1% of women and vaginal delivery for 40% of
cases. The forceps were applied to 4 parturients. For women with PE, AGOG suggestions for
the mode of delivery recommends the analysis of fetal gestational age, fetal presentation,
cervical status and maternal-fetal condition [3]. The number of days of hospitalization did not
exceed 7 day for mild illness. In 30% of cases hospitalization exceeded 12 days, with a
maximum of 21 days for premature delivery and severe form of the disease.
As for newborns, three of them were declared dead antepartum and one postpartum
immediately. Seven newborns had gestational age under 30 weeks, 8 were under 35 weeks
and 10 under 38 weeks. Of all newborns, 46,15% had a normal birth weight and 10% had less
than 2000 g, with a favorable progression.
The Minitab 18 program can offers relevant correlations and Matrix Covariance, limited to
groups of three variables. So, significant statistical Matrix Correlation have been
demonstrated between proteinuria and diastolic blood pressure values at presentation (Pearson
Correlation = 0,984) or CRP values (P = 0,993), between gestational age and diastolic blood
pressure value at admision (P = 0,902) and after treatment (P = 0,919) – Fig. 1.

Fig. 1. The Minitab 18 graph: Correlation between gestational age, DBP at admision and DBP with treatment

It is a moderate signification between the severity of eclampsia and the prematurity of birth
(P = 0,652) or BMI (P = 0,791).
The multivariate statistic analysis in Unscrable programs shows that variables have the
tendendecy to group in two clusters: first with the degree of parity, the moment of diagnosis,
the severity of edema and the number of days of hospitalization which are related to diastolic
blood pressure (at admision and after treatment), gravity of preeclampsia, postponing birth
and maternal complications – Fig. 2.

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Fig. 2. Dendrogram with clusters of variables similarity

The first subset of variables from the second cluster contains: pregnancy monitoring, CRP
and proteinuria value, which will influence the type of birth and the occurrence of fetal
complications, as well as the evolution of diastolic hypertension in the first 4-6 hours. This
subset is correlated with gestational age, body mass index, pregnant age, hemoglobin value
and hospitalization rates for premature delivery – Fig. 2.
Majority of studies are demonstrate the priority of systolic blood pressure values. In this
study, the most correlation was demonstrated for dyastolic blood pressure values both in
Minitab 18 and Unscrable program.
For 70% of cases the multivariate statistic analysis PCA with two principal components,
unit area normalization and Varimax rotation in Unscramble X program shows a significant
correlation between gestational age below 24 weeks with preeclampsia, frequency of maternal
complications, and duration of hospitalization. Another relevant correlation is between low
gestational age and parity, then with the moment of PE diagnosis – Fig. 3.

Fig. 3. PCA with two principal components, unit area normalization and Varimax rotation in Unscramble X
program

For 19% of cases there is a negative correlation in PE occurrence between advanced


gestational age and maternal age. Pregnancy age between 32 and 36 weeks it’s statistically
correlate with fetal complications frequency, high BMI and premature birth.
In the same statistical program, if analytical variables are considered to be PE severity, the
graphs reveal a significant positive correlation for 50% of cases between the severity of PE
forms and some variables: patient age, prematurity range, CRP and proteinuria values – Fig.
4.
Also, another positive correlation it is observed between PE forms and presence of edema
and the evolution of diastolic blood pressure values.

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For 34% of cases there is a negative correlation between the severity of PE forms and
gestational age, BMI, risk of premature delivery, also risk of fetal complication and parity.

Fig. 4. PCA with two principal components, unit area normalization and Varimax rotation in Unscramble X
program – PE forms

So, the significant variables for patient management in this study are: on the one hand
gestational age, BMI, CRP and proteinuria values at the same time as hypertension
evolutionin the first hours and on the other hand, parity, edema, diagnosis moment and severe
form of PE.

Conclusions

The number of cases of preeclampsia (PE) has increased in recent years due to the accurate
identification of the women who are at increased obstetrical risk. However, PE remains an
important pathology associated with pregnancy, with potentially unfavorable evolutions for
both the mother and the fetus, even at their death. A good communication between patient and
health care provider is the key to recognize the early signs of diagnosis and also the successful
management of preeclampsia.
We believe that in order to make useful management recommendations, the statistical
methods used for data interpretation are very important. If the PE definition criteria are
considered, the treatment focuses on hipertension values as the main contributor factor for the
complications prevention. The multivariate statistical programs can target the most important
correlation of variables and suggests the parameters to make follow up. It is possible that the
correct assessment of the medical management of the desease to be made according to all the
variables, correlated with the severity of the PE forms and of the BP values. The results of the
study are limited by retrospective analysis. Prospective longitudinal studies are needed to
analyze the evolution of pregnancy in women who have risk factors for the occurrence of PE,
also lait-their postpartum evolution.

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Publications/Committee-Opinions/ Committee-on-Obstetric-Practice/Emergent-Therapy-for-Acute-
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6.
7. McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ.(2008). Cardiovascular sequelae of
preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J, 156(5), pp. 918-30.
8. Uzan, J. Carbonnel, M. Piconne, O. Asmar, R. Ayoubi, J.-M. (2011). Pre-eclampsia: pathophysiology,
diagnosis, and management. Vasc Health Risk Manag, 7, pp. 467-74.
9. Minire A, Mirton M, Imri V, Lauren M, Aferdita M.(2013). Maternal complications of preeclampsia.
Med Arch.;67(5), pp. 339-41.

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Romanian Prenatal Care: Certainties and Controversies

POP Daria Maria1, NICULA Renata Lacrimioara1, FLORESCU Fulga1,


TODEA Cezarin1, MOCAN-HOGNOGI Radu Florin1, DICULESCU Doru1,
MIHU Dan1
1“IULIU HATIEGANU” University of Medicine and Pharmacology Cluj-Napoca, 2nd Department of Obstetrics and
Gynaecology, Cluj-Napoca, (ROMANIA)
Email: [email protected]

Abstract

Innovations in the field of genetic screening technologies impose a global update in current
prenatal care protocols. Now more than ever, the foetus is regarded as a distinct patient with
undeniable rights when medical manoeuvers are performed, for diagnostic or therapeutic
purposes.
Non-invasive prenatal testing (NIPT) represents a novelty in detecting chromosomal
anomalies trough free-cell DNA testing from maternal blood which is performed between 10-
20 weeks of gestation. NIPT presents certain advantages (high sensitivity and specificity, non-
invasive) but induces a series of moral, bioethical and legal controversies which must be taken
into consideration. Currently, their popularity among professional societies is increasing but it
is recommended to interpret their results along with genetic counselling in order to help future
parents to make an informed decision. Nevertheless, NIPT cannot substitute prenatal
ultrasound screening which still has a central role in prenatal care.
Our paper focuses on the certainties and controversies of modern prenatal care in
Romanian context, given the particularities of Romanian patients but also the need to align
our current protocols to those of other European countries.
Keywords: foetus, prenatal care, chromosomal aneuploidies

Introduction

Innovations in the field of genetic screening technologies impose a global update in current
prenatal care protocols. Now more than ever, the foetus is regarded as a distinct patient [1]
and parents must be well informed when deciding the future evolution of a pregnancy.
Prenatal care aims to offer patients prenatal genetic diagnosis along with sufficient
information about any test availability, benefits, limitations and risks in order for them to
make what we call an ‘informed decision’ [2], offering parents control over their reproductive
future.
As opposed to other diagnostic procedures, prenatal diagnosis often results in unfavourable
results which conduct to a serious dilemma: accepting a child’s condition or terminating a
pregnancy. Given the importance of their choice, some couples need certainties that exceed
the cut-off of 1 in 200 or 1 in 300 considered as ‘low risk’ in first trimester screening, thus
requiring invasive testing. As medical professionals, we need to make sure we offer enough
information and support during a stressful time during pregnancy, as well as reconsider the
appropriate choices we offer to pregnant women.
Romania is an Eastern European country which joined the EU in 2007. Its current
population reaches 19,594 mil (2018), based on the latest United Nations estimates, with

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60,2% of the population in urban area. Since 2005, the natality in Romania has decreased so
that in 2013, we had the lowest number of live births since 2000: 182 313 [3].
Our paper focuses on the certainties and controversies of modern prenatal care in
Romanian context, given the particularities of Romanian patients but also the need to align
our current protocols to those of other European countries.

Screening and prenatal diagnostic

Habitually, non-invasive screening for trisomy 21 and other aneuploidies in pregnancy


implies analysing placental-derived biochemical markers such as: pregnancy-associated
plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG) combined
with ultrasound evaluation of nuchal translucency thickness (NT). Additionally, there is the
possibility of integrated/sequential screen (first and second trimester screening) along with a
quadruple screen (alpha-fetoprotein, human chorionic gonadotropin, estriol and inhibin A).
These programs now reach a detection rate of up to 88-96% for Down syndrome and up to
85-95% for trisomy 18 [4], depending on whether screening is performed in the first or
second trimester of pregnancy, or both. The positive predictive value in general population
reaches 3,4% [5]. Additionally, the false positive rate (normal pregnancies incorrectly
identified as being at high risk) is 5,4%, thus subjecting more future mothers to invasive
procedures [6] because the screen-positive ‘high-risk’ subgroup will be offered: CVS
(chorionic villi sampling) or amniocentesis (depending on the gestational age) to actually
diagnose the disease in question, only then making prenatal care, diagnostic. Invasive
procedures carry associated risks which, however small, induce psychological stress on future
parents.

Non-invasive prenatal testing

Non-invasive prenatal testing (NIPT) represents a novelty in detecting chromosomal


anomalies trough cell-free foetal DNA (cffDNA) testing from maternal blood. Although,
cffDNA can be detected in maternal serum as early as 5-7 [7] weeks of gestation, NIPT is
usually performed after 10 weeks, when the amount of cffDNA is higher and the results, more
reliable.
Since its introduction to the medical community in 2011 (Hong Kong) [8], NIPT gained a
role in modern prenatal care, but is not currently diagnostic thus is not marketed directly to
patients and should be ordered by a physician. Currently, NIPT is offered in over 60 countries
on six continents, with North America being the leader consumer, followed by Europe [9].
Several studies designed to evaluate the performance of commercial non-invasive tests
reported higher rates in sensitivity (true positive rate) and specificity (true negative rate),
close to 100% for trisomy 21 and 97% for trisomy 18 [10]. Also, the false positive rate is
significantly lower when compared to first trimester screening (0,06% compared to 5,4%)
[11], this being one of the most valuable advantages of NIPT: less positive results translate
into lower rates of invasive procedures. It is also possible for NIPT to determine foetal sex
and paternity, even foetal rhesus D status and thus help rhesus D negative mothers to get
better prenatal care [12, 13].
So far, NIPT shows superior performance over classic first trimester screening, with high
specificity (but not 100%) and predictive positive value (81% in general population, 76-81%
in low-risk population) [11]. Since the performance is not absolute, especially when low-to-
medium risk population is concerned, NIPT still needs confirmation by invasive testing.
Currently, the American Congress of Obstetricians and Gynaecologists (ACOG)
recommend NIPT for pregnancies with increased risk for foetal aneuploidies, such as:

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maternal age over 35, first trimester ultrasound findings suggesting increased risk for foetal
aneuploidies, history of prior pregnancy with aneuploidies, positive results in first trimester
screening for aneuploidies [14].
The International Society of Ultrasound in Obstetrics and Gynaecology (ISUOG) adopted
several guidelines in their Consensus Statement [15]:
• NIPT is not a diagnostic test therefore confirmatory invasive testing is required in the
presence of any abnormal results; NIPT has not been evaluated extensively in low-risk
populations, in which its positive predictive value is lower than in high-risk
populations;
• NIPT may be discussed as an alternative to patients who are not sufficiently reassured
by an ‘intermediate risk’ result;
• In the presence of a foetal structural anomaly detected by ultrasound, further testing
should be considered in spite of a normal NIPT result obtained previously;
• Variations in NIPT performance by different providers should be investigated further.
Since NIPT is becoming more accepted by medical associations and its availability
increases not only for trisomies but also for other genetic syndromes, it becomes natural to
choose non-invasive testing as a first line of prenatal care. However, ultrasound evaluation of
first trimester pregnancies cannot be replaced, more so since clinicians may encounter cases
where NIPT and invasive testing give discordant results [16]. It is becoming clear that we
need to revise the prenatal care protocols heaving in mind the multitude of information
available but also the fact that multiple testing can lead to increased number of positive
results, thus making a decision more difficult.

Romanian prenatal care

Romanian health care system has suffered changes over the past 20 years along with
economic and cultural dynamics of a country in transition from communism to democracy.
Prestigious institutions of higher education along with easy access to information have
produced highly trained specialists, willing to align Romania to any other EU country as far
as medical care is concerned. Unfortunately, there are other factors which tip the scale: the
inevitable changes in the social structure caused demographic alterations such as low birth
rates and demographic ageing [3]. Romania ranks first along with Bulgaria regarding the
number of adolescent pregnancies, with 676 pregnancies in 2015, 9,78% from total number of
births.
Young age at birth combined with low socio-economic status and poor prenatal care often
lead to poor outcomes at birth. This segment of population could benefit from revised prenatal
protocols.
Currently, Romanian prenatal care protocols advise women with risk factors (maternal age
> 35, antecedents of foetal demise, genetic conditions, abnormal ultrasound findings
concerning the foetus and amniotic fluid, intrauterine growth restriction) [17, 18] to undergo
prenatal screening wich is available to them under certain regulations in the public healthcare
system.
NIPT has become available in Romania in the last few years but not through public health
care system and the cost of these investigations is restrictive to low income populations. Also,
access to information about NIPT tend to be limited to urban areas (academic medical
centres), whereas patients with low socio-economic status lack proper prenatal care.

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Conclusions

NIPT has proven its value as an alternative to classical first trimester screening, with high
sensitivity and specificity rates as well as the lowest false positive rate available on the market
(other than invasive testing). As research progresses, NIPT could provide answers for a
variety of detectable conditions, making the decision of testing in such manner very attractive
to future parents. However, this decision carries a spectrum of ethical issues, the most critical
being the entire process of “informed consent” along with appropriate emotional and clinical
support during NIPT. Since NIPT is a non-invasive procedure with compelling results, both
patients and physicians feel there is less pressure into understanding the limitations and
obtaining a written consent as compared to invasive testing [19]. It is imperative that the
results of NIPT testing should be thoroughly revised with a certified prenatal genetic
counsellor [20].
At the moment, NIPT is the best-performing screening test for trisomy 21 [21], but it is not
a diagnostic test. It important to remember that the value of any screening test depends on the
overall value of the screening-diagnosis-intervention program into which the test is
incorporated.
This is why Romanian prenatal care should reconsider its protocols but in an integrated,
specific manner, keeping in mind the rights of the foetus as a patient. Because the foetus’s
approach as a patient is always through the maternal organism, its options as the patient must
each time be seriously considered.

REFERENCES

1. Sen C, Chervenak FA, Simeoni U, Antaklis A, Carbonell-Estranyl X, McCullough L, et al., Istanbul


declaration on ethics in perinatal medicine. (2009) J Perinatal Med. 37:N1-3.
2. Petersen OB, Vogel I, Ekelund C, Hyett J, Tabor A; Danish Fetal Medicine Study Group; Danish
Clinical Genetics Study Group. Potential diagnostic consequences of applying non-invasive pre-natal
testing: population-based study from a country with existing first-trimester screening. Ultrasound
Obstet Gynecol 2014; 43: pp. 265-271.
3. Baetica R. Marriages and births in Romania. Romania between modernism and traditionalism. (2015).
Eurostat Statistics Explained.
http://ec.europa.eu/eurostat/statisticsexplained/index.php?title=Marriages_and_births_in_Romania
4. Cuckle H, Benn P, Wright D. Down syndrome screening in the first and/or second trimester: model
predicted performance using meta-analysis parameters (2005). Semin Perinatol. 29: pp. 252-257.
5. Ekelund CK, Jørgensen FS, Petersen OB, Sundberg K, Tabor A; Danish Fetal Medicine Research
Group. Impact of a new national screening policy for Down’s syndrome in Denmark: population based
cohort study. (2008) BMJ; 337: a2547.
6. Evans MI, Henry GP, Miller WA, Bui TH, Snijders RJ, Wapner RJ, Miny P, Johnson MP, Peakman D,
Johnson A, Nico-laides K, Holzgreve W, Ebrahim SA, Babu R, Jackson L. International, collaborative
assessment of 146,000 prenatal karyotypes: expected limitations if only chromosome-speci c probes and
uorescent in-situ hybridization are used. (1999) Hum Reprod; 14: pp. 1213-1216.
7. Boon EM, Faas BH. Benefits and limitations of whole genome versus targeted approaches for
noninvasive prenatal testing for fetal aneuploidies. Prenat Diagn. 2013;33(6): pp. 563-568.
8. Lau TK, Chan MK, Lo PS, et al., Clinical utility of noninvasive fetal trisomy (NIFTY) test – early
experience. J Matern Fetal Neonatal Med. 2012;25(10): pp. 1856-1859.
9. Daniel WS, Chervenak FA, McCullough LB et al., Ethical dimensions of periviability-A statement of
the World Association of Perinatal Medicine. (2010) J. Perinat. Med. 38: pp. 579-583.
10. Norton M, Brar H, Weiss J, Karimi A, et al., Non-invasive chromosomal evaluation (NICE) study:
results of a multicenter, prospective, cohort study for detection of fetal trisomy 21 and trisomy 18.
(2012) Am J Obstet Gynecol. 207(2):137.e1-8.
11. Norton et al. Non- invasive examination of trisomy (NEXT) using cell free DNA analysis.(2015) N
Engl J Med. 23; 372(17): pp. 1589-97.
12. Goodspeed TA, Allyse M, Sayres LC, Norton ME, Cho MK. Translating cell-free fetal DNA
technology: Structural lessons from non-invasive RhD blood typing. (2013) Trends Biotechnol. 31(1):
pp. 7-9.

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13. Clausen FB. Integration of noninvasive prenatal prediction of fetal blood group into clinical prenatal
care. (2014) Prenat Diagn.34(5):pp. 409-415.
14. The American College of Obstetricians and Gynaecologists Committee on Genetics [homepage on the
Internet]. The Society for Maternal-Fetal Medicine Publications Committee. Committee Opinion
Number 545; 2012. Noninvasive Prenatal Testing for Fetal Aneuploidy. Available from:
http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-
Genetics/Noninvasive-Prenatal-Testing-for- Fetal-Aneuploidy. Accessed July 28, 2014.
15. ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal
ultrasound practice. (2014) Ultrasound Obstet Gynecol. 44: pp. 122-123.
16. Srebniak MI, Diderich KE, Noomen P, Dijkman A, Vries F, Opstal DV. Abnormal NIPT results
concordant with the karyotype of the cytotro-phoblast, but not re ecting the abnormal fetal karyotype.
(2014) Ultrasound Obstet Gynecol.;44(1): pp. 109-111.
17. Programul naţional de sănătate a femeii şi copilului. Prevenirea malformaţiilor congenitale prin
diagnostic pre- şi postnatal
18. http://old.ms.ro/documente/anexa%207%20la%20norme%20mama%20si%20copil_14877_17049.pdf
19. Mărginean C, Mărginean C O, Bănescu C, Meliț L, Tripon F, Iancu M Impact of demographic, genetic
and bioimpedance factors on gestational weight gain and birth weight in a Romanian population.
Medicine 2016, 95:27(e4098), ISSN 0025-7974, online ISSN 1536-5964, I F 2.133
http://dx.doi.org/10.1097/MD.0000000000004098
20. Leeflang MM, Deeks JJ, Gatsonis C, et al., Systematic reviews of diagnostic test accuracy. (2008) Ann
Intern Med; 149: pp. 889-97.
21. Bernhardt BA, Kellom K, Barbarese A, Faucett WA, Wapner RJ. An exploration of genetic counselors’
needs and experiences with prenatal chromosomal microarray testing. J Genet Couns 2014 Feb 27.
22. Verweij EJ, Jacobsson B, van Scheltema PA, et al., European non-invasive trisomy evaluation (EU-
NITE) study: a multicenter prospective cohort study for non-invasive fetal trisomy 21 testing. (2013)
Prenat Diagn; 33: pp. 996-1001.

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Ultrasound Evaluation and Management of Adnexal Masses


During Pregnancy

DICULESCU Doru1, MIHU Dan, FLORESCU Fulga1, CIORTEA Răzvan1,


MĂLUȚAN Andrei1, OANCEA Mihaela1, BUCURI Carmen1, IUHAS Cristian1
1Second Department of Obstetrics and Gynecology, University of Medicine and Pharmacy “Iuliu Hațieganu” Cluj-Napoca,
(ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected], [email protected]

Abstract

Adnexal masses are reported in 4% of all pregnant women. Incidence is higher in the first
trimester of pregnancy due to the use of ultrasound, while with the advancing gestational age,
incidence decreases through spontaneous resolution of many of these masses. The majority of
adnexal masses are of ovarian origin, but paraovarian (paratubal) cysts, hydrosalpinx and
pedunculated subserosal fibroids can also be found. The most frequently encountered benign
ovarian tumors during pregnancy are corpus luteum cysts, mature teratomas and
cystadenomas.
Ovarian cancer during pregnancy is extremely rare, occurring in 1 in 18,000 pregnancies.
Ultrasound is usually sufficient to decide about the management of an adnexal mass during
pregnancy. Serial measurements of the adnexal mass size and documentation of ultrasound
characteristics can influence the expectant management decision, surgical management and
the mode of delivery. The use of MRI is reserved for cases with uncertain ultrasound
diagnosis.
Surgery should be planned between gestational weeks 17-22, in order to minimize the risk
of spontaneous abortion. Surgical intervention in the last trimester of pregnancy is associated
with a 50% risk of premature birth. Adnexal lesions can be approached by laparoscopy or
laparotomy.
Sometimes, elective cesarean section is chosen. In cases treated conservatively by
expectant management, imaging reassessment is recommended at 6-8 weeks postpartum.
Keywords: adnexal masses, ultrasonography, ovarian cysts, pregnancy

Introduction

Adnexal masses are diagnosed during pregnancy on ultrasound scanning or at the time of
cesarean section. Most of these masses are of ovarian origin.

Epidemiology

Adnexal masses are reported in 4% of all pregnant women (1, 2) and according to some
authors, in up to 10% (3, 4).
Incidence is higher in the first trimester of pregnancy due to the use of ultrasound, while
with the advancing gestational age, the incidence of adnexal masses decreases through
spontaneous resolution of many of these. Thus, in the first 5 weeks of pregnancy, adnexal
masses were reported in 8.8% of pregnant women undergoing ultrasound examination (5).

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Similarly, Condous et al., identified ovarian cysts in 6.1% of pregnant women examined
by ultrasound before the 14th week of pregnancy (6).
The incidence of ovarian disease detected at the time of cesarean section is reported to be
0.5% (1). The majority of adnexal masses are of ovarian origin, but paraovarian cysts,
hydrosalpinx and pedunculated subserosal fibroids can also be found. Almost all ovarian
masses diagnosed during pregnancy are benign, while the overall incidence of ovarian cancer
in pregnant women varies between 0.004-0.04% (1, 7). Ovarian cancer occurs in 1 in 18,000
pregnancies (8). A large retrospective analysis showed that 2.1% of adnexal masses during
pregnancy had a malignant potential or were cancers (9).
The most frequently reported malignancy during pregnancy and in the postpartum period
seems to be breast cancer (10).
The incidence of complex or simple but persistent ovarian cysts larger than 6 cm in size is
only 0.07% (11). The majority of complex ovarian cysts are either benign teratomas (mainly
dermoid cysts) or endometriomas. Other pathologies include paraovarian cysts and
cystadenomas. A review of the largest series of patients evidences three types of benign
ovarian tumors that are more frequently found during pregnancy: corpus luteum cysts, mature
teratomas and cystadenomas (12, 13).

Diagnosis and ultrasound evaluation

Diagnosis is based on ultrasound. The aim of ultrasound is to detect and determine the
origin of an adnexal mass, to characterize its morphology. This procedure is usually sufficient
to make decisions about the management of an adnexal mass during pregnancy. The final goal
of the imaging evaluation of adnexal masses is to differentiate cases in which conservative
management with observation is possible from cases that require surgery.
Some ultrasound characteristics may represent diagnostic clues (5, 14, 15, 16). Thus,
follicular cyst is usually less than 3 cm in size, without internal echoes; corpus luteum cyst is
between 3-6 cm in size, with a characteristic color Doppler appearance of circumferential
“ring of fire”; theca lutein cysts are multilocular; cystadenoma is predominantly cystic, but
may have internal papillae; hemorrhagic cysts have internal echoes with sludge;
endometriomas are hypoechogenic cysts, with a homogeneous or trabecular content;
teratomas have multiple echogenicities and cystic components and may have shadowing
calcifications; dermoid cyst is a combination of hyper- and hypoechogenic content, with
shadows; a complex benign adnexal mass has septa, thick content, but no papillae; a
borderline adnexal mass has a smooth capsule, intracystic papillae, no solid parts; a suspect
adnexal mass has solid parts, a capsule or irregular limits, irregular vascularization, ascites.
The presence of internal papillary excrescences increases sensitivity for the diagnosis of
malignancy.
There is no ultrasound system allowing a reliable diagnosis of ovarian malignancy (3, 17).
However, there are many ultrasound characteristics of an adnexal mass that are associated
with an increased risk of malignancy: a size over 5 cm, solid components, a
heterogeneous/complex appearance, excrescences, papillary structures, internal septa,
bilaterality, irregular limits, increased vascularization, low flow resistance and presence of
ascites (3). The combination of these aspects increases sensitivity in predicting malignancy.
An adnexal mass size, as an instrument for benign-malignant differentiation during
pregnancy, of less than 5 cm was not associated with malignancy (3, 18, 19). Ultrasound is
used as an adjuvant in the diagnosis of ovarian torsion, evidencing an enlarged, edematous,
solid or cystic ovary, with interrupted arterial and/or venous blood flow to the ovary on
Doppler ultrasound. Ovarian torsion is a clinical diagnosis, and ultrasound should be used
only to provide additional information supporting diagnosis. This point of view is illustrated

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by the findings of a study in which 19% of patients with ovarian torsion had normal
preoperative Doppler flow to the affected adnexa (20).
Malignant masses are more vascularized compared to benign lesions, which have reduced
or no blood flow. In potentially malignant or malignant tumors, flow resistance is low, but
this is also true for many benign conditions such as endometriomas, corpus luteum cysts and
other complex benign ovarian masses. Due to increased pelvic blood supply during
pregnancy, the degree of overlap of these (pulsatility and resistance) indices in benign and
malignant lesions makes Doppler imaging unreliable in this situation (21). In a prospective
study by Wheeler and Fleischer, the overlap of blood flow patterns in benign and malignant
tumors was such that the false positive rate was close to 48%, which led to an incorrect
assignment of malignant potential to benign tumors (21). Another analysis in this area
concluded that Doppler ultrasound was not useful for diagnosis compared to the use of
ultrasound morphology alone (22).

Other diagnostic modalities

MRI without contrast can be safely used to evaluate adnexal masses during pregnancy (5).
MRI has a better diagnostic value than ultrasound for degenerative pedunculated uterine
leiomyomas, paraovarian cysts, endometriotic cysts and dermoid cysts. MRI can be
particularly useful in evaluating a potentially malignant ovarian mass due to its ability to
identify vegetations in cystic tumors and necrosis in solid tumors. MRI can also be useful in
the diagnosis of conditions mimicking the torsion or rupture of an ovarian tumor, such as
appendicitis and inflammatory bowel disease (1, 29). However, MRI is more expensive and
more time-consuming compared to ultrasound. Currently, the use of MRI during pregnancy is
reserved for cases in which ultrasound diagnosis is uncertain.
Serum tumor markers, such as CA125, AFP, beta-HCG, serum inhibin, and even LDH,
have limited diagnostic utility during pregnancy. These tumor markers are physiologically
secreted during fetal development by the placenta, decidual cells, and can also be associated
with fetal aberrations (1, 3, 5, 30).

Complications of ovarian tumors during pregnancy

The complications are the same as for ovarian tumors outside pregnancy: torsion, rupture,
hemorrhage, infection. Specific to pregnancy is the risk of dystocia at birth, which occurs
when large adnexal masses are interposed between the fetal presentation and the birth canal
(2-17%) (5, 14, 15).
During pregnancy, the progressive enlargement of the uterus, which displaces the ovaries
out of the pelvis, increases the risk of torsion, particularly at the beginning of the second
trimester of pregnancy. The risk also increases during postpartum uterine involution. The rate
of torsion in published series varies from 1 to 12% (5). Rupture, bleeding and infection seem
to be less frequent, representing less than 1% (5). It has been estimated that an adnexal mass
6-10 cm in size has a 3 times higher risk of torsion than outside this range (23) or a 60% risk
at 10-17 weeks, with the highest frequency at 15-16 weeks of gestation (24).

Management of adnexal masses during pregnancy

The majority of adnexal masses during pregnancy are benign, an overwhelming proportion
(80-90%) will resolve spontaneously, and most pregnant women seem to be asymptomatic (1,
3, 5, 14, 15). Thus, an adequate management option is ultrasound monitoring in each trimester
of pregnancy.

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Simple cysts, less than 5-6 cm in diameter, diagnosed before 16 weeks of gestation, do not
require additional evaluation and will resolve spontaneously during pregnancy (1, 14, 15).
However, cysts with a complex appearance require additional evaluation regardless of their
size. A multivariate analysis found that the best predictors of persistence were a complex
appearance and a size larger than 5 cm (25).
In patients who deliver by cesarean section, the adnexa should be evaluated at the time of
surgery, and planning of the delivery by cesarean section should be reserved for suspect
complex masses or tumors that can prevent vaginal delivery (14, 15). With patients who
deliver vaginally, imaging should be assessed at 6-8 weeks postpartum.
Patients who have ultrasound findings with very high suspicion of malignancy or those
who develop significant symptoms should be subjected to surgical resection (3). Also, serial
measurements of the size of an adnexal mass can influence the expectant versus surgical
management decision (14, 15).
Surgery, if performed, has the lowest fetal morbidity between 17-22 weeks (14, 15, 26).
There is evidence supporting a negative pregnancy outcome in patients undergoing surgery
in the first trimester or after 24 weeks of gestation (3). Hess et al., reported that patients who
underwent emergency surgical interventions for torsion, rupture or hemorrhage had a higher
incidence of abortion and premature birth compared to women who underwent elective
laparotomy (27).
Abortion rates ranged between 0-4.7%, and premature births accounted for 12% (3).
Laparotomy in the third trimester of pregnancy was associated with a 50% risk of
premature birth (5).
The standard surgical approach is, according to some authors, laparotomy not laparoscopy,
especially to avoid uterine lesions in the second trimester (1). However, the disadvantages of
laparotomy include, among others, a limitation of the patients’ mobility, which increases the
risk of postoperative thromboembolism in a patient population with an already high risk (3).
Patients who require surgery during the first trimester, particularly before 10-12 weeks,
should be supplemented with progesterone in order to support pregnancy in case of
intraoperative damage to the corpus luteum (3, 5). Patients undergoing surgery between 24-34
weeks should receive prophylactic steroids for the improvement of lung maturation, given the
increased risk of premature labor. Tocolysis will also be considered for prevention of
premature birth after the 24th week of pregnancy. Persistent, simple unilocular cysts, without
solid components, with a size larger than 10 cm can be aspirated transvaginally or
transabdominally, under ultrasound guidance, using a fine needle (28). This procedure is only
indicated if the cyst induces pain or is likely to cause fetal malpresentation or obstruction
during labor. Aspiration should be performed after 14 weeks of pregnancy in order to
minimize damage to the corpus luteum (1).
In patients with ovarian cancer, chemotherapy should be avoided in the first trimester
because of teratogenic effects or pregnancy termination will be considered, but chemotherapy
is used in the second and third trimesters, as cancer evolution is more worrying than fetal
impairment. This last aspect also relies on the absence of adverse fetal effects reported in
limited clinical studies.
Cisplatin is preferred to carboplatin during pregnancy, due to a low incidence of
thrombocytopenia and to a lower transplacental transfer (3).

Conclusions

The use of ultrasound has led to an increase in the incidence of adnexal pathology
diagnosed during pregnancy. Ultrasound is usually sufficient to make decisions about the
management of an adnexal mass.

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The majority of these adnexal masses are benign ovarian cysts and will resolve
spontaneously, without surgery. Ovarian cancer is extremely rare in pregnant women.
The use of MRI during pregnancy is reserved for cases in which ultrasound diagnosis is
uncertain.
If there are no suspicions of malignancy or significant complications such as torsion,
surgery is not indicated. Planning of surgery is recommended at 17-22 weeks to minimize the
risk of abortion. Adnexal lesions can be approached by laparoscopy or laparotomy, depending
on the operator’s experience and the patient’s preference.
The treatment of a persistent, complex, large ovarian tumor can be the reason for elective
cesarean section. Thus, imaging reassessment is indicated at 6-8 weeks postpartum.

REFERENCES

1. Spencer CP, Robarts PJ. Management of adnexal masses in pregnancy. The Obstetrician &
Gynaecologist 2006; 8: pp. 14-19.
2. Hill LM, Connors-Beatty DJ, Nowak A, Tush B. The role of ultrasonography in the detection and
management of adnexal masses during the second and third trimesters of pregnancy. Am J Obstet
Gynecol 1998;179: pp. 703-7.
3. Alpa M Nick, Kathleen Schmeler. Adnexal Masses in Pregnancy. Perinatology 2010; 2: pp. 13-21.
4. Schwartz, N., I.E. Timor-Tritsch, E. Wang, Adnexal masses in pregnancy. Clin Obstet Gynecol, 2009.
52(4): pp. 570-85.
5. Creasy RK, Resnik R, Iams JD. Maternal-Fetal Medicine: Principles and Practice 2013; pp. 1161-1166.
6. Condous G, Khalid A, Okaro E, et al.: Should we be examining the ovaries in pregnancy? prevalence
and natural history of adnexal pathology detected at first-trimester sonography. Ultrasound Obstet
Gynecol.2004. 24: pp. 62-66.
7. Sherard GB 3rd, Hodson CA, Williams HJ, Semer DA, Hadi HA, Tait DL. Adnexal masses and
pregnancy: a 12-year experience. Am J Obstet Gynecol 2003; 189: pp. 358-63.
8. Malhotra N, Puri R, Malhotra J, Kurjak A, Chervenak FA. Donald School Manual of Practical
Problems in Obstetrics. Jaypee Brothers Medical Pub; 1 edition (May 30, 2012), p. 225.
9. Leiserowitz, G.S., et al., Adnexal masses in pregnancy: how often are they malignant? Gynecol Oncol,
2006. 101(2): pp. 315-21.
10. Smith LH, Dalrymple JL, Leiserowitz GS, Danielsen B, Gilbert WM. Obstetrical deliveries associated
with maternal malignancy in California, 1992 through 1997. Am J Obstet Gynecol 2001;184: pp. 1504-
13.
11. Platek DN, Henderson CE, Goldberg GL. The management of a persistent adnexal mass in pregnancy.
Am J Obstet Gynecol 1995;173: pp. 1236-40.
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surgical management. Am J Obstet Gynecol. 181: pp. 19-241999.
13. Schmeler KM, Mayo-Smith WW, Piepert JF, et al.: Adnexal mass es in pregnancy: surgery compared
with observation. Obstet Gynecol. 105(Pt 1): pp. 1098-1103, 2005.
14. Hoover K, Jenkins TR: Evaluation and management of adnexal mass in pregnancy. Am J Obstet
Gynecol. 205 (2): pp. 97-102, 2011.
15. Yacobozzi M, Nguyen D, Rakita D: Adnexal mass es in pregnancy. Semin Ultrasound CT MR. 33(1):
pp. 55-64, 2012.
16. Zanetta G, Mariani E, Lissoni A, et al.: A prospective study of the role of ultrasound in the management
of adnexal mass es in pregnancy. BJOG.110: pp. 578-583, 2003.
17. Tailor, A., et al., Sonographic prediction of malignancy in adnexal masses using multivariate logistic
regression analysis. Ultrasound Obstet Gynecol, 1997. 10(1): pp. 41-7.
18. Schmeler, K.M., et al., Adnexal masses in pregnancy: surgery compared with observation. Obstet
Gynecol, 2005. 105(5 Pt 1): pp. 1098-103.
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J Obstet Gynecol. 189: pp. 358-363, 2003.
20. Chiou, S.Y., et al., Adnexal torsion: new clinical and imaging observations by sonography, computed
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21: pp. 194-199, 2003.

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23. Koo YJ, Kim TJ, Lee JE, et al.: Risk of torsion and malignancy by adnexal mass size in pregnant
women. Acta Obstet Gynecol Scand. 90: pp. 358-361, 2011.
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93(4): pp. 585-9
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undergoing surgical management. Am J Obstet Gynecol, 1999. 181(1): pp. 19-24.
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30. Bon GG, Kenemans P, Verstraeten AA, Go S, Philipi PA, van Kamp GJ, et al., Maternal serum Ca125
and Ca15-3 antigen levels in normal and pathological pregnancy. Fetal Diagn Ther 2001; 16: pp. 166-
72.

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Congenitally Corrected Transposition of the Great Vessels – Case


Presentation

DICULESCU Doru1, POIENAR Alexandra Andreea2, BALTOAICA Razvan2,


PORUMB Ciprian Gheorghe1, BLAGA Ligia1, MIHU Dan1
1Universitatea de Medicina si farmacie Iuliu Hatieganu, Cluj-Napoca, (ROMANIA)
2Spitalul Clinic Judetean, Cluj-Napoca, Romania, Clinica Dominic Stanca (ROMANIA)
Emails: [email protected], [email protected]

Abstract

Introduction
Congenital heart defects represent the most common severe malformation. Congenitally
corrected transposition of the great vessels is one of the rarest congenital cardiac defects. The
diagnosis can be difficult to assess.

Methodology
We evaluated a twenty two year old patient who was referred to us for anomaly scan of a
21 weeks and 5 days pregnancy. The patient had an amniocentesis performed in another
hospital and the results were pending at the moment of our evaluation.

Our scan finds


discordance of atrio-ventricular junction (left atrium connected with right morphological
ventricle; right atrium connected with left morphological ventricle); inversed setting of the
atrio-ventricular valves; ventriculo-arterial discordance (right morphological ventricle
connected with the aorta; left morphological ventricle connected with the pulmonary artery;
the two great vessels are parallel and the aorta is situated anterior and to the left of the
pulmonary artery).

Conclusion
We raise the suspicion of congenitally corrected transposition of the great vessels and
referred the patient for an echocardiography in a specialised centre, which will confirm our
diagnosis.
Keywords: ventricular morphology, fetal scan, congenitally corrected transposition of the great vessels

Introduction

Congenital heart defects are the most common congenital malformation. Half of these
cases are minor and may be surgically corrected with ease, while the rest represent the major
congenital anomalie responsible for neo-natal or infantile death [1].
The congenitally corrected transposition of the great vessel (ccTGV) can be with atrio-
ventricular concordance or without atrio-ventricular concordance [2]. ccTGV is a rare
pathology, representing less than 1% of the total of congenital heart defects [3] and it’s
incidence is 0.02 per 1000 live births [4].
Anatomically, ccTGV is characterised by a normal systemic venous drainage and normally
positioned atrial cavities. The two atriums are connected with inversed ventricles: right atrium

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connected with left morphological ventricle and left atrium connected with right
morphological ventricle, thus defining the atrio-ventricular discordance. The ventricles are
connected with opposite arteries: right morphological ventricle connected with the aorta and
left morphology ventricle connected with the pulmonary artery, thus defining the the
ventriculo-arterial discordance. In a normal situs setting, the aorta goes anterior and to the left
of the pulmonary artery. This position allows a normal blood flow. The right ventricle and the
tricuspid valve are responsible for the systemic circulation [5].
ccTGV can be associated with other intracardiac lesions: ventricular septal defect,
pulmonary stenosis, Ebstein anomaly, complete atrio-ventricular block. In case of association
of any of these anomalies with the ccTGV, surgical correction or placing of a pace maker may
be needed immediately after birth [2], [6].
The main complications are due to the fact that the right ventricle is responsible for the
systemic circulation. It can develop right ventricle insufficiency and regurgitation through the
tricuspid valve. This situation is aggravated with age [5].
Prenatal diagnosis of ccTGV is a great ultrasound challenge. This anomaly can be
overlooked at the routine second trimester scan due to the difficult visualisation of the
ventriculo-arterial discordance and of the parallel disposition of these vessels [7].
Foetal development and foetal growth is rarely influenced by this pathology. The majority
of the pregnancies with a foetus with ccTGV have a physiologic evolution and s neo-natal
survival rate of 82% [8].
The association with other extra cardiac malformations or chromosomal anomalies is
exceptional [2].

Methodology

Maternal data
Twenty-two year old patient, gesta 1, para 0, caucasian, with no significant medical or
obstetrical history. The patient is 168 cm tall and 62 kg at the moment of the evaluation. The
pregnancy was obtaines spontaneously and the patient was administered Folic acid, 40
micrograms per day until the 12th week of gestation.

First trimester screening


Showed a 60mm embryo (pregnancy dating at 12 weeks and 4 days); nuchal fold 2.2mm,
foetal heart rate 140 bpm. BetaHCG level was 0.44 MoM; PAPP-A level was 0.88 MoM.
Combined risk was calculated at 1/14000 for Trisomy 21 and 1/100000 for Trisomy 13 and
18.

Second trimester scan


Was conducted at 21 weeks and 5 days: biparietal diameter (DBP) 52.3mm; head
circumference (HC) 190.2mm (56th percentile); abdominal circumference (AC) 167mm (64th
percentile); femoral length (FL) 38mm (80th percentile); estimated foetal weight (EFW) 469g.
The placenta is anterior. The amniotic fluid is normal, with the deepest vertical pouch
(DVP) of 51mm. Umbilical cord with 3 vessels. Active foetal movements.
The foetal anatomy is normal, except for the cardio-vascular system. Foetal sex: male.
The Doppler studies show: right uterine artery: PI 1.23, Vmax 80 cm/s, no notch; left
uterine artery: PI 1.02, Vmax 105 cm/s, no notch (within normal ranges; low risk of
preeclampsia or foetal growth restriction).
Transvaginal ultrasound: cervix length 33mm; no vasa praevia; distance between the
inferior border of the placenta and the internal os is 40mm.

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Foetal echocardiography
Normal situs solitus, with the stomach position to the left (Fig. 1); cardio-thoracic index is
0.5; cardiac apex oriented to the left at a 45° angle.
Normal venous systemic drainage (Fig. 2) and normal pulmonary venous drainage.
Foramen ovale present in the mid third of the interatrial septum, with the valve present in the
left atrium. Normal blood flow, from the right to the left.
Visible atrio-ventricular discordance: left atrium connected with right morphological
ventricle and right atrium connected with left morphological ventricle. Patent atrio-ventricular
valves with inversed offsetting (Fig. 3). No visualisation of atrio-ventricular regurgitation (at
color flow mapping and pulse wave Doppler). Complete ventricular septum. Normal
biventricular kinetics.
Visible discordance of ventricular-arterial connection: right morphological ventricle
connected with the aorta ad left morphological ventricle connected with the pulmonary artery.
The two arteries are parallel, with the aorta being oriented anterior and to the left of the
pulmonary artery. This disposition modifies the 3 vessels view (Fig. 4 and Fig. 5), and give
the impression of a false V-sign.
Normal looking arterial valves; blood flow without aliasing, without arterial regurgitation.
Normal trifurcation of the pulmonary artery in left pulmonary artery, right pulmonary
artery and ductus venosus, without aliasing. Aortic arch to the left of the trachea. Normal
looking right subclavial artery (Fig. 6).
Normal foetal heart rate (145 beats per minute), without pericardial effusion.

Cardiac biometry (within normal range)


Aortic diameter, measured al valve level, in diastole in 3.5mm (73rd percentile). Pulmonary
artery diameter is 4mm (61st percentile). Right pulmonary artery is 2.8mm; left pulmonary
artery is 2.9mm (Fig. 7). Aortic arch is 2.6mm (52nd percentile). Arterial duct is 2.8mm (69th
percentile).

Doppler studies (within normal range)


The pulmonary veins show normal pattern (Fig. 8). Ductus venosus with positive a wave,
PIV 0.878. The systemic veins have normal pattern. Mitral valve E/A 0.6; Tricuspidian valve
E/A 0.6 (Fig. 9); Velocity of the aorta is 67.8cm/s; velocity of the pulmonary artery is
69.2cm/s; PI of the mid cerebral artery is 2.04; PSV 30.8cm/s. Atrio-ventricular interval is
100ms.
We rise the suspicion of congenitally corrected Transposition of the great vessels and we
refer the patient for counselling in a specialised centre.

Additional investigations
Amniocentesis was performed: the chromosomal analysis identified a normal male foetal
karyotype, without numeric or structural modifications.

Management
The patient was referred to a foetal cardiology department where she received counselling
regarding the cardiac defect and the possibility to perform neo-natal corrective surgery.
Foetal growth and amniotic fluid were periodically evaluated.

Outcome
A c-section was scheduled at 38 weeks and 5 days and the patient gave birth to a baby boy,
2950g, APGAR 10.

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A neo-natal echocardiography was performed which confirmed the diagnosis. The


ultrasound also found minor tricuspid insufficiency, patent foramen ovale, and small
persistent arterial duct.
Corrective surgery was not necessary. The follow-up included ultrasound every 3 months
for the first year of life, in a specialised centre.

Discusions

The congenitally corrected transposition of the great vessels is a rare pathology, difficult to
diagnose prenatally [9].
The diagnosis is usually made in the second trimester. The mean gestational age at the
moment of diagnosis is 25.5 weeks [4].
The natural evolution of isolated ccTGV may be asymptomatic due to the corrected
hemodynamic [7]. Three elements have an impact over the evolution: right ventricle function,
tricuspid function and development of arrhythmias. Without surgical correction, the right
ventricle must develop enough pressure for the systemic circulation but it’s anatomy does not
allow this, thus it may develop right ventricle insufficiency. The consequence is tricuspid
regurgitation. The association of these two conditions leads to right heart insufficiency [10],
[11].

Conclusions

Pre-partum diagnosis of congenial heart defects is important for establishing the


surveillance of the pregnancy. Also, this allows to better inform the parents of the neo-natal
evolution and possible complications of the defect.

Fig. 1. normal, situs solitus (stomach and heart Fig. 2. normal venous systemic drainage
ex oriented to the left) (the two cava veins enter the right ventricle)

Fig. 3. atrio-ventricular discordance and Fig. 4. aorta anterior and to the left of the
inversed offsetting of the atri-ventricular valves pulmonary artery

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Fig. 5. parallel aorta and pulmonary artery Fig. 6. normal right subclavial artery, in front
of the trachea

Fig. 7. normal pulmonary arteries Fig. 8. normal pattern of the pulmonary veins

Fig 9. normal E/A fraction of tricuspid valve

REFERENCES

1. Abuhamad A. Chaoui R. (2010). A Practical Guide to Fetal Echocardiography. NORMAL AND


ABNORMAL HEARTS. Lippincott Williams & Wilkins.
2. Allan L. Cook A. Huggon I. (2009). Fetal Echocardiography. A Practical Guide. Cambridge University
Pres.s.
3. Kasar T. et al., (2018). Rhythm disturbance and treatment strategies in children with congenitally
corrected transposition of the great arteries. Congenital Heart Disease.
4. Palladini A. et al., (2006). Diagnosis, characterisation and outcome of congenitally corrected
transposition of the great arteries in the fetus: a multicentre series of 30 cases. Ultrasound Obstet
Gynecol 27, pp. 281-285.
5. Huhta J. (2011). The Natural History of Congenitally Corrected Transposition of the Great Arteries.
World Journal for Pediatric and Congenital Heart Surgery 2, pp. 59-63.
6. Van Praagh R. et al., (1998). Pathologic anatomy of corrected transposition of the great arteries:
medical and surgical implications. Am Heart J 135, pp. 772-285.
7. Zhang Y. (2011). Prenatal diagnosis of fetal congenitally corrected transposition of the great arteries.
PRENATAL DIAGNOSIS 31, pp. 529-535.

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8. Sharland G. (2005). Atrioventricular and ventriculoatrial discordance (congenitally corrected


transposition of the great arteries): echocardiographic features, association and outcome in 34 fetuses.
Heart 91, pp. 1453-1458.
9. Zhang Y. et al., (2005). Prenatal diagnosis of fetal congenitally corrected transposition of the great
arteries. Fetal Diagn Ther 20, pp. 9-16.
10. Kutty S. et al., (2018). Contemporary management and outcomes in congenitally corrected
transposition of the great arteries. Heart, pp. 1-8.
11. Lenoir M. et al., (2018). Outcomes of the anatomical repair in patients with congenitally corrected
transposition of the great arteries: lesson learned in a high-volume centre. European Journal of Cardio-
Thoracid Surgery 0, pp. 1-7.

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Preoperative Risk Assessment of Malignancy in Ovarian Tumors


and Correlation with Histopathological Outcome

DIJMARESCU Lorena1, VRABIE Sidonia1, MANOLEA Magdalena1,


NOVAC Marius2, ILIESCU Dominic1, TUDORACHE Stefania1, CAMEN Ioana1
1Department of Obstetrics & Gynecology, University of Medicine and Pharmacy Craiova, (ROMANIA)
2Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy Craiova, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected]

Abstract

Introduction
Estimating the risk of malignancy and establishing the management of ovarian tumors is a
constant challenge of modern medicine since although the incidence of appearance tumors
diagnosed with ultrasound is high, the prevalence of ovarian cancer is low.

Material and methods


The study included 45 women evaluated for adnexal tumors. The surgical decision was
taken through a diagnostic algorithm that included clinical and risk factors, 2D, 3D and
Doppler ultrasound evaluation, and the study of serum markers. The histopathological
evaluation of the parts made it possible to establish the accuracy of the preoperative diagnosis.

Results
The diagnostic algorithm classified 31 cases as having an increased risk of malignancy, 5
endometriomas and 9 persistent menopausal cysts. Following the histopathological evaluation
of the surgical parts, the diagnosis of ovarian neoplasm was established in 19 cases distributed
as follows: of the 31 suspected cases only at 15 confirmed malignancy, neoplasia being over
diagnosed in 16 cases. Of the 9 cases of persistent menopausal cysts with benignity
parameters, 4 cases proved to be malignant, in which case neoplasia was clinically
underestimated. Cases of ovarian endometrioma were confirmed histopathologically.

Conclusions
When deciding on the type of surgery for an ovarian cancer patient, estimating the risk of
malignancy is essential. Benign tumors can be managed conservatively or laparoscopically,
avoiding unnecessary costs and morbidity. Preoperative risk assessment of malignancy in
ovarian tumors has become an important issue in gynecology, the concern that a tumor in an
older woman may be an early cancer, makes many women with small tumors subject to
unnecessary surgery, despite the fact that the vast majority of these tumors are considered to
be benign.
Keywords: ovarian cancer, ultrasound, serum markers

Introduction

While the occurrence of tumors in the adnexal region is very common (up to 20%), the
prevalence of ovarian cancer is low (approximately 0.2-0.3% in postmenopausal women. [1]

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To detect a woman with ovarian cancer using screening methods, about 5 women would
recommend surgery, so 1 in 5 women will have a declared ovarian cancer.
The optimization of diagnostic performance by transvaginal ultrasound has been attempted
by creating various approaches to characterizing ovarian tumors: recognition models, simple
scoring systems, statistical derivation systems, probability predictors based on logistic
regression analysis and complex mathematical models. [7] Ultrasound characteristics must be
correlated with the clinical history, as well as clinical signs and symptoms. [8] It is clear that,
with the increased rate of use of ultrasound, adnexal tumors are more and more often found by
chance when an ultrasound for another pathology is performed. (2)

Methods of Early Detection of Ovarian Cancer

Bourne and Fickler indicated the combination of advanced ultrasound with serum CA-125,
thus significantly detecting both ovarian cancer and ovarian cancer mortality. [4, 5]
In 2003, a new serum biomarker, HE4, was proposed as a first or second line test for
ovarian epithelial cancers [6].
HE4 in the literature was evaluated as a more specific marker than the CA-125 alone and
very helpful in combination with CA-125 for malignancy prediction risk - ROMA score.
The IOTA-International Tumor Ovarian Analysis Group has developed and validated two
ultrasound-based logistic regression models (LR1 and LR2) that estimate the risk of
malignancy in adnexal tumors. (Table.1)
In clinical practice, the detected annexed masses can be classified according to the “simple
rules” of International Tumor Ovarian Analysis (IOTA). IOTA is based on the identification
of simple features during conventional ultrasound examination and has a high sensitivity.
However, the rate of false positive results is high. Approximately 40-50% of women with
malignant and inconclusive IOTA results have benign ovarian tumors. [5, 7, 8]

B-rules M-rules
B1-Unilocular cyst M1-Unregular solid tumors
B2-Presence of solid components M2-Ascitis
with the largest solid component <7 mm

B3-Presence of acoustic shadow M3-At least 4 papillary structures

B4Multilocular smooth tube with the M4-Large multilocular solid tumors with the largest
largest diameter <100mm diameter ≥100mm
B5-avascular M5- Severe vasculature
Table. 1

If one or more M-rules are applied in the absence of a B-rule, the tumor is classified as
malignant.
If one or more B-rules are applied in the absence of a M-rule, the tumor is classified as
benign.
If both M-rules and B-rules apply, the tumor cannot be classified. If no rules apply, the
tumor cannot be classified.

Methods

The study included 45 women evaluated for anaplastic tumors in the Filantropia Clinical
Hospital of Craiova. The decision of the surgery was taken through a diagnostic algorithm

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that included the clinical study and risk factors, first the 2D, 3D and Doppler ultrasound
evaluation and then the serum marker study.
Following correlation with histopathological results obtained on IOTA surgical exercise,
we obtained an over-assessment rate of 65% (tumors that proved to be benign), 0.2%
underestimation (tumors that were found to be malignant) and a correct diagnosis of 33.8%.
(Table. 2)

IOTA Malign Benign Total


Nr/% Nr/% Nr/%
31/68.8 14/92.85 45/33.8
19/61.29 1/0,2 45/65.58

Table. 2

We then analyzed the data obtained by applying the pre and post menopause ROMA
algorithm so that it gives us the best sensitivity, using as a limit level the value of 12.5 for the
premenopausal ROMA and the value of 14.4 for the postmenopausal ROMA.
A diagnostic over-assessment rate was obtained – 62.32%, diagnosis underestimation –
0.30% and a correct diagnosis – 37.38%.
ROME is a simple score that shows excellent diagnostic performance for EOC
postmenopausal, and less premenopausal.
By using additional corroborated investigations, IOTA and ROMA algorithm, an
improvement in the correct diagnostic rate of 37.38% was obtained compared to 33.38%.
Also, an overvaluation rate, 63.5, versus 65%. The results of this study show that the
correct pre-operative diagnosis of ovarian tumors is difficult, not correlating with
histopathological results.
It was not possible to establish reproductive ultrasound characteristics of these tumors, so
the recommendation of the histopathological examination for a suspected ovarian tumor mass
remains valid.

Case 1. 61-year-old patient, ROMA=87, RMI score -1011.2; IOTA-M, the result of the
histopathological-cystadenoma mucinous joint test; surgery was put at high risk: diagnosis
overage. Fig. 1, Fig. 2.

Fig. 1. Complex adnexal tumor with intracystic vegetations

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Fig. 2. Severe high-grade carcinoma, papillary pattern with numerous mitoses

Case 2. Patient 44 years old, ROMA=108.9, RMI score -400.72, IOTA-M,


histopathological examination – haemorrhagic luteal cyst, well differentiated ADK, mixed
Branner tumour, diagnosis correct. High value may be related to endometrial pathology. Fig.
3.

Fig. 3. Transvaginal ultrasound image of the left ovary shows a complex ovarian cystic mass with mildly
echogenic contents

Conclusions

All these features suggest that with the appreciation of common features associated with
appropriate pathologies, ultrasounds should be able to reliably diagnose and differentiate
certain specific types of ovarian pathology.

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Concern that a tumor in an older woman may be an early cancer, makes many women with
small tumors subject to unnecessary surgery with clear morbidity despite the fact that the vast
majority of these tumors are considered to be benign.
Preoperative risk assessment of malignancy in ovarian tumors has become an important
problem in gynecology due to widespread use of laparoscopy in gynecological surgery.
Studies have not shown that using a biochemical model or marker for ovarian malignancies
would be superior to ultrasound subjective assessment and Doppler findings by an
experienced ultrasound.

REFERENCES

1. Reade CJ, et al., (2013) Risks and benefits of screening asymptomatic women for ovarian cancer: a
systematic review and meta-analysis. Gynecol Oncol, 130: pp. 674-81.
2. Patel MD, et al., (2013) Managing incidental findings on abdominal and pelvic CT and MRI, part I
white paper. J Am Coll Radiol, 10(9): pp. 675-81.
3. Finkler NJ, et al., (1998) Comparison of serum CA 125: clinical impression, and ultrasound in the
preoperative evaluation of ovarian masses. Obstet Gynecol 1988; 72(4); pp. 659-64.
4. Bourne TH, et al., (1993) Screening for early familial ovarian cancer with transvaginal ultrasonography
and colour blood flow imaging. BMJ 06(6884): pp. 1025-9.
5. 5.Timmerman D, et al., (2010) Simple ultrasound rules to distinguish between benign and malignant
adnexal masses before surgery: prospective validation by IOTA group. BMJ. 341:c6839.
6. Glimelius, B. & Lahn, M. (2011) Window-of-opportunity trials to evaluate clinical activity of new
molecular entities in oncology. Ann. Oncol. 22, pp. 1717-1725.
7. Tudorache Stefania (2017) Ovarian Tumors – Pattern Recognition and Limits of the
Method.Descriptive Review. Conference Proceedings Filodiritto International Proceedings, 5 th
Congress of The Romanian Society of Ultrasound in Obstetrics and Gynecology, First Ed Published
June 2017, pp. 617-622, ISBN 978-88-95922-88-1.
8. Liliana Novac, Mihaela Niculescu, Cristina Simionescu, M.R.Stanescu, M. Novac, Bilateral struma
ovarii – a case mimicking an ovarian neoplasm, Eur.J.Gynaec.Oncol., vol. XXIX, number 4, pp. 414-
416, 2008, ISSN 0392-2936.

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Ultrasound Manifestations in Gestational Diabetes

DRAGOI Vlad2, CERCEL Roxana2, LEPADAT Cosmin2,


HORHOIANU Irina Adriana1,2, NEDELCU Silvia2, ICHIM Mircea2,
MUNTEANU Diana2, EDDAN-VISAN Lucica2, GRIGORIU Corina1,2
1Medical University Carol Davila Bucharest, Obstetrics & Gynecology Department (ROMANIA)
2Bucharest Emergency University Hospital (ROMANIA)
Emails: [email protected], [email protected]

Abstract

Introduction
Gestational diabetes (GDM) has always been one of the most intricate pathologies
encountered in pregnancy. Whether we are discussing about monitoring the patient and the
fetus’ outcomes, delivery and treatment options, ultrasound findings, GDM has raised a lot of
concerns over the years.

Material and methods


Our objective is to highlight the main manifestations of this pathology that affect both the
mother (obesity, risk of preeclampsia/eclampsia) and the fetus (IUGR because of placental
deterioration, dysfuction or failure – by monitoring Doppler umbilical and uterine velocimetry
values, polyhydramnios – by measuring amniotic liquid levels, macrosomia because of
maternal hyperglycemia and fetal hyperinsulinemia – by assessing fetal biometric parameters,
shoulder dystocia).
A meticulous ultrasound examination is required in order to prevent sudden complications
that may arise at various gestational ages. A statistical study was carried out in our clinic
(Obstetrics – Gynecology of the Emergency University Hospital Bucharest) on a population
of 40 patients diagnosed with GDM between October 2016 and January 2018. A series of
ultrasound parameters have been analyzed in regard with pregnancies which develop without
complications and the way they influence treatment protocol in these particular cases:
amniotic liquid levels, fetal biometry, fetal annexes, Doppler velocimetry, as well as certain
findings in association with other pathologies: pregnancy induced hypertension or
preeclampsia/eclampsia.

Conclusions
A thorough ultrasound examination and follow-up are essential in order to establish an
adequate therapeutic conduct in order to prevent the complications that might arise during the
pregnancy, as well as before and after the delivery.
Keywords: gestational diabetes, ultrasound, preeclampsia, polyhydramnios, macrosomia, fetal

Introduction

Gestational diabetes is characterized by a significant increase of the glycemia firstly


occurring usually in the second or third trimester of pregnancy, in patients who normally
would have displayed standard (average) results in the past. This clinical pathology represents
a major public health crisis because it is often linked with an increased perinatal risk

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experienced through macrosomia, a high percentage of fat tissue of the fetus, preeclampsia or
fetal prematurity. [1]
The diagnosing of gestational diabetes is settled once the OMS-recommended glucose
tolerance test has been applied to the patient in the timeframe of the 24th and the 28th week of
gestation. In order for the testing to be accurate and prove valid results, the patient will have
to abstain from consuming food for a minimum of 8 hours before the blood sampling, and
also refraining from consuming any beverages, smoking or even gum chewing due to artificial
sweeteners tainting the results. The testing implies having the patient’s glucose blood drawn
early in the morning on an empty stomach, and afterwards having been given to consume 250
ml of water in which 75 g anhydrous glucose has been dissolved. The following step consists
of 2 consecutive blood samplings, first one to be drawn at the one-hour mark after the glucose
ingestion, and the second sample to be drawn once the 2-hour mark has been reached. The
cut-off values are the following: early morning – 92mg/dL, after the 1-hour mark – 180
mg/dL, after the 2-hour mark – 153 mg/dL. The diagnosis is settled if at least one of these
results shows increased norms other than the cut off values. [2]
In the case of gestational diabetes, due to the increased levels of the glycemia, the glucose
surpasses the placenta through the fetal blood circulation and stimulating the insulin secretion
of the fetus which will act upon the well-being of the insulin dependent organs, thus resulting
in macrosomia. A fetus with macrosomia will usually weigh around 4500g, and this fact itself
would be a risk factor at childbirth due to the complications the size of the fetus poses such
as: shoulder dystocia, brachial plexus injuries, collarbone fractures and maternal birth trauma
of the bladder, perineum or anal sphincter. The newborns whose mothers are diagnosed with
diabetes often show an enlarged abdomen growth, fat tissue being stored in the upper part of
the body. [3-5]
The majority of obstetricians use ultrasound testing to detect and assess the weight of the
fetus, the most important guideline being the abnormal abdominal girth which is significantly
larger than average to the infants whose mothers are diagnosed with gestational diabetes (6).
The ultrasound is also used for screening and tracing out any fetal deformities or
conditions. The risk of developing fetal malformation for infants from diabetic mothers is
significantly higher than infants from non-diabetic mothers, this likelihood reaching an
increase of 10%. [7-8]
The most frequent changes shown on ultrasound testing in the case of a pregnant patient
with gestational diabetes consist of: asymmetrical macrosomia [6-7], increased percentage of
fat tissue of the infant, a thickening of the septum and ventricular walls, these mentioned
above being changes resulting from cellular hypertrophy through hyperinsulinism. Also,
another frequent shown difference consists of a pathological increase of amniotic fluid
volume and thickened placental walls with an undeveloped layout caused by the glycogen
deposits. [9-14]
Perovic et al., researched a study case in which has been proven that the undeveloped
layout of the placenta is the most accurate predicament factor for gestational diabetes. The
research compared the frequency between the pathological guidelines found in pregnant
patients who show no OGTT modifications and the frequency for those who show abnormal
results of the OGTT. The undeveloped layout of the placenta has been detected accurately in
84,8% of the patients diagnosed with gestational diabetes and as for the non-diabetic patients,
only a small percentage of 11,7% has been detected, thus proving that studying the structure
of the placenta is an important factor towards reaching an early diagnosis of gestational
diabetes. Increased growth of the placenta was present in 75,8% of the patients with
gestational diabetes and in only 26% of patients with no OGTT modifications. Cardiac width
was present in 66,7% of children from mothers with gestational diabetes and only in 6,5%
from mothers with no OGTT modifications.

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54,5% of children from mothers with gestational diabetes presented increased adipose
subcutaneous tissue and only 5,3% from mothers with no OGTT modifications. [14]

Materials and methods

Our goal is to present the main manifestations of this pathology that affect both the mother
(obesity, risk of preeclampsia/eclampsia) and the fetus (IUGR because of placental
deterioration, dysfunction or failure – by monitoring Doppler umbilical and uterine
velocimetry values, polyhydramnios as a result of polyuria and lung liquid production – by
measuring amniotic liquid levels, macrosomia because of maternal hyperglycemia, fetal
hyperinsulinemia and the rise of insulin like growth factors such as c peptide levels – by
assessing fetal biometric parameters, shoulder dystocia that prompts the obstetrician to
perform a caesarean section, neonatal hypoglycemia).
A meticulous ultrasound examination is required in order to prevent sudden complications
that may arise at various gestational ages.
A statistical study was carried out in our clinic (Obstetrics – Gynecology of the Emergency
University Hospital Bucharest) on a population of 40 patients diagnosed with GDM between
October 2016 and January 2018.
A series of ultrasound parameters have been analyzed in regard with pregnancies which
develop without complications and the way they influence treatment protocol in these
particular cases: amniotic liquid levels, fetal biometry, fetal annexes, Doppler velocimetry, as
well as certain findings in association with other pathologies: pregnancy induced hypertension
or preeclampsia/eclampsia.

Results

The results of our study are as follows: out of the 40 patients, only 15 needed to be on
treatment with insulin in order to control their gestational diabetes, the majority (22) was only
required to maintain a strict diet. Six cases had a high uterine artery pulsatility index, eleven
were diagnosed with polyhydramnios and six with olygohydramnios.
The pregnancies had the following associated pathologies: 3 cases of preeclampsia, 2
pregnancy induced hypertension, 1 of preexisting hypertension, 4 of thrombophilia, 3 of
placenta praevia, 1 case of single umbilical artery, 1 epilepsy, 1 Crohn’s disease, 1
supraventricular tachycardia with WPW syndrome.
Out of the 40 fetuses, 18 had a normal fetal biometry, 14 were LGA (large for gestational
age) and 8 were SGA (small for gestational age).

Conclusions

We feel that a correct and thorough ultrasound examination and follow-up are essential in
order to establish an adequate protocol and therapeutic conduct. It is important to correctly
diagnose and treat such a condition in a multidisciplinary manner to prevent the complications
that might arise during the pregnancy, before and after the delivery as to make sure that both
the mother and the fetus/newborn’s welfare are optimal.

REFERENCES

1. Obstetrics, Gynaecology & Reproductive medicine, Volume 27, Issue 6, June 2017, pp. 171-176.
2. Jacques Wallach. Afecţiuni endocrine. În Interpretarea testelor de diagnostic. Editura Stiinţelor
Medicale, Romania, 7 ed., 2001, pp. 807-818.

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3. Spellacy WN, Miller S, Winegar A, Peterson PQ. Macrosomia – maternal characteristics and infant
complications. Obstet Gynecol 1985;66: pp. 158-61.
4. American College of Obstetricians and Gynecologists. Fetal macrosomia. ACOG Practice Bulletin No.
22. ACOG: Washington, DC; 2000. Available from: http://www.acog.org/ member_–
access/lists/practbul.cfm [last accessed 30 Oct 2013].
5. Lipscomb KR, Gregory K, Shaw K. The outcome of macrosomic infants weighing at least 4500 g: Los
Angeles County+University of Southern California experience. Obstet Gynecol 1995;85: pp. 558-64.
6. Gilbert WM, Nesbitt TS, Danielsen B. Associated factors in 1611 cases of branchial plexus injury.
Obstet Gynecol 1999;93: pp. 536-40.
7. Ahmed, Badreldeen, et al., “Role of ultrasound in the management of diabetes in pregnancy”. The
Journal of Maternal-Fetal & Neonatal Medicine” 28.15 (2015): pp. 1856-1863.
8. Mills JL, Knopp RH, Simpson JL, et al., Lack of relation of increased malformation rates in infants of
diabetic mothers to glycemic control during organogenesis. N Engl J Med 1988;318: pp. 671-6.
9. Gandhi JA, Zhang XY, Maidman JE. Fetal cardiac hypertrophy and cardiac function in diabetic
pregnancies. Am J Obstet Gynecol 1995; 173: pp. 1132-1136.
10. Preece R, Jovanovic L. New and future diabetes therapies: Are they safe during pregnancy? J Matern
Fetal Neonatal Med 2002; 12: pp. 365-375.
11. Hornberger LK. Maternal diabetes and the fetal heart. Heart 2006; 92: pp. 1019-1021.
12. Zamlynski J, Bodzek P, Olejek A, Manka G, Grettka K, KobylecZamlynska B. [Correlation between
amniotic fluid index (AFI) and glucose concentration in amniotic fluid, glycaemia, glycosylated
haemoglobin concentration during normal pregnancy and pregnancy complicated by insulin-dependent
diabetes mellitus]. Med Wieku Rozwoj 2005; 9: pp. 407-416.
13. Bethune M, Bell R. Evaluation of the measurement of the fetal fat layer, interventricular septum and
abdominal circumference percentile in the prediction of macrosomia in pregnancies affected by
gestational diabetes. Ultrasound Obstet Gynecol 2003; 22: pp. 586-590.
14. Perović, Milan, et al., “Sensitivity and specificity of ultrasonography as a screening tool for gestational
diabetes mellitus”. The Journal of Maternal-Fetal & Neonatal Medicine 25.8 (2012): pp. 1348-1353.

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Feasibility of a Novel Ultrasonographic Evaluation of the


Cerebral Ventricular System in the First Trimester

DRĂGUȘIN Roxana-Cristina1, ȘOROP-FLOREA Maria1,


PĂTRU Ciprian-Laurențiu1, ZORILĂ Lucian1, MARINAȘ Cristian2,
DINU Marina3, CERNEA Nicolae3, TUDORACHE Ștefania3,
ILIESCU Dominic Gabriel1
1 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, County Emergency Hospital
of Craiova, Department of Ultrasound in Obstetrics and Gynecology SC ENDOGYN AM, (ROMANIA)
2 Department of Human Anatomy, University of Medicine and Pharmacy of Craiova, County Emergency Hospital of Craiova,

Department of Ultrasound in Obstetrics and Gynecology SC ENDOGYN AM, (ROMANIA)


3 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, County Emergency Hospital

of Craiova, (ROMANIA)
Emails: [email protected], [email protected], [email protected],[email protected],
[email protected], [email protected].

Abstract

Introduction/Objective
The fetal central nervous system (CNS) disorders are usually difficult to diagnose in the
first trimester, as the cerebral structures are continuousely developing and changing until mid-
pregnancy. A relatively new approach was proposed to efficiently diagnose major CNS
abnormalities, including neural tube defects (NTDs), early in pregnancy. This consists in
evaluating the cerebral ventricular system (CVS). The aim of this prospective study, was to
establish the feasibility of a more detailed first trimester ultrasound protocol, in terms of
visualization and detection rates of abnormal cases.

Methods/Methodology
We included in the study all pregnancies examined between September 2016 and January
2018, at the 11-13 weeks morpho-genetic screening. The scanning protocol included the
assesssment of the lateral ventricles, the third ventricle, aqueductus of Sylvius and the fourth
ventricle, namely intracranian translucency (IT). We calculated the visualization rates and
noted the aspect of all parameters in abnormal CNS cases.

Results
A group of 712 first trimester fetuses (703 normal cases and 9 CNS major abnormalities
detected during pregnancy) were examined. All the above CVS features could be seen in the
normal fetuses group. The abnormal group included open spina bifida, anencephaly,
holoprosencephaly, cephalocele, hydrocephaly and a case with massive cerebral haemorrhage.
The CVS features were abnormal in all cases, except the cerebral haemorrhage, that was an
unexpected finding in the third trimester.

Conclusion
Our study indicates that the evaluation of the CVS early in pregnancy, is feasible and has
the potential to efficiently detect major CNS abnormalities, such as NTDs and
holoprosencephaly.
The visualization rates may reach 100% with small if any supplementary investigation
time.

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The benefit of this protocol is to be investigated in larger series regarding anomalies that
have later manifestations in pregnacy. Obviousely, cerebral disorders with sudden
manifestations such as haemorrhage or infections are not targeted by this protocol.
Keywords: cerebral ventricular system, ultrasound, pregnancy, anomaly

Introduction/Objective

The importance of the first trimester ultrasonographic examination is worldwide


recognized especially for the correct location of the pregnancy including rulling out ectopic
pregnancy, assessment of fetal viability, confirmation of gestational age, establishment of
chorionicity in multiple gestation and evaluation of pelvic masses, if present [1]. More,
obstetric sonography proved a longtime ago to be useful in visualization of fetal anatomy. The
first case of anencephaly diagnosed sonographically was in 1972, at 17 weeks of pregnancy
[2]. Several years later, Green and Hobbins described the first trimester fetal anatomy
examined by transabdominal ultrasound (US) [3]. The transvaginal approach was introduced
in 1989, as a revolutionary technique with major breakthroughs in prenatal diagnosis of fetal
anomalies [4]. In 1992, Nicolaides reported nuchal translucency ≥3 mm as a first trimester
sonographic marker for detection of chromosomal defects [5]. Almost 20 years later, the
concept of turning the pyramid of care was introduced, with the emphasis placed on the first,
rather than the third trimester of pregnancy [6]. Nowadays, the first trimester US has two
major objectives: finding additional sonographic markers that increases the accuracy and
sensitivity of detecting chromosomal abnormalities, especially Down syndrome and also
improving the early detection of congenital anomalies. The first trimester assessment of the
CNS is considered of highly importance as fetal CNS anomalies are extremely severe, with
limited therapeutic solutions and the worst short-term and long-term prognosis. Major CNS
abnormalities can be diagnosed in the first trimester, even before 14 weeks, such as acrania,
exencephaly, anencephaly, holoprosencephaly, cephalocele, hydrocephaly and spina bifida
[7]. Today, the assessement of the CNS is perfomed in many institutions, however it is
considered a very difficult examination as the CNS is a continuousely changing system and
many anomalies are defined as evolving diseases. Still, it is important to examine the CNS in
the first trimester, even for a suspicion of anomaly. Many studies have reported the
sonographical exam of the CNS as being feasible, mostly done by transabdominal approach,
using the transvaginal approach in selected cases. In 2012, a study reported the evaluation of
the fetal CVS system in the first trimester fundamental in the early diagnosis of open spina
bifida. In the present study, we propose a relatively new approach to efficiently detect any
CNS anomalies that consists in evaluating the CVS. The aim of the prospective study was to
establish the feasibility of a more detailed first trimester US protocol in term of visualization
and detection rates of abnormal cases.

Methods/Methodology

The study was conducted in the County Emergency Hospital of Craiova between
September 2016 and January 2018. We included in the study all singleton pregnancies that
presented for the 11-13 weeks morpho-genetic screening. All scans were performed by five
experienced doctors using a Voluson 730, GE E8 and E10; GE Medical Systems.
Transabdominal approach was preferred in most cases and transvaginal sonography was
carried out only in few selected cases in order to obtain good visualization of the fetal CNS.
Three different planes of the brain, in transverse and sagittal view, were obtained: the
lateral third-ventricle plane, the trans-thalamic plane and the fourth-ventricle plane (Fig. 1.).

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All recommended guidelines for fetal CNS examinations were respected. The scanning
protocol aimed to assess of the lateral cerebral ventricles, the third ventricle, aqueductus of
Sylvius and the fourth ventricle or IT.

Fig. 1. The proposed protocol of CVS in the first trimester: a. transverse view of the brain showing the lateral
third-ventricle plane (arrow); b. transverse view of the brain showing the third ventricle and aqueduct of Sylvius
(arrow); c. sagittal view of the brain showing the fourth ventricle or intracranial translucency (arrow).

Results

The study included 712 pregnancies examined at the first trimester scan using the CVS
protocol examination proposed. We reported 8 cases of major first trimester CNS anomalies
(2 cases of open spina bifida, 2 cases of anencephaly, 1 case of holoprosencephaly, 1 case of
cephalocele and 2 cases of hydrocephaly). We noted all different normal and abnormal
aspects of the CVS in these cases (Tabel 1.). 1 case, declared negative at the first trimester
evaluation, presented at the beginning of the third trimester with important cerebral
disruption, that proved to be due to a massive intracerebral haemorrage. The visualization rate
reached 100% with some supplementary investigation time in some cases with unfavourable
fetal position or maternal high body mass index. We noted the CNS features in the positive
abnormal cases (Tabel 1.). In 21 pregnancies at the first examination we noted some
anomalies (Tabel 2.), but after re-evaluation and/or switching to the a transvaginal approach
we declared only 5 cases positive that proved normal in the second trimester.

Table 1. First trimester ultrasonographic features of the CVS in all CNS anomalies detected during the study
9 CNS ANOMALIES The lateral The third The aqueduct of The fourth
ventricles and the ventricle Sylvius ventricle
choroid plexus
Open Spina Bifida + + + +
Open Spina Bifida + + - -
Anencephaly + + + +
Anencephaly + + + +
Holoprosencephaly + + - +
Cephalocele + - + +
Hydrocephaly + - + +
Hydrocephaly + + + +
Cerebral haemorrhage - - - -
+ (abnormal ultrasonographic image), - (normal ultrasonographic image).

Table 2. First trimester ultrasonographic features of the CVS in the reported false positive cases at the first
examination
703 normal fetuses The lateral ventricles The third The aqueduct The fourth
21 false positive cases and the choroid plexus ventricle of Sylvius ventricle
682 cases - - - -
3 cases of cephalocele - - + +
12 cases of open spina + + - -
bifida

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3 cases of + - + +
holoprosencephaly
3 cases of + - - -
hydrocephaly
+ (abnormal ultrasonographic image), - (normal ultrasonographic image).

Table 3. First trimester ultrasonographic features of the CVS in the reported false positive cases at the second
examination
703 normal fetuses The lateral ventricles and The third The aqueduct of The fourth ventricle
5 false positive cases the choroid plexus ventricle Sylvius
698 cases - - - -

2 case of open spina bifida + + - -

1 case of holoprosencephaly + - + +

2 cases of hydrocephaly + - - -

+ (abnormal ultrasonographic image), - (normal ultrasonographic image)

Both cases of open spina bifida detected in our study, described classically the “dried up
brain” and the “crash sign” (Fig. 2.).

Fig. 2. Transverse view of the first trimester CVS in a case of open spina bifida:
a. The “dried up” sign; b. The “crash” sign

Both cases of anencephaly presented with disruption of all CVS parameters (Fig. 3.)

Fig. 3. Sagital view of the fetal CNS in a case of anencephaly

All cases of holoprosencephaly and hydrocephaly detected using the CVS protocol
presented with anomalies of the lateral ventricle plane (Figure 4).

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Fig. 4. Transverse view of the fetal CNS: a. holoprosencephaly; b. hydrocephaly

After statistical analysis, our study declared an accuracy of 99,16% of detection of CNS
major malformations after examining the proposed CVS parameters. The sensitivity of the
examination protocol was 88,98% and the specificity of 99,29% (Tabel 3.).

Tabel 3. Statistical results of the study


Sensitivity 88,89 51,75%-99,72%
Specificity 99,29% 98,35%-99,77%
Positive Likehood Ratio 124,98 50,64-308,46
Negative Likehood Ratio 0,11 0.02-0,71
Disease Prevalence 1,26% 0,58%-2,39%
Positive Predictive Value 61,54% 39,33%-79,79%
Negative Predictive Value 99,86% 99,10-99,98%
Accuracy 99,16% 98,17%-99,69%

Discussion

The findings of this study demonstrate that examination of the fetal CVS in the first
trimester has a great detection rate for fetal anomalies as proven in previous studies [8, 9]. We
declared negative 703 fetuses after using both transabdominal, but also transvaginal approach
in selected cases. As mentioned previously, transvaginal sonography improved considerably
the detection conditions, especially in cases of maternal high body mass index [10]. In normal
fetuses, we noted that the area of lateral ventricles and the diameter of the roof of the third
ventricle increased, the diameter of the aqueduct of Sylvius decreased and normal
visualization of the fourth ventricle. In cases with open spina bifida, we noted that the the
lateral ventricle area, the diameter of the aqueduct of Sylvius and the diameter of the fourth
ventricle were significantly decreased, underlying the results of important publications [11-
15]. The detection of holoprosencephaly and anencephaly in the first trimester was considered
without difficulty using the proposed protocol of examination and confirmed postabortion by
fetal autopsy. In fact, all the anomalies detected in our study were subsequently confirmed by
fetal autopsy, demonstrating a good corelation as stated before [16, 17, 18]. However, some
major CNS anomalies such as haemorrage and infection, can not be detected in the first
trimester, even by experienced examiners using high resolution ultrasound equipment.
Because their development can be later, couple counselling should be proper regarding the
benefits and limitations of first trimester anomaly scan [19].

Conclusion

Our study showed that the evaluation of the CVS, early in pregnancy is feasible and has a
great potential to efficiently detect major CNS abnormalities. Still, cerebral disorders with
sudden manifestations such as haemorrhage or infections can remain undetectable until late in
pregnancy. Also, we highlight the fact that it is important to look at the CVS in the first

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trimester for proper couple counselling. Still, the first trimester sonographic assessment does
not replace the second trimester evaluation.

Acknowledgements
This paper was published under the frame of European Social Found, Competitivity
Operational Programme 2014-2020, POC-A.1-A.1.2.1-D-2015, Contract nr. 75/08.09.2016,
MYSMIS Code: 105076.

REFERENCES

1. Ran Neiger; Review First Trimester Ultrasound in Prenatal Diagnosis – Part of the Turning Pyramid of
Prenatal Care, J Clin Med. 2014 Sep 5;3(3): pp. 986-96. doi: 10.3390/jcm3030986.
2. Campell, S.; Holt, E.M.; Johnston, F.D.; May, P. Anencephaly: Early ultrasound diagnosis and active
management. Lancet 1972, 2, pp. 1226-1227.
3. Green, J.J.; Hobbins, J.C. Abdominal ultrasound examination of the first trimester fetus. Am. J. Obstet.
Gynecol. 1988, 159, pp. 165-175.
4. Rottem, S.; Bronshtein, M.; Thaler, I.; Brandes, J.M. First trimester transvaginal sonographic diagnosis
of fetal anomalies. Lancet 1989, 1, pp. 444-445.
5. Nicolaides, K.H.; Azar, G.; Byrne, D.; Mansur, C.; Marks, K. Fetal nuchal translucency: Ultrasound
screening for chromosomal defects in first trimester of pregnancy. BMJ 1992, 304, pp. 867-869.
6. Nicolades, K.H. Turning the pyramid of prenatal care. Fetal Diagn. Ther. 2011, 29, pp. 183-196.
7. Souka, A.P.; Nicolaides, K.H. Diagnosis of fetal abnormalities at the 10-14-week scan. Ultrasound
Obstet. Gynecol. 1997, 10, pp. 429-442.
8. Iliescu DG, S Tudorache, , A Comanescu, L Novac, P Antsaklis, N Cernea; Reability of frsttrimester
structural sonografic extended evaluation, Ultrasound in Obstetrics & Gynecology, Volume 40, S1, pp.
9-10, 2012, pp. 188-189.
9. Iliescu D., Tudorache Ş., Comanescu A., Căpitănescu R., Manolea M., Novac M., Cernea N., Novac L.
Feasbility of neurosonogram adjusted with recently described markers at the 11-13+6 week scan.
Advance in Perinatal Medicine, Conference Proceedings Citation Index, a Web of Science® database,
pp. 143-148; Conference Proceedings Citation Index, a Web of Science® database, ISBN 978-88-6521-
027-7; 2010
10. S Tudorache, Iliescu Dominic Gabriel, A. Comanescu and N. Cernea Early fetal anatomic surveillance.
Transabdominal and transvaginal first trimester scan. How good are we? Ultrasound in Obstetrics &
Gynecology, Volume 38, Issue S1, 2011, pp. 188-189.
11. Loureiro T1, Ushakov F, Montenegro N, Gielchinsky Y, Nicolaides KH, Cerebral ventricular system in
fetuses with open spina bifida at 11-13 weeks’ gestation, Ultrasound Obstet Gynecol. 2012 Jun;
39(6):620-4. doi: 10.1002/uog.11079.
12. Iliescu D, Comănescu A, Antsaklis P, Tudorache S, Ghiluşi M, Comănescu V, Paulescu D, Ceauşu I,
Antsaklis A, Novac L, Cernea N. Neuroimaging parameters in early open spina bifida detection. Further
benefit in first trimester screening? Rom J Morphol Embryol. 2011; 52(3): pp. 809-17.
13. Stefania Tudorache, A. Turcu Stiolica, D.G. Iliescu, M. Florea, R. Dragusin, D. Cernea Modelling
isolated spina bifida screening performance using axial and sagittal views of the brain and spine natomy
at the 11-13 week scan. Ultrasound in Obstetrics & Gynecology Volume 46, S1 2015, p. 67.
14. Stefania Tudorache,Iliescu Dominic Gabriel, Adina Turcu, Maria Florea, Roxana Drăguşin, Liliana
Novac, Cernea Nicolae, Daniela Cernea, First Trimester Anomaly Scan-The Last Redoubt Won: Open
Spina Bifida, Donald School Journal of Ultrasound in Obstetrics and Gynecology, January-March 2015;
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15. Iliescu D, Comănescu A, Antsaklis P, Tudorache S, Ghiluşi M, Comănescu V, Paulescu D, Ceauşu I,
Antsaklis A, Novac L, Cernea N. Neuroimaging parameters in early open spina bifida detection. Further
benefit in first trimester screening? Rom J Morphol Embryol. 2011; 52(3): pp. 809-17.
16. Șorop-Florea M, Capitanescu R, Drăgușin RC, Pătru CL, Zorilă LG, Ciurea R, Marinaș C, Tudorache S,
Novac M, Dragoescu A, Stoica A, Gheonea M, Coleta E, Stepan A, Simionescu C, Cara M, Cernea N,
Iliescu DG. Correlations of the Fetal Anomaly Scan with Fetal Autopsy Results. Conference
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88-1.

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17. Mărginean C, Suciu H, Brînzaniuc K, Mărginean O Ethical considerations in screening and ultrasound
diagnosis of fetal heart defects. Revista Română de Bioetică, 2014, 4: pp. 120-125, FI: 0.462 , ISSN:
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Antsaklis A., Challenges in sonographic detection of fetal major structural abnormalities at the first
trimester anomaly scan, Donald School J Obstet Gynecol, 2015; 9(3): pp. 239-259.

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Detection of Conotruncal Anomalies in the First Trimester, Using


an Optimized Morphological Protocol

ȘOROP-FLOREA Maria1,2, DRAGUȘIN Roxana Cristina1,2,


PATRU Ciprian-Laurențiu1,2,3, ȘOROP Virgiliu Bogdan4,
ZORILĂ George Lucian1,2, MARINAȘ Cristian1,5, DINU Marina3,
NOVAC Marius6, CARA Monica1, TUDORACHE Ștefania1,3,
CERNEA Nicolae1,3, ILIESCU Dominic-Gabriel1,2,3
1 University of Medicine and Pharmacy of Craiova (ROMANIA)
2 ENDOGYN AM, Department of Imaging in Obstetrics and Gynecology, Craiova (ROMANIA)
3 Department of Obstetrics and Gynecology, Prenatal Diagnostic Unit, University Emergency Hospital, Craiova (ROMANIA)
4 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy “Victor Babeș” Timișoara (ROMANIA)
5 Department of Anatomy, University of Medicine and Pharmacy Craiova (ROMANIA)
6 Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy Craiova (ROMANIA)

Email: [email protected]

Abstract

Introduction/Objectives
To evaluate effectiveness of the late first trimester (FT) detection of conotruncal anomalies
(CTA) on fetal echocardiography, using an optimized morphological protocol.

Methods/Methodology
Our prospective study consecutively enrolled pregnancies referred for early anomaly scan.
A morphologically optimized protocol was used to evaluate. We used re-examination by a
team of specialists, subsequent re-examination (second trimester and postpartum) and
pathological examination, as the reference standard methods.

Results
The group of 500 pregnant women was examined between January 2015 and January 2018
and a detailed late first trimester early anomaly screening was performed. Of these, 14 fetuses
(2.8%) were diagnosed to have CTA, representing 20% of the total anomalies diagnosed
during the study period. Conotruncal defects were as follows: tetralogy of Fallot (TOF);
transposition of the great arteries (GAT); double aortic arch (DAA); right aortic arch left
ductus (RAA-LD); right aortic arch (RAA).

Conclusions
Conotruncal anomalies can be diagnosed by early prenatal echocardiography with a high
degree of accuracy. The most indicative sign of conotruncal anomalies is the abnormal V-
sign.
Isolated CTA are more common and most of these may have a favorable outcome.
Keywords: conotruncal anomalies, fetal echocardiography, first trimester

Introduction/Objective

Conotruncal anomalies are a broad category of congenital heart disease (CHD) that
includes a variety of conditions like Tetralogy of Fallot (TOF) and its variants absent

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pulmonary valve (TOF-APV) and pulmonary atresia (TOF-PA), double outlet right ventricle
and its variants (DORV), Transposition of great arteries (TGA) and persistent truncus
arteriosus (TA). These are relatively common anomalies in the post-natal series comprising
about 10-12% of all congenital heart defects (CHD) diagnosed after birth [1, 2].
However, prenatal diagnosis of these anomalies is more challenging since most of these
anomalies have a normal four-chamber view during routine fetal heart screening [3-7]. The
prevalence in reported fetal series varies from 2.5-21% with a diagnostic accuracy of 75-90%
for achieving a complete diagnosis [8-13]. Accurate echocardiographic diagnosis in utero
permits counseling of the parents with regard to prognosis and treatment options. It is of
paramount importance when termination of pregnancy is being considered for the more severe
cases. Therefore, the aim of this study was to define the accuracy of fetal echocardiography
for the prenatal diagnosis of conotruncal anomalies and to examine the prognosis of those
fetuses identified.

Materials and methods

Prospective study of 500 consecutive pregnant women examined at 12 to 13+6 gestational


weeks (GW), using an optimized morpho-genetic ultrasound protocol. Parental consent was
obtained for all investigations. Our aim was to evaluate effectiveness of the late first trimester
(FT) detection of conotruncal anomalies (CTA) on fetal echocardiography, using an
optimized morphological protocol (Table 1). Definition of fetal conotruncal anomalies was
attempted from multiple scan planes including four-chamber, long- and short-axis as well as
aortic arch and ductal arch views. Doppler color flow mapping and pulsed Doppler
interrogation were used to facilitate identification of great vessel relationship, location and
severity of ventricular outflow obstruction.

Table 1. Standard planes and targets in cardiac evaluation


Standard planes Targets of evaluation
• Abdominal situs with the stomach in the left abdominal side
and aorta to the left of the spine;
• The four chambers of the heart with the heart lying on the left
side angled at 45 from the midline, occupying one quarter of the
chest; atrioventricular valve offsetting;
• The aorta arising centrally in the heart from the left placed
Transversal sweep gray-scale ventricle and crossing to the fetal left side over the ascending
aorta;
• Interventricular septum; when possible – septo-aortic continuity
in the left outflow view;
• The anteriorly positioned ductal arch, converging with the
transverse aortic arch on the left side of the fetal spine, with
approximative similar size.
• Equal filling of both ventricles in the four chambers view
• Emergence of aorta with deduction of septo-aortic continuity
based on the entire aortic flow arising from the visualized left
Color-flow Doppler investigation ventricle;
(in order to increase the accuracy and to • Arterial duct outflow: visualization with power Doppler. ‘X’
shorten the examination time) sign (the crossing of the main pulmonary artery with the aorta);
• The transversal course of the two arches: ‘b’ sign (the straight
line of the pulmonary artery surrounded by aortic arch; ‘V’ sign
(the connection of the aorta and ductus arteriosus).
• Tricuspid valve flow assessment, to search for significant
Pulsed Doppler – investigation regurgitation.
(assessment of functional parameters) •Ductus venosus flow assessment, to search for reversed “a”-
wave.

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Ultrasound morphological assessments were performed in the Prenatal Diagnostic Unit of


the University Emergency County Hospital Craiova by sonographers with extensive
experience in first trimester genetic anomaly scan. The acquisition of images were realized
transabdominally and transvaginally, using probes from GE Voluson medical Systems.
Transabdominal approach was preferred in most cases and transvaginal sonography was
carried out only in few selected cases in order to obtain good visualization of the fetal heart.
Only the patients with extended first trimester anomaly scan and complete follow-up were
considered. We used as controls the serial scans, follow-up scans, the secondary experienced
team evaluation, pediatric cardiologist examination, pathologic and neonatal evaluations.
Post-natal echocardiography was also performed as soon as feasible after birth using a
standard protocol for pediatric echocardiography.

Results

The group of 500 pregnant women was examined between January 2015 and January 2018
and a detailed late first trimester early anomaly screening was performed. All pregnant
women fulfilled the study requirements, with a median maternal age of 28 years (26 vs. 28
years). Of these, 14 fetuses (2.8%) were diagnosed to have CTA, representing 20% of the
total anomalies diagnosed during the study period. Conotruncal defects were as follows:
tetralogy of Fallot (TOF-n=3) (Fig. 1); transposition of the great arteries (GAT-n=5); double
aortic arch (DAA- n=1); right aortic arch –left ductus (RAA-LD-n=3); right aortic arch
(RAA- n =2). The most common anomaly diagnosed was GAT (35,71%) (Fig. 2). We noted
all different normal and abnormal aspects of these cases. The visualization rate reached 98%
with some supplementary investigation time in some cases with unfavourable fetal position or
maternal high body mass index.

B
.

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Fig. 1. A. First trimester: tetralogy of Fallot (TOF) and right aortic arch (RAA – prenatal ultrasound and
conventional autopsy correlations; B. Microarray CGH has detected multiple microdeletions and
microdunctions; C. abnormal profile and discordance between great arteries.

Fig. 2. Types of conotruncal anomalies diagnosed (N = 14)

According to statistical analysis, our study found an accuracy of 99,16% of detection of


CAT malformations after examining the proposed parameters. The sensitivity of the
examination protocol was 93,33% and the specificity of 99,59%. (Fig. 3)

0,00% 20,00% 40,00% 60,00% 80,00% 100,00%

93,33%
Se (DR)

99,59%
Sp

0,41%
FPR

7%
FNR

12,50%
FDR
87,50%
PPV
99,79%
NPV
Fig. 3. Statistical results of the study

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Discussion

This study shows that conotruncal anomalies can be diagnosed in fetal life by
echocardiography with a high degree of accuracy [14-17]. Difficulties in defining the spatial
relationship of the great arteries are a limiting factor in diagnosing conotruncal anomalies in
some instances. Despite this, the accuracy of prenatal diagnosis of conotruncal anomalies
including the great vessel orientation was 90% in this study [18]. As mentioned previously,
transvaginal sonography improved considerably the detection conditions, especially in cases
of maternal high body mass index [19, 20]. The main advantages of a FT anomaly scan using
an extended protocol is the early reassurance regarding fetal anatomy, and that the option of
earlier and safer termination of pregnancy is offered for the majority of MA, with less
parental psychological morbidity [21, 22, 23]. Furthermore, couples prefer earlier screening,
when possible [24, 25].

Conclusion

Conotruncal anomalies can be diagnosed by early prenatal echocardiography with a high


degree of accuracy. The most indicative sign of conotruncal anomalies is the abnormal V-
sign.
The prognosis of the fetuses with chromosomal abnormalities or extracardiac anomalies
was worse than that of the fetuses without. Focus in developing countries should shift towards
earlier referral, improving awareness about treatment options and a comprehensive evaluation
for associated anomalies.

Acknowledgements
This paper was published under the frame of European Social Found, Competitivity
Operational Programme 2014-2020, POC-A.1-A.1.2.1-D-2015, Contract nr. 75/08.09.2016,
MYSMIS Code: 105076.

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life. Accuracy of diagnosis, associated defects and outcome. Eur J Obstet Gynecol Reprod Biol. 2009;
146: pp. 55-60.

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10. Paladini D, Rustico M, Todros T, Palmieri S, Gaglioti P, Benettoni A, et al., Conotruncal anomalies in
prenatal life. Ultrasound Obstet Gynecol. 1996; 8: pp. 241-6.
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diagnosis of conotruncal malformations: Diagnostic accuracy, outcome, chromosomal abnormalities
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diagnosis of 1006 consecutive cases of congenital heart disease in the fetus. J Am Coll Cardiol. 1994;
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13. Khoshnood B, Vigan CD, Vodovar V, Goujard J, Lhomme A, Bonnet D, et al., Trends in prenatal
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14. Davis GK, Farquhar CM, Allan LD, et al., Structural cardiac abnormalities in the fetus: reliability of
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15. Pătru CL, Iliescu DG, Tănase F, Drăgușin RC, Șorop-Florea M, Căpitănescu R, Comănescu A, Pană
RC, Zorilă LG, Marinaș MC, Novac M, Stoica A, Sîrbu M, Cernea N, Tudorache S. Fetal Heart in the
First Trimester. The Added Value of the Outflow Tracts Evaluation. Conference Proceedings, 5th
Congress of The Romanian Society of Ultrasound in Obstetrics and Gynecology, Targu Mures,
Romania, 20-22 April 2017, First Ed Published June 2017, pp. 471-475, ISBN 978-88-95922-88-1.
16. Șorop-Florea M, Capitanescu R, Drăgușin RC, Pătru CL, Zorilă LG, Ciurea R, Marinaș C, Tudorache S,
Novac M, Dragoescu A, Stoica A, Gheonea M, Coleta E, Stepan A, Simionescu C, Cara M, Cernea N,
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Congenital Acute Leukemia Diagnosed at a Fetus with Down


Syndrome Echographic Particulars

GARDESCU Marie Jeanne1, MUNTEANU Andreea3, BACESCU Lucia2,


CONCI Stelian1, EDU Antoine1, MATEESCU Nicolae1
1 Nicolae Malaxa Hospital Obstetrics Gynecology Clinic, Bucarest, (ROMANIA)
2 Nicolae Malaxa Hospital Neonatology Section, Bucarest, (ROMANIA)
3 Medlife Clinic Echography Departament (ROMANIA)

Abstract

Congenital acute leukemia has been diagnosed within a newly born affected by the Down
syndrome of a pregnant woman that has not been hospitalised until the third trimester. The
ultrasonographic examination performed at 32 weeks revealed: fetus hidrops, hypertelorism,
the absence of the nasal bone hepato spleno megaly, septal ventricular defect and the factor
that has requested the immediate extraction of the fetus: the reversal of the cerebro-placentary
ratio. Postpartum, the leukemia diagnosis has been confirmed by hematological analyses. The
new born was resuscitated and rebalanced postpartum, having a lengthy recovery, specific
oncological treatment was provided in the specialised clinic.
Keywords: Down, Leukemia, Hepatosplenomegaly, Hidrops

Introduction

Congenital acute leukemia is a rare pathology frequently associated with a fatal evolution,
most of the reported neonatal cases have been non limphoblastic leukemias compared to acute
leukemias diagnosed at older children which were limphoblastic [1].
Occurrence of congenital leukemia is of 1:5000000 birth [2].
Leukemia is defined as being congenital when diagnosed at birth and during the first
month of life with symptoms in the first 3-6 weeks of life.
Congenital acute leukemia is a rare disease and the prognostic is low, most of the new born
do not survive childhood [4].
The differential diagnosis includes congenital infections with leukemical responses, severe
eritroblastosis, hereditary neuroblastoma [5].
Criteria to be met in order to diagnose congenital leukemia are the proliferation of
immature leucocitary cells [6], the spread of immature white cells within the hematogen
marrow, the absence of other illnesses that might imitate leukemical responses (hereditary
syphilis, group incompatibility or TORCH infections [7]).
Congenital acute leukemia is associated sometimes with chromosomial anomalies such as
Down Syndrome. The chromosomial aberration of the Down Syndrome is the basis of an
unstable hematopoiesis which may lead to transitory mieloprolipherative disorders that can
resemble spontaneous remission leukemia [3].
On the other side, the Down Syndrome is the most frequently traceable aneuploidis at
birth, being a trisomy (the 21th pair contains the third chromosome). The occurrence is 1:450-
1:900 at new born babies [8].
Fenotypical features of the Down Syndrome: flat profile, oblic palpebral slots, epicantic
fold, low implanted ears, displasies, macroglosia, short neck, excessive tissue at nape level,

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clinodactilis, transverse palm folt, increased distance between the thumb and the other fingers,
small stature, mental retard, gastrointestinal obstructive illness, congenital cardiac illness [9],
male infertility celiac disease condition, obesity diabetis, blood diseases (acute myeloid
leukemia, acute lymphatic leukemia, Alzeimer dementia [10].
Echographic features: increased nucal translucence, absence of nasal bone, flat profile,
brachicephaly, ventricular megaly and other cardiac malformations: typically the
atrioventricular septal defect, ventricular septal defect, Fallot tetralogy, gastrointestinal
anomalies such as duodenal athresy, oesophagus athresy, hyperechogenous bowels,
clinodactilism, lack of the middle phalange ossification of the 5th finger [11].
The prenatal diagnosis consists of screening tests and genetic diagnosis.
The populational screening for the 21 trisomy must be compulsory, as old maternal age
does not indicate such an important factor anymore as the Down Syndrome may occur to
young women as well.
The biochemichal screening (triple and quadruple test), combined screening (biochemical
and echographic 11-14 weeks, integrated screening: the fatal free DNA analysis) [12].
The genetic diagnosis is represented by the cariotyp performed further to chorionic villus
biopsy or further to amniocentesis [13].
The specific literature informs only about a few such cases of congenital leukemia
associated with the Down Syndrome.

A case study

We are going to present the case of a fetus with Down Syndrome and congenital leukemia.
The 39 year-old patient having been diagnosed with XG IVP, 33 week pregnancy living
fetus, breech presentation, intact membranes, presents herself with a view to medically check
her pregnancy.
The patient comes from rural environment and has never been consulted before.
From her cases history: 3 normal births (1998, 1999, 2015), all healthy children, latest birth
being complicated with a 4th degree perineal tear.
At a first routine echography performed on a device with modest technical features, there
have been noticed polihidramnios and obstruction of the gastric pouch as pathological
elements.
The patient is advised to undertake an ultrasonographic screening examination for the 3rd
trimester which brings out stronger relief: hypertelorism (picture 1); the nasal bone hipoplasy
(picture 2), macroglosy, ventricular septal defect (picture 3), hepatomegaly, ascites (picture
4), the infiltration of the soft tissues (picture 5) polihidramniosis (picture 6) the reverse of the
placental – cerebral ratio (picture 7/8).

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Fig. 1. Fig. 2.

Fig. 3. Fig. 4.

Fig. 5. Fig. 6.

Fig. 7. Fig. 8.

The termination of the birth is decided by urgent caesarian section due to the uncertain
fetal status.
A living female fetus is extracted 3000 g/48 cm 6 APGAR Score, with a severe general
condition, pale teguments, acrocianosis, dismorphic facies, typical of the Down Syndrome:
hypertelorism, transversal palpebral slots, open mouth with lingual protrusion, high pointed

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palate, low implanted ears, short neck pterigium colli unique pall fold, short legs, rough skin
hypoton with low reactivity polipneic, systolic heart murmur of the II/III degree in the area
IV, SPO2 93%.
The abdomen is enlarged in volume, the liver at 4 cm under the rib rebord, the spleen at 2
cm under rips.
Laboratory analyses: hemoleucogram (HLG): 103000 leucocytes U/L out of which 51000
lymphocytes, 5800 neutrophiles 139000 U/L trombocytes and hemoglobin (Hb) 8 gr/dl.
There has been injected the eritrocitary and trombocitary mass in 2 stages due to anemia
(minim 6 g/dl Hb) and due to severe reduction of trombocites at a minimum of 28000 U/L.
Doring hospitalisation a transfer to a specialised clinic was intended, unsuccessful
however, due to lack of places.
There has been requested cardiac consultation in the pediatric clinics where cardiac
ultrasound was performed initially confirming the ventricular septal defect and recommending
diuretical treatment and corticotherapy.
The evolution was slowly pavourable and the patient was released from hospital after a
month with a satisfying overall status, pale pinkish teguments pulmonary and cardiac
balanced state, with a volume enlarged abdomen: liver at 1-2 cm under rib rebord.
The baby is fed with maternal milk, has spontaneous mictions and intestinal transit. Weight
at releasing from hospital was 2770 g.
The mother’s postsurgical state was favourable. They were adviced to seek assistance at
the Pediatrics Oncological Clinic for specific treatment.

REFERENCES

1. Waseen Iqbal, Faisal Khan, M. Muzaffar, Umar Awab Khan , Mahmood-ur-Rehman, Masood A Khan,
Abdul Bari. International Journal of Pathology 2005 3(2): pp. 100-101 ‘’Congenital Leukemia in Down
Syndrome.
2. Pui C.H., Kane JR, Crist W.M. Biology and treatment of infant leukemia (Medscape).
3. Bhatt S. Rhona Schrek, John Metal 2002 Am. J. Med. Genet. 58; pp. 310-314 ‘’Transient leukemia with
Trisomy 21’’.
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infant acute lymphocytic leukemia Blood 1988; 71: pp. 1438-1447.
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Genetic Disorders” (Medscape).

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Etiopathogenic, Clinical, Imagistic and Histopathological Aspects


Regarding the Involvement of Urinary Infection in Premature
Birth with Hypotrophic Fetuses

GHEORGHE Ioan Ovidiu1, RACA Nicolae2


1 Work Medicine TG-JIU (ROMANIA)
2 Department of Obstetrics-Gynecology (ROMANIA)

Abstract

The study performed on a number of 1252 premature births, of which 365 with
hypotrophic fetuses (2015-2017) in the clinics of Craiova studied a possible involvement of
urinary infection in the onset of chorioamniotitis that triggered premature births and
hypotrophic fetuses. Urinary infection was present in 174 casesi (3.03%). Most of the cases
were represented by pyelonephritis (91%) with E.COLI. The passing of germs and their toxins
in the blood and their reach to the utero placental structures is quite possible.
CHORIOAMNIOTITIS, sometimes with a subclinical evolution, is mainly responsible for
premature births and hypotrophic fetuses. The study using clinical, bacteriological, imagistic
and histopathological examinations confirmed all the above. The inflammatory process of
chorioamniotitis is responsible for the secretion of prostaglandins, with the onset of premature
uterus contractions, as well as for a poor development of the fetus, 26.4% of pregnant women
with urinary infection having a premature delivery with hypotrophic fetuses.
Keywords: urinary infection, premature birth, fetal hypotrophy

Introduction

Although urinary infection during pregnancy was observed for a long time, it was not
given the proper attention, as it was considered a rare accident with a benign evolution. The
notion of urinary infection represents a general term by which we understand the presence and
multiplication of germs in the urine, the urinary tract and the kidney. The presence of urinary
infection is characterized by the highlighting of significant bacteriuria (21). For confirming
the presence of significant bacteriuria, even asymptomatic, it is required that the presence of
pathogenic germs to exceed 10.5-10.6/ml urine (17.4). The frequency of urinary infection
during pregnancy varies between 2-10% (21). There should be highlighted that asymptomatic
bacteriuria is more frequent in pregnant women than in non-pregnant ones, and that the
genital, digestive and urinary systems have proximity relations, thus influencing each other
regarding their pathology (3, 21). More than 80% of urinary infections are caused by E.COLI
(18).
Symptomatic and asymptomatic bacteriuria may be associated with prematurity, fetal
hypotrophy, preeclampsia, amniotitis (10). The changes of the urinary system during
pregnancy, namely the increase of volume due to a high blood flow and also the dilation of
urinary ways due to endocrine changes, but also the change of the immunologic response,
lead to a higher frequency of urinary infection during pregnancy (5, 12, 16). Asymptomatic
bacteriuria is present during between 4-8% pregnancy, mainly in the 1st trimester. The gram
negative germs (E. COLI AND PROTEUS PSEUDOMONAS) are involved in 90% of the
cases, but there are also involved positive gram germs and Chlamydia microplasma (18). The

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data in the literature show that a high number of pregnant women with asymptomatic
bacteriuria may develop further lesions specific to pregnancy pyelonephritis (21, 17).
Symptomatic bacteriuria during pregnancy has variable symptoms, from cystitis to
pyelonephritis (21). Most of the time, the germs have an intestinal or vaginal origin. From
herem they reach the kidneys, through the urinary ways. There is also included the bladder-
urethral reflux (22, 23). The risk for fetal death is quite low, still the risk for premature birth,
fetal hypotrphy, preeclamsia and chorioamniotitis is quite high (3, 20).
The diagnosis of urinary infection is made based on the clinical state (dysuria, fever, pain
abover the pubic area), but there are also found leukocyturia, hematuria, bacteriuria. The MRI
ultrasound supports the diagnosis. The test for antibody fixation in the pathogen
microorganism is used for germ localization. The treatment purpose is to maintain the general
state and antibiotic according to the antibiogram. There are also treated the genital and
intestinal infections. And there are also removed the factors favoring the infection – kidney
stones, etc. (23).
Commonly, the healing process lasts for 7-14 days.
Premature birth is defined as a birth that takes place between 28-37 weeks, with a fetus
under 2500 grams, the WHO reduced the gestational age and also imposed other criteria.
Premature birth varies between 4% in Belgia and 44% in Pakistan. In Romania, the
numbers vary around 10%. A newborn is HYPOTROPHIC WHEN THE BODY WEIGHT
AND/OR SIZE are below a limit established for a reference population. The causes of fetal
hypotrophy may be numerous, namely diseases of the mother or fetus, infectious, vascular,
tumoral, utero-placental processes, poor nutrition, etc. The clinical, imagistic, biochemical
observation of the fetus and of the amniotic liquid or the placenta confirms the diagnosis of
hypotrophy and its evolution. THE MECHANISM through which urinary infection triggers a
premature birth and fetal hypotrophy is quite complex, either hyperthermia, or metabolic,
ionic, enzymatic changes, the most severe being the entering of germs and their toxins in the
blood, reaching the utero-pacental structures, thus causing chorioamniotitis (5). Clinically, the
process is a severe acute one, but, most of the time, it progresses to symptoms and signs, the
state leading to a premature birth and fetal hypotrophy (13). In PLACENTAL
CHORIOAMNIOTITIS, the membranes lose their shine; they present small abscesses and
surface necroses. The placental vessels are thrombotic and the leukocyte infiltrate is a massive
one.

Materials and Methods

In objectivizing the infectious urinary pathology in premature birth and fetal hypotrophy,
we statistically studied the presence of urinary infection in a group of 1252 premature births,
of which 363 with hypotrophic fetuses in the clinics of Craiova in the last 3 years. We
excluded other CLEARLY involved factors. For supporting the involvement of urinary
infection, there was clinically highlighted urinary infection. The germs were determined by
urine full exam, and also a possible presence of the germs in the amniotic liquid, in the
placenta, being retained the presence of the same germs in the urine and amniotic structures.
For determining the presence of germs in the urine and amniotic liquid there were
performed inseminations on a blood agar plaque with a diameter of 15cm. The number of
colonies was highlighted after 24 hours. Of the colonies, there was harvested for germ
highlighting. In pregnant women with clear urinary infections and with amniotic infection,
there was dosed interleukin-6, whose values are increased in infectious processes and it is
involved in the onset of uterine contractions through prostaglandins (ELLISA test). The
harvesting of amniotic liquid was done at delivery or by amniotic puncture. The diagnosis of
premature birth, fetal hypotrophy, urinary infection, chorioamniotitis was established through

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anamnesis, clinical examination, biological samples, imagistic examination, histopathological


examination, germ determination. For the determination of results there was used the
STUDENT test.

Results

Out of the total number of 9062 births in the clinics of Craiova in the last 3 years, there
were recorded 1252 premature births, of which 363 were with hypotrophic fetuses.

Table 1A.
According to the test, there was found a high number of premature births of 13.8%, of which 28% are
hypotrophic fetuses. Due to the fact that the numbers vary a little every year, we took into consideration a single
year regarding premature birth and premature births with hypotrophic fetuses.

Table 1B. Total urinary infection cases during pregnancy in the last 3 years (2015-2017)
Total birhts Total urinary infections
9062 274/3.03%

Most clinical forms are pregnancy pyelonephrites (91%), the major involved germ being
E.COLI.
Asymptomatic bacteriuria was found in 2.1% of the total number of births regarding the
premature births, namely premature births with hypotrophic fetuses.
Table.2
The most frequent causes are given by the maternal medical factors, but there are also
involved multiple fetal-placental factors.
Table 3
Table 4
Table 5
Table 6 Profession of pregnant women with urinary infection:
- workers 33%
- housewives 27%
- clerks 21%
- agricultoare 17%
The study of vaginal flora in pregnant women with urinary infections did not show any
major changes in comparison to the vaginal flora of pregnant women without urinary
infection.
Ethiopatogenetic, clinical and histopathological aspects on the involvement of urinary
infections outbreak in preterm births with fetal hypotrophy

Table 1. The number of premature births and births with hypotrophic fetuses
Year 2015 2016 2017 Total
Total births 3312 2950 2800 9062
Premature births 452 420 380 1252 (13,8% in all births)
Premature births with hypotrophic fetuses 131 110 121 363 (28% in all premature births)

Table 2. Causes of premature births and premature births with hypotrophic fetuses.
Year 2017
Causes Total premature Total premature births with
hypotrophic fetuses (121)
Medical maternal factors 150 (39,4%) 68 (56,14%)
Feto-placental factors 60 (15,7%) 22 (18,1%)
Social and economic factors 50 (13,1%) 20 (16,5%)
Unknown factors 120 (31,5%) 11 (9%)

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Table 3. Urinary infection involved in premature births with hypotrophic fetuses


Total premature births with hypotrophic fetuses Urinary foci clearly involved
121 32 (26,4%)

Table 4. Germ colonies grown from amniotic fluid cultures and urinary infection and common germs involved
Number of colonies in Number of colonies in Common germs
urinal foci amniotic fluid cultures
Studied pregnancies with 20 15 staphylococcus
premature birth and streptococcus
hypotrophic fetuses (30 E. coli
cases) enterobacteria
Control group (30 cases) 3 5 Proteus

Table 5. Amniotic fluid IL6 titers in pregnant women with preterm hypotrophic fetuses
Premature births with hypotrophic fetuses – in 57 ng/ml
pregnancies with uritary foci
Pregnancies without urinary pathology (births with 52 ng/ml
eutrophic fetuses)

Discussion of Results

The percentage of premature births in the studied area was 13.8% and, of these, 28% were
births with hypotrophic fetuses (Table 1A); the percentages are higher than the mean values
all over the country, this being explained by the poor nutrition in the area (5, 12). Causes of
premature birth and fetal hypotrophy are complex ones, our study showing a major
involvement in pregnancies of HBP, urinary infections, or other fetal-placental conditions
associated to pregnancy, lifestyle and work conditions, with 30-40% unknown factors (Table
2). There should be underlined that urinary infection is highly involved in premature birth and
fetal hypotrophy (Table 1B). A quite frequent asymptomatic evolution of urinary infection
makes it to remain unobserved, leading even to septic states (20, 21, 22). In Table 3 there may
be observed that of a total 121 premature births with hypotrophic fetuses in 2017, 32 cases
(26.4%) came from pregnancies with urinary infections. The urinary infectious pathology
during pregnancy causes changes of the renal function, with vomiting, with changes in the
placental exchanges, with effects upon the growth and development of the conception
product; a very severe situation is when the germs and their toxins enter from the urinary
foccus into the blood, that may reach the utero-placental structures in the amniotic liquid, thus
causing their infection, namely chorioamniotitis (17, 9, 20). Data on chorioamniotitis (9) are
known in the specialized literature, but there is little data on the involvement of urinary
infection. The damaging of utero-placental tissues leads to the interference in the growth and
development of the conception product. The clinical forms of chorioamnititis are rare, acute,
they generally progress with faded symptoms or without any symptoms al all (21, 22), a fact
that was highlighted by us in the clinically monitored cases and by germ detection,
histopathological and imagistic examinations.

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The utero-placental infection, including of the fetus sometimes, leads, most of the time, to
a premature births and fetal hypotrophy, fetal death during premature death. It is well-known
the fact that (14, 15) the affected utero-placental structures release phospholipase A2 and
interleukins that play a part in the synthesis of prostaglandins that cause uterine contractions
and premature birth (Table 5). The release in the blood of germs and their toxins is done with
intermission from the septic urinary foccus, before the bacteremia remain constant. Pregnant
women with urinary infection are predisposed to over 12% of births with hypotrophic fetuses
(9).
Besides the germ colonies found in the amniotic liquid and infected urine (Table 4), we
observed that the vaginal flora of normal pregnant women, without any ruptured membranes,
and the vaginal flora of pregnant women with urinary infection did not differ much (1, 23).
The pregnant women included in the study had infected membranes until delivery. The
placentas and membranes under study, where chorioamniotitis was involved, lose their shine,
have grey color and present small abscesses in a macroscopic view. The umbilical cordons are
edematous, with areas of thrombosis and necrosis, the microscopic study showing a massive
leukocyte infiltrate, sub chorionic abscesses, thrombophlebites and necrosis.

Conclusions

1) The bacterial flora from the infected urine by bacteremia may determine utero-
placental septic foccus, most of the time leading to premature birth and fetal
hypotrophy.
2) Urinary infection was present in 3.03% of the group of studied pregnant women (9062
births).
3) Of the total of premature births with fetal hypotrophy, 26.4% are found in pregnancies
with urinary infection.
4) Germs, toxins and destruction materials from the infectious urinary foccus may reach,
via blood, to the utero-placental structures, amniotic liquid and fetus, thus causeing
chorioamnititis and fetal suffering.
5) Chorioamniotitis progresses, most of the time, with faded symptoms or without any
symptoms at all, but it affects the fetus, who dies or develops with growth restrictions.
6) Decidual cells, amniotic cells under the action of pathogen agents, secrete interleukins
that lead to the increase of prostaglandin number, which leads premature birth.
7) The histopathological examination of the placenta, the bacteriological and imagistic
examinations showed the presence of chorioamniotitis, even in the absence of clinical
symptoms.

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REFERENCES

1. Newton E R Bacterial Vaginosis And Intramniotic Infection – Amj.Obs-Gynecol 1997 pp. 176-179.
2. Reid G. Probiotics How Microorganisms Complete Jana, 1966 276 29-30.J.M.
3. Savage D.C. Microbial Ecology Of The Gastrointestinal Tract Ann.Rev. Microbial, 1987 31, pp. 107-
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4. Stamm N Cateter-Asociated Urinary Tract Infection Am.J.Med. 1991 91 655.
5. Munteanu I. Raca N., Tratat De Obstetrica, Ed. Academiei 2006 pp. 1115-1130.
6. Crisan N. Nasterea Prematura Ed. Info 2001.
7. Raca N. Ginecologie Editura Medicala Craiova, 2005.
8. Teodorescu M. Patologia Placentei Ed. Flacla 1997, 113-120, 143-154
9. Friptu V. Afectiuni Purulente Septice In Obstretica Ed. Testemiteanu 2003 Chisinau 167-184.
10. Goldenberg-Intrauterin Infection And Preterm Delivery N.Enbl.J.Med 2005 1500-1507.
11. Moraru I.Anatomie Patologica Ed.Medicala 1990 202-247.
12. Raca N.Obstetrica Ed.Editura Medicala Universitara Craiova 2005.
13. Denson C.The Action Of Prostaglandine In The Uman Cervix Am.J.Obst.Gynecol 1999 614-620.
14. Wong X Trudinger B,A Proinflamatory Cytokine Response Is Present In The Placental Vasculare In
Placental Insufficiency Am.J.Obstet.Gynecol,2003 1145-1451.
15. Dafnis E.The Effect Of Pregnancy On Renal Fuction Am.J.Med.Sci.1992 184-205.
16. Millar L K.Urinary Tract Infection,Complicating Pregnancy Inf.Clin.North.Am.1997 13-26.
17. Gi Lstrop Lc.Urinary Tract Infection During Pregnamcy Obstet .Ginecol Clin North Am. 2001 581-591.
18. Sanberg T.Efficacy Of Long-Term Antimicrobian,Prophylaxi After Acut Pyelonephritis In Pregnacy
Am.J,Obst.Ginecol,1991 221-223.
19. Particularitatiile Evolutiei Sarcinii La Gravidele Cu Pielonefrita Ed.Testemetian Chisinau-Catedra De
Obst.-Ginec.2013.
20. Kaas E.Bacteriuria And Pyelonephritis Of Pregnancy Arch.Inter,Med.1990 105-104.
21. Zosin C.Bolile Renale Care Apar In Cursul Sarcinii Si Postpartum Ed.Facla Timisoara 1995 185-209.
22. Gregor I.Prevention Of Premature Birth And Treatment For Genital Tract Infection Am.J.Ostet-
Ginecol.1995 157-167.
23. Gazdac R. Pielonefrita Gravidica Teza De Doctorat 2003 Umf Craiova.

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Does the Romanian Population Give the Necessary Importance


for Obstetric Ultrasound Examination and Pregnancy Follow-Up?

GHEORGHIU Diana Claudia1, SOCEA Bogdan1,2, CONSTANTIN Vlad Denis1,2,


GHEORGHIU Nicolae2, CĂLIN Florin Daniel1,2, DAVIȚOIU Bogdan Andrei1,
ROȘU George-Alexandru1, MATEI Alexandra1, VIEZUINĂ Roxana1
1“Sf Pantelimon” Clinical Emergency Hospital, Pantelimon Blvd, no 340-342, 021661, Bucharest (ROMANIA)
2Carol Davila University of Medicine and Pharmacy, Dionisie Lupu St, no 37, 020021, Bucharest (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

The objective of our study was to find out the real importance of rightly pregnancy follow-
up and obstetric ultrasound examination between Romanian pregnant women. We developed
a retrospective, populational-based study (based on volunteering and anonymity), between
March and April 2016, which included 169 patients admitted for birth assistance to the
Department of Obstetrics and Gynecology from “Sf Pantelimon” Clinical Emergency
Hospital, Bucharest, in that time period. Out of 169 patients, 144 patients (85,2%) have been
to the doctor for periodic follow-up and 89 of them (52,7%) affirmed that they have had more
than 10 follow-up visits during pregnancy. 51 patients (30,2 %) have had they pregnancy
followed-up only at the obstetrician and with every visit they also have had performed and
obstetric ultrasound examination. 88 of them (52,1%) where examined by the obstetrician and
also by their family physician, a fact that leaded to a percentage of 82,3% (139 of 169 cases)
of obstetrician involvement and use of obstetric ultrasound examination in pregnancy follow-
up in our study group.
Keywords: obstetric ultrasound, pregnancy follow-up, medical education, reproductive health, quality of life

Introduction

The fact that the modern obstetrical diagnosis [1-21], but especially the gynecological one
[22-28], cannot be conceived in the absence of obstetrical-gynecological ultrasound is no
longer just a “slogan” or a simple medical marketing policy. Also, the fact that a good
reproductive health reflects a better quality of women's lives and that these are closely
correlated with a high level of healthcare are almost axiomatic statements today [21]. The
utility of quarterly obstetric ultrasound examination is today postulated by most guides and
studies on rightly pregnancy follow-up (regardless if it’s a low-risk or high-risk pregnancy)
[1-16]. Although these are obvious to the medical professionals, laypersons do not see these
facts in the same manner. Motivated, among other things, by these observations and with the
desire to determine the exact importance bestowed by pregnant women from Romania
regarding rightly pregnancy follow-up and obstetric ultrasound examination performed with
the occasion of periodic follow-up visits during pregnancy, we developed a retrospective,
populational-based study (conducted by means of volunteering and anonymity) between
March and April 2016, which included a number of 169 pregnant women admitted for birth
assistance to the Department of Obstetrics and Gynecology from “Sf Pantelimon” Clinical
Emergency Hospital, Bucharest, in that time period [15]. The study also had the explicit

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purpose of investigating the addictive behaviors of the Romanian pregnant population


regarding tobacco products, alcohol and drugs [15].

Methods

This retrospective, populational-based study [20] included 169 pregnant women (N=169)
admitted for birth assistance to the Department of Obstetrics and Gynecology from “Sf
Pantelimon” Clinical Emergency Hospital, Bucharest (tertiary maternity center – a centre of
excellence, which offers tertiary care services and has complex capabilities, handling cases
from both the capital and the rest of the country), in the period between March 1st, 2016 –
April 30th, 2016. We included in our study 169 pregnant women that gave birth in this
department, from a total number of 1474 women admitted for birth assistance to our
department, meaning 11,46% of the postpartum females of this tertiary maternity center from
2016. From the 169 births of those pregnant women included in the study resulted 172
newborns (3 pregnant women with multiple pregnancy, each of them with two fetuses),
meaning a percentage of 11,48% from the 1497 newborns that were born in this department in
2016 [15]. The study involved questioning of anonymous, voluntary, unpaid patients through
a questionnaire that included 14 statistical questions. For the 14 close-ended questions the
respondents were supposed to tick the answer with a simple “X”. The filling in of the opinion
poll was also the informed consent for participation in the study and publication of its results
in scientific papers. In order to preserve anonymity, data contained in the database can not
lead to the identification of the respondent or the fetus [15].
The inclusion criteria (which had to be fulfilled simultaneously) were: pregnant woman
that gave birth in the the Department of Obstetrics and Gynecology of “Sf Pantelimon”
Clinical Emergency Hospital, Bucharest, in the period between March 1st, 2016 – April 30th,
2016, which wanted to respond voluntarily, anonymously and uncompensated (material or
other nature) to the opinion poll and to participate anonymously, voluntarily and
uncompensated in the study; patients who agreed that the data related to the newborns
resulted from theirs pregnancies (number of fetuses, gestational age, fetal weight, APGAR
score) as well as obstetrical history data can be used in the study (and the resulting scientific
publications). The inclusion criteria did not allow discrimination of the study participants in
any way (depending on education, schooling, ethnicity, nationality, age, social origin, marital
status, economic status, religion, political beliefs, occupation, race etc.). In order to achieve
this goal, after we explained to patients, in layman's terms, what are the objectives, usefulness
and stages of the study, any patient who wanted to participate anonymously, voluntarily and
unpaid in the study was accepted after expressing her free consent for participation. The only
exclusion criterion from the study (applied immediately) was the verbal refusal to participate.
The study also included patients who did not know how to write and read – these ones
have being helped by the research team to fill in the answer to the questions.
In order to be as objective as possible and for patients to participate voluntarily (without
feeling that they would be discriminated against or disadvantaged in any way if they refuse),
they were interviewed about their willingness to participate in the study and the questionnaire
was given to them for filling in on the day (calendar day) immediately following that in which
they gave birth.

Results and Discussions

After a prior demographic description of the patient group (N=169), in Table no. 1 we
included the main conclusive data of our study on correct or incorrect pregnancy follow-up
included in the study and the performance or non-performance of obstetrical ultrasound

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examination during these pregnancies [15]. In order to better manage the information, we
pointed out the discussions for each of the features of the batch studied in the last column of
the table.

Table 1. Characteristics of the patients included in the study


Variable Value (N=169) Percentage Discussions
Patient age (years)
13-17 12/169 7,1%
18-20 20/169 11,8%
21-24 26/169 15,4% Patients in the 25-29 years old interval
25-29 53/169 31,4% predominate; widened range 25-34 years
30-34 41/169 24,3% represent 94/169 cases (55,7%)
35-39 14/169 8,3%
40-44 3/169 1,8%
45 and above - -
Tuition level (classes)
0 11/169 6,5%
Patient with secondary education level
1-4 (primary education) 9/169 5,3% predominate (9-12 classes), followed by the
5-8 (gymnasium) 32/169 18,9% ones with higher education.
9-12 (secondary education) 58/169 34,3% Patients very little or not at all schooled (0-4
Vocational school 9/169 5,3% classes) = 20/169 (11,8%).
Higher education 50/169 29,6%
Primiparous 90/169 53,2%
Primiparous predominate
Multiparous 79/169 46,7%
Follow-up visits
Yes 144/169 85,2% Patients who didn’t have any follow-up visits
during pregnancy constitute a minority in the
No 25/169 14,7% study group (14,7%).

No. of follow-up visits


0 25/169 14,8% 64.7% of the patients include in the study
1-5 33/169 19,5% group had a reasonable follow-up during
6-9 22/169 13,0% pregnancy (6 follow-up visits or more).
10 or more 89/169 52,7%

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Table 1. (cont’d)
Variable Value (N=169) Percentage Discussions

Type of follow-up visit 25/169 14,8%


None
Family physician (without obstetrical
5/169 3,0% The obstetrician and the obstetrical
ultrasound examination)
ultrasound examination were involved in
Obstetrician (with
82,3% of the cases (139/169 cases).
obstetrical ultrasound examination) 51/169 30,2%
Both (with
obstetrical ultrasound examination)
88/169 52,1%
Do patients find it useful to have a
pregnancy followed-up by a physician
and to have had performed obstetric A minority of patients thinks that pregnancy
ultrasound examination during follow-up and Obstetric ultrasound
pregnancy? examination is useless.
Yes 165/169 97,63%
No 4/169 2,36%

Does the patients consider useful pre-


and postnatal education (“Pregnant
A minority of patients thinks that this kind of
women school”/ ”Parents school”) ?
health education is useless.
Yes
148/169 87,57%
No
21/169 12,42%

Average gestational age (at birth) of 37.95 +/- 2.248


the fetuses born from the pregnancies weeks -
included in the study group 38.0 [38.0,39.0]

Conclusions

Patients who didn’t have any follow-up visits during pregnancy constitute a minority in the
study group (25 out of 169 cases = 14,7%).
64.7% of the patients include in the study group had a reasonable follow-up during pregnancy
(6 follow-up visits or more).The obstetrician and the obstetrical ultrasound examination were
involved in 82,3% of the pregnancies analyzed in our study (139 out of 169 cases).
A minority of patients thinks that pregnancy follow-up and obstetric ultrasound examination
are useless (4 out of 169 cases = 2,36%) and a larger minority of patients thinks that pre- and
postnatal education (“Pregnant women school”/“Parents school”) are useless (21 out of 169 cases
= 12,42%).
These figures should motivate healthcare professionals of all levels and the institutions with
jurisdiction in the field to promote as much as possible and intensively health education among
children, adolescents, young people and pregnant women.

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17. Navolan, D; Birsasteanu, F; Carabineanu, A; Cretu, O; Badiu, DL; Ionescu, CA; Mehedintu, C; Vladareanu,
S; Craina, M; Boia, M; Ciohat, I; Craciunescu, M; Simu, S; Nemescu, D – Does Active Smoking Influence
the Second Trimester Biochemical Markers Concentrations? – REVISTA DE CHIMIE Volume: 68 Issue:
10 pp. 2234-2236.
18. Mihai Dimitriu, Mihail Bănacu, Ina Popescu, Roxana Viezuină, Alexandra Matei, Crîngu Ionescu –
Nașterea la adolescente – o problemă de sănătate publică în România – Forum Ginecologia.ro 2018, Ediția
a V-a, București, 23-24.03.2018, Ginecologia.ro, Anul VI,Nr. 19 (1) 2018, DOI: 10.26416/Gine.19.1.2018
pag. 56, ISSN 2344-2301, e-ISSN 2457-3566, ISSN-L 2344-230.
19. Novac, Liliana; Tudorache, Stefania; Manolea, Magda; et al. Edited by: Vladareanu, S; Marginean, C;
Vladareanu, R – The Use of Doppler Ultrasound as Early Parameter for Detection of Fetal Compromise in
Restricted Fetuses – 5th Romanian Congress of the Romanian-Society-of-Ultrasound in Obstetrics &
Gynecology, Targu Mures, APR 20-22, 2017, pp 445-449.
20. Novac, Liliana; Niculescu, Mihaela; Manolea, Maria Magdalena et al. – The vasculogenesis – a possible
histological identification criterion for the molar pregnancy; ROMANIAN JOURNAL OF
MORPHOLOGY AND EMBRYOLOGY 2011, Volume: 52 Issue: 1, pp. 61-67.
21. Mocuță Dorina, Popvici Laura Roxana, Dumitriu Anca Silvia, Burlibașa Liliana, Ionescu Crîngu Antoniu,
Sfeatcu Ruxandra – Life quality – condition of social welfare – Metalurgia International, Volume: 14, pp.
62-64, 2009, Accession Number: WOS:000272155900013 , ISSN: 1582-2214.
22. Olaru Gabriel Octavian, Cringu Ionescu, Anca Lesnic, George Alexandru Filipescu, Liana Ples – Ethical
and medicolegal aspects of the therapeutic abortion – our experience, Rom Journal Leg Med 2018, (26) pp.
82-85.
23. Crîngu Antoniu Ionescu, Ina Popescu, Mihail Bănacu, Mihai Dimitriu – Lifestyle Changes and Weight Loss:
Effects in PCOS (Cap. 4) in „Debatable Topics in PCOS Patients” – Edited by Neeraj Kumar Agrawal and
Kiran Singh, InTech, ISBN 978-953-51-3812-9, Print ISBN 978-953-51-3811-2, publicated in February 14,
2018 under CC BY 3.0 license – DOI: 10.5772/intechopen.68300;
http://dx.doi.org/10.5772/intechopen.73298.
24. Ionescu Crîngu, Bănacu Mihail, Popescu Ina, Ionescu Andra, Vlădăreanu Simona, Dimitriu Mihai –
Ultrasound diagnosis of endometrial cancer in asymptomatic menopausal women – 5th Congress of the
Romanian Society of Ultrasound in Obstetrics and Gynecology, Târgu Mureș, 20-22 april 2017, June 2017,
ISBN 978-88-95922-88-1, pp. 199-202, Accession Number: WOS: 000406419700034.
25. Bogdan Socea, Laura Ileana Socea, Ovidiu Gabriel Bratu, Bogdan Mastalier, Mihai Dimitriu, Alexandru
Carap, Vlad Denis Constantin - Recurrence Rates and Mesh Shrinkage After Polypropylene vs. Polyester
Mesh Hernia Repair in Complicated Hernias – Materiale Plastice (Bucharest),
http://www.revmaterialeplastice.ro, Chem. Abs.: MPLAAM 55 (1) (1-136), ISSN 0025-5289, Vol. 55, no. 1
March, 2018, pp.79-81.
26. Crîngu Antoniu Ionescu, Dan Navolan, Alina Călin, Alexandra Matei, Roxana Bohîlțea, Mihai Dimitriu,
Corina Ilinca, Liana Pleș – Hormonal contraception in postpartum patients with gestational diabetes
mellitus – Revista de Chimie, www.revistadechimie.ro, REV.CHIM.(Bucharest), 69, No. 2,2018, Vol.69,
no. 2, February, 2018, pp. 478-483, ISSN 0034-7752, ISSN-L 1582-9049, Chem.Abs.:RCBUAU69(2) (291-
538).
27. Crîngu Antoniu Ionescu, Simona Vlădăreanu, Liana Pleș, Mihai Cornel Traian Dimitriu, Gheorghe Oto
Furău, Teodora Camelia Vlădescu, Alina Mihaela Călin, Nuți Daniela Oprescu – Synchronus bilateral
primary ovarian carcinoma – case presentation – Romanian Journal of Morphology and Embryology –
Rom J Morphol Embryol 2017, 58(1):219-223, Romanian Academy Publishing House, Volume 58 Number
1, 2017, pp. 219-223, ISSN (print): 1220-0522, Accession Number: WOS: 000402584100032, PubMed ID:
28523322.
28. Socea Bogdan, Alexandru Carâp, Smaranda Alexandru, Moculescu Cezar, Bobic Simona, Dimitriu Mihai,
Socea Laura, Vlad Denis Constantin – Delayed Recognition of a Sigmoid Colon Iatrogenic Lesion
Following Total Abdominal Hysterectomy in a Patient with a Previous Episode of Acute Diverticulitis – The
13th National Congress of Urogynecology UROGYN 2016, România – November 2016, ISBN 978-88-
95922-78-2, Accession Number: WOS: 000389054300009

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The Role of Theoretical Ultrasound Training in Improving the


Estimated Fetal Weight

GRAMA Ovidiu1, GLIGA Marius1, VOIDĂZAN Septimiu2


1UMPh Târgu-Mureș, Obstetrics-Gynecology 2 Department (ROMANIA)
2UMPh Târgu-Mureș, Epidemiology Department (ROMANIA)
Emails: [email protected], [email protected], [email protected]

Abstract

Introduction
Ultrasound is considered to be the first-line method in imaging investigation of women’s
health. The accuracy of the ultrasound is primarily dependent on the operator’s ability to use the
device to obtain representative images and then interpret them. The education and training of
medical staff performing ultrasounds is therefore crucial.

Methods
We conducted a study at the Obstetrics and Gynecology Clinic 2 Târgu-Mureş in which we
compared the accuracy of the ultrasound fetal weight estimation to women who gave birth to our
clinic before and after a theoretical instruction to remind the rules for carrying out the specific
measurements.

Results
In the first group we included 921 patients who delivered in our clinic between January and
October 2017 and who had an ecographic fetal wight estimation during the respective admission.
The second group was formed of 456 patients who delivered between November 2017 and
March 2018 and who had an ecographic fetal wight estimation after physicians had been trained.
There was an improvement in the accuracy of the measurements made after the training, in
terms of weight estimates closer to birth weight (61.53% of specialist doctors and 56.25% of
resident doctors), but the results weren’t statistically significant.

Conclusions/Discussion
Continuous training is a means of improving the quality of ultrasound examinations.
Keywords: ultrasound, estimated fetal weight, birth weight

Introduction

Ultrasound is considered as the first-line imaging method of choice in women’s health. It is a


simple, accurate and safe technique, making it amenable to use in both developed and
underdeveloped countries. Ultrasonography is used both for screening and as a diagnostic tool in
the presence of clinical symptoms. [1] In modern obstetrics, estimated fetal weight is bounded
with decisions related to prematurity, intrauterine growth restriction and macrosomy. [2] The
accuracy of ultrasonography is linked to several technical factors, including those associated with

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both patient and machine. However, it is dependent primarily on the skill of the operator in using
the equipment in order to obtain and interpret representative images. The teaching and training of
medical health professionals performing ultrasonography is, therefore, crucial. It is the view of
the ISUOG Education Committee that systematic training in ultrasonography can increase the
efficiency of the learning process. [1]
There are several calculation formulas for estimating fetal weight, which are using one or
more parameters, usually the most commonly used associate the biometry of the femur with that
of the abdomen and possibly the skull (femur length – FL, transverse abdominal diameter – TAD,
abdomen circumference – AC, biparietal diameter – BPD). Accuracy is 5-10%. [2] In the second
trimester of pregnancy, BPD accurately reflects gestational age, with a variation of 7 to 10 days.
The variability of estimated gestational age and fetal weight increases as pregnancy
progresses. Individual measurements are the least accurate in the third trimester, with sonography
accuracy ranging from up to 3-4 weeks. [3]

Methodology

We conducted a study at the Obstetrics and Gynecology Clinic 2 Târgu-Mureş in which we


compared the accuracy of the ultrasound fetal weight estimation in the women who gave birth in
our clinic. This study was performed in two stages.
In the first stage, we followed the ultrasound estimated fetal weight (EFW) in the patients who
presented themselves in our service for delivery and we compared it with the birth weight (BW)
of the newborn. After this first stage, we conducted a theoretical course of reminding the
principles of making the correct ultrasound measurements, which was attended by all physicians
who are currently doing fetal ultrasounds measurements, residents and specialists. After the
course, we followed the second stage of our study, which also looked at the EFW and compared it
to BW, trying to see if there was an improvement in its accuracy.
In the first batch we studied 921 pregnant women who were hospitalized in our clinic between
January and October 2017 and in the second batch we included 456 pregnant women hospitalized
between November 2017 and March 2018. The criterion for inclusion in both lots was the
existence of an ultrasound EFW performed during hospitalization with a maximum of 24 hours
before birth.
Measurements were performed with a GE Logiq S6 ultrasound, and the calculation formula set
on this ultrasound was that developed by Hadlock. The measured parameters for estimating fetal
weight were: biparietal diameter (BPD), abdominal circumference (CA), femur length (FL) and
in some cases cranial circumference (HC).

Results

In the first stage from 921 births resulted 930 newborns. We applied the tests for Gaussian
distribution, resulting that the datas have Gaussian distribution. The paired t-test was applied
without any significant differences between the EFW and the actual BW (p-0.70). Average of
EFW was 3200 grams, and BW was 3197 grams, and the mean of differences was 3.75 grams
(CI95% = -15.67 at 23.18). (Fig. 1, Table 1)

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p-0.70
6000

4000

grame
2000

0
Gr. estimata Gr. nastere

Fig. 1. EFW vs BW in the first stage

Table 1. First stage statistic values


EFW BW
Number of values 930 930
Minimum 1200 1410
Median 3200 3205
Maximum 4750 4770

Mean 3200 3197


Std. Deviation 490,1 529,4
Lower 95% CI 3169 3163
Upper 95% CI 3232 3231

In the second phase of the study, conducted after the course, 456 newborns were enrolled. The
data also had Gaussian distribution. We applied the paired t-test without significant differences
between EFW and BW (p-0.33, 3236 g vs. 3222 g); the average of the differences between
estimated mean weight and birth weight was higher than the first step (13.81 with CI95% = -
13.97 to 41.58). (Fig. 2, Table 2)
p-0.33
6000

4000
grame

2000

0
Gr. estimata Gr. nastere

Fig. 2. EFW vs BW in the second stage

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Table 2. Second stage statistic values


EFW BW
Number of values 456 456
Minimum 1350 1200
Median 3277 3220
Maximum 5850 5530

Mean 3236 3222


Std. Deviation 473,1 514,1

Lower 95% CI 3192 3175


Upper 95% CI 3279 3269

We also compared the differences in weights in stage 1 vs. the differences in weights in stage
2, the result being also insignificant statistically (p-0.56). (Table 3)

Table 3. The differences in weights in stage 1 vs. the differences in weights in stage 2
Mean ± SEM of differences in 1st stage -3.752 ± 9.910 N=930
Mean ± SEM of differences in 2nd stage -13.81 ± 14.17 N=456

The results could not reveal an improvement in the weight estimation after attending the
theoretical course, but it is worth pointing out that the weight estimation was anyway very close
to BW also before the course.
In addition to the overall comparison of the fetal weight estimated by the ultrasound and the
weight at birth, we followed the same thing individually to the physicians, the results obtained
being shown in the table 4.

Table 4. Mean ± SEM of differences – specialist physicians


p value Mean ± SEM of Mean ± SEM of
differences in 1st stage differences in 2nd stage
Specialist physician 1 0,7029 15.96 ± 33.59 N=90 -2.493 ± 33.08 N=67
Specialist physician 2 0,9054 -13.00 ± 31.45 N=111 -3.739 ± 78.78 N=23
Specialist physician 3 0,3062 29.17 ± 26.31 N=115 -19.74 ± 42.04 N=57
Specialist physician 4 0,2848 52.70 ± 56.93 N=40 -47.12 ± 74.20 N=26
Specialist physician 5 0,8761 14.20 ± 38.88 N=54 4.800 ± 44.43 N=35
Specialist physician 6 0,0828 5.478 ± 26.91 N=113 -64.81 ± 28.69 N=77
Specialist physician 7 0,6301 64.61 ± 46.49 N=56 28.00 ± 57.46 N=31
Specialist physician 8 0,0077 -97.87 ± 26.67 N=95 18.63 ± 31.46 N=51
Specialist physician 9 0,2849 -26.21 ± 33.29 N=86 47.81 ± 71.03 N=36
Specialist physician 10 0,4446 65.75 ± 84.95 N=4 -64.29 ± 111.2 N=7
Specialist physician 11 0,4755 -14.14 ± 37.47 N=59 -91.25 ± 92.88 N=8
Specialist physician 12 0,0278 141.5 ± 60.00 N=14 504.0 ± 165.8 N=3
Specialist physician 13 0,1928 -24.84 ± 31.75 N=82 -101.3 ± 47.25 N=33

The results were statistically significant only in the case of 2 specialist physicians, in one case
with an improvement in the weight estimate, and in the other case with an increase in the
difference between the estimated weight and the actual weight at birth, but in this case there were
very few ecographic estimates in the second stage, which probably influenced the outcome.
If the difference between EFW and BW is closer to 0, the estimation of fetal weight is more
accurate, and the proximity closer to 0 in the second step signifies an improvement in the

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estimation of fetal weight. This was observed in the case of 8 doctors, representing 61.53% of
specialist physicians.
For resident doctors, the results were synthesized in Table 5.

Table 5. Mean ± SEM of differences – resident physicians


p value Mean ± SEM of differences Mean ± SEM of
in 1st stage differences in 2nd stage
Resident physician 1 ALB 0.10 -73,143±42,565 N=74 -214,880±59,591 N=25
Resident physician 2 DUM 0.91 -74,433±54,399 N=37 -61,429±112,617 N=7
Resident physician 3 FIL 0.59 -113,672±37,245 N=108 -83,227±44,919 N=44
Resident physician 4 GHE 0.26 41,644±31,407 N=111 -41,667±65,019 N=21
Resident physician 5 ION 0.38 51,593±38,791 N=95 -4,389±49,659 N=36
Resident physician 6 NEG 0.24 69,038±33,737 N=110 1,000±52,672 N=32
Resident physician 7 OPR 0.77 60,852±57,342 N=36 86,667±99,319 N=9
Resident physician 8 PAL 0.18 -30,783±62,128 N=43 -180,500±66,625 N=20
Resident physician 9 PAP 0.36 -90,927±46,533 N=56 -15,200±76,932 N=15
Resident physician 10 POL 0.25 43,727±51,868 N=42 -98,556±99,319 N=9
Resident physician 11 RAC 0.16 -59,400±36,957 N=103 28,605±48,335 N=38
Resident physician 12 ROT 0.45 -62,133±76,932 N=20 20,400±133,250 N=5
Resident physician 13 SIM 0.75 45,316±48,335 N=45 40,000±112,617 N=7
Resident physician 14 SPA 0.66 -7,256±47,711 N=49 30,300±94,222 N=10
Resident physician 15 TOT 0.38 -32,636±44,919 N=60 35,500±74,489 N=16
Resident physician 16 VLA 0.25 125,042±60,820 N=46 -105,818±63,525 N=22

The results were not statistically significant, but an improvement in the ultrasound weight
estimate for 9 resident doctors was observed, (56.25%).

Discussions

For the prediction of fetal weight a variety of formulas are used. There is no consensus on
formulas derived from measurements of fetal parts. Race and parity are important parameters to
consider when applying to general population growth curves. Birth weight rates vary from one
population to another, depending on ethnicity, the environment, and socio-economic
circumstances. Fetal growth formulations provide weight estimates with errors of up to 20%
compared to actual birth weights. [4]
Despite the considerable improvements in ultrasound imaging equipment, the precision of fetal
weight estimation has not changed since the development of formulas more than 3 decades ago.
Formulas designed for single pregnancies can also be used to estimate weight in twins because
the formulas specifically developed for them are not more accurate. [5]
The use of customized growth curves appropriate to the local population can help improve the
accuracy of fetal biometric estimation. [4]
Inter and intraobservative variability is great for estimating fetal weight. Higher quality scans
result in more accurate weight estimates. Thus, attempts should be made to minimize this
variability by calculating the average of several measurements of each part of the body, using
careful measurement techniques and optimizing image quality so that the anatomical markers are
clear. [5]
There are studies who pointed out the correlation between excessive gestational weight gain,
according to the IOM recommendations and increased birth weight. [6, 7, 8, 9] New studies
highlighted a significant increase in birth weight and BMI to newborns with polymorfism of
LEPR rs1137101 gene, and that the calculated newborn’s risk percentage for child obesity was

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greater for the variant allele of the TGF-β1 869 T > C polymorphism and also for the wild-type C
allele of the PPARγ2 34 C > G gene polymorphism. [10, 11, 12]

Conclusions

Although the results were not statistically significant, an improvement in the ultrasound
weight estimation was seen in 61.53% of specialist doctors and 56.25% of resident doctors.
Continuous training is a means of improving the quality of ultrasound examinations.

REFERENCES

1. ISUOG Education Committee recommendations for basic training in obstetric and gynecological ultrasound.
Ultrasound Obstet Gynecol 2013 DOI: 10.1002/uog.13208.
2. Mărginean C., Introducere în ecografia obstetricală și ginecologică, University press, Târgu-Mureș, 2008, p.
148
3. Cunningham F., Kenneth L., Bloom S.,Williams Obstetrică – ediția 24, Editura Hipocrate, București, 2017
Cap. Imagistică fetală pp. 194-230.
4. Kuriak A, Chervenak FA, Vlădăreanu R. Donald School – Tratat de Ultrasonografie în Obstetrică și
Ginecologie – Ediția a treia, Editura Medicală Amaltea, București, 2012 Cap. Biometria fetală pp. 199-204.
5. Norton ME, Scoutt LM, Feldstein VA, Vlădăreanu RM Callen – Ultrasonografie în Obstetrică și
Ginecologie – Ediția a 6-a, Editura Hipocrate, București 2017 Cap. Biometria și creșterea fetală pp. 118-
131.
6. Rasmussen KM, Yaktine AL (eds). Weight gain during pregnancy: reexamining the guidelines. Institute of
Medicine (IOM) and National Research Council (NRC) Committee to Reexamine IOM Pregnancy Weight
Guidelines, National Academies Press, Washington, DC, USA, 2009, Available from: http://www.ncbi.
nlm.nih.gov/books/NBK32813/.
7. Mărginean C, Bănescu C, Mărginean CO, Tripon F, Melit LE, Iancu M, Glutathione S-transferase (GSTM1,
GSTT1) gene polymorphisms, maternal gestational weight gain, bioimpedance factors and their relationship
with birth weight: a cross-sectional study in Romanian mothers and their newborns Romanian Journal Of
Morphology And Embryology 2016, 58(4): pp. 1285-1293, ISSN (print) 1220-0522, ISSN (on–line) 2066-
8279,
8. Haugen M, Brantsæter AL, Winkvist A, Lissner L, Alexander J, Oftedal B, Magnus P, Meltzer HM.
Associations of prepregnancy body mass index and gestational weight gain with pregnancy outcome and
postpartum weight retention: a prospective observational cohort study. BMC Pregnancy Childbirth, 2014,
14:201.
9. Faucher MA, Barger MK. Gestational weight gain in obese women by class of obesity and select
maternal/newborn outcomes: a systematic review. Women Birth, 2015, 28(3): e70–e79.
10. Mărginean C, Mărginean CO, Iancu M, Meliț LE, Tripon F, Bănescu C The FTO rs9939609 and LEPR
rs1137101 mothers-newborns gene polymorphisms and maternal fat mass index effects on anthropometric
characteristics in newborns – A cross-sectional study on mothers-newborns gene polymorphisms. The FTO-
LEPR Study (STROBE-compliant article) Medicine 2016, 95:49(e5551), ISSN 0025-7974, online ISSN
1536-5964, IF 2.133 http://dx.doi.org/10.1097/MD.0000000000005551
11. Mărginean C, Mărginean C O, Iancu M, Szabo B, Cucerea M, Meliț L E, Crauciuc A, Bănescu C The role
of TGF-β1 869 T>C and PPAR γ2 34 C>G polymorphisms, fat mass and anthropometric characteristics in
predicting childhood obesity at birth A Cross-Sectional Study according the parental characteristics and
newborn’s risk for child obesity. The Newborns obesity’s risk -NOR-Study (STROBE-compliant article).
Medicine 2016, 95:29(e4265), ISSN 0025-7974, online ISSN 1536-5964, IF 2.133,
http://dx.doi.org/10.1097/MD.0000000000004265
12. Mărginean C, Mărginean C O, Bănescu C, Meliț L, Tripon F, Iancu M Impact of demographic, genetic and
bioimpedance factors on gestational weight gain and birth weight in a Romanian population. Medicine
2016, 95: 27(e4098), ISSN 0025-7974, online ISSN 1536-5964, I F 2.133
http://dx.doi.org/10.1097/MD.0000000000004098.

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Cesarean Section and Hernia Repair: A Merged Intervention

GRIGORIU Corina1,2, HORHOIANU Irina Adriana1,2, DRAGOI Vlad2,


LUTIC Catalin3, GRIGORIU Mihai1,3
1 Medical University Carol Davila Bucharest, Obstetrics & Gynecology Department, (ROMANIA)
2 Obstetrics – Gynecology Department, Bucharest Emergency University Hospital, (ROMANIA)
3 General Surgery Department 1, Bucharest Emergency University Hospital, (ROMANIA)

Email: [email protected]

Abstract

Introduction
With the advanced age at which women choose to become pregnant and the increase in the
incidence of obesity, there are increases in the incidence of associated pathology, such as the
abdominal wall defects (umbilical, paraumbilical or inguinal hernia).

Material and Method


We evaluated the duration of the intervention, the complication rate, the pain perception, the
recovery time and the satisfaction rate in a group of patients who benefited from the surgical cure
of a hernia at the same time with the cesarean section cesarean (17), with an average age of 33
years compared to a similar group of patients (18) who only underwent the obstetric intervention.

Results
The operating time was prolonged on average by 22 minutes, the recovery was excellent, the
complication rate low (minimal postoperative hemorrhage, wound infections). Both external and
internal suture techniques have been applied. In this way, under the same anesthesia (loco-
regional), in a single hospitalization, the patient received the cure of a surgical pathology with
potential for complication in a difficult time (confinement). Patients received postoperative
analgesia on the peridural catheter (maintained on average 48 hours postoperatively, with a
median 12 hours prolongment for the hernia group). The lactation installation was similar in both
groups. There were no recurrences of hernias during the observation period (between 18-60
months).

Conclusions
Combined surgical intervention (repair of umbilical, paraumbilical or inguinal hernia) at the
same time of the cesarean section is safe and quick, avoiding repeated hospitalization and
providing a high level of satisfaction among patients (an important element being avoidance of
separation from the newborn for another surgical procedure).
Keywords: cesarean section, hernia repair, combined surgical intervention

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Introduction

With the advanced age at which women choose to become pregnant and the increase in the
incidence of obesity, there are increases in the incidence of associated pathology, such as the
abdominal wall defects (umbilical, paraumbilical or inguinal hernia).
There are multiple retrospective studies that showed cases where pregnant women developed
abdominal wall defects during pregnancy. Umbilical hernias are the 3rd most common type of
hernias and pregnancy has been demonstrated to be an important etiological factor in the
development of this certain abdominal wall pathology. [1] Although the incidence in pregnancy
for such defects is rare (0.08%), pregnant patients should consider weight-control, avoiding
extreme physical activities, stool softeners and abdominal binders. [2-3]
In the literature there are few studies that analyzed the feasibility of a combined intervention
for both the delivery and the repair of the abdominal wall defect. The first reported case of a
combined intervention was in 1987. [4]
For example, Ochsenbein-Kolble et al., had a population of 8 women who underwent both
surgical procedures (five of which had an inguinal hernia repair and three were known to have an
umbilical hernia). Although the registered surgery time was reported to be significantly longer in
the combined group, the hemorrhage risk was the same in both groups. The hospitalization period
was the same in each group, 7 out of 8 patients were satisfied with the combined procedure and
recommended it because of the benefits of having a single surgery and because there was no
separation between the mother and the newborn. [5] Augustin et al., also noted that a single
incision and the need for a single given anesthesia are also important details that need to be taken
into account. [3]
Steineman et al., had a study which involved 14 patients who desired to be treated for both
surgical conditions. As in previous cases, the operating time was increased with 20 minutes for
the internal hernia repair and 34 minutes for the external repair. Although, the hemorrhage risk
was the same for both groups, this study had the highest hernia recurrence rate (4 out of 14
cases). [6] Gabriele et al., mentioned the fact that 4 cases in their study developed symptomatic
bacteriuria treated with standard antibiotic therapy and a urinary disinfectant. [7]
Jensen et al., published a systematic review which analyzed 31 relevant papers (23 of which
were case reports) published between January 1984 and May 2013. Out of these 31 published
studies, seven articles examined the advantages of a merged intervention. Although 6/7 of studies
did not report any postoperative complications, two studies highlighted a 13% wound
complication rate. [8] That, however, is not a general rule. Gnhman et al., observed that a wound
infection appeared in 6 patients out of a total of 48 and a single case of recurrent hernia. [9]

Materials and methods

Our proposed study was achieved through the hard work of both the Obstetrics – Gynecology
and the General Surgery department. We had a population of 35 pregnant patients who also
presented an abdominal wall defect which we split into two groups: one which benefited from the
surgical cure of an umbilical hernia at the same time with the cesarean section (17), with an
average age of 33 years compared to a similar group of patients (18) who only underwent the
obstetric intervention. The purpose was to evaluate some essential parameters of the combined
surgery: the duration of the intervention, the complication rate, the pain perception, the recovery
time and the satisfaction rate for the 1st group.

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Results

The results were as follows: the operating time was prolonged on average by 22 minutes with
an excellent recovery rate and the complicate rate was low (minimal postoperative hemorrhage
3/17, wound infections 2/17).
Patients received postoperative analgesia on the peridural catheter (maintained on average 48
hours postoperatively, with a median 12 hours prolongment for the hernia group).
The lactation installation was similar in both groups and most importantly there were no
recurrences of hernias during the observation period (between 18-60 months).

Discussion and conclusions

Under the same anesthesia (loco-regional), in a single hospitalization, the patient received the
cure of a surgical pathology with potential for complication in a difficult time (confinement).
Combined surgical intervention (repair of umbilical, paraumbilical or inguinal hernia) at the
same time of the cesarean section is safe and quick.
There was a high level of satisfaction among patients (an important element being avoidance
of separation from the newborn for another surgical procedure).
In conclusion, due to all the mentioned facts and the positive outcome, we recommended
pregnant women with abdominal defects to undergo a merged intervention that saves valuable
time for both the mother and the newborn, hospitalization costs and avoids the need to perform an
additional surgical procedure.

REFERENCES

1. Dabbas N, Adams K, Pearson K, Royle G, Frequency of abdominal wall hernias: is classical teaching out of
date? JRSMShort Rep 2(1):5.
2. Kulacoglu H, Umbilical Hernia Repair and Pregnancy: Before, during, after…, Front Surg. 2018 Jan 29;5:1.
3. Augustin G, Matosevic P, Kekez T, Majerovic M, Delmis J, Abdominal hernias in pregnancy, J Obstet
Gynaecol Res. 2009 Apr;35(2):203-11.
4. Altchek A, Rudick J. Preperitoneal herniorrhaphy: adjunct to cesarean section. Obstet Gynecol. 1987;70(3,
pt 2):470-471.
5. Ochsenbein-Kölble N, Demartines N, Ochsenbein-Imhof N, Zimmermann R, Cesarean section and
simultaneous hernia repair, Arch Surg. 2004 Aug;139(8):893-5.
6. Steinemann DC, Limani P, Ochsenbein N, Krähenmann F, Clavien PA, Zimmermann R, Hahnloser D,
Suture repair of umbilical hernia during caesarean section: a case-control study, Hernia. 2013
Aug;17(4):521-6.
7. Gabriele R, Conte M, Izzo L, Basso L, Cesarean section and hernia repair: simultaneous approach, J Obstet
Gynaecol Res. 2010 Oct;36(5):944-9.
8. Jensen KK, Henriksen NA, Jorgensen LN, Abdominal wall hernia and pregnancy: a systematic review,
Hernia. 2015 Oct;19(5):689-96.
9. Ghnnam WM, Helal AS, Fawzy M, Ragab A, Shalaby H, Elrefaay E, Paraumbilical hernia repair during
cesarean delivery, Ann Saudi Med. 2009 Mar-Apr;29(2):115-8.

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Bacterial Strains Isolated from Post-Surgical Infections Diagnosed in


an Obstetrics Department in Timișoara

HÂNCU Iasmina1, ILINCA Laurențiu1, GOLDIȘ Anca1, HUDAC Rareș1,


GHEORGHE Cosmin1, HORHAT Delia1, BAGIU Iulia1, DRAGOMIR Tiberiu1,
DIACONU Mircea1, KRASTA Anca1, NITU Razvan1, DRAGOMIR Adriana1
1University of Medicine and Pharmacy “Victor Babeș” Timișoara (ROMANIA)
Emails:[email protected], [email protected], [email protected], [email protected]

Abstract

The objectives of this study were to specify the involvement of bacterial strains in the etiology
of surgical site infections diagnosed in the Obstetrics Department and their antimicrobial
resistance pattern.
From the 168 specimens collected from 109 patients with post-surgical infection symptoms
occuring during hospitalization, 58 samples were positive.
For 64 bacterial strains, involved in the etiology of surgical site infections, identification and
extensive antimicrobial tests were performed with the help of the automatic Vitek2 System
(bioMerieux France).
In surgical wound secretions S. aureus strains were predominant. Uterine cultures revealed the
presence of numerous Gram negative bacilli.
Of the 93 surgical wound secretions collected after surgical procedures in the Obstetrics
department, 46 (49.46%) were positive, representing 2.08% of the total number of patients in this
department who were included in the study. In this study, 12 patients (0.54%) have been reported
with endometritis.
Surgical site infections are most often produced by multiresistant germs.
Keywords: nosocomial infections, post-surgical infections, endometritis, multiresistant germs

Introduction

Surgical site infections affect body tissues, cavities and organs manipulated during surgery,
generally within 30 days of a surgical procedure [1, 2, 3].
Post surgical site infections are classified into the following categories [1, 4, 5]:
• superficial incisional – involves only the skin or subcutaneous tissue;
• deep incisional – involves deep tissues;
• Organ/space – involves any part of the anatomy, other than an incision, opened or
manipulated during surgery and includes postoperative endometritis.
Endometritis may occur early, during the first 48 hours after surgery, especially after delivery
by caesarean section [6].
More frequently, surgical site infections are caused by endogenous flora found in the
endometrium but, it can also originate from exogenous sources [1, 6, 7].

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Material and method

The study was conducted in the Obstetrics Department of the Timişoara Clinical Emergency
County Hospital and included 64 bacterial strains isolated in post-surgical infections from 2208
patients, from January to December 2015.
The objectives of this study were to determine the bacterial strains involved in the etiology of
surgical site infections diagnosed in the Obstetrics Department and their antimicrobial resistance
pattern.
The specimens originated from the current clinical activity, being collected by the healthcare
staff according to sample collection protocols.
With the purpose of monitoring the nosocomial bacterial strains responsable for post-surgical
infections, two sampling procedures were performed, the first upon hospital admission and the
second at the onset of clinical signs of infection. Regarding surgical wound infections, we
monitored the presence of purulent drainage or abscess formation, whereas for puerperal
endometritis either of the following criteria must be met in order to establish the diagnosis: fever
(>38 oC), abdominal pain, uterine tenderness (often difficult to distinguish from incisional
tenderness in patients who have had a cesarean delivery) and purulent uterine discharge.
The first sample collection included the collection of perineal exudates, vaginal and
endocervical secretions. It was performed on all the patients admitted during the period taken into
consideration.
Regardind the second sample collection, the specimens were collected only from patients
presenting infection symptoms and they varied according to the infection site. Hence, we
collected a variety of body fluids such as: wound secretions, uterine discharge, blood and
peritoneal fluid.
This study includes only the bacterial strains isolated in nosocomial infection cases. A part of
them were probably selected from the endogenous flora of the patients, but with different
locations from the initial ones. We excluded the strains isolated in the same biological product
upon both collections. The study does not include anaerobic bacteria due to the lack of isolation
conditions.
A particular attention was paid to the interpretation of uterine cultures, where the purity degree
of primary cultures is crucial.
The highest number of positive samples was represented by surgical wound secretions.
All the strains involved in the etiology of surgical site infections were identified in the
Laboratory of the Timişoara Clinical Emergency County Hospital using the Vitek 2 Compact
automated system (bioMerieux).
The resistance pattern of the isolated germs was assessed by performing the MIC (Minimum
Inhibitory Concentration) test, with automated reading and classification into resistance
phenotypes by use of the Vitek 2 Compact analyzer, according to the CLSI (Clinical Laboratory
and Standards Institute Inc.).
For the extended spectrum beta-lactamases (ESBL) detection we performed the Vitek ESBL
test (AST-GN27 cards), which includes cefotaxime and ceftazidime, alone and in combination
with clavulanic acid.

Results

Of the 168 specimens collected from 109 patients with post-surgical infection symptoms
occuring during hospitalization in the Obstetrics Department, 58 samples were positive. In most

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samples involved in surgical site infections, a single bacterial species was isolated, while in pluri-
microbial samples, S. aureus most frequently accompanied enterobacteria.
In surgical wound secretions S. aureus strains were predominant, these being also isolated in
association with E. coli and Proteus mirabilis. In uterine cultures Serratia marcescens was
isolated together with Pseudomonas aeruginosa, one strains of S. aureus with E. coli or
Klebsiella pneumoniae, respectively (Table 1).

Table 1. Isolated germs from surgical site infection


Specimens Bacterial strains Uterine Wound Peritoneal Blood
discharge secretions fluid

No. No. No. No.

Escherichia coli 2 13 - -

Klebsiella pneumoniae 1 2 1 -

Proteus mirabilis - 4 - -

Enterobacter cloacae - 2 - -

Citrobacter koseri 1 - - -
Morganella morganii 1 - - -

Serratia marcescens 1 1 - -

Acinetobacter baumannii 1 1 - -

Pseudomonas aeruginosa 1 4 - -
Staphylococcus aureus 7 20 - -

Enterococcus faecalis - 1 - -

All (n=64) 15 48 1 -

Regarding S. aureus, we isolated 27 strains (42.18%). Of these, 14 strains (51.85%) presented


the MRSA (methicillin-resistant Staphylococcus aureus) phenotype.
MRSA strains are resistant to methicillin and other semisynthetic antistaphylococcal
penicillins (e.g., oxacillin, dicloxacillin, and nafcillin). Frequently this phenotype confers
resistance to most beta-lactam antimicrobial agents with the exception of the anti-MRSA
cephalosporins (eg, ceftaroline and ceftobiprole) [8].
Studying the antimicrobial resistance pattern in the case of 15 E. coli strains, revealed that five
strains (33.33%) belonged to the ESBL phenotype. All these strains also presented resistance
phenotypes for other antimicrobial agents.
The ESBLs are beta-lactamases capable of conferring bacterial resistance to penicillins and
cephalosporins (but not the cephamycins or carbapenems) by hydrolysis of these antibiotics, and
which are inhibited by beta-lactamase inhibitors such as clavulanic acid or tazobactam.
Klebsiella pneumoniae strains were the second most frequent enterobacteria involved in post-
surgical infections (four strains, representing 6.25%). The two Klebsiella pneumoniae strains
belonging to the ESBL phenotype are real nosocomial strains belonging to the XDR (extensively
drug-resistant) germs resistant to at least four classes of antibiotics.

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In our study, other enterobacteria were represented on a lower number of strains. Thus, we
isolated four (6.25%) Proteus mirabilis strains. These strains did not pose special problems
regarding antimicrobial resistance, two producing a high level of penicillinase, other two strains
presenting isolated resistance to fluoroquinolones.
The two Serratia marcescens isolated strains were multidrug-resistant (ESBL producers, with
associated aminoglycoside and trimethoprim-sulphamethoxasole resistance).
We also isolated two Enterobacter cloacae strains, one of these being multidrug-resistant to
beta-lactam antibiotics (ESBL), aminoglycosides, fluoroquinolones and trimethoprim-
sulphamethoxasole.
Other ESBL producing enterobacteria were represented by Citrobacter koseri and Morganella
morganii, both isolated in patients with endometritis.
The isolated Gram negative non-fermentative bacilli were represented by five strains of
Pseudomonas aeruginosa representing 7.81% of the total number of nosocomial strains. All the
isolated strains were resistant to aminoglycosides and fluoroquinolones, two of them were
penicillinase producers and the other two cephalosporinase producers. All the isolated
Pseudomonas aeruginosa strains were sensitive to imipenem.
The two Acinetobacter baumannii isolated strains came from a patient with a post-caesarean
section surgical wound infection and from another patient with endometritis, respectively. One of
these strains only produced penicillinase, while the other also produced cephalosporinase. None
of the strains isolated by us was resistant to carbapenem or colistin.

Discussions

Post-surgical infections represent the most important localisation of nosocomial infections [9,
10].
Of the 93 surgical wound secretions collected after surgical procedures (episiotomies
included), 46 (49.46%) were positive, representing 2.08% of the total number of patients included
in the study. After natural delivery, 15 (1.64%) post-episiotomy infections were recorded,
whereas 29 (2.23%) caesarean sections became complicated by an infectious process.
Of the 11 peritoneal fluid samples collected after caesarean sections, only one was positive
(0.07% of 1296 caesarean sections).
Reported to the patient turnover in our study, the percent of surgical site infections represented
2.62%, the value being concordant to the 1.2%-5.2% frequency obtained in other international
studies [11, 12].
The incidence of surgical site infections, varies between 5.6-11.8/100 surgical procedures.
Higher values were found in Brazil and Nigeria, where these infections complicate around
30% of surgical procedures [13, 14, 15].
Part of the post-surgical nosocomial infections that became clinically evident during the first
30 days after surgery, were observed after the patients were discharged from hospital. Thus, we
cannot state with certainty that, during the study period, we have diagnosed all the infections that
occured following the performed surgical procedures.
Studies performed in Europe reported a third most frequent position, with a percent of 17 for
nosocomial surgical wound infections, after urinary and lower respiratory tract infections [16, 17,
18, 19]. The 71 post-surgical infections diagnosed by us represent 21.38% of the total number of
nosocomial infections in the studied department.
According to the WHO, the first place in the etiology of surgical wound infections is occupied
by S. areus followed by Gram negative bacilli.

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Our study also found, in surgical wound infections, S. aureus to be the most frequently
isolated conditionally pathogenic species with 20 strains (41.66%). In surgical wound secretions,
two of the S. aureus strains were associated with E. coli and Proteus mirabilis.
Enterobacteria occupied the second place in the etiology of surgical wound infections with 13
E. coli, two Klebsiella pneumoniae, four Proteus mirabilis, two Enterobacter cloacae and one
Serratia marcescens strains, respectively.
Gram negative, non-fermentative bacilli were far less represented, with only four
Pseudomonas aeruginosa strains and one Acinetobacter baumannii strains isolated.
Of the other Gram positive cocci we isolated one Enterococcus faecalis strain.
Regarding the infection source, pathogenic germs causing post-surgical infections are aquired
either endogenously, from the organism’s own microbial flora, or exogenously through contact
with the medical staff. It is assumed that within 24 hours after a surgical procedure, most wounds
successfully close, in case no secondary incision or drainage have been practiced. Thus, most
pathogens, either endogenous or exogenous, enter the organism during the surgical procedure [20,
21].
Endometritis may occur early, during the first 48 hours after delivery, especially after
caesarean section, or later, after three days or up to six weeks, more frequently after vaginal
delivery. Most lately confined women readmitted to hospital for postnatal endometritis had
delivered naturally, this category not being included into the study.
Postpartum endometritis has been reported to occur after less than 3% of vaginal deliveries
and 5% to 95% of cesarean sections [22, 23]. The variation in infection rates results from the
prevalence risk factors in the population studied and from the way that patients are managed [1].
In this study, 12 patients (0.54% of the patient turnover in the department) have been reported
with the diagnosis of endometritis (three after vaginal deliveries and nine after cesarean sections).
In these patients, uterine cultures revealed the presence of numerous Gram negative bacilli
with two E. coli strains and one Klebsiella pneumoniae, Citrobacter koseri, Morganella
morganii, Serratia marcescens, Acinetobacter baumannii, Pseudomonas aeruginosa strains,
respectively. Additionally, seven S. aureus strains were isolated, two of which were associated
with E. coli and Klebsiella pneumoniae, respectively. The Serratia marcescens strain was isolated
together with one Pseudomonas aeruginosa strain.
In recent years, surgical site infections, as well as other types of nosocomial infections, have
been found increasingly resistant to antibiotics, both in the case of gram positive and gram
negative bacteria. For this purpose, in our previous studies, we investigated some bioactive
molecules which can be used in different infections [24, 25, 26, 27].
The 14 MRSA strains isolated in Obstetrics Department represent 51.85% of the S. aureus
strains. Similar results to those of our study have been reported in other studies, with 54.5% of S.
aureus strains being methicillin-resistant [18, 28, 29].
In this study 13 (86.66%) of E. coli strains were resistant to amino- and ureidopenicillins. In
2007 the results of certain studies on the resistance pattern of E. coli strains, showed that of 28
states, 23 reported over 50% aminopenicillins resistant strains. The resistance to III/IVrd
generation cephalosporins also significantly increased between 2001-2007, this being reported in
19 of 26 European countries [28].
Data concerning the aminoglycosides resistance of E. coli strains obtained in our study,
showed a percentage of 20-33.33% and is concordant with that reported for E. coli strains in other
17 of 26 European countries, where the resistance was 25%-38%. The ECDC (European Centre
for Diseases Prevention and Control) reported for Romania records over 25% E. coli strains
resistant to aminoglycosides [28].

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Of the 15 E. coli strains isolated by us, 26.66% presented a high level of resistance to
quinolones. In 24 of the 26 European countries included in the ECDC report for 2009, the
resistance to fluoroquinolones increased from 7% (in 2001) to 40% (in 2007), with an average of
25% recorded in 10 countries [28].
Minimal invasive surgery, either laparoscopic or vaginal surgery, generates small incisions
and is associated with lower risk of wound infection [30].

Conclusions

Of the 168 specimens collected in 109 patients (4.93% of the total number of patients), with
surgical site infection symptoms occuring during hospitalization, 58 (34.52%) were positive with
64 bacterial isolated strains. The 58 post-surgical infections represented 2.62% of the total
hospital admissions during the studied period, this percent being also found in international
reports.
Surgical site infections are frequent infections, most often produced by multidrug-resistant
germs, involving high costs and risks impossible to eliminate completely.
Implementing appropriate surveillance methods, doubled by correct and timely reporting, will
allow the avoidance of extreme, life-threatening cases.

Informed consent of Patients and Study Participants


This study was approved by the local Ethics Comittee. The patients were included in our study
only after obtaining their informed consent.

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6. Emmons SL, Krohn M, Jackson M, Eschenbach DA. (1988). Development of wound infections among
women undergoing cesarean section. Obstet Gynecol; 72: pp. 559-564.
7. Roberts S, Maccato M, Faro S, Pinell P.(1993) The microbiology of post-cesarean wound morbidity. Obstet
Gynecol; 81: pp. 383-386.
8. Axente, C., Muntean, D., Baditoiu, L., Moldovan, R., Hogea, E., Horhat, F., et al., (2017). Beta-lactam
resistance mechanisms in pathogens isolated from patients admitted to intensive care unit. Rev.Chim. 68(6),
pp. 1223-1226.
9. Licker,M., Moldovan, R., Hogea, E., Muntean, D., Horhat, F., Baditoiu, L., et al., (2017). Microbial biofilm
in human health-an updated theoretical and practical insight. Romanian Journal of Laboratory Medicine
25(1), pp. 9-26.
10. Axente, C., Licker, M., Moldovan, R., Hogea, E., Muntean, D., Horhat F., et al., (2017). Antimicrobial
consumption, costs and resistance patterns: a two year prospective study in a Romanian intensive care unit.
BMC Infectious Diseases 17(1), pp. 358-366.

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11. Gastmeier P et al., (2006). Effectiveness of a nationwide nosocomial infection surveillance system for
reducing nosocomial infections Journal of Hospital Infection, 64: pp. 16-22.
12. Horhat, F G., Gundogdu, F., David, V., et al., (2017). Early Evaluation and Monitoring of Critical Patients
with Acute Respiratory Distress Syndrome (ARDS) Using Specific Genetic Polymorphisms. Biochemical
Genetics 55(3) pp. 204-211.
13. Kesah CN et al., (2004). Aerobic bacterial nosocomial infections in paediatric surgical patients at a tertiary
health institution in Lagos, Nigeria Nigerian Postgraduate Medical Journal, 11: pp. 4-9.
14. Oliveira AC, Carvalho DV. (2004). Postdischarge surveillance: the impact on surgical site infection
incidence in a Brazilian university hospital American Journal of Infection Control, 2004, 32: pp. 358-361.
15. Allegranzi B et al., (2011). Burden of endemic health care-associated infection in developing countries:
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16. Chiţă, T., Timar, B., Muntean, D., Bădiţoiu, L. Horhat, F. Hogea, E. Moldovan, R. Timar, R. Licker, M.
(2017). Urinary tract infections in Romanian patients with diabetes: prevalence, etiology, and risk
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17. Licker, M., Anghel, A., Moldovan, R., Hogea, E., Muntean, D., Horhat, F., et al., (2015). Genotype-
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26. Danciu, C., Borcan, F., Soica, C., Zupko, I., Csanyi, E., Ambrus, R., Muntean, D., et al., (2015).
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27. Oprean, C., Zambori, C., Borcan, F., Soica, C., Zupko, I., Minorics, R., Bojin, F., et al., (2016). Anti-
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28. ECDC, Stockholm, Sweden. (2009). Antimicrobial resistance and healthcare-associated infections
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29. David, V., Ercisli, M,. Rogobete, A,. et al., (2017) Early Prediction of Sepsis Incidence in Critically Ill
Patients Using Specific Genetic Polymorphisms. Biochemical Genetics 55(3), pp. 193-203.
30. Pirtea L, Sas I, Ilina R, Grigoras D: Transversal incision of the vagina favors the remaining of the tape in the
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urinary incontinence; BMC Surg. 2015 Jul l7; 15:84

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The Low Birth Weight Infant – Cause and Effect

HASMASANU Monica Gabriela1*, IGHIAN Ioana Daria2*, MATYAS Melinda1*,


ZAHARIE Gabriela Corina1*
1Iuliu Haţieganu University of Medicine and Pharmacy, Department of Neonatology, Cluj-Napoca, (ROMANIA)
2Emergency Hospital County Cluj-Napoca, (ROMANIA)
* All authors had the same contribution
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Low birth weight is associated with prematurity and/or intrauterine growth restriction.

The objectives
Of this study were to evaluate the incidence of low birth weight infants, to identify the risk
factors of premature birth and to analyse early onset morbidities.

Methodology
This is a retrospective, descriptive study of the newborns that were admitted to the neonatal
intensive care unit of the Obstetrics and Gynaecology Clinic I in Cluj-Napoca, during January-
June 2016. In this study we included 74 infants with a birth weight lower than 2500 grams.

Results
The analysis of the pathologies presented during pregnancy revealed that gestational
hypertension was one of the risk factors associated with premature birth, this being the case in 22
pregnant mothers that gave birth to children weighing under 2500g. The delivery method of
children weighing less than 2500g was caesarean section in a significantly higher percent. In
regards to early onset morbidities, 76% of the cases had respiratory distress and 14% needed
surfactant administration. Hypoglycaemia was transitory, and it subsided after an adequate
glucose intake.

Conclusions
Gestational hypertension was one of the risk factors associated with birth weight under 2500
grams. Respiratory distress was the main early onset morbidity. Respiratory distress and
hypoglycaemia are the predominant complications of the newborn weighing fewer than 2500
grams and with intrauterine growth restriction.
Keywords: low birth weight, morbidity, prematurity

Introduction

Low birth weight is associated with prematurity and/or intrauterine growth restriction, which
is defined as weight and somatic development less than the 10th percentile on the growth chart
according to gestational age [1]. In Romania preterm birth rate is 14-15%, almost double the

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amount of some of the other countries in Western Europe [2]. In a large number of cases it is
difficult to determine the etiological factors.
In the target group of newborns mortality is inversely proportional to gestational age [3].
Improvement of prenatal care has led to a better rate of survival for these children, which is
correlated with birth weight: 20% for those weighing 500-600g, 85-90% for those weighing
1250-1500g and 99% for 1500-2000g [Errore. Il segnalibro non è definito.]. Prenatal mortality
is 5-20% greater for newborns with intrauterine growth restriction, particularly if it is associated
with preterm birth [4]. Also, 20% of stillbirths associate intrauterine growth restriction. Providing
for low birth weight infants is focused on mimicking the conditions in utero in order to obtain an
optimal development. Caring begins by correctly monitoring at risk pregnancies, especially when
it comes to high risk of premature birth.
The objectives of this study were to evaluate the incidence of low birth weight newborns, to
identify the risk factors of premature birth and to analyse early onset morbidities.

Methodology

This is a retrospective, descriptive study of the newborns that were admitted to the neonatal
intensive care unit of the Obstetrics and Gynecology Clinic I in Cluj-Napoca, during January-
June 2016. In this study we included 74 infants with a birth weight lower than 2500 grams.
The data for this research was collected by analysing the observation charts of the 74 infants
hospitalised in the intensive care unit. Information about the mothers was gathered: age, place of
origin, ethnicity, smoking and alcohol consumption, gravidity and parity, gestational
hypertension and the gestational age at which it first manifested and other gestational pathologies.
Information gathered about the newborn: anthropometric characteristics: birth weight, length,
head circumference, ponderal index, gestational age, sex, method of birth, dexamethasone use,
Apgar score at 1 minute and 5 minutes, resuscitation in the delivery room, type of respiratory
support, early onset morbidities: respiratory distress and surfactant administration, trauma, heart
failure, hyperbilirubinemia, hypocalcaemia, hypoglycemia, intracerebral haemorrhage, early and
late onset sepsis. A secondary variable was calculated based on the primary variables: Ponderal
index (PI) [5]: PI=100xweight (grams)/length(cm3).
The statistical analysis of the data was completed using Epi Info.

Results

We evaluated the characteristics of 74 infants weighing under 2500gr. They were hospitalised
in the neonatal intensive care unit.
The analysis of maternal case history revealed that the mother’s average age is 30.5±5.2 years.
By analysing the mother’s living conditions and place of origin we concluded that most of the
mothers were from urban areas: 38 cases versus 36 cases rural area, but without a statistically
significant difference (p 0.453). By analysing the ethnicities of the group we obtained a
distribution of 3 ethnicities, most newborns being of Romanian ethnicity, 56 cases (76%),
Hungarian 8 cases and Roma 20 cases. We evaluated the mothers’ use of toxic substances during
pregnancy, specifically smoking and alcohol intake. In this group 6.5% of the mothers smoked
during the pregnancy, the mean number of smoked cigarettes being 3.37±1.2 cigarettes/day. As
regards alcohol consumption, none of the mothers admitted to drinking alcohol during pregnancy.
Most of the cases in our group were firstborns, with a mean gravidity of 2 and parity of 1.54.

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By analyzing the pathology ofpregnancywe concluded that gestational hypertension was one
of the risk factors associated with preterm birth, this being the case with 22 pregnant mothers that
gave birth to children with a weight of under 2500g. A statistically significant number of cases
(67%) had no gestational hypertension (Fig. 1).

Fig. 1. Gestational hypertension

Gestational hypertension was diagnosed at 29.1±3.21 weeks gestation. Of the total cases, 32
presented with pregnancy related pathologies (43%), and 42 had no pathologies (57%). The
medical history is presented in Table I.

Table I. Medical history


Medical history No. of cases
Hypertension present before pregnancy 4
Neurofibromatosis, thyroid goiter, galactoma 2
Multinodular goiter, hyperprolactinemia 2
Abdominal trauma 2
Rheumatoid arthritis, operated peritonitis 2
Myeloproliferative syndrome, thrombocytosis 2
Spherocytosis, splenomegaly 2
Myasthenia gravis 2
Operated Omphalocele 2
Operated tuberculosis 2
Gastritis 2
Hashimoto thyroiditis 2
Hypothyroidism, obesity 2
Thrombophilia 3
Right lung pleurisy 1
TOTAL 32

Dexamethasone was administeredin 50 cases (68%), a significantly higher percent compared


to 24 cases (32%) that did not recieve the medication. The anthropometric characteristics of the
group are presented in Table II.

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Table II. Anthropometric characteristics


Weight Length Head circumference Ponderal index Gestational
(grams) (cm) (cm) age (weeks)
Mean 1632.02±234.7 43.37±21.8 29.7±8.5 1.99±0.3 34.2±2.5

This group was predominantly comprised of newborns weighing between 1500-1999g. The
weight distribution is displayed in Fig. 2

Fig. 2. Distribution as regards birth weight

16 cases (22%) had a birth weight of less than 1000g, 10 cases (13%) were between 1000-
1499g, 28 cases (38%) were between 1500-1999g, and 20 cases (27%) were between 2000-
2500g. Of the total number of 74 infants with low birth weight, 56 cases (76%) were female and
18 cases (24%) were male.
The delivery method of children weighing under 2500g was a significantly higher percent
through caesarean section 76%, breech presentation 3% and cranial presentation 21%. The mean
Apgar score at 1 minute is 7.78±2.1, and at 5 minutes 8.67±2.6. In the delivery room, 22 cases
(59%) needed ventilation, and the remaining 15 cases (41%) needed just routine care, no other
maneuvers. 12 cases (16%) from the study group required respiratory support through mechanical
ventilation, 36 cases (49%) required nCPAP type ventilation, 10 cases (13%) required free-flow
oxygen delivery, and 16 cases did not need any respiratory support. The morbidities of the study
group are presented in Table III.

Table III. Early onset morbidities


Morbidity Present N (%) Absent N (%) P
Respiratory distress 56 (76) 18 (24%) 0.003
Signs of birth trauma 14 (19) 60 (81) 0.681
Intrauterine growth restriction 56(76) 18(24) 0.003
Hyperbilirubinemia 60 (81) 14 (19) 0.169
Early onset sepsis 14 (19) 60 (81) 0.134
Late onset sepsis 10 (14) 64 (86) 0.421
Hypoglycemia 34 (46) 40 (54) 0.004
Hypocalcaemia 0 (0) 74 (100) -
Heart failure 8 (11) 66 (89) 0.214
Intracerebral hemorrhage 6(8.10) 68 (91.89) 0.342

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By analyzing the elements of birth trauma, we have concluded that in the majority of cases the
trauma was minimal: caput succedaneum, ecchymosis, excoriation, suffusions, adiponecrosis and
we had just one case of femur fracture following a difficult birth in breech presentation.
By analysing respiratory distress: 14% of cases required surfactant administration When
hypoglycemia occurred, it was immediately after birth; however it was corrected after an
adequate intake of enteral and/or parenteral glucose and was interpreted as transitory
hypoglycemia. The mean age for intrauterine growth restriction diagnosis was 30.2±3 weeks.
The catch-up growth period was on average in 8.59±3 days and total enteral nutrition was
achieved in 6.35± 2 days.

Discussion

We analyzed the factors that led to preterm birth of low birth weight infants; these were either
directly linked form the data we had on the newborns, or indirectly linked form data regarding the
mother, as well as apparent morbidities for the newborn.
Maternal nutrition is important for fetal development and in determining birth weight, as
demonstrated by large studies from Holland and China [6, 7].
The ethnicity of the majority of the newborns was Romanian in 76% of the cases, followed by
Roma 13% and Hungarian 11%. By evaluating toxic substances consumed during pregnancy we
found an average of 6.5% mothers that smoked during pregnancy, but none declared any alcohol
consumption. Exposure to cigarette smoke during pregnancy may lead to low birth weight by
deteriorating blood flow in the fetal blood vessels [8]. Cessation of smoking in the first trimester
until 32 weeks prevents weight loss, head circumference and brain:body ratio deficiency but it
does not affect the stature deficit [Errore. Il segnalibro non è definito.]. Gestational
hypertension was one of the pathologies of pregnancy. Out of the total of 74 cases, 67% had no
pathology, and 3% had no prenatal care. The risk of developing intrauterine growth restriction is
high in a pregnant mother with hypertension and preeclampsia, and it increases with the severity
of preeclampsia [9, 10, 11, 12]. The average gestational age of establishing a diagnosis was
29.1±2.3 weeks. With regard to medical history, there were 21 cases that had none (57%), and the
percent of mothers that had a medical history was 43%.
The birth method of children weighing under 2500g was cesarean section for a significantly
higher percent (76%), rather than a natural birth, which occurred for 21% of cases, and 3% of the
cases were breech presentation. As was expected and, as well, correlated with other studies [13,
14, 15], cesarean section was performed for a significantly higher number of newborns and so
birth trauma was seldom encountered.
In this study we noticed that there were a high number of early onset morbidities. These were:
respiratory distress, birth trauma, intrauterine growth restriction, hyperbilirubinemia, early [16]
and late onset sepsis, hypoglycemia, hypocalcemia, cardiac insufficiency and cerebral
hemorrhage. Complications with early onset for the low birth weight infant were low Apgar,
hypoxia, hypoglycemia, hypothermia, necrotizing enterocolitis, sepsis, hyperbilirubinemia [17],
respiratory distress and with late onset retinopathy of prematurity [18, 19, 20]. In our study
respiratory distress was observed in a statistically significant number of cases, 76%,while 24%
(18 cases) had no respiratory distress. By analyzing the cases of respiratory distress we found that
14% required surfactant administration. Respiratory distress is caracteristic for preterm newborn
and the oxidative stress is more severe in preterm than in term neonates. The antioxidant defense
of preterm less developed than in term neonates, mainly the enzymatic antioxidant defense [21]

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In regard to birth trauma we discovered that the majority of cases had minor trauma: caput
succedaneum, ecchymosis, excoriations, suffusions, adiponecrosis and just one case of femoral
fracture after a difficult birth in breech presentation. The number of cases that had birth trauma
was 14 (19%), and 60 cases (81%) had no trauma.
Intrauterine growth restriction was one of the major morbidities affecting a large number of
low birth weight infants, it presented in 76% of cases, while 24% (18 cases) had no growth
restriction. The mean gestational age for establishing the diagnosis of intrauterine growth
restriction was 30.2±2.1 weeks.
Hyperbilirubinemia also affected a large number of newborns (81%, 60 cases), while 14 cases
(19%) didn’t present with hyperbilirubinemia.
Early onset sepsis was present in 19% of cases and late onset sepsis was identified in 19% of
cases. Hypoglycemia was present in 34 cases (46%), and absent in 40 cases (54%). None of the
cases developed hypocalcemia. Cardiac insufficiency was observed in 4 cases, 33 cases had no
cardiac insufficiency and 3 cases presented with cerebral hemorrhage.
Ortigosa et al., identified a high incidence of hypoglycemia and cerebral hemorrhage in late
preterm infants that also correlated with IUGR in comparison with those that had adequate weight
[22].

Conclusions

Gestational hypertension was one of the risk factors associated with birth weight of under
2500 grams. Respiratory distress was the main early onset morbidity. The predominant
complications of the newborn weighing under 2500 grams and intrauterine growth restriction are
respiratory distress and hypoglycemia.

REFERENCES

1. Unterscheider J, Daly S, Geary MP, Kennelly MM, McAuliffe FM, O’Donoghue K, Hunter A, Morrison JJ,
Burke G, Dicker P, Tully EC, Malone FD. (2013) Optimizing the definition of intrauterine growth
restriction: the multicenter prospective PORTO Study. Am J Obstet Gynecol 208(4), pp. 290.e1-6.
2. Maria Stamatin. (2009) Neonatologie. Ed. Gr. T. Popa. Iaşi, pp. 70.
3. Matthews TJ, MacDorman MF, Thoma ME.(2015) Infant Mortality Statistics From the 2013 Period Linked
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5. Lindley AA, Becker S, Gray RH, Herman AA. (2000) Effect of continuing or stopping smoking during
pregnancy on infant birth weight, crown-heel length, head circumference, ponderal index, and brain:body
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Cohortprofile: the Dutch Hunger Winter families study. Int J Epidemiol. 36(6), pp. 1196-1204.
7. Chen H, Nembhard WN, Stockwell HG. (2014) Sex-Specific effects of fetal exposure to the 1959–1961
Chinese famine on risk of adult hypertension. Matern Child Health J. 18(3), pp. 527-533.
8. Milnerowicz-Nabzdyk E, Bizon A. (2014) Effect of cigarette smoking on vascular flows in pregnancies
complicated by intrauterine growth restriction. Reprod Toxicol. 50, pp. 27-35.
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Pregnancy and Childbirth. 6:16.
10. Rasmussen S, Irgens LM. (2008) History of fetal growth restriction is more strongly associatedwith severe
rather than milder pregnancy-induced hypertension. Hypertension. 51(4), pp. 1231-1238.
11. Procopciuc LM, Caracostea G, Zaharie G, Puscas M, Iordache G, Popa M, Colcear D, Olteanu I, Stamatian
F. (2011) Maternal/newborn genotype contribution of the renin-angiotensin system (Met235Thr,

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Thr174Met, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A- AT2R2, 83A/G-REN) to the risk of pre-
eclampsia: a Romanian study. J Renin Angiotensin Aldosterone Syst. 12(4), pp. 539-548.
12. Procopciuc LM, Caracostea G, Zaharie G, Stamatian F. (2014) Maternal/newborn VEGF-C936T interaction
and its influence on the risk, severity and prognosis of preeclampsia, as well as on the maternal angiogenic
profile.J Matern Fetal Neonatal Med. 27(17), pp. 1754-1760.
13. Baschat A.A. Fetal responses to placental insufficiency: An update. (2004) BJOG Int J Obstetrics Gynaecol.
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14. Sehested LT, Pedersen P.(2014) Prognosis and risk factors for intrauterine growth retardation. Dan Med J.
61, A4826.
15. Lees C, Marlow N, Arabin B, Bilardo CM, Brezinka C, Derks JB, et al., (2013) Perinatal morbidity and
mortality in early-onset fetal growth restriction: cohort outcomes of the trial of randomized umbilical and
fetal flow in Europe (TRUFFLE). Ultrasound Obstet Gynecol, 42 pp. 400-408.
16. Mocan L, Matea C, Tabaran FA, Mosteanu O, Pop T, Puia C, Agoston-Coldea L, Gonciar D, Kalman E,
Zaharie G, Iancu C, Mocan T. (2016). Selective in vitro photothermal nano-therapy of MRSA infections
mediated by IgG conjugated gold nanoparticles. Sci Rep. 23, pp. 6:39466.
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retinopathy of prematurity: outcomes after 7 years of treatment G J Pediatr Ophthalmol Strabismus. 51(1),
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Retinopathy of Prematurity J Ophthalmol. pp. 102582.
20. Nicoară SD, Ștefănuţ AC, Nascutzy C, Zaharie GC, Toader LE, Drugan TC. (2016). Regression Rates
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Laser: 8-Year Retrospective Analysis. Med Sci Monit. 10;22, pp. 1192-1209.
21. M. Matyas, G. Zaharie (2018). Paticularities of oxidative stress in newborn. in: Novel prospects in oxidative
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22. Ortigosa Rocha C, Bittar RE, Zugaib M. (2010) Neonatal outcomes of late-preterm birth associated or not
with intrauterine growth restriction. Obstet Gynecol Int. pp. 231842.

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Congenitally Corrected Transposition of the Great Arteries – an


Apparently “Benign” Condition

HERGHELEGIU Catalin Gabriel1,2, CIUTACU Laura Andreea1,


FETECAU Andreea Catalina1, IOAN Raluca Gabriela1,2, NEACSU Adrian2,
OPRESCU Daniela Nuti1,2
1INSMC Alessandrescu Rusescu, Bucuresti, (ROMANIA)
2UMF Carol Davila, Bucuresti, (ROMANIA)
Email: [email protected]

Abstract

Congenitally corrected transposition of the great arteries (ccTGA), also known as


atrioventricular and ventriculoarterial discordance is a complex type of heart defect that accounts
for less than 1% of the total cases of congenital heart disease. This type of malformation
encompasses a heterogeneous group of abnormalities, but the characteristic feature of all cases is
the discordance at both the atrioventricular and ventricular junctions, resulting in a
physiologically “corrected” circulation. The fetal echocardiography should focus on identification
of the morphologic left and right ventricles, as the diagnosis of ccTGA is primary based on the
recognition of atrioventricular discordance. The best way to assess ventricular morphology is by
studding the 4 chamber view, because it is the easiest to obtain by the sonographer and it offers a
detailed image of both atria and ventricle anatomy. Although an apparently “benign” condition,
ccTGA has a poor long term outcome with dysfunction of the systemic right ventricle occurring
with increasing frequency as the patients get older, thus the majority of patients with associated
abnormalities develop clinical heart failure.
Keywords: congenital heart disease, congenitally corrected transposition of the great arteries

Introduction

Congenitally corrected transposition of the great arteries (ccTGA), also known as


atrioventricular and ventriculoarterial discordance is a complex type of conotruncal heart defect,
that accounts for less than 1% of the total cases of congenital heart disease [1]. This pathology
encompasses a heterogeneous group of abnormalities, but the characteristic feature of all cases is
“a double discordance” at both the atrioventricular and ventricular junctions, with normal veno-
atrial connections, resulting in a physiologically “corrected” circulation [2]. This condition is
frequently missed at routine ultrasound exams due to the difficulty to visualize the double
discordance [1].

Embryologic development

By day 21, the primitive heart tube is composed of and endocardial tube surrounded by
myocytes that will form the myocardium. It is suspended only cranially and caudally at the level
of the pericardial cavity. On day 23, a process of elongation begins to take place, thus the heart

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tube is bent to the right forming an “S” shape. This normal rightwards looping leads to a correct
spacial relationship of the future heart chambers, placing the right ventricle on the right, the left
ventricle on the left and also bringing the atria to the right and posterior of the ventricles. The
great arteries arise from a common trunk between the 3th-4th week [2], [4].
The responsible pathophysiologic mechanisms for ccTGA is believed to be an abnormal left-
looping of the primitive cardiac tube, resulting in an abnormal orientation of the heart so that the
morphologic right ventricle becomes left sided, receiving blood from the left atrium while the
morphologic left ventricle becomes right sided, receiving blood from the right atrium. Also the
conotruncal septum fails to rotate leading to a disarrangement of the outflow tracts. Thus the right
ventricle ejects blood into the aorta and the left ventricle into the pulmonary artery [2], [5], [6].
The de-oxygenated blood arrives in the right atrium, remains to the right side of the heart them
it is pumped by the morphologic left ventricle through the pulmonary artery to the lungs, the
returning oxygenated blood in channeled to the left side of the heart and is pumped by the
morphologic right ventricle through the aorta, hence the name of “corrected” transposition.

Ultrasound Diagnostic

From a diagnostic point of view, this condition is considered a conotruncal heart defect
alongside other malformations such as: transposition of great arteries, double outlet right
ventricle, common arterial trunk [7], [8]. This type of malformations are the hardest to detect
prenatally and are most likely to be misdiagnosed [9].
The first step is identifying the normal situs and orientation of the heart, knowing that as much
as 25% of fetuses have dextrocardia or mesocardia [10]. The echocardiography should focus on
identification of the morphologic left and right ventricles, as the diagnosis of ccTGA is primary
based on the recognition of atrioventricular discordance. The best way to assess ventricular
morphology is by studding the 4 chamber view, because it is the easiest to obtain by the
sonographer and it offers a detailed image of both atria and ventricle anatomy [11].
As described earlier the morphologic right ventricle that is characterized by the presence of the
moderator band, irregularity of the endocardial surface, a more triangular shape and chordal
attachment of the atrioventricular valve directly to the septum, is located on the left side of the
heart. The morphologic left ventricle characterized by a smooth surface, an elongated appearance,
a clear apex and with the chordal attached to the apex, is located on the right side.
Also the valve “offset” is inverted with the left valve attached closer to the apex. anterior [10],
[12], [13].
Color Doppler is most often used to exclude other frequently associated abnormalities such as:
ventricular septal defect, pulmonary stenosis, tricuspid valve regurgitation [10].
Using the latest 3D ultrasound technology like STIC and TUI it can be possible to obtain at the
same time both images of the anatomy of the heart cambers and also images showing the origin
and course of the great vessels [10], [14].

Prognosis

The natural history of isolated ccTGA is highly variable and depend mainly on 3 parameters:
function of the morphologic right ventricle that needs to sustain systemic blood pressure, function
of the tricuspid valve and development of arrhythmias. In the long term, the extra strain that is
exerted on the morphologic right ventricle leads to heart failure due to its thinner walls and lack
of anatomic adaptations in sustaining high blood pressure [6]. Over time the ventricle stars to

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dilate and tricuspid regurgitation occurs, that worsens even more the ventricular function [15]. So
although the immediate prognostic is good but the long-term outcome is generally poor, as one
third of patients develop cardiac heart failure by the age of 50, moreover in case with associated
heart defects like: ventricular heart defects, pulmonary stenosis, Ebstein’s anomaly, tricuspid
regurgitation and heart block nearly all cases wild develop systemic ventricle dysfunction at a
young age. [16].
The key to a good management of this pathology is the prevention of systemic ventricle
dysfunction and dilation. Some authors have suggested that early tricuspid valve replacement
may be a solution in selected cases of ventricle dilatation in an attempt to preserve heart function.
Also medical treatment with afterload reduction seems to preserve longer the systemic
ventricular function [16]. Patients with depressed morphologic right ventricle or systemic
ventricle, but with normal morphologic left ventricle can be considered for the double switch
operation [6], [16].

Discussions

As presented above, ccTGA represents a difficult diagnosis, often missed by ultrasound


screening. Most often, the diagnostic is suspected due to a slightly abnormal 4 chamber view that
is observed while routine scanning. This confirms the fact that the 4 chamber view remains the
most important tool for identifying cardiac abnormalities in our opinion and is the most
accessible to obtain cardiac view regardless of fetal position. Also other abnormalities such as
vascular shunts, aneurysms and even severe malformations involving the central nervous system
like Gallen vein aneurysm, can lead to an abnormal 4 chamber view [17]. We can say that the 4
chamber view represents an “image” for the function of the whole cardiovascular system and
slight disturbances in the hemodynamic balance lead to a discrepancy in the size and function of
the heart chambers.
Although an apparently “benign” condition, ccTGA has a poor long term outcome with
dysfunction of the systemic right ventricle occurring with increasing frequency as the patients get
older. About 60-70% of patients with associated abnormalities have clinical heart failure by the
age of 45 years [16]. Among the common associated heart defects we find: ventricular heart
defects, pulmonary stenosis, Ebstein’s anomaly, tricuspid regurgitation and heart block. In our
case the discrepancy in size between the aorta and pulmonary artery suggested a pulmonary
stenosis that greatly worsens the prognosis.

REFERENCES

1. Y. Zhang, A. Cai, W. Sun, Y. Guo, and Y. Zhao. (2011) “Prenatal diagnosis of fetal congenitally corrected
transposition of the great arteries,” Prenat. Diagn., vol. 31, no. 6, pp. 529-535, Jun.
2. J. Smith, A. Sproul, D. Watson, and Y. Kandasamy. (2014), “Congenitally corrected transposition of the
great arteries,” J. Neonatal Nurs., vol. 20, no. 1, pp. 43-52, Feb.
3. A. Moorman, S. Webb, N. A. Brown, W. Lamers, and R. H. Anderson. (2003), “Development of the heart:
(1) formation of the cardiac chambers and arterial trunks.,” Heart, vol. 89, no. 7, pp. 806-14, Jul.
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great arteries: an update.,” Curr. Treat. Options Cardiovasc. Med., vol. 9, no. 5, pp. 407-13, Oct.
6. S. Kutty, D. A. Danford, G.-P. Diller, and O. Tutarel. (2018), “Contemporary management and outcomes in
congenitally corrected transposition of the great arteries.,” Heart, p. heartjnl-2016-311032, Jan.

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7. D. A. Goor and J. E. Edwards. (1973), “The spectrum of transposition of the great arteries: with specific
reference to developmental anatomy of the conus.,” Circulation, vol. 48, no. 2, pp. 406-15, Aug.
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SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY, pp. 294-297.
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echocardiogram,” Am. J. Cardiol., vol. 94, no. 5, pp. 688-689, Sep.
10. A. Abuhamad and R. Chaoui. (2010), A practical guide to fetal echocardiography : normal and abnormal
hearts. Wolters Kluwer Health/Lippincott Williams & Wilkins
11. C. G. Herghelegiu, I. Dragan, N. Suciu, and N. D. Oprescu. (2017), “A Simplified Protocol for Congenital
Heart Disease,” in 5TH CONGRESS OF THE ROMANIAN SOCIETY OF ULTRASOUND IN OBSTETRICS
AND GYNECOLOGY, pp. 298-302.
12. R. L. McEwing and R. Chaoui. (2004), “Congenitally corrected transposition of the great arteries: clues for
prenatal diagnosis,” Ultrasound Obstet. Gynecol., vol. 23, no. 1, pp. 68-72, Jan.
13. G. Sharland, R. Tingay, A. Jones, and J. Simpson. (2005), “Atrioventricular and ventriculoarterial
discordance (congenitally corrected transposition of the great arteries): echocardiographic features,
associations, and outcome in 34 fetuses,” Heart, vol. 91, no. 11, pp. 1453-1458, Nov.
14. C. A. Ionescu, D. Gheorghiu, B. Davitoiu, I. Pacu, and T. Vladescu. (2009), “Visualization of the
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15. U. Lundstrom, C. Bull, R. K. Wyse, and J. Somerville. (1990), “The natural and &quot;unnatural&quot;
history of congenitally corrected transposition.,” Am. J. Cardiol., vol. 65, no. 18, pp. 1222-9, May.
16. T. P. Graham et al., .( 2000), “Long-term outcome in congenitally corrected transposition of the great
arteries,” J. Am. Coll. Cardiol., vol. 36, no. 1, pp. 255-261, Jul.
17. D. Herghelegiu, C. A. Ionescu, I. Pacu, R. Bohiltea, C. Herghelegiu, and S. Vladareanu. (2017). “Antenatal
diagnosis and prognostic factors of aneurysmal malformation of the vein of Galen,” Med. (United States),
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Pregnancy after Ovarian Cancer – Case Report

HERGHELEGIU Catalin Gabriel1,2, CARBUNARU Ana Elena1,


MOLDOVEANU Amira1, FETECAU Andreea Catalina1, IOAN Raluca Gabriela1,2,
OPRESCU Daniela Nuti1,2
1INSMC Alessandrescu Rusescu, Bucuresti, (ROMANIA)
2UMF Carol Davila, Bucuresti, (ROMANIA)
Email: [email protected]

Abstract

Ovarian cancer is the seventh most common cancer in women and is the leading cause of death
among gynecologic malignancies. Due to the often asymptomatic nature of the early stage
disease, many cases are not diagnosed until they evolve to advanced stages. It is a disease of
postmenopausal women, still many cases occur in fertile women. We report an unusual case – a
pregnancy obtained after fertility sparing surgery for stage I ovarian cancer. Because ovarian
cancer can occur at any age, and because young women wish to preserve their fertility, in recent
decades an increase the patients choosing conservative treatment is seen. Conservative surgery,
preserving at least one ovary and the uterus, has been described as a therapeutic option for
ovarian cancer since the mid ‘80s. Although this treatment remains controversial, several studies
concluded that fertility sparing surgery represent a viable option for women with stage I ovarian
cancer, the 5-year survival rates being similar to patients treated by radical surgery.
Keywords: Ovarian cancer, pregnancy, fertility spearing surgery

Introduction

Ovarian cancer is the seventh most common cancer in women and is the leading cause of death
among gynecologic malignancies [1], [2]. Due to the often asymptomatic nature of the early stage
disease, many cases are not diagnosed until they evolve to advanced stages, thus it represents one
of greatest clinical challenges for the gynecologist. One way to improve the detection rate of
early stage patients is with the use of ultrasound imaging, that represents an excellent screening
method for other malignancies like endometrial cancer [3], [4]. A number of guidelines and
protocols, like the IOTA score, have been proposed in an effort to increase the diagnostic rate in
early stage patients [5], [6]. Although it is a disease of postmenopausal women, approximately
12% of cases occur in women aged less than 45 years [7].
Due to the changes in our society women tend to give birth to their first child at an older age,
so it becomes more common to encounter young women diagnosed with early stage ovarian
neoplasm that wish to preserve their reproductive capability.

Case report

A 32 year old woman presented to our institution with a positive pregnancy test and 3 months
amenorrhea. From her medical history we recall that she was diagnosed with stage IA serous

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ovarian carcinoma 2 years ago. Not having children she opted for fertility spearing surgery and
underwent left salpingo-oophorectomy, also multiple peritoneal biopsies were taken and all
proved to be negative. The oncology board also recommended systemic therapy so the patient
underwent platinum based chemotherapy.
The ultrasound exam revealed a 12 weeks normally developing fetus. The patient was
informed that a pregnancy after conservative surgery for ovarian cancer can increase the risk for
disease recurrence but she decided to continue the pregnancy. We decide a follow up plan with
ultrasound scans every 2 weeks and tumor markers taken every 6 weeks. At the ultrasound exam
no adnexal masses were identified and the growth and development of the fetus was normal.
CEA and CA-125 levels did not show a significant rise over the course of the pregnancy.
At 37 weeks the patient presented to the hospital for premature rupture of membranes and she
delivered by Cesarean section a healthy baby. With this occasion, a “second-look” evaluation of
the peritoneal cavity was performed and there were no signs of disease recurrence.

Discussions

Despite advancements in medical oncology and molecular therapies, radical surgery remains
the main choice of treatment in a great deal of gynecologic cancers, like ovarian cancer,
endometrial cancer, verrucous carcinoma of the cervix [8], [10]. In the case of ovarian cancer,
occult metastasis in the contralateral ovary occur in 2-12% of cases and also the rare possibility
of synchronous bilateral primary ovarian carcinoma makes choosing conservative surgery a
difficult decision [11], [12]. Also in some cases gynecologic cancers can generate totally
abnormal and chaotic metastasis [13], [15], so a systemic therapy to target these remote sites is
always welcomed.
Nonetheless because ovarian cancer can occur at any age, and because young women wish to
preserve their fertility, in recent decades an increase the patients choosing conservative treatment
is seen. Conservative surgery, preserving at least one ovary and the uterus, has been described as
a therapeutic option for ovarian cancer since the mid ‘80s [10], [16], [18]. Although this
treatment remains controversial, several studies concluded that fertility sparing surgery represent
a viable option for women with stage I ovarian cancer, the 5-year survival rates being similar to
patients treated by radical surgery [19]. Because it is usually recommended to take a biopsy from
the contralateral ovary and moreover, if the patient undergoes chemotherapy, the follicular
reserve is partially depleted. In these cases of poor ovarian reserve, determined most accurately
by AMH levels, a possible option can be IVF although data are lacking on ovarian cancer relapse
rates after gonadotropic stimulation [20], [23]

REFERENCES

1. B. M. Reid, J. B. Permuth, and T. A. Sellers, “Epidemiology of ovarian cancer: a review.,” Cancer Biol.
Med., vol. 14, no. 1, pp. 9-2, Feb. 2017.
2. H. E. Dinkelspiel et al., “Long-term mortality among women with epithelial ovarian cancer.,” Gynecol.
Oncol., vol. 138, no. 2, pp. 421-8, Aug. 2015.
3. [I. Jacobs et al., “Sensitivity of transvaginal ultrasound screening for endometrial cancer in postmenopausal
women: A case-control study within the UKCTOCS cohort,” Lancet Oncol., vol. 12, no. 1, pp. 38-48, 2011.
4. A. Neacsu, “EARLY DIAGNOSIS OF ENDOMETRIAL CANCER.”
5. N. Nunes, G. Ambler, X. Foo, J. Naftalin, M. Widschwendter, and D. Jurkovic, “Use of IOTA simple rules
for diagnosis of ovarian cancer: meta-analysis,” Ultrasound Obstet. Gynecol., vol. 44, no. 5, pp. 503-514,
Nov. 2014.

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6. C. Ionescu, M. Banacu, I. Popescu, A. Ionescu, S. Vladareanu, and M. Dimitriu, “Ultrasound Diagnosis of


Endometrial Cancer in Asymptomatic Menopausal Women,” in 5TH ROMANIAN CONGRESS OF THE
ROMANIAN SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY, 2017, pp. 199-202.
7. R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer statistics, 2016,” CA. Cancer J. Clin., vol. 66, no. 1, pp. 7-
30, Jan. 2016.
8. R. M. Anghel et al., “Good Prognosis Went Badly: Fulminant Evolution of a 29-Year-Old Patient with
Verrucous Carcinoma of the Cervix,” J. Adolesc. Young Adult Oncol., vol. 6, no. 3, pp. 499-502, May 2017.
9. N. Colombo et al., “Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and
follow-up,” Ann. Oncol., vol. 24, no. suppl_6, pp. vi33-vi38, Oct. 2013.
10. J. A. Ledermann et al., “Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical
Practice Guidelines for diagnosis, treatment and follow-up,” Ann. Oncol., vol. 24, no. suppl 6, pp. vi24-
vi32, Oct. 2013.
11. P. Ratanasrithong and M. Benjapibal, “Pregnancy Outcomes after Conservative Surgery for Early-Stage
Ovarian Neoplasms,” Asian Pac. J. Cancer Prev., vol. 18, no. 8, pp. 2083-2087, 2017.
12. C. A. Ionescu et al., “Synchronous bilateral primary ovarian carcinoma – case presentation.,” Rom. J.
Morphol. Embryol., vol. 58, no. 1, pp. 219-223, 2017.
13. M. L. Marcu, A. Neacşu, C. Stoica, N. Bacalbaşa, A. Contolenco, and E. Radu, “Clinical and pathological
features of splenic metastasis from cervical squamous cell carcinoma,” Rom J Morphol Embryol, vol. 58,
no. 4, pp. 1157-1164, 2017.
14. Q. LIU, Q.-Q. YU, H. WU, Z.-H. ZHANG, and R.-H. GUO, “Isolated gastric recurrence from ovarian
carcinoma: A case report,” Oncol. Lett., vol. 9, no. 3, pp. 1173-1176, Mar. 2015.
15. Y. Gunay, E. Demiralay, and A. Demirag, “Pancreatic Metastasis of High-Grade Papillary Serous Ovarian
Carcinoma Mimicking Primary Pancreas Cancer: A Case Report,” Case Rep. Med., vol. 2012, pp. 1-3, Jul.
2012.
16. P. E. Schwartz, “Combination chemotherapy in the management of ovarian germ cell malignancies.,”
Obstet. Gynecol., vol. 64, no. 4, pp. 564-72, Oct. 1984.
17. R. T. Morris, D. M. Gershenson, E. G. Silva, M. Follen, M. Morris, and J. T. Wharton, “Outcome and
reproductive function after conservative surgery for borderline ovarian tumors.,” Obstet. Gynecol., vol. 95,
no. 4, pp. 541-7, Apr. 2000.
18. P. Morice et al., “Recommendations of the Fertility Task Force of the European Society of Gynecologic
Oncology about the conservative management of ovarian malignant tumors.,” Int. J. Gynecol. Cancer, vol.
21, no. 5, pp. 951-63, Jul. 2011.
19. J. M. Schilder et al., “Outcome of reproductive age women with stage IA or IC invasive epithelial ovarian
cancer treated with fertility-sparing therapy.,” Gynecol. Oncol., vol. 87, no. 1, pp. 1-7, Oct. 2002.
20. P. R. Jirge, “Poor ovarian reserve.,” J. Hum. Reprod. Sci., vol. 9, no. 2, pp. 63-9, 2016.
21. P. Morice et al., “Results and fertility after conservative treatment of invasive epithelial ovarian cancer,”
Gynecol. Obstet. Fertil., vol. 30, no. 9, pp. 684-91, Sep. 2002.
22. I. Pacu, C. Ionescu, S. Vladareanu, M. Banacu, A. Neacsu, and A. Calin, “Predictive Value of the AMH
level and serum estradiol for ovarian hyperstimulation syndrome in the assisted human reproduction,” Rev.
Chim., vol. 68, pp. 1118-1121, 2017.
23. M. Feichtinger and K. A. Rodriguez-Wallberg, “Fertility preservation in women with cervical, endometrial
or ovarian cancers.”

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The Diagnostic Power of Ultrasound in Postmenopausal Bleeding

HERGHELEGIU Catalin Gabriel1,2, CIUTACU Laura Andreea1,


COROCEA Karina1, IONASCU Adrian Bradut1, IOAN Raluca Gabriela1,2
1INSMC Alessandrescu Rusescu, Bucuresti, (ROMANIA)
2UMF Carol Davila, Bucuresti, (ROMANIA)
Email: [email protected]

Abstract

Ultrasonography has important implications for the selection of patients for whom biopsy
curettage is considered necessary. One of the most common symptoms in gynaecology is
abundant bleeding. In post-menopause, bleeding may occur in a number of pathologies such as:
polyps, hyperplasia or cancer.
The objective of the paper is to correlate the visualisation of the endometrial details (thickness
and structure of the endometrium) and the selection of patients who benefit from endometrial
biopsy. From an ultrasound point of view, endometrial hyperplasia is difficult to differentiate
from endometrial cancer. Neoplasia is suggested by a thickness of the endometrium of over 10
mm and with an irregular contour. The discontinuity of the hypoechoic myometrium can be seen
in advanced forms of endometrial cancer. Endometrial hyperplasia is characterized by diffuse
thickening of the endometrium. Polyps are visualised as masses with increased echogenicity,
which contrasts with the hypoechogenicity of the surrounding endometrium of the uterine cavity.
The colour Doppler usually identifies a vascular pedicle. Transvaginal ultrasound allows the
measurement of the thickness of the endometrium and the visualisation of its structure, thus
helping decide which patients benefit the most from endometrial biopsy.
Keywords: transvaginal ultrasonography, endometrial biopsy

Introduction

One of the most common symptoms in gynaecology is vaginal bleeding commonly found in:
adenomyosis, endometrial hyperplasia, endometrial adenocarcinoma and ovarian tumours [1, 2].
Ultrasonography has important implications for the selection of patients for whom biopsy is
considered necessary. The causes of vaginal bleeding vary depending on the age of the patients.
At reproductive age the most common causes are endometriosis, ovarian pathology and uterine
fibromas. Frequently submucosal fibroids can affect the endometrial surface causing abundant
bleeding [3, 4]. In post-menopause, bleeding may occur in a number of pathologies: polyps,
hyperplasia or cancer.
Endometrial thickness visualized by transvaginal ultrasound in a postmenopausal woman
should be less than or equal to 5 mm and denotes endometrial atrophy [5, 6].
In post-menopause, bleeding may occur in a number of pathologies: polyps, hyperplasia or
cancer. Endometrial hyperplasia is represented by thickening of the endometrium with an
increase in of size glands and a high gland/stromal ratio [7]. Proliferative endometrial lesions are
classified as simple or complex hyperplasia, with or without atypia. Hyperplasia is simple or

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complex depending on the absence or presence of architectural anomalies (glandular


agglomeration or complexity). Atypical hyperplasia is characterized by nuclear atypia. Atypical
endometrial hyperplasia is associated with the subsequent development of adenocarcinoma [8, 9].
Endometrial adenocarcinomas are of two types: Type I, includes 75% of cases, is oestrogen
dependent, of histological low grade, derived from atypical endometrial hyperplasia; Type II is
without a precursor lesions and with more aggressive clinical development. Clinical and
morphological differences are due to genetic differences [10, 11].
There is currently no screening for endometrial cancer in women with high or medium risk.
The visualisation of endometrial ultrasound heterogeneity or fluid collection requires biopsy in
order to exclude malignancy [12-14].
The Doppler study of endometrial vascularisation does not provide relevant information
because it does not reveal significant differences between benign and malignant tumours in terms
of resistivity and pulsatility indices [15, 16]. Last but not least, the ultrasound examination is
routinely extended to the entire pelvis and adjacent organs, as gynecologic cancers can have in
some case atypical metastases located in the spleen, pancreas or stomach [17-19].
The objective of the paper is to correlate the visualisation of the endometrial details (thickness
and structure of the endometrium) and the selection of patients who benefit most from
endometrial biopsy.

Material and Method

We have studied 28 patients aged 50-60 years who have experienced vaginal bleeding as the
main symptom. The genital clinical examination highlights the atrophied vagina and vulva, with
whitish or reddish, very friable areas and with thin, dry mucous membrane. The same atrophic
changes were seen at the level of the cervix. Bimanual palpation revealed a normal or slightly
enlarged uterus, of quasi-normal consistency and non-palpable adnexal areas.

Results and Discussions

In postmenopausal women, the endometrium was visualised as a hyperechoic line and the
endometrium thickness measured by transvaginal ultrasound was less than or equal to 5 mm,
bleeding was caused to endometrial atrophy (16 cases, 57%). The risk of hyperplasia or
adenocarcinoma in these patients is low and therefore endometrial biopsy is not recommended.
Polyps were visualised as masses with increased echogenicity, which contrasts with the
hypoechogenicity of the surrounding endometrium in the uterine cavity (3 cases, 12%). The
colour Doppler identifies the vascular pedicle.
Endometrial hyperplasia was revealed by diffuse thickening of the endometrium (5 cases,
17%). The colour Doppler had a limited role in the assessment of endometrial hyperplasia,
highlighting a relative increase in vascularisation.
From an ultrasound point of view, endometrial hyperplasia is difficult to differentiate from
endometrial cancer. Malignancy was suggested by a thickness of the endometrium of over 10 mm
and an irregular contour (4 cases, 14%). The discontinuity of the hypoechoic myometrium
appearance can be seen in advanced forms of endometrial cancer. Although the role of
transvaginal ultrasound in the detection of endometrial cancer is limited, the benefit of
ultrasonography is to detect invasive forms by visualisation of the depth of direct invasion of the
myometrium and superficial invasions of endometrial cancer. Non-invasive tumours can be
differentiated from invasive tumours through the hypoechoic subendothelial line, which is the

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internal area of the myometrium. The colour Doppler reveals increased vascularisation in the
tumour.

Conclusions

Transvaginal ultrasound is a valuable investigation by offering the possibility to evaluate the


endometrial details in most patients. It allows the measurement of the thickness of the
endometrium and the visualization of its structure. Also colour Doppler can be used to investigate
the vascularisation of different lesions. This investigation is useful in the selection of patients
who can benefit from endometrial biopsy.

REFERENCES

1. Braila M, Brăila A D , Neacsu A, Gogănău A. (2017). Treatment of Dysmenorrhea in Adenomyosis.


Clinical Study for a Period of 3 Years. Proceedings of the 14 th National Congress of Urogynecology and the
National Conference of the Romanian Association for the Study of Pain, Filodiritto Editore – Proceedings,
pp. 325-327.
2. Brăila A D, Brăila M, Cornițescu F et al., (2008). Benign ovarian tumors. Anatomo-clinical, diagnosis, and
therapeutical aspects. Gineco.eu 4(3), pp. 178-185.
3. Brăila M, Brăila A, Neacşu A, Gogănău A. (2017).Treatment of Pelvigenital Pain Syndrome in External
Endometriosis. Clinical Study for a Period of 3 Years, Proceedings of the 14 th National Congress of
Urogynecology and the National Conference of the Romanian Association for the Study of Pain, Filodiritto
Editore – Proceedings, pp. 328-330.
4. Klimentova D V, Brăila A D, Simionescu C, Ilie I, Brăila M. (2012). Clinical and paraclinical study
regarding the macro and microscopic diagnosis of various anatomo-clinical forms of operated uterine
fibromyoma. Romanian Journal of Morphology and Embryology 53(2), pp. 369-373.
5. Goldstein S R, Nachtigall M, Snyder J R. (1990). Endometrial assessment by vaginal ultrasonography
before endometrial sampling in patients with postmenopausal bleeding. Am J Obstet Gynecol 163, p. 119.
6. Granberg S, Wikland M, Karlsson B. (1991). Endometrial thickness as measured by endovaginal
ultrasonography for identifying endometrial abnormality. Am J Obstet Gynecol 164, p. 47
7. Ellenson L H, Ronnett B M, Kurman R J. (2011). Precursor lesions of endometrial carcinoma. In Kurman
RJ, Ellenson LH, Ronnett BM (eds): Blaustein s Pathology of the Female Genital Tract. New York,
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8. Brăila A D, Klimentova D V, Damian C M, Brăila M. (2012). Endometrial proliferative lesions associated
with uterine fibromatosis. Romanian Journal of Morphology and Embryology 56(3), Supp, pp. 743-747.
9. Neacşu A, Marcu M L, Stānicā C D, Brāila A D, Pacu I, Ioan R G, Grigorescu C C, Ionescu C A. (2018).
Early Diagnosis of Endometrial Cancer. Romanian Journal of Morphology and Embryology 59(2).
10. Bansal N, Yendluri V, Wenham R M.(2009). The molecular biology of endometrial cancers and the
implications for pathogenesis, classification, and targeted terapies. Cancer Control 16 (1), p. 8.
11. Hecht J L, Mutter G L. (2006). Molecular and pathologyc aspects of endometrial carcinogenesis. J Clin
Oncol 24 (29), p. 4783.
12. Dubinsky T J. (2004). Value of sonography in the diagnosis of abnormal vaginal bleeding. J Clin
Ultrasound 32, p. 348.
13. Krissi H, Bar-Hava I, Orvieto R. (1998). Endometrial carcinoma in a post-menopausal women with atrophic
endometrium and intracavitary fluid: a case report. Eur J Obstet Gynecol Reprod Biol 77, p. 245.
14. Sheikh M, Sawhney S, Khurana A. (2000). Alteration of sonographic texture of the endometrium in
postmenopausal bleeding. A guide to further management. Acta Obstet Gynecol Scand 79, pp. 1006.
15. Bourne T H. (1995). Evaluating the endometrium of postmenopausal women with transvaginal
ultrasonography. Ultrasound Obstet Gynecol 6, p. 75.
16. Sheith S, Hamper U M, Kurman R J. (1993). Thickened endometrium in postmenopausal women:
songraphic-pathologic correlation. Radiology 187, p. 135.
17. Marcu M L, Neacşu A, Stoica C, Bacalbaşa N, Contolenco A, and Radu E. (2017). Clinical and pathological
features of splenic metastasis from cervical squamous cell carcinoma. Romanian Journal of Morphology and
Embryology 58 (4), pp. 1157-1164.

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18. Liu Q, Yu Q-Q, Wu H, Zhang Z-H, and Guo R-H. (2015).Isolated gastric recurrence from ovarian
carcinoma: A case report. Oncol. Lett. 9 (3), pp. 1173-1176.
19. Gunay Y, Demiralay E, and Demirag A. (2012). Pancreatic Metastasis of High-Grade Papillary Serous
Ovarian Carcinoma Mimicking Primary Pancreas Cancer: A Case Report. Case Rep. Med. 2012, pp. 1-3.

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Ultrasound Diagnosis of Haemorrhagic Syndrome in the Second


Half of Pregnancy

SERBAN Oana1, IOAN Raluca Gabriela1,2


1INSMC Alessandrescu Rusescu, Bucuresti, (ROMANIA)
2UMF Carol Davila, Bucuresti, (ROMANIA)
Email: [email protected]

Abstract

Bleeding during the second and third trimester of pregnancy has specific clinical significance,
summing both serious and normal or expected situations. The differential diagnosis for this
condition includes abruptio placentae, placenta previa, preterm labor, and bleeding from various
lesions of the cervix and lower genital tract. One-third of fetuses die when vaginal bleeding
occurs after 20 weeks of gestation. The concept of abruptio placentae is used for the acute ascent
of the normally inserted placenta before the foetus is expelled. Placenta ascent with retroplacental
hematoma formation is the most common cause that can determine disseminated intravascular
coagulation. In abruptio placentae, the hematoma is located between the basal plate (the maternal
surface of the placenta) and the uterine wall. In the slight and intermediate forms of acute ascent
of the normally inserted placenta, a homogeneous area of echogenicity located in retroplacental
position places the diagnosis of hematoma between the placenta and the myometrium. Ultrasound
examination in dynamics may indicate the evolution of the hematoma.
The placenta praevia defines the placenta that completely or partially covers the internal
cervical opening and is clinically manifested by haemorrhage. The topographic location of the
placenta and its relationship to the internal cervical opening support the diagnosis of low inserted
placenta. Nevertheless, it is difficult to assess the ultrasound differential diagnosis between
marginally and partially inserted placenta.
The objective of the paper is the efficacy of fetal-adnexal ultrasound monitoring as a non-
invasive, rapid, cheap and accurate method in improving the vital and functional foetal-maternal
prognosis.
Keywords: haemorrhagic syndrome, abruptio placentae, low inserted placenta

Introduction

Haemorrhagic syndrome in the second half of pregnancy is a severe accident that endangers
the life of the foetus and the mother [1]. Bleeding during the second and third trimester of
pregnancy has specific clinical significance, summing both serious and normal or expected
situations. The differential diagnosis for this condition includes abruptio placentae, placenta
previa, preterm labor, and bleeding from various lesions of the cervix and lower genital tract.
The concept of abruptio placentae is used for the acute ascent of the normally inserted placenta
before the foetus is expelled. Placenta ascent with retroplacental hematoma formation is the most
common cause that can determine disseminated intravascular coagulation. The mechanism that
determines the consumption of procoagulant factors is the activation of intravascular coagulation.

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There are significant amounts of procoagulants in the retroplacental hematoma, but it does not
justify all lost fibrinogen [2]. Levels of fibrin degradation products are higher in the peripheral
blood than in the uterine cavity [3]. The consequence of intravascular coagulation is the
activation of plasminogen in plasmin that lyses fibrin micro-embolies to maintain the
permeability of microcirculation [4-6]. In the case of extended placental ascent with dead foetus,
there are pathological levels of degradation products of fibrinogen-fibrin and D-dimers in the
maternal serum.
The placenta praevia defines the placenta that completely or partially covers the internal
cervical opening and is clinically manifested by haemorrhage. Coexisting placenta praevia and
placenta accreta syndromes contribute to maternal morbidity and mortality rates [7]. A tripling of
the maternal mortality rate in pregnant women with placenta praevia has been described. [8].
Preterm delivery is a major cause of perinatal death [9], and tripling of neonatal mortality rates
has been reported for USA in the cases of placenta praevia, caused by premature deliveries [10].
There is a significantly increased risk of neonatal death even for term-born foeti [11]. This is
also due to foetal anomalies that are 2 to 3 times more common in placenta praevia pregnancies
[12-14].
The objective of the paper is the efficacy of fetal-adnexal ultrasound monitoring as a non-
invasive, fast, cheap and accurate method in improving the vital and functional foetal-maternal
prognosis.

Material and Method

The research was carried out on a sample of 34 pregnant women, of which 29 were in the third
trimester of pregnancy and 5 in the second trimester of pregnancy, aged 30 to 45, multi-gesta
(VG-IXG), multi-para (IIIP-VIP). For patients in the second trimester of pregnancy there were
diagnosed 3 cases of placenta praevia and 2 cases of premature ascent of normally inserted
placenta with retroplacental hematoma formation. For pacients in the third trimester, there were
discovered 8 cases of retroplacental hematoma and 21 cases of placenta praevia. Biochemical and
ultrasound investigations were performed, and pacients were monitored.

Results and Discussions

Of 10 pregnant women with retroplacental hematoma, 3 were diagnosed as abruptio placenta


due to severe bleeding and this led to dead intrauterine foetus and 7 pregnant women completed
pregnancy with caesarean section with favourable outcome for both mother and foetus. Of the 24
cases with placenta praevia (70%), 11 pregnant women were advised and subjected to caesarean
section for abundant bleeding, in 13 cases there was a vaginal delivery because it was about low
inserted placenta. In abruptio placentae (3 cases), the location of the hematoma is between the
basal plate, the maternal surface of the placenta and the uterine wall. In the slight and
intermediate ascent forms of the normally inserted placenta (7 cases), a homogeneous
echogenicity area located in retroplacental position places the diagnosis of hematoma between the
placenta and the myometrium. Ultrasound examination in dynamics may reveal the evolution of
the hematoma and may be suggestive for establishing the conduct in completing the pregnancy
[15, 16, 17].
The topographic location of the placenta on the lower uterine segment and its relationship to
the internal cervical opening, at a distance of approximately 2 cm, support the diagnosis of low
inserted placenta (13 cases) or placenta praevia (11 cases) when the internal cervical opening was

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partially or completely covered by the placenta. Nevertheless, it is difficult to assess the


ultrasound differential diagnosis between marginally and partially inserted placenta.
There are studies that focus on foetal monitoring inside the uterus, leading to a rapid detection
of these conditions. When obstetrical history suspects such events, an active monitoring of the
foetal status is recommended. In case of outpatient surveillance, there are attempts to monitor
foetal heart function with sensors integrated into textile [18]. There are studies in our country that
provide for the development of intelligent textile systems to monitor vital functions [19].

Conclusions

Ultrasound is the most useful diagnostic method in haemorrhagic syndrome in the second half
of pregnancy, being accessible, non-invasive, fast, cheap and accurate. The vital and functional
foetal-maternal prognosis can be improved if the foetus and the foetal appendages are monitored
by ultrasound.

REFERENCES

1. Braila A D, Brăila M, Alkrayem N, Gogănău A. (2017). Uterine Haemostasis In Puerperality By Radical


And Conservative Surgical Procedures, Filodiritto International Proceedings, Congress of the Romanian-
German Society of Obstetrics-Gynecology, pp. 81-83.
2. Pritchard J A, Brekken A L.(1967). Clinical and laboratory studies on severe abruption placentae. Am J
Obstet Gynecol 97, p. 681.
3. Bonnar J, McNicol G P, Douglas A S. (1969). The behavior of coagulation and fibrinolytic mechanisms in
abruptio placentae. J Obstet Gynecol Br Commons Comw 76, p. 799.
4. Braila A D, Marinov Krastev B, Mihai-Zamfir E, Caraveteanu D C, Al Krayem N, Braila M, Velea R,
Neacsu A. (2017). Uteroplacental apoplexy associated with invasive cervical neoplasm. Romanian Journal
of Morphology and Embryology 58(4), pp. 1465-1470.
5. Brăila A D, Gluhovschi A, Neacșu A, Lungulescu C, Brăila M, Cotoi B V, Goganau A. (2018). Placental
abruption. etiopathogenic aspects, diagnostic and therapeutic implications. Romanian Journal of
Morphology and Embryology 59(1).
6. Brăila A D, Forțofoiu C, Zamfir E M, Velea R, Brăila M. (2017). Eclampsia And Epilepsy. Differential
Diagnosis. Associated Diagnosis, Filodiritto International Proceedings, Congress of the Romanian-German
Society of Obstetrics-Gynecology, pp. 84-87.
7. Lai J, Caughey A B, Qidwai G I. (2012). Neonatal outcomes in women with sonographically identifed
uterine leiomyomata. J Matern Fetal Neonatal Med 25 (6), p. 710.
8. Oyelese Y, Smulian J C. (2006). Placenta previa, placenta accreta and vasa previa. Obstet Gynecol 107, p.
927.
9. Norgaard I N, Pinborg A, Lidegaard O. (2012). A Danish national cohort study on neonatal outcome in
sigleton pregnancies with placenta previa. Acta Obstet Gynecol Scand 91(5), p. 546.
10. Salihu H M, Li Q, Rouse D J. (2003). Placenta previa: neonatal death after live births in the United States.
Am J Obstet Gynecol 188, p. 1305.
11. Ananth C V, Smulian J C, Vintzileos A M. (2003). The effect of placenta previa on neonatal mortality: a
population based study in the United States, 1989 through 1997. Am J Obstet Gynecol 188, p. 1299.
12. Crane J M G, Van Den Hof M C, Dodds L. (1999). Neonatal outcomes with placenta previa. Obstet
Gynecol 93, p. 541.
13. Brăila M, Alkraiem N, Velea R, Brăila A D. (2017). Severe Fetal Malformations. Frequency, Diagnosis,
Obstetrical Conduct, Filodiritto International Proceedings, Congress of the Romanian-German Society of
Obstetrics-Gynecology, pp. 88-90.
14. Braila A, Braila M B, Dira L M, Vaduva C. (2017). Normal Twin Pregnancy to Term Three Years after a
Girl with Siamese Twin, Filodiritto International Proceedings, The 5th Romanian Congress of Ultrasound in
Obstetrics and Gynecology, p. 137.

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15. Brăila A D, Brăila M, Velea R, Neacșu A. (2017). Delivery Management: Past, Present And Perspective,
Filodiritto International Proceedings, Congress of the Romanian-German Society of Obstetrics-Gynecology,
pp. 77-80.
16. Brăila M, Neacșu A, VeleaR, Brăila A. (2017). Caesarian Section And The Forceps Use -5 Year Study In
Craiova Scju Maternity Section ,Filodiritto International Proceedings, Congress of the Romanian-German
Society of Obstetrics-Gynecology, pp. 91-94.
17. Brăila A, Gogănău A., Brăila M., Neacşu A. (2017). Caudal analgezia continues in controled birth. 5 year
clinical study, Proceedings of the 14th National Congress of Urogynecology and the National Conference of
the Romanian Association for the Study of Pain, Filodiritto Editore – Proceedings, pp. 323-324.
18. Chen W, Hu J, Bouwstra S, Oetomo S B. (2011). Sensor integration for perinatology research. International
Journal of Sensors Networks 9(1), pp. 38-49.
19. Onose G, Chendreanu C, eacsu A, Grigorean V, Stambu V, Toader C, Spanu A, Andone I, Anghelescu A,
Onose L, Haras M, Sinescu C J, Artino M, Ciornei C, Mirea A. (2009). Smart textiles for noninvasive
monitoring of physiological signals. Industria Textila 60(3), pp. 124-133.

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Prenatal Detection of Limb-Body Wall Defects and Amniotic Bands


Syndrome

ILIESCU Dominic-Gabriel1,2,3, CERNEA Nicolae1,3, TUDORACHE Ştefania1,3,


ȘOROP-FLOREA Maria1,2, DRĂGUŞIN Roxana-Cristina1,2,
MARINAȘ Marius-Cristian1,3, CĂPITĂNESCU Răzvan-Grigoraş1,3,
MOFLEANU Andra3, DIJMĂRESCU Lorena1, MANOLEA Maria-Magdalena1,
PĂTRU Ciprian-Laurenţiu1,2,3, TĂNASIE Delia-Roxana3,
ZORILĂ George-Lucian1,2,3
1 University of Medicine and Farmacy of Craiova, (ROMANIA)
2 SC ENDOGYN AM, Craiova, Department of Obstetrics and Gynecology, (ROMANIA)
3 Department of Obstetrics and Gynecology, Emergency County Hospital from Craiova, (ROMANIA)

Abstract

Amniotic band syndrome (ABS) includes a set of fetal abnormalities due to the presence of
fibrous bands that entangle or entrap fetal segments. The objective of the study was to evaluate
the role of an optimized protocol to correctly diagnose the spectrum of ABS anomalies. We
report a series of 7 cases diagnosed antenatally by ultrasound in the Department of Obstetrics and
Gynecology of ENDOGYN AM and confirmed together with the University Hospital team.
We used an extended and optimized fetal morphologic protocol. We correlated the antenatal
data with the anatomopathological examination. Because of the possibility of a genetic
abnormality, fetal karyotype was performed in all cases.
We encountered a large spectrum of fetal abnormalities, but all the cases evaluated in the first
trimester were correctly diagnosed. The high frequency of ultrasound diagnostic markers such:
entanglement or irregular amputations of extremities and fingers and/or toes and oligohydramnios
was not confirmed in our series. We diagnosed a wide spectrum of congenital abnormalities
associated with visible amniotic bands and constriction rings, including neural tube, orofacial and
visceral defects. Fetal karyotyping was useful to avoid misdiagnosis and incorrect information of
recurrence risk. In all suspected cases the anatomopathological examination confirmed the
antenatal findings.
ABS can be efficiently diagnosed early in pregnancy using an extended protocol that correctly
diagnose fetal anomalies involving the craniofacial region, trunk and extremities. The most
important diagnostic criteria are visible amniotic bands and constrictions rings, but the main fetal
anomalies may include other features than irregular amputations of limbs, toes or fingers.
The typical features of body stalk anomaly can be detected by ultrasound by the end of the
first trimester, which is important for the patient counseling and management.
Keywords: prenatal diagnosis, amniotic band syndrome, body-stalk anomaly, autopsy, genetics

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Introduction

Body stalk anomaly (BSA) and amniotic band syndrome (ABS) are rare fetal sporadic
polymalformative syndromes, similar, but with certain differences. BSA is a combination of
abnormalities involving the cranium (exencephaly, encephalocele, facial clefts), body wall
(toraco/abdominalskizis), limb defects, with persistent extra embryonic coelomic cavity. BSA
results from the breakdown of ectodermal placode involving the early embryonic folding process
ABS is characterized by the presence of thin fibrous bands attached to fetal body parts and
causing constrictions and/or amputations.
For the gestational age of which bands formation affects the development, there are several
types of malformations. In early stages of development, ABS will severely damage the product of
conception resulting deformities on different levels, such as fetal head (anencephaly, cleft face,
hydrocephaly) abdominal wall (gastroschisis, omphalocele). In later stages of development,
usually involves limbs or fingers, with amputation or only scars and signs, at various levels. The
damage may be milder, manifesting as a localized annular constriction where the membrane
entrapped the limb, with distal lymphedema and swallowing. [1]
Russo and colleagues postulated the presence of two clearly distinguishable phenotypes as a
consequence of different pathogenetic mechanisms. The first phenotype can be related to an early
vascular disruption and presents with craniofacial defects, amniotic bands and/or adhesions. The
second phenotype is attributable to an intrinsic embryonal maldevelopment and shows no
craniofacial defects, but urogenital anomalies, anal atresia, abdominal placental attachment,
together with persistence of the extra-embryonic celomic cavity. [2]
Up to 70% of all amniotic bands seen on prenatal ultrasound disappear upon repeated
ultrasound. Innocent amniotic band, that doesn’t interfere with the fetus movement and doesn’t
attach fetal tissue, pose no risk to the fetus. [3]
For BSA, 2 of the 3 following anomalies criteria must be present: exencephaly/encephalocele,
thoraco/abdomino-schisis (midline defect), limb defect (club foot, polydactyly, oligodactyly,
syndactyly, brachydactyly).
Genetics: Usually ABS and BSA have normal karyotype, but body stalk anomaly may also be
associated with placental trisomy 16 or maternal uniparental disomy 16 [4]. The chance of
recurrence is very low in subsequent pregnancies. [5, 6, 7, 8, 9, 10, 11, 12]
Epidemiology of amniotic band syndrome: Multiannual multicenter international study
describes a prevalence of 1/11.200 newborns, some have found a prevalence of less than
1/18.000, others higher prevalence of about 1/1,200 probably related to the miscarriages,
stillborn, and newborns inclusion.
Epidemiology of body stalk anomaly: There are many prevalence data described, with
significant differences between them. Mann concluded a prevalence of 1/14.000 [13], Morrow
[14] 1/22.000, Pumberger 1/14.000, Daskalakis 1/7.500 [15], Kurosawa 0,3/10.000 newborn. [16]
Risk factors: In a large and comprehensive literature review, Pietro et al., [17] described
different risk factors, such as firstborn; medication drug use like misoprostol, and vaginal
bleeding during first trimester. The role of the hypoxia mechanism of living at high altitude was
associated to ABS [18].
In a study in Bolivia, ethnicity was a factor [19], with a familial recurrence for the risk of
ADAM (Amniotic deformity, adhesion, and mutilation) sequence. This was higher among first
and second-degree relatives, when compared to general prevalence.
For prenatal invasive diagnostic methods, like amniocentesis, several authors had been able to
reproduce experimentally typical amputations (cranial malformations and syndactyly). The

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vascular changes, and hemorrhage or hematoma was the primary event. In some cases, secondary
adhesions to the amnion could exist [20]. In early chorionic villus sampling (CVS), there was an
association between amniotic bands and limb shortening.
60% of the mothers, delivering ABS fetuses, report history of trauma to the uterus, low birth
weight (<2,500 g), maternal illness during pregnancy, maternal drug exposure (e.g., cocaine,
mifepristone), maternal hemorrhage, attempted abortion in the first trimester. [21]

Methodology

In our research, we have diagnosed antenatally 7 patients with BSA / ABS between years
2016-2018, in the Department of Obstetrics and Gynecology and in SC ENDOGYN AM and
have been confirmed together in an extent team, at the University Hospital. We used an extended
and optimized fetal morphologic protocol. We correlated the antenatal data with the
anatomopathological examination. Because of the possibility of a genetic abnormality, fetal
karyotype was performed in all cases and it was useful to avoid misdiagnosis and incorrect
information of genetic recurrence risk.

Results

During 2 years, we examined 3150 patients and selected 7 cases of amniotic band syndrome
and body-stalk anomaly.
We encountered a large spectrum of fetal abnormalities, such as: constriction bands across the
face – facial clefts or deformation of the calvarium – neural tube defects: if complete, the fetus
appears anencephalic, if partial, the fetus may appear to have an encephalocele, deformation of
the pelvis, short umbilical cord with abdominal wall defect, etc.
The distribution of the cases was: 4 cases with ABS (3 of them interphering with the neuro and
viscerocranium and one associated to abdominal wall formation) (Fig. 1, 2, 3) and 3 BSA that
associated abdominal wall defects, short umbilical cord, malposition of the inferior limbs and, in
one case, lower spine formation with a large meningocel.

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Fig. 1. Amniotic band syndrome. 13 weeks of GA.


Amniotic band that interferes with neurocranium development.
(Arrow)

Fig. 2. Amniotic band syndrome. 23 weeks of GA


Bilateral club foot.

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Fig 3. Amniotic band syndrome. 19 weeks of GA. Amniotic band that intercepts viscero- and neurocranium
development (blue arrow). Anencephaly aspect (yellow arrow)

Entanglement or irregular amputations of extremities and fingers and/or toes, published with a
high frequency in other studies, was not confirmed in our series.
In all suspected cases the autopsy confirmed the antenatal findings.
For all the cases, we analysed genetic karyotype, from fetal tissue, with normal results for all
of the probes.

Discussion

In ABS the fetus may be severely affected: spine contracted, organs formed in perplexing and
bizarre proportions, head may be completely misshapen or absent.
There are Two main ABS phenotypes:
The placental-cranial type: involves craniofacial defects (encephalocele/exencephaly & with
facial clefts) + amniotic bands between the cranial defects and placenta. The pathogenic
mechanism proposed is early vascular disruption. The placental-abdominal type: no craniofacial
defects are present, involves urogenital anomalies, anal atresia, lumbosacral meningocele, short
cord, persistence of extraembryonic coelom and intact amnion. Seems to be due to intrinsic
abnormal embryonic development. In our cases, no urogenital, anal atresia, or abdominal
placental attachment defects were present, but we found head anomalies, such as acrania,
exencephaly, facial cleft, abdominal wall defects and short umbilical cord. Our presented cases
belong to both phenotypes, 3 cases from all 4 (ABS) presented cranio-facial defects and one case
described as the second type, the placental-abdominal one.

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Our study reported a much higher incidence compared to literature, of 2.2/1000, compared to
0.2-0.3/1000 as a published mean. We found no explanation regarding this higher rate, but we
had few cases for resuming a conclusion, needing a larger populational study.
Bugge has already mentioned that small umbilical cord and kyphoscoliosis are almost
invariably present in BSA [22]. In one of our cases, we identified a pelvis, abdominal wall defect
and in the lower spine, a large meningocele present at this level.
The typical features of BSA and early, severe, ABS can be detected by ultrasound in the first
trimester, which is important in the case management, since most of them are incompatible with
life, knowing that early therapeutic abortion has many advantages compared to the second or the
third trimester termination of pregnancy . Consequently, these anomalies should be distinguished
from other etiologies. 3 of our cases had gestational age between 11-14 weeks of gestation, and in
all cases, we correctly diagnosed the anomaly and having no false negative results.
Although most fetal anomalies are readily diagnosed by ultrasound, complete autopsy is
mandatory, to confirm a prenatal diagnosis and to assess other anomalies, that may have been
omitted.
Another purpose is to obtain tissue for microscopic examination and genetic exams. All of our
genetic exams had normal karyotype. Usually, fetuses with BSA and ABS have a normal
karyotype, although uniparental disomy 16 has also been reported to BSA [23].

Conclusions

ABS can be efficiently diagnosed early in pregnancy using an extended protocol that correctly
diagnose fetal anomalies involving the craniofacial region, trunk and extremities. The most
important diagnostic criteria are visible amniotic bands and constrictions rings, but the main fetal
anomalies may include other features than irregular amputations of limbs, toes or fingers.

Acknowledgements
This paper was published under the frame of European Social Found, Competitivity
Operational Programme 2014-2020, POC-A.1-A.1.2.1-D-2015, Contract nr. 75/08.09.2016,
MYSMIS Code: 105076.

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7. R. J. Morrow, M. J. Whittle, M. B. McNay, P. A. M. Raine, A. A. M. Gibson, and J. Crossley, “Prenatal


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Fetal Heart: Early Diagnosis Versus Follow-Up

ILIESCU Dominic-Gabriel1,2,3, CERNEA Nicolae1,3, TUDORACHE Ștefania1,3,


ȘOROP-FLOREA Maria1,2, DRAGUȘIN Roxana Cristina1,2,
ZORILĂ George Lucian1,2, ȘOROP Virgiliu Bogdan4, DRĂGOESCU Alice5,
CARA Monica-Laura1
1 University of Medicine and Pharmacy of Craiova (ROMANIA)
2 ENDOGYN AM, Department of Imaging in Obstetrics and Gynecology, Craiova (ROMANIA)
3 Department of Obstetrics and Gynecology, Prenatal Diagnostic Unit, University Emergency Hospital, Craiova (ROMANIA)
4 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy “Victor Babeș” Timișoara (ROMANIA)
5 Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy Craiova (ROMANIA)

Email: [email protected]

Abstract

Introduction/Objectives
Congenital heart defects (CHDs) are the leading cause of infant mortality due to birth defects.
The shift to early screening for fetal anomalies from the last years, determined extensive
research on the detection of CHDs. The objective of our study was to highlight the efficiency of
an optimized first trimester (FT) ultrasound protocol to diagnose CHDs.

Methods/Methodology
We present a series of cases diagnosed antenatally by using an extended and optimized fetal
ultrasound protocol in the Department of Obstetrics and Gynecology of ENDOGYN AM and
confirmed together with the University Hospital team regarding the imagistic and
anatomopathological examinations. In a review of the recent literature we comment on the recent
advances in the ultrasound diagnosis and the implications in general practice and outcome of
affected fetuses.

Results
We present a large spectrum of fetal cardiac abnormalities, were the cases evaluated early in
pregnancy were correctly diagnosed. Anatomopathological examination confirmed the antenatal
findings. Early assessment of the fetal heart it is supposed to imply a high level of expertise.
However, a properly trained FT investigator, familiar with grey-scale and Doppler
requirements necessary to investigate easily supposed detectable markers as tricuspid
regurgitation and ductus venosus flow, should easily perform a color cardiac sweep.

Conclusion
The detection of major CHDs at the end of the FT is nowadays strongly influenced by their
association with some 20 years old markers, such as nuchal translucency, ductus venosus blood
flow and tricuspid regurgitation. Still, the FT limitations of fetal cardiac evaluation and follow-up
echocardiography must be borne in mind.
Keywords: congenital heart disease, fetal anomalies, prenatal diagnosis, ultrasound

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Introduction/Objective

Congenital heart diseases (CHD) are the most common anomalies, with an estimated incidence
of 4-13 per 1000 live births. The fetal heart has the highest probability of major anomalies [1, 2].
A proper antenatal and neonatal management depends on the accuracy of the prenatal
diagnosis. In the last 30 years extensive studies have reported the prenatal diagnosis of cardiac
defects during the second trimester of pregnancy [3]. However, in the last 15 years, with the shift
in screening for aneuploidies to the first trimester, extensive research has concentrated on early
screening and detection of CHDs [4-10]. High risk population is mainly targeted, but CHD is
more prevalent in low risk pregnancies, as shown in various researches, even using only minimal
screening [11]. Although studies have shown that fetal echocardiography at the end of the first
trimester (FT) represents a very important tool in the diagnostic of major heart disease [12], the
second trimester (ST) morphological scan should still be considered for confirmation.
The objective of our study was to highlight the importance of an optimized FT ultrasound
protocol to diagnose CHDs.

Methods

We present a series of cases evaluated antenatally by using an extended and optimized fetal
ultrasound protocol in the Department of Obstetrics and Gynecology of ENDOGYN AM and
confirmed in the Prenatal Diagnosis Unit, together with the University Hospital team regarding
the imagistic and anatomopathological examinations. The particularities of these cases are
discussed, in terms of early features of CHDs and false positive or false negative results. Patients
were scanned by experienced physicians by using Voluson E10 and 730 – GE Healthcare
Systems. Gestational age ranged between 11 weeks and 13 weeks + 6 days (45-84 mm) and was
calculated on the measurement of the fetal crown-rump length (CRL). The fetal heart was
examined in grey scale and color Doppler, starting with the evaluation of the four-chamber view;
this included the evaluation of the heart area (no more than one third of chest area), and axis,
right- and left-sided structures approximately equal, the normal offset of the two atrio-ventricular
valves. The left and right ventricular outflow tracts were evaluated in regards with their size,
crossing, confluence and flow direction, as presented in previous communications [13, 14].
Between 18-20 weeks of gestation a follow-up scan was performed. After confirmation,
appropriate counseling and management were provided by interdisciplinary team (obstetrician,
geneticist, neonatologist – pediatrician, pediatric cardiologist). When CHD was suspected, the
antenatal diagnosis was compared with the pathological examination and postnatal assessment.

Results

We demonstrate that a large spectrum of fetal cardiac abnormalities evaluated early in


pregnancy were correctly diagnosed including hypoplastic left and right heart and conotruncal
anomalies (Fig. 1). Color Doppler or directional power Doppler represents in our experience the
main tool to investigate the morphology and function of the FT fetal heart early in pregnancy, as
published before [13-16]. Serial scans with reexaminations, transvaginal scan or rescheduled
during the next days may be helpful for specific situations of not satisfactory visualization of
anatomical structures (unfavorable fetal position, unfriendly maternal conditions) or for better
visualization of fetal abnormalities (Fig. 2). Pitfalls in first-trimester imaging of the fetal heart are

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related to the adequacy of the examination, including image resolution, fetal position and
movements and the clarity in relation to the size of the structures being examined (Fig. 3).

Fig. 1. Congenital heart disease diagnosed in the first trimester. A: atrio-ventricular septal defect; B: common arterial
trunck; C: hypoplastic right heart with lack of right ventricle filling and regurgitation (C1) and revered flow in right
ventricle outflow tract (C2); D: double aortic arch; E: Fallot tetralogy with aortic origyn from both ventricles (E2)
and hypoplastic pulmonary artery (E3); F: right aortic arch with left ductus in duplex evaluation – grey scale and
directional power Doppler; G: transposition of great arteries with parallel course of the great arteries in duplex
evaluation – grey scale and directional power Doppler.

Fig. 2. Cardiomyopathy in the first trimester triploid fetus, evaluated by transvaginal approach, due to the
unfavourable fetal position and oligohydramnios (left image). Increased area of the heart, bilateral echogenic
ventricular focuses (right image).

Fig. 3. False positive results at the first trimester anomaly scan, suspecting atrio-ventricular septal defect (B) in a
fetus situated far from the probe and with unfavourable position (A); hypoplastic right heart with apparently
diminutive right ventricle (D) and right outflow tract (E) in a pregnancy accompanied by large fibromyomas (C).

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Discusions

Congenital heart diseases (CHD) are the most common congenital anomalies and most cases
occur in the low-risk population [11]. The development of high resolution ultrasound machines
allowed a better visualization of the fetal heart in the FT [12-15]. Still, in our opinion, the use of
an appropriate optimized protocol is critical for a satisfactory detection rate. According to the
literature, although visualization of fetal cardiac anatomy is already possible at the end of the FT,
normal results from echocardiographic examinations at any time of pregnancy do not exclude
CHD, because some cardiac lesions may evolve in utero as gestational age advances or even
occur later during pregnancy: hypoplastic left heart syndrome, coarctation of the aorta,
endocardial fibroelatosis due to aortic stenosis, pulmonary stenosis, tetralogy of Fallot [18-20].
Other heart defects such cardiomyopathy or cardiac tumors may evolve even after birth [18,
21]. Ventricular septal defects were the most missed lesions during prenatal echocardiographic
evaluation because of limited resolution, the small size of the lesion and low flow velocities in the
FT. Many cardiac defects may be asymptomatic, both during pregnancy and immediately after
birth and even during the first days of life [22, 23]. Our study results support recent statements [2,
24] that the FT scan has become the first anomaly scan, and has the potential to detect structural
heart defects also [25]. This offers the couples the desired early reassuring in the vast majority of
cases [26], and the opportunity of an early decision to terminate the pregnancy in rare cases of
severe CHDs [27]. As cardiac lesions may evolve or even occur later during pregnancy, a second
and even a third trimester cardiac examination should be considered [28-32].

Conclusion

The detection of major CHDs at the end of the FT is nowadays strongly influenced by their
association with some 20 years old markers, such as nuchal translucency, ductus venosus blood
flow and tricuspid regurgitation. However, the use of optimized protocols is greatly improves the
detection rate. A policy decision is necessary to shift this diagnosis towards the direct
investigation of the heart, considering the strong literature evidence and the progress of
technology. Still, follow-up echocardiography must be borne in mind, because of the dynamic of
heart development during pregnancy.

Acknowledgements
This paper was published under the frame of European Social Found, Competitivity
Operational Programme 2014-2020, POC-A.1-A.1.2.1-D-2015, Contract nr. 75/08.09.2016,
MYSMIS Code: 105076.

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detection rate of structural abnormalities in the first trimester using an extended examination protocol.
Ultrasound Obstet Gynecol. 2013 Sep; 42(3): pp. 300-9.
15. Pătru CL, Iliescu DG (autor corespondent), Tănase F, Drăgușin RC, Șorop-Florea M, Căpitănescu R,
Comănescu A, Pană RC, Zorilă LG, Marinaș MC, Novac M, Stoica A, Sîrbu M, Cernea N, Tudorache S.
Fetal Heart in the First Trimester. The Added Value of the Outflow Tracts Evaluation. Conference
Proceedings, 5th Congress of The Romanian Society of Ultrasound in Obstetrics and Gynecology, Targu
Mures, Romania, 20-22 April 2017, First Ed Published June 2017, pp. 471-475.
16. Gheorman L, Iliescu D (autor coresp), Ceauşu I, Paulescu D, Pleşea IE, Gheorman V. Importance of early
complex evaluation in high-risk pregnancy associated to diabetes mellitus. Case presentation and review of
the literature. Rom J Morphol Embryol. 2011; 52(3 Suppl): pp. 1127-32.
17. Ştefania Tudorache, Anda Ungureanu, Roxana Cristina Drăguşin, Florea Maria Şorop, Monica Laura Cara,
D. G. Iliescu, First trimester diagnostic accuracy of a two-dimensional simplified ultrasound technique in
congenital heart diseases and greatarteries anomalies. Obstet and Gynecol LXIV, 2016, pp. 165-176.
18. Khalil A, Nicolaides KH. Fetal heart defects: Potential and pitfalls of first-trimester detection. Seminars in
Fetal & Neonatal Medicine. 2013.
19. Smrcek JM, Berg C, Geipel A, Fimmers R, Axt-Fliedner R, Diedrich K, Gembruch U. Detection Rate of
Early Fetal Echocardiography and In Utero Development of Congenital Heart Defects. J Ultrasound Med.
2005, 25: pp. 187-196.
20. Carvalho JS, Moscoso G, Tekay A, Campbell S, Thilaganathan B, Shinebourne EA. Clinical impact of first
and early second trimester fetal echocardiography on high risk pregnancies. Heart. 2004, 90: pp. 921-926.
21. Chaoui R, Nicolaides KH. From nuchal translucency to intracranial translucency: towards the early
detection of spina bifida. Ultrasound Obstet Gynecol. Feb, 2010 , 35(2): pp. 133-8.
22. Iliescu D, Tudorache S, Comanescu A, Antsaklis P, Cotarcea S, Novac L, Cernea N, Antsaklis A. Improved
detection rate of structural abnormalities in the first trimester using an extended examination protocol.
Ultrasound Obstet Gynecol 2013; 42: pp. 300-9.
23. Mărginean C, Mărginean C O, Muntean I, Togănel R, Meliț L E, Mărginean M O, Gozar L
Ultrasonographic features of the persistence of superior left vena cava and pathological cardiac associations
in fetus. Cases series. Med Ultrason 2016, 18(2): pp. 214-217.
24. Smrcek JM, Berg C, Geipel A, Fimmers R, Axt-Fliedner R, Diedrich K, et al., Detection rate of early fetal
echocardiography and in utero development of congenital heart defects. J Ultrasound Med. 2006; 25(2): pp.
187-96.
25. Becker R, Wegner RD. Detailed screening for fetal anomalies and cardiac defects at the 11-13-week scan.
Ultrasound Obstet Gynecol. 2006 Jun; 27(6): pp. 613-8.

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26. Rasiah SV, Publicover M, Ewer AK, Khan KS, Kilby MD, Zamora J. A systematic review of the accuracy
of first-trimester ultrasound examination for detecting major congenital heart disease. Ultrasound Obstet
Gynecol. 2006; 28(1): pp. 110-6.
27. Carvalho JS, Moscoso G, Tekay A, Campbell S, Thilaganathan B, Shinebourne EA. Clinical impact of first
and early second trimester fetal echocardiography on high risk pregnancies. Heart. 2004; 90(8): pp. 921-6.
28. Gozar L, Mărginean C, Togănel R, Muntean I, The role of echocardiography in fetal tachyarrhythmia
diagnosis. A burden for the pediatric cardiologist and a review of the literature, Med Ultrason 2017, 19(2):
pp. 232-235.
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of the fetal common arterial trunk. A case series, Med Ultrason 2018 4; 1(1): pp. 100-104.
30. Mărginean C, Mărginean C O, Muntean I, Toganel R, Voidăzan S, Gozar L The role of ventricular
disproportion, aortic, and ductal isthmus ultrasound measurements for the diagnosis of fetal aortic
coarctation, in the third trimester of pregnancy. Medical Ultrasonography, 2015, 17 (4): pp. 475-481.
31. Muntean I, Mărginean C, Stanca R, Togănel R, Pop M, Gozar L. Prenatal diagnoses of an uncommon
isolated obstructed supracardiac total anomalous pulmonary venous connection – case report and review of
the literature (CARE compliant), Medicine 2017, 96:5

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Definitive Diagnosis of Major Central Nervous System


Abnormalities – More Than a Challenge

ILIESCU Dominic-Gabriel1,2, TUDORACHE Stefania1,


DRĂGUȘIN Roxana Cristina1,2, MANOLEA Maria Magdalena1, VRABIE Sidonia1,
Lorena Anda DIJMARESCU1, ZORILA Lucian George1,2
1Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, (ROMANIA)
2Department of Ultrasound in Obstetrics and Gynecology SC ENDOGYN AM, Craiova, (ROMANIA)
Email: [email protected]

Abstract

The fetal central nervous system (CNS) presents a fine neurodevelopment of a complex
anatomy which changes rapidly. Major CNS abnormalities can be detected early in pregnancy, in
the first trimester (FT) due to high advances of ultrasound technology and also to an increased
sonographer familiarity with scanning. However, some CNS disorders can only be confirmed in
the second trimester (ST) of gestation. Some anomalies may appear suddently due to extrinsec
factors, so careful examination throughout pregnancy remains warranted. The aim of this article
is to summarize benefits, limitations and challenges of ultrasound diagnosis and subsequent
confirmation of major CNS abnormalities.
Keywords: congenital abnormalities, central nervous system, prenatal ultrasound, perinatal autopsy

Introduction/Objective

An accurate prenatal diagnosis of fetal CNS anomalies is important because of the high
incidence in newborns (0.5-1%) and miscarriages (3-6%) [1, 2]. The SNC is the most affected
site in chromosomal aberrations. It is also correlated with the greatest social impact on
short/medium and long term with the need for centers of care, recovery, special care career,
special jobs and integration, family burden with limited possibilities for recovery. A good
knowledge of normal neuroembryology and early markers of disease is fundamental for an early
ultrasound diagnosis [3, 4]. Fortunately, the most prevalent and severe CNS anomalies have been
reported to be easily detectable in the FT allowing a detection rate close to the routine ST CNS
scan [3]. An important limitation of the FT diagnosis is represented by the further dynamic of the
CNS development, as many disorders such as neural migration, proliferation and organization,
and acquired lesions (infections, hemorrhage and tumors) occur later in pregnancy [5, 6]. An
important challenge is represented by the confirmation of diagnosis, important for couple’s
counselling, regarding recurrence and specific tests or prophylaxis in future pregnancies.
Perinatal autopsy remains the gold standard for diagnosis confirmation. A good correlation of
approximately 80% with the prenatal US has been reported [5]. In addition, there are great
expectations from the genetic investigation for a better characterization of CNS abnormalities [7].
The present study has two major objectives: to certify the accuracy of US diagnosis of fetal
CNS anomalies and to establish the concordance of prenatal diagnosis with autopsy/postnatal
evaluation.

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Methods

We report a prospective study for 3 years, October 2014- October 2017 that took place in 3
Antenatal Diagnosis Units that included the Emergency County Hospital of Craiova, Materna
Clinic and Ginecologiq Clinic. All pregnancies that presented for ultrasound screening,
emergency presentations or referrals from other hospitals were included in the study. We
excluded all pregnancies that did not have complete follow-up. All major CNS abnormalities
diagnosed before 24 weeks were proposed for therapeutic termination of pregnancy (TOP) as
stated by current legislation. We performed fetal or perinatal autopsy for confirmation of
diagnosis and all surviving cases beneficiated from a transfontanellar US, magnetic resonance
imaging or computer tomography along the clinical neurological exam. All cases were counselled
and managed in a multidisciplinary team that included the obstetrician, the pediatric surgeon, the
pathologist, the genetician,the pediatric neurologist, the neonatologist and also the radiologist.
Fetal autopsy was performed in the Pathology Laboratory of the Emergency County Hospital
of Craiova. Fetal brain is difficult to evaluate as it is fragile and proned to early autolysis and also
because of the low differentiation of structures at native examination. We used a special protocol
of initial formalin fixation, disection and isolation (Fig. 1).

Fig. 1. Autopsy protocol for fetal brain isolation

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Results

We examined pregnancies in the FT (1943 cases), in ST before 24 weeks of gestation (2384


cases), and 1969 cases after 24 weeks of gestation (GW). We lost to follow-up 354 cases after the
FT scan and 853 cases after the ST scan. We found 12 major CNS anomalies in the FT, 25 CNS
anomalies in the ST before 24 GW and 12 were detected after 24 weeks of pregnancy (Fig. 5).
Global CNS anomalies were found in 5,6% and major conditions represented 1,84%. The most
frequent malformations found in the FT were the neural tube defects (NTD), 75% of the detected
CNS anomalies. All NTDs and holoprosencephalies presented in the FT were detected, with no
false positive and false negative results.
Regarding the evolution of the diagnosed pregnancies, 53% were terminated using specific
medication, 10% of the fetuses presented with intrauterine fetal demise (IUFD) and 15%
presented with peripartum fetal demise, 12% continued pregnancy and resulted in live births, and
10% requested surgical TOP, where autopsy was not possible (Fig. 1).

Fig. 1. Outcome of the affected pregnancies

25 CNS anomalies were detected in the ST before and after 24 weeks of gestation, of wich
36% were detectable in the FT (NTDs and holoprosencephaly), but the pregnant women did not
attend the respective evaluation. Similarly, 12 cases were detected after 24GW, of wich 75%
were potentially detectable in previous US examinations.
There was a high accuracy of CNS abnormalities’ detection in the FT and ST scans: 99.81%
vs. 99.79%, but the sensitivity was higher in the ST (89.29% vs. 80.0%). Regarding the corelation
between the US evaluation and the autopsy results, we found a full agreement in 84%.
In 5%of cases, the autopsy found structural abnormalities that were not found by the US exam
and in 11% of cases the US diagnosis was not fully confirmed by the ultrasound.

Discussion

The fetal CNS along cardio-vascular evaluations are challenging, as the brain and heart are
highly evolving organ systems [8]. Still, some prevalent major anomalies of these systems are
easily detectable in the FT and also in the ST as shown in this paper and previous research [9-15].

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Although the transabdominal approach was most frequently used in routine screening, in some
selected cases the transvaginal scan proved useful to complement the examination, especially in
the FT difficult examinations and the agenesis of corpus callosum cases. As remarqued in other
studies [16-19], the pathology was not easy to perform because of the small FT brain dimensions,
and brain tissue characteristics, but the brain fixation and dissection protocol enabled us to
efficiently explore and confirm the targeted CNS malformations. Still, brain damage was a
limitation when performing an autopsy for confirmation of the diagnosis in the intrauterine fetal
deaths. This is commonly seen even at later gestational ages [16, 18]. When an anomaly with
dynamic evolution pattern was suspected in the FT, further serial re-evaluation in the ST were
done to certainty the diagnosis and to better counsel the couple as stated before [20, 21].
Overall, the study proved a high accuracy in early detection of major CNS anomalies and also
a good correlation with the autopsy results, which represents an important step in the
development of ethical and medico-legal aspects of the therapeutic abortion related to fetal major
abnormalities [22, 23].

Conclusions

Many major CNS anomalies, such as acrania, alobar holoprosencephaly, cephaloceles, and
spina bifida can be diagnosed early in pregnancy, if we look actively of every fetus undergoing
FT. Other conditions such as vermian anomalies and agenesis of the corpus callosum, can only be
confirmed in the ST. So, even if the FT screening for CNS anomalies is highly efficient it is not a
substitute for the ST anomaly scan. However, no matter how efficient and correct the prenatal
diagnoses become, a pathological verification is desirable in order to ensure the quality control.
Thus, the increased diagnostic accuracy in antenatal ultrasonography emphasizes the need for
more expertise/experts in perinatal autopsy. The present study reported a high grade of
concordance with the autopsy diagnoses: the main diagnosis was correct in 100% of the cases
with no true false-positive cases.

Acknowledgements
This paper was published under the frame of European Social Found, Competitivity
Operational Programme 2014-2020, POC-A.1-A.1.2.1-D-2015, Contract nr. 75/08.09.2016,
MYSMIS Code: 105076.

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11. Gheorman L, Iliescu D (autor coresp), Ceauşu I, Paulescu D, Pleşea IE, Gheorman V. Importance of early
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Low Birth Weight: Third Trimester Fetal Biometry Assessment


Versus Actual Birth Weight

IONESCU Cringu1, MATEI Alexandra2, GHEORGHIU Diana2, BANACU Mihai1,


POPESCU Ina2, IONESCU Andra2, VIEZUINA Roxana2, CALIN Dan1
1“Carol Davila” University of Medicine and Pharmacy Bucharest (ROMANIA)
2“St. Pantelimon” Emergency Hospital Bucharest (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Introduction/Objective
Nowadays Obstetrical and Neonatal practice are facing severe drawbacks caused by the “low
birth weight” issue complicating high-risk pregnancies. Multiple factors especially those related
to the mother herself like associated comorbidities or the absence of proper antenatal follow-up
are susceptible to compel this unfavourable outcome. Active screening through non invasive
paraclinical investigations like ultrasound examination of the fetus is set to detect early deviations
from normal growth curves and furthermore to initiate efficient diagnosis and treatment
plannning. This study aims to present the experience of our Department regarding the efficiency
of antepartum ultrasound examination in patients with low birth weight newborns.

Materials/Method
We developed a prospective case-control study in the Obstetrics and Gynecology Department
of “St. Pantelimon” Emergency Hospital in Bucharest referring to all patients admitted for
delivery. We considered to be low birth weight all newborns measuring less than 2500g at birth.
We sought to analyze the efficiency of fetal biometry in assessing newborns’ weight by
comparing data from patients who delivered low birth weight babies – case group, with data
collected from patients with normal birth weight babies – control group. A statistical analysis was
performed on custom ultrasound parameters followed by data appraisal between case and control
groups as well as taking into consideration corresponding literature reports.

Results
Seventy patients have been introduced in our study: 35 women with low birth weight
newborns in the case group and 35 women with normal birth weight newborns with no
documented comorbidities that could affect fetal intrauterine growth matched the control group.
We found that abdominal circumference and biparietal diameter were significantly lower in
the case group compared to control data. Particular ultrasound features were noticed for patients
known to have medical affections influencing fetal intrauterine growth. Infering the results from
our clinic in the european medical background allowed us to report lower biometric values in our
study even in the control group.

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Conclusion/Discussion
The first day of last menstrual period was a decissive item for ultrasound examination of
fetuses from unsupervised pregnancies. Particular aspects of maternal pathologies causing
intrauterine growth restriction were brought into attention by ultrasound evaluation. Third
trimester fetal biometry had high accuracy in predicting fetal birth weight; fetal growth curves
obtained by biometry measurements showed marked variations between normal birth weight and
low birth weight offsprings.
Keywords: low birth weight, ultrasound, fetal biometry, growth curves

Introduction

Nowadays Obstetrical and Neonatal practice are facing severe drawbacks caused by the “low
birth weight” issue complicating high risk pregnancies. Multiple factors especially those related
to the mother herself like associated comorbidities or the absence of proper antenatal follow-up
are susceptible to compel this unfavourable outcome. Since mothers tend to neglect their state of
health or accept inadmissible high risks from the desire to have children [1], active screening
through non invasive paraclinical investigations like ultrasound examination of the fetus becomes
compulsory in order to detect early deviations from normal growth curves and furthermore to
initiate efficient diagnosis and treatment plannning.
While major changes of the anatomical features of the fetus may appear at the first trimester
imagistic evaluations making early anomaly scan compulsory to be performed at the end of the
first trimester [2], prediction of low birth weight newborns is more often addressed to second and
third trimester ultrasound examination.
When a high-risk pregnancy is suspected to influence fetal development, Doppler velocities
are useful as a specific clinical tool to determine if a placental insufficiency may lead to
intrauterine growth restriction [3], [4]. As shown in literature, when considering restricted
fetuses, abnormal Doppler velocimetry is associated with the highest risk of poor fetal prognosis
compared with fetuses that have alarming values of non-stress test or biophysical profile [5].
Nevertheless, the same examination approach is implemented when no maternal comorbidities
are detected but fetal weight does not match the corresponding growth curves.
Globally, prematurity is the leading cause of death in children under the age of 5 years [6].
Considering prematurity as background for multiple entities such as low birth weight infants
(weight below 2500 g), very low birth weight newborns (weight below 1500 g and/or gestational
age below 32 weeks) and small for gestational age offsprings (birth weight less than 10th centile
for gestational age) [7], [8], and taking into consideration the fact that an estimated 15 million
babies are born too early every year [6], we developed an interest in reporting the current status
of our clinic regarding this healthcare matter.
This study aims to present the experience of our Department regarding the efficiency of
antepartum ultrasound examination in patients with low birth weight newborns.

Materials/method

A prospective case-control study was developed in the Obstetrics and Gynecology Department
of “St. Pantelimon” Emergency Hospital in Bucharest between December 2017-March 2018
referring to all patients admitted for delivery. A total number of 70 patients were included in our
study design, each group gathering an equal number of 35 patients.

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Additionally, inclusion criteria in the case (treatment) group were: delivery between December
2017 to March 2018 of a low birth weight newborn. Patients who delivered twins were also added
if at least one of the babies met the inclusion criteria. We considered to be low birth weight all
newborns measuring less than 2500g at birth. Control group was formed of 35 subjects
resembling the demographic variables of case group patients but who gave birth to normal birth
weight babies. Maternal comorbidities which could affect intrauterine fetal growth were
established as exclusion criteria from our study groups. Data on patients was collected from
admission charts, birth registries as well as from medical records accessed through Info World
medical software.
We sought to analyze the efficiency of fetal biometry in assessing newborns’ weight by
comparing data from patients who delivered low birth weight babies – case group, with data
collected from patients with normal birth weight babies – control group. A statistical analysis was
performed on custom ultrasound parameters followed by data appraisal between case and control
groups as well as taking into consideration corresponding literature reports.
Our analysis is based on descriptive statistics (mean, minimum, maximum, centiles and
number of cases), on correlational statistics (Eta correlations for nominal by interval associations
and Pearson correlations for bivariate associations of two interval variables, together with the
Chi-square statistical significance related value) and on linear regressions for testing the
statistical significance of BPD (biparietal diameter), HC (head circumference), AC (abdominal
circumference) and FL (femor length) measures between treatment and control groups,
controlling for echo graphical gestational age. All results are presented as a comparison between
the treatment group (Total N=35) and the control group (Total N=35). The software used were
Microsoft Office 365 – Excel, version 1804 and IBM SPSS Statistics, version 22.

Results

Descriptive statistics show a mean age of about 28 years of age for both treatment and control
groups. The minimum age is 15 years for both groups, whereas the maximum age value is 41 in
the control group and 20 in the treatment group.
Maternal weight is higher for the control group, with a mean value of 81.8 kg, in comparison
with the treatment group which has a mean of 72.85 kg. The BMI (Body Mass Index) value in
turn is similar between groups, with a value around 30 kg/m2. The maximum categories for both
groups go into the obese category, with 35 kg/m2 for the treatment group, and a 39 kg/m2 for the
control group. With respect to weight gain, 9.2 kg is the mean of the treatment group and 13.45
kg is the mean of the control group.
Fetal weight varies as well. The mean value is 2050g for the treatment group and 3270 g for
the control group. For the treatment group, the minimum is 700g, whereas the maximum is 2870
g (we included in the case group patients who delivered twins as long as at least one of them is
low birth weight). The minimum value of the control group was 2840 g, and the maximum value:
4000g.
Gestational age of mothers under 18 years of age is, on average, 37 weeks for the treatment
group and 38 weeks for the control group, whereas the gestational age of the mothers of 18 years
of age or above is more different between groups, with 34.65 weeks for the treatment group and
38.27 weeks for the control group.
Twenty-two (22) patients (62.85%) from treatment group had premature deliveries: from 26 to
36 weeks of gestation while in the control group only 4 patients (11.42%) gave birth at 36 weeks
of gestation.

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With respect to the correlation between maternal age and gestational age, the higher the age,
the lower the gestational age in the treatment group (Pearson coefficient of -0.201), whereas the
Pearson correlation is positive in the control group (0.050, but low in value), meaning that the
higher the age, the higher the gestational age. At the same time, searching for a connection
between maternal age and fetal weight, we observed that in the treatment group the higher the
age, the lower the fetus weight (Pearson correlation is -0.111), while in the control group the
relation is positive, meaning that the higher the maternal age, the higher the fetal weight (Pearson
correlation is 0.136).
The ultrasound gestational age is not statistically significant correlated with the type of birth,
but the coefficients are positive for both case and control groups (0.353 and 0.169 respectively).
In case group there were 19 cesarean sections and 16 vaginal deliveries of which 12
respectively 10 occured at preterm. Comparison with control group is shown in Fig. 1 below.

Fig 1. Comparison on type of births depending on gestational age in case (left) vs control group (right)

Correlation between ultrasound gestational age and BPD is a positive, strong and statistically
significant correlation in the treatment group (Pearson correlation of 0.893, 99.9% confidence
level), but not statistically significant in the control group (Pearson correlation of 0.446).
Correlation between ultrasound gestational age and HC is a positive and statistically
significant relation in both groups, with a moderate correlation in the control group (0.548 at a
confidence level of 95%) and a strong to perfect correlation in the treatment group (0.924 at a
confidence level of 99.9%). Also, correlation with AC and FL present similar patterns, with a
Pearson coefficient of above 0.9, statistically significant at a 99.9% confidence level in the
treatment group and a Pearson coefficient of about 0.2 not statistically significant in the control
group. Comparison of biometry parameters BPD, HC, AC and FL by ultrasound estimated
gestational age in the two samples is shown in Fig. 2; we can notice a stronger positive
association between variables in the treatment group than in the control group. Thus, for higher
values of ultrasound gestational age our sample showed with a higher probability based on
graphical representations higher values of BPD, HC, AC and FL in the treatment group.

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Case group Control group

Fig. 2. Comparison between case and control groups regarding BPD and AC by ultrasound gestational age

Considering the connection between actual and ultrasound gestational age and fetal weight in
each sample group, we can notice based on graphical representations a higher association
between fetal weight and actual or ultrasound gestational age in the treatment group than in the
control group. This pattern means that there is a higher variation and a stronger association
between the two variables in the treatment group than in the control group. In the control group,
the association is low to inexistent (Fig. 3).

Fig. 3. Gestational age (weeks) by fetal weight (g) in the case (left) vs control group (right)

Discussion/conclusions

It is said that modern development can be sustainable only if it is focused on human being and
his physical, mental and socio-economical welfare, while attempting to make a distinction
between the concept of “life quality” and that of “health” [9]. Growth as a perpetual phenomenon

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recollects its roots in the early stages of conception, where genetic and environmental factors
collude to maintain a balance compatible with life.
Fourteen patients in case group (40%) did not attend any antenatal consults and only 5 of them
could recall the last menstrual period. In this situation, estimation of gestational age could be
made on proper medical information, essentially based on the last menstrual period. Ten patients
in case group (28.57%) were diagnosed with pathologies that could interfere with normal fetal
intrauterine growth like Hypertension, Preeclampsia or Thrombophilia. Even though the
pregnancy outcome can be severely influenced by these comorbidities, their simple diagnosis
does not make a rule out of it. There have been case reports of patients diagnosed with severe
hypercoagulable conditions like primary myelofibrosis which resulted in the birth of healthy
newborns [10]. In our study only 4 of these patients had ultrasound examination which showed
specific Doppler velocimetry alterations along with placental structural changes but these remarks
did not take part in the purpose of this report. We do acknowledge that a pregnancy outcome is
strongly influenced by the evolution of the fetal-placental unit [11].
Lately, obstetricians have shown an understandable interest on maternal weight oscillations
during pregnancy. It has already been established that the weight of pregnant women inversely
correlates with first trimester biochemical markers values [12] whereas our study underlined the
fact that the medium weight gain was lower for patients who delivered low birth weight newborns
compared to those who did not. Because an unbalanced metabolism as additional burden for
obese women is difficult to control, many of them expose themselves at greater risk for
unplanned higher risk pregnancy [13].
Our results concluded that abdominal circumference and biparietal diameter were significantly
lower in the case group compared to control data. From this point of view, recent studies revealed
that the contribution of genetic factors to birth size is smaller than that of shared environmental
factors [14]. Adversely, women with endometriosis or adenomyosis had higher odds of preterm
delivery and having a child that was small for gestational age compared to women without these
conditions [15].
We underline human error in archiving or collecting medical data as plausible sources of
biased information.
The possible limitations of our study reside in the reduced neonatal follow-up of the newborns
as well as in the absence of further investigation of maternal medical conditions which could
interfere with fetal growth. Moreover, we did not explore the impact of different types of assisted
reproduction techniques as part of current practice for the treatment of couple infertility [16] on
fetal biometry. For long term initiative it seems compelling to survey routine histopathological
examination of the placenta after birth [17] since this procedure succeeded in confirming
remarkable diagnoses.
On the other hand, we consider the conjunction of third trimester biometry along with
maternal and fetal weight to be a strongpoint of this report, especially in the approach of
pregnancies with no additional paraclinical investigations – the affiliation of gestational age, high
maternal age, overweight or obesity and low education to sudden intrauterine death [18] already
being confirmed in literature.
Keeping in mind the continous evolution of ultrasound resources such as 3D power Doppler
advantages: highlighted anatomical details, removed angle dependence and aliasing distortions
[19] or the new technique called STIC (spatial and temporal image correlation) which marked a
major progress over the last ten years [20] – all set to ease fetal ultrasound investigation, we take
into account future perspectives on analyzing intrauterine growth restriction on the base of
previously diagnosed maternal conditions [21].

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REFERENCES

1. Olaru G, Ionescu C, Lesnic A et al., Ethical and medico-legal aspects of the therapeutic abortion -our
experience Rom J Leg Med 2018, (26), pp. 82-85.
2. Şorop-Florea M, Ciurea RN, Stepan AE et al., The importance of perinatal autopsy. Review of the literature
and series of cases. Rom J Morphol Embryol. 2017; 58(2): pp. 323-337.
3. Moldoveanu A, Oprescu D, Catanescu N et al., The Role of Fetal Doppler Monitoring in Preeclampsia
With/without Intrauterine Growth Delay. Conference Proceedings of the 5th Congress Of The Romanian
Society Of Ultrasound in Obstetrics and Gynecology.20-22 April 2017.Tg-Mures, Romania. pp. 401-405.
4. Petca A.*, Vlădăreanu S.*, Zvâncă M., Boț M., Vlădăreanu R. (*autori cu contribuție egală).Timing for the
delivery of intrauterine growth restricted fetus – a resolvable issue. PROCEEDINGS OF THE 49TH
ANNUAL SCIENTIFIC MEETING OF THE EUROPEAN SOCIETY FOR CLINICAL
INVESTIGATION. 2015. pp. 273-277. ISBN: 978-88-7587-719-4. Publicat în European Journal of Clinical
Investigation EJCI, volum 45, supliment S2, ISSN: 1365-2362.
5. Novac L, Tudorache S, et al., The Use of Doppler Ultrasound as Early Parameter for Detection of Fetal
Compromise in Restricted Fetuses. Conference Proceedings of the 5 th Congress Of The Romanian Society
Of Ultrasound in Obstetrics and Gynecology.20-22 April 2017.Tg-Mures, Romania. pp. 445-449.
6. http://www.who.int/news-room/fact-sheets/detail/preterm-birth
7. http://www.who.int/elena/titles/review_summaries/zinc-pregnancy/en/
8. Hernandez MI, Rossel K, Pena V et al., Patterns of Infancy Growth and Metabolic Hormonal Profile Are
Different in Very-Low-Birth-Weight Preterm Infants Born Small for Gestational Age Compared to Those
Born Appropriate for Gestational Age. Horm Res Paediatr. 2018 May 15: pp. 1-13.
9. Mocuta D, Popovici LR, Dumitriu AS et al., Life quality – condition of social walfare. Metalurgia
International. 2009. Volume: 14. Issue 5. pp. 62-64.
10. Bohaltea R, Cirstoiu M, Ionescu C et al., Primary myelofibrosis and pregnancy outcomes after low
molecular-weight heparin administration A case report and literature review. MEDICINE Volume: 96 Issue:
46 Article Number: e8735 Published: NOV 2017.
11. Zorila L, Iliescu DG, Dragusin R et al., Stillbirth in dichorionic twins discordant for major and minor
anomaly, followed by asynchronous delivery – a rare occurrence. Case presentation., Romanian Journal of
Morphology and Embriology, 2016, 57(3): pp. 1117-1123.
12. Navolan D, Ionescu CA, Carabineanu A et al., Influence Of Weight Of Pregnant Women On First Trimester
Biochemical Markers Values. Revista De Chimie Volume: 68 Issue: 12, 2017: pp. 2836-2838.
13. Ionescu C, Navolan D, Calin A et al., Hormonal Contraception in Postpartum Patients with Gestational
Diabetes Mellitus. Revista De Chimie Volume: 69 Issue: 2 pp. 478-483.
14. Yokoyama Y, Jelenkovic A, Hur Ym et al., Genetic And Environmental Factors Affecting Birth Size
Variation: A Pooled Individual-Based Analysis Of Secular Trends And Global Geographical Differences
Using 26 Twin Cohorts. Int J Epidemiol. 2018 May 19.
15. Bruun Mr, Arendt Lh, Forman A et al., Endometriosis And Adenomyosis Are Associated With Increased
Risk Of Preterm Delivery And A Small For Gestational Age Child: A Systematic Review And Meta-
Analysis. Acta Obstet Gynecol Scand. 2018 May 12.
16. Pacu I, Ionescu C, Vladareanu S et al., Predictive Value of the AMH Level and Serum Estradiol for Ovarian
Hyperstimulation Syndrome in the Assisted Human Reproduction. Revista De Chimie Volume: 68 Issue:5:
pp. 1118-1121
17. Bratila E, Ionescu C, Vladescu C et al., Gestational choriocarcinoma after term pregnancy: a case report –
Romanian Journal of Morphology and Embryology.Volume:56.2015. Issue: 1, pp. 267-271.
18. Ionescu A, Popescu I, Banacu M et al., Is it possible to predict stillbirth in the third trimester? Conference
Proceedings of the 5th Congress Of The Romanian Society Of Ultrasound in Obstetrics and Gynecology.20-
22 April 2017.Tg-Mures, Romania. pp. 194-198.
19. Herghelegiu D, Ionescu C, Pacu I et al., Antenatal diagnosis and prognostic factors of aneurysmal
malformation of the vein of Galen A case report and literature review. MEDICINE Volume: 96 Issue: 30
Article Number: e7483. Published: JUL 2017.
20. Ionescu C, Gheorghiu D, Davitoiu B et al., Visualization of the atrioventricular valve plane in fetuses with
atrioventricular defect using STIC technique. GINECO RO 2009 Volume: 5 Issue: 4, pp. 210-215.
21. Burnei-Rusu, A., Zamfirescu, V., Bot, M., Traistaru, A., Boiangiu, A., Cotman, R., Vladareanu, R. (2007).
Intrauterine Growth Restriction – Predictive Markers in Early Pregnancy. Proceeding paper for the 5th
Romanian Congress of the Romanian Society of Ultrasound in Obstetrics and Gynecology, pp. 155-159.

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The Heart Which “Looks Different”

KOVACS Tunde1, NEMETI Georgiana2, STAMATIAN Florin1


1IMOGEN, Centre For Advanced Research, Cluj-Napoca, (ROMANIA)
2Obstetrics and Gynecology, Mother and Child Department, University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-
Napoca, (ROMANIA)
Emails: [email protected], [email protected], [email protected]

Abstract

Congenital heart diseases are among the most common fetal abnormalities. Given their
increased incidence in pregnancies without any risk factors, universal screening by prenatal
echocardiography is mandatory. Ultrasound evaluation alows for the detailed description of
cardiac anatomical details, assessment of the hemodynamic stability of the fetus, estimation of
potential disease pogression in utero and to determine the need for medical/surgical interventions
after birth. This in turn leads to referral of complex caes to fetal cardiology units for evaluation
and counseling to ensure individualized care and thus to improve the short-term and long-term
outcomes of affected neonates, especially those with cyanotic congenital heart diseases. In this
review, we approached the most commonly encountered cardiac abnormalities of the fetal heart.
Keywords: cardiac heart defects, ultrasound, perinatal, fetal cardiology

Introduction

The frequency of congenital heart diseases (CHD) is of ≈1% in liveborn neonates, with similar
prevalence throughout world, and of 10% in aborted fetuses [1], [2]. This class of fetal
abnormalities is associated with significant morbidity and mortality in the affected children. It is
essential to increase the detection rate of CHD in order to determine the prognosis of the child
and allow parents to reach informed decisions concerning management. At the same time,
postnatal outcome may be improved by optimizing perinatal management.
Pregnant women with a family history of CHD, diabetes mellitus, exposure to cardiac
teratogens in the early prenatal period and those in whom fetal arrythmias or extracardiac
anomalies (increased nuchal translucency, hydrops foetalis) are diagnosed constitute the high risk
category of pregnant women and should be reffered for scanning and counseling in a specialised
perinatal medicine center. However, as many as 90% of patients who deliver neonates with CHD
come from the low risk populations [3].
Every pregnant patient should undergo a comprehensive ultrasonographic examination of the
fetal anatomy including a detailed evaluation of the heart between 18 and 22 weeks of gestation
to rule out structural abnormalities and to assess for soft markers as a sign of chromosomal
abnormalities. Examining the fetal heart anatomy and function is however appropriate later in
gestation, depending on the clinical situation [4], [5], [6], [7], since screening may not identify
diseases that progress in utero from subtle pathology to more obvious disease closer to term.
One of the main goals for a fetal echocardiogram is to confirm the presence or absence of
cardiac disease. It includes imaging acquisition of the position, size, structure, function and

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rhythm of the fetal heart from multiple angles at any gestational age using the segmental analysis
approach as a comprehensive study based on an extensive checklist. If this scan is abnormal, the
examiner should characterize these abnormalities, develop an accurate differential diagnosis of
the most probable defects, and counsel parents whose fetuses will require immediate medical or
surgical intervention after birth. Newborn dependency on the patency of the ductus arteriosus is
perhaps the most important reason for fetal cardiac evaluation [8], [9], [10].
Fetal cardiac screening required by international guidelines consists of the four-chamber, right
ventricular outflow tract and left ventricular outflow tract views [5], [6], [7]. The three-vessel
view is also often used in screening. These views are essential for a complete evaluation of the
fetal heart.
In this review, we chose to address the most commonly encountered cardiac abnormalities at
the fetal cardiac scan and classifiy them according to the planes in which they are best identified:
the four chamber view, the outflow tract views, imaging of the right heart.

Anomalies picked on the four chamber view

Atrioventricular septal defect – This abnormality has also been described as an endocardial
cushion defect or atrioventricular canal. It is characterized by an incomplete atrial and ventricular
septation and the lack of separation between the mitral and tricuspid orifices. The atrioventricular
septal defect (AVSD) can have a partial/incomplete form when only the atrial or ventricular
communication persists and a complete form when both atrial and ventricular septation is
incomplete [11], [12]. All the clinical forms involve an intrinsic abnormality of the
atrioventricular valves. The AVSD is most commonly identified on the apical four-chamber view
by spotting a left atrioventricular valve attached to the ventricular septum at the same level as is
the right atrioventricular valve, losing the normal differential insertion. The septum primum is
absent. The four-chamber view is also ideal for Doppler interrogation of the atrioventricular
valves which are insufficent. The parasternal or subcostal short-axis views provide a detailed
picture of the atrio-ventricular valve anatomy.

Ventricular septal defects – The interventricular septum is a strand of muscular and


membranous tissue which separates the right and left ventricles. The normal interventricular
septum extends between the cardiac apex and the atrial septum. Formation of the interventricular
septum begins around the 28th day of gestation when the median muscular ridge begins to
invaginate. The free edge of the muscular septum fuses with the membranous septum formed by
the endocardial cushions at approximately 49 days gestation [13]. Ventricular septal defects
(VSD) are the result of the maldevelopment of the embryonic muscular septum, endocardial
cushions or the excess resorption of the muscular septum resulting in an abnormal hemodynamic
communication between the right and left ventricles and causing a left-to-right shunt. VSD is
among the most common cardiac anomalies, accounting for 20%-40% of congenital heart defects
[14]. A large VSD is easily diagnosed on the four-chamber view alone. For smaller defects color
Doppler US may be needed, while some cases may not be detected until after birth. For an
accurate diagnosis the examiner must approximate the ideal 90° insonation of the interventricular
septum.

Hypoplastic left heart syndrome – consists of the identification of a small left ventricle
associated with aortic atresia and an atretic/hypoplastic mitral valve. The early developmental
changes that lead to hypoplastic left heart syndrome are unknown. However, the development of

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the cardiac chambers is dependent on the flow of blood through the chambers and not the
pressure within the chamber walls. Therefore, it is hypothesized that decreased flow in the left
ventricle causes hypoplastic left heart syndrome. In making the diagnosis, the four-chamber view
is usually sufficient to demonstrate the abnormalities. However, the base view may be helpful in
documenting the disproportionately smaller aorta in comparison to the pulmonary artery [15],
[16].

Critical aortic stenosis – This malformation is suggested by the finding of a dilated, poorly
contracting left ventricle, with echogenic ventricular walls and papillary muscles of the mitral
valve (which is characteristic for associated endocardial fibroelastosis) [17]. The mitral valve
may be restrictive and it may be difficult to demonstrate forward flow across the aortic valve in
these cases. However, Doppler velocities across the aortic valve may be normal or only mildly
elevated, in cases with significant left ventricular compromise, shadowing the severity of the
obstruction [18], [19].

Severe coarctation of the aorta – When facing a ventricular size discrepancy on the four-
chamber view we initially suspect a possible coarctation of the aorta, but this estimation has only
moderate sensitivity. Such an observation mandates further investigation for additional
intracardiac lesions: mitral valve abnormalities, VSD, left ventricular outflow tract obstruction.
To date, the most sensitive diagnostic feature for coarctation of the aorta is the presence of a
transverse aortic arch and isthmic narrowing on parasagittal views [20]. When fetal diagnosis of
coarctation is suspected or ascertained, delivery must be set in a centre where specialised cardiac
care can be offeres. Ductus arteriosus patence must be ensured immediately after birth and to gain
time before surgery.

Right heart anomalies

Tricuspid atresia – The prenatal diagnosis of tricuspid atresia is suspected during routine
obstetric ultrasound given the asymmetric development of the two ventricles on the four-chamber
view. After examining the right ventrucle outflow tract we identify the absence of tricuspid valve
movement and the lack of flow velocities across the tricuspid valve in pulsed and color Doppler
investigations. We must establish the hemodynamic and functional impact of the defect in order
to estimate fetal prognosis as early as possible. Some cases of tricuspid atresia will be associated
with the presence of a VSD, which helps maintain a forward pulmonary blood flow. However,
these cases frequently develop cardiac failure caused by the high cardiac output. In the absence of
a VSD survival of these neonates is dependent on the patency of the ductus arteriosus as the only
source of pulmonary flow.

Pulmonary atresia with intact ventricular septum – This is a rare abnormality sometimes
described as a ‘hypoplastic right heart’, terminology which is many times improper because the
right ventricle is not always hypoplastic and right ventricular hypoplasia does not represent a
landmark of this malformation [21]. Pulmonary atresia with intact ventricular septum is in fact
the complete obstruction of the pulmonary outflow tract in the presence of an intact ventricular
septum, associated with underdevelopment of the right ventricular cavity which is hypertrophied,
muscle-bound, and hypertensive. On ultrasound, the heart commonly exhibits a very small right
ventricle in mid-gestation on the four-chamber view. Sometimes these fetuses are picked up
during the first trimester with the erroneous diagnosis of either atresia or critical stenosis. Other

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times, the right ventricle might show a normal appearance at the 18-22weeks but have an
impaired development and a much smaller ventricular size at birth [22]. The neonate with this
condition will present with a duct-dependent circulation requiring prompt medical/surgical
attention to maintain hemodynamic stability.

Ebstein’s anomaly – is a result of the abnormal attachment of the septal and posterior
tricuspid valve leaflets. The leaflets are deformed, thickened, hardly mobile towards their tips and
the right ventricle becomes split into two chmabers: one, the upper, atrialized portion, made up of
parts of the ventricular free wall and septum above the functional opening of the tricuspid valve;
the second, lower portion, is represented by the infundibulum. The ultrasound image of a dilated
right atrium on the four-chamber view raises suspicion of an Ebstein’s anomaly, but in many
fetuses the right atrium becomes significantly enlarged only late in the second trimester. It is
mandatory to always evaluate both atrioventricular valves as lack of mobility associated with
insufficiency of the tricuspid valve might be the only clue for diagnosis during the early second
trimester.

Outflow tract anomalies

Double outlet right ventricle – DORV – is described as the emergence of both the pulmonary
artery and the aorta originating from the morphological right ventricle [23]. Less strict criteria
have been proposed, stating that one complete arterial trunk and at least half of the other arterial
trunk arise from the right ventricle [24], [25]. DORV most frequently occurs with situs solitus
and concordant atrioventricular connection but it may occur with any atrial situs or
atrioventricular connection. VSDs are present in most cases but in rare cases the ventricular
septum may be intact. Even in patients without heterotaxy DORV is associated with a high risk of
early neonatal demise and the need for complex postnatal management. In this respect,
morphologic subtype, irrespective of prior postnatal diagnosis, is a major determinant of outcome
[26].

Double outlet left ventricle – is represented by the aorta and pulmonary artery which arise
predominantly or exclusively from the left ventricle. It is a very rarely encountered cardiac
abnormality. DOLV is frequently associated with a VSD which may be subaortic, subpulmonary
or, least frequently, doubly committed or non-committed [27].

Transposition of the great arteries – refers to a condition in which the aorta arises from the
right ventricle and the pulmonary artery from the left ventricle. It is among the most frequent
cyanotic heart diseases, and most affected neonates are undiagnosed as fetuses. If transposition
occurs with concordant atrioventricular connection in which the morphologically right atrium
connects to the morphologically right ventricle and the morphologically left atrium to the
morphologically left ventricle, it is called complete transposition. When atrioventricular
connection is discordant, the condition is called congenitally corrected transposition, circulation
becomes physiologically corrected although double errors occur [28]. In the majority of cases
with complete transposition, there is situs solitus and levocardia. The right ventricle is the right-
sided and anterior ventricle. The four-chamber view is usually normal when there is no associated
lesion. The three vessel and trachea view demonstrates a solitary transverse aorta. On sagittal
sections the aortic arch may be shifted anteriorly, with the ductal arch towards its posterior

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aspect. Both arches may demonstrate a parallel configuration without depicting the normal
spiraling.

Tetralogy of Fallot – is a complex malformation represented by the combination of VSD,


overriding aorta, pulmonary artery stenosis and right ventricular hypertrophy. Right ventricular
hypertrophy may not be overt in utero given the shunts existing in the fetal circulation [29].
Tetralogy of Fallot is easily missed if the four-chamber view is obtained posteriorly, at the
level of the atrioventricular valves. Therefore, in order to achieve the prenatal diagnosis of
tetralogy of Fallot, it is mandatory to look on the five-chamber view. Here the overriding aorta
appears dilated and the subaortic ventricular septal defect can be visualised. Postnatal
management depends on the severity of the stenosis and the pesence of associated extracardiac
anomalies. Cases with decreased or diastolic retrograde flow across the ductus arteriosus require
prostaglandin administration after delivery to maintain patence.

Truncus arteriosus – also known as ‘common arterial trunk’ is a rare congenital cardiac
malformation characterised by a single great artery arising from the base of the heart, which
supplies the systemic, coronary, and pulmonary circulations [30]. VSD is a commonly associated
defect. Truncus arteriosus results from a failure in the process of septation during ventricular
outflow and proximal heart development. This condition is fatal during the first year of life and
neworns require surgery for correction of the defects. On ultrasound, the four-chamber view may
keep its normal appearance. The visualisation of two vessels at the level of the three vessel view
raises suspicion of a truncus arteriosus. Care must be taken to differentiate from pulmonary
atresia with ventricular septal defect and absent or hypoplastic main pulmonary arterial trunk and
aortic atresia with hypoplastic ascending aorta which have the same appearance of the three
vessel view. The truncal valve may have two to five cusps, it is almost always in fibrous
continuity with the mitral valve and it will more often be regurgitant than stenotic. The ductus
arteriosus will be absent in approximately half of cases [31], [32].

Discussion

Fetal ultrasound has known a tremendous development during recent years, both from the
technological point of view, as well as from the standardisation of practice point of view giving
obstetricians the ability to detect fetal cardiac maformations prenatally and ensure timely referral
in specialized centers for adequate perinatal management. The accuracy of prenatal diagnosis in
the modern era is based on the effective collaboration between geneticists, paediatric
cardiologists, and obstetricians since congenital heart disease is often associated with extracardiac
anomalies or part of genetic syndromes. For the better understanding and management of the
fetus as a patient, a new multi-disciplicary specialty has emerged, fetal cardiology. This leads to
the improvement in both short-term and long-term outcomes of affected neonates, especially for
those with cyanotic congenital heart diseases.
Fetal echocardiographic assessment of an affected pregnancy should be performed sufficiently
early to provide time for additional testing, including amniocentesis for fetal karyotype or other
appropriate testing to facilitate counseling, to provide the pregnant patient with as many options
as possible for the pregnancy and for delivery planning. The detalied evaluation of fetal anatomy,
widely spread as the mid gestation scan (18-22 weeks), is mandatory for the early diagnosis and
correct evaluation of cardiac abnormalities, alongside central nervous system, skeletal, gastro-
intestinal or genitorinary tract malformations [33], [34], [35], [36], [37].

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‘Standard of care’ in fetal ultrasound today comprises the complete, segmental evaluation of
the heart: systemic and pulmonary venous returns, detailed intracardiac anatomical landmarks,
visualisation of the great vessels and branch pulmonary arteries, evaluation of aortic and ductal
arches. It is now expected that ultrasound will be able to diagnose structural heart disease with
minute details. However, description of the anatomical sequence in not enough in these cases,
because hemodynamic stability of the fetus must be assesed, as well as the potential pogression of
the disease in utero, and fetal adaptation to the extrauterine environment.
The current trend among fetal medicine specialists is to consider the fetus as a patient, to
personalize antenatal care to ensure a better transition to postantal life.

Conclusions

Fetal cardiac care has refined tremendously. The role of the obstetrician is to incorporate
detailed segment-specific fetal cardiovascular anatomy into the routine evaluation of all
pregnancies. Abnormal findings on routine obstetric ultrasound mandate urgent fetal
echocardiogram by an experienced sonographer, especially in cases at risk for fetal
cardiovascular compromise. The prenatal diagnosis and management provides time for family
counseling, plan delivery and post natal management thus heping to improve fetal and postnatal
outcomes.

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London: Greenwich Medical Press, 2000: pp. 305-21.
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29. Simpson LL. Structural cardiac anomalies. Clin Perinatol 2000; 27: pp. 839-862.
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32. Volpe P, Paladini D, Marasini M et al., Common arterial trunk in the fetus: characteristics, associations, and
outcome in a multicentre series of 23 cases. Heart 2003; 89: pp. 1437-41.
33. Micu R, Chicea AL, Bratu DG, N, Nemeti G, Chicea R. Ultrasound and magnetic resonance imaging in the
prenatal diagnosis of open spina bifida. Medical Ultrasonography 2018; 2: pp. 221-227.
34. Grigore AM, Nemeti G, Micu R. The role of 4D US in evaluation of fetal movements and facial expressions
and their relationship with fetal neurobehaviour. Medical Ultrasonography 2018; 1: pp. 88-94.
35. Gupta AK, Guglani B. Imaging of congenital anomalies of the gastrointestinal tract. Indian J Pediatr. 2005
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37. Hindryckx A, De Catte L. Prenatal diagnosis of congenital renal and urinary tract malformations. Facts,
Views & Vision in ObGyn. 2011; 3(3): pp. 165-174.

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Selective Intrauterine Growth Restriction in Twins

MANOLEA Maria Magdalena1, VRABIE Sidonia Cătălina1,


SĂNDULESCU Sidonia Maria1, NOVAC Liliana1, NEAMȚU Simona2,
DIJMĂRESCU Lorena1
1 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy Of Craiova (ROMANIA)
2 Department of Hematology, University of Medicine and Pharmacy Of Craiova (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected]

Abstract

The aim of this study was to evaluate the association of birth weight discordance with different
combinations of placental umbilical cord insertions in a group of both mono and dichorionic
twins. For the selected cases we analyzed the birth weight, chorionicity and placental
particularities, the umbilical cord and placental umbilical cord insertion type. The rate of
abnormal cord insertions was higher in monochorionic twins, than in dichorionic, while a highly
significant association between abnormal cord insertions and sIUGR and an unequal placental
sharing in these cases was also noticed.
Keywords: selective intrauterine growth restriction, chorionicity, placental umbilical cord insertion

Introduction

Selective intrauterine growth restriction (SIUGR) is found more often in monochorionic than
in dichorionic twins, usually due to an unequal placental sharing [1]. The clinical outcome is
linked to the characteristics of placental vascularisation and anastomoses [2] and in order to
improve the quality of life of premature neonate in twin monochorial pregnancy [3] it may lead
even to prolongation of pregnancy after preterm dismiss in utero or even after delivery of one
fetus [4]. The risk of fetal sufference can be calculated for each pregnancy based on the age of
pregnant women, the values of first trimester biochemical and ultrasound markers [5].
Selective intrauterine growth-restriction (SIUGR) affects 12-15% of the monochorionic
pregnancies [6]. Diagnosis is based on an estimated fetal weight (EFW) in one twin of <10th
percentile, or an intertwin EFW discordance ≥25% [7].
The aim of this study was to evaluate the association of birth weight discordance with different
combinations of placental umbilical cord insertions in a group of both mono and dichorionic
twins.

Methods

For this study we selected 52 twin pregnancies. Cases of fetal malformation and twin-to-twin
transfusion syndrome were excluded from the study. For the selected cases we analyzed the
following parameters: the birth weight, dividing the selected case in two groups: Normal weight
(NW) and with intrauterine growth restriction (IUGR) meaning <10th percentile on twins’ growth

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charts, chorionicity and placental particularities, the umbilical cord and placental umbilical cord
insertion type.

Results

From the 52 pair of twins, 12 of them were found with intrauterine growth restriction (IUGR).
From the 52 pair of twins, 28 were dichorionic and 24 monochorionic. The rate of abnormal
cord insertions was 58,3% (14/24) in monochorionic twins, higher than in dichorionic (Fig.1).
We have also noticed a highly significant association between abnormal cord insertions and
sIUGR and an unequal placental sharing in these cases (Fig. 2). Nonselective intrauterine growth
restriction was noticed in only 2 cases 1 monochorionic and 1dichorionic twins. SIUGR was
specifically found in monochorionic twins and may be an important indicator of adverse outcome
in these cases (Fig. 3).

25

20

15 Normal cord
insertion
10 Abnormal cord
insertion
5

0
Dichorionic

Fig. 1. Cord insertion in dichorionic and monochorionic groups

Fig. 2. Velamentous insertion of the umbilical cord in a case with monochorionic biamniotic twins

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30

25

20
NW
15
non-sIUGR
10 sIUGR

0
Dichorionic Monochorionic

Fig. 3. Distribution of the two groups normal weight (NW) and with intrauterine growth restriction (IUGR) between
the dichorionic and monochorionic pregnancies

Discussions

Monochorionic pregnancies with selective intrauterine growth restriction may be associated


with remarkable differences in clinical behavior and outcome. This is due mainly to the idea
already postulated in our previous studies in concordance with other literature data of the tight
link between a pregnancy evolution and the placental vascular bed pattern changes [8]. Unequal
placental sharing is the most important factor determining the appearance of growth discordance,
but the clinical evolution is largely influenced by the pattern of placental anastomoses [9].
We found a higher rate of abnormal cord insertions in monochorionic twins, than in
dichorionic. Monochorionic twins with velamentous cord insertion are at increased risk of
birthweight discordance and selective fetal growth restriction. Moreover, velamentous cord
insertion is associated with morbidity and mortality with a significantly reduced survival beyond
neonatal period in cases that were not prenatally diagnosed [10]. Sonographic delineation of the
placental cord insertion could be of value in the antenatal stratification of twin pregnancies [11].
Placental dysplasia in the smaller twin may cause abnormal cord insertion and unequal
placental sharing. The inter-twin anatomoses influence the umbilical cord artery (UA) Doppler
and natural pathogenesis of sIUGR. Gou C. et al., reported in 2017 that 73.9% of smaller twins in
sIUGR cases had marginal or velamentous cord insertions and less placental sharing [12].
In our study sIUGR was specifically found in monochorionic twins while nonselective
intrauterine growth restriction was noticed in only 2 cases. A 2012 study found an overall IUGR
incidence (including sIUGR and non-sIUGR) in twin pregnancies was 23.2%. The sIUGR
incidence was ten times greater than that of non-sIUGR. Monochorionicity and monozygosity
were risk factors for overall IUGR, especially for the sIUGR. Both the sIUGR and non-sIUGR
groups had more intrauterine fetal death and neonatal death than the normal growth group. The
sIUGR group had more brain injury than the normal growth group [13].

Conclusions

Abnormalities of cord insertions are associated with discordance of birth weight mostly in
monochorionic comparing to dichorionic twins. SIUGR is therefore a complex management

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problem for the fetal medicine specialist, especially if we take in account that early severe forms
are associated with intrauterine demise or neurological adverse outcome for both twins.

REFERENCES

1. Lopriore E, Pasman SA, Klumper FJ, Middeldorp JM, Walther FJ, Oepkes D. Placental characteristics in
growth-discordant monochorionic twins: a matched case-control study. Placenta. 2012; 33: pp. 171-4.
2. Buca D, Pagani G, Rizzo G, Familiari A, Flacco ME, Manzoli L, Liberati M, Fanfani F, Scambia G,
D’Antonio F. Outcome of monochorionic twin pregnancy with selective intrauterine growth
restrictionaccording to umbilical artery Doppler flow pattern of smaller twin: systematic review and meta-
analysis. Ultrasound Obstet Gynecol. 2017 Nov; 50(5): pp. 559-568.
3. Mocuta D, Popovici LR, Dumitriu AS, Burlibasa L, Ionescu CA, Sfeatcu R. Life quality-condition of social
welfare. Metalurgia International 2009: Volume: 14, pp. 62-64
4. Văduva CC, Constantinescu C, Ţenovici M, Văduva AR, Niculescu M, DiŢescu D, Albu CC, Albu DF.
Delayed interval delivery in twin pregnancy – case reports. Rom J Morphol Embryol. 2016; 57(3): pp.
1089-1098.
5. Navolan D, Ionescu CA, Carabineanu A, Birsasteanu F, Cretu O, Szasz F, Vladareanu, S Ciohat I, Gidea R,
Nemescu D, Farcas S, Andreescu N, Simu S, Stoian D Influence of weight of pregnant women on first
trimester biochemical markers values. Revista de Chimie, 2017, Volume: 68 Issue: 12, pp. 2836-2838.
6. Lewi L, Van Schoubroeck D, Gratacós E, Witters I, Timmerman D, Deprest J. Monochorionic diamniotic
twins: complications and management options. Curr Opin Obstet Gynecol. 2003;15: pp. 177-94.
7. Rustico MA, Consonni D, Lanna M, Faiola S, Schena V, Scelsa B, Introvini P, Righini A, Parazzini C, Lista
G, Barretta F, Ferrazzi E. Selective intrauterine growth restriction in monochorionic twins: changing
patterns in umbilical artery Doppler flow and outcomes. Ultrasound Obstet Gynecol. 2017 Mar; 49(3): pp.
387-393.
8. Manolea MM, Dijmărescu AL, Popescu FC, Novac MB, Ditescu D. Evaluation of the implantation site
morphology in spontaneous abortion. Rom J Morphol Embryol. 2015; 56(1): pp. 125-31.
9. Bennasar M, Eixarch E, Martinez JM, Gratacós E. Selective intrauterine growth restriction in
monochorionic diamniotic twin pregnancies. Semin Fetal Neonatal Med. 2017 Dec; 22(6): pp. 376-382.
10. Siminel MA, Gheonea C, Stănescu MR, Comănescu AC, Dijmărescu AL, NeamŢu SD, Cotoi BV,
NedelcuŢă RM, Niculescu EC. Velamentous insertion of the umbilical cord vessels with vasa praevia a case
report. Rom J Morphol Embryol. 2015; 56(1): pp. 301-8.
11. Kalafat E, Thilaganathan B, Papageorghiou A, Bhide A, Khalil A The significance of placental cord
insertion site in twin pregnancy..Ultrasound Obstet Gynecol. 2017 Oct 4.
12. Gou C, Li M, Zhang X, Liu X, Huang X, Zhou Y, Fang Q. Placental characteristics in monochorionic twins
with selective intrauterine growth restriction assessed by gradient angiography and three-dimensional
reconstruction. J Matern Fetal Neonatal Med. 2017 Nov; 30(21): pp. 2590-2595.
13. Gao Y, He Z, Luo Y, Sun H, Huang L, Li M, Zhou Y, Chen B, Fang Q.Selective and non-selective
intrauterine growth restriction in twin pregnancies: high-risk factors and perinatal outcome. Arch Gynecol
Obstet. 2012 Apr; 285(4): pp. 973-8.

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Fetal Heterotaxia – A Diagnosis with Multiple Possibilities

MĂRGINEAN Claudiu1, GOZAR Liliana2, TOGĂNEL Rodica2,


MUNTEAN Iolanda2, MĂRGINEAN Cristina Oana3, SĂSĂRAN Vlăduț Bogdan4
1 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy Tîrgu Mureș, Gheorghe Marinescu street no
38, 540136, (ROMANIA)
2 Department of Pediatric Cardiology, University of Medicine and Pharmacy Tîrgu Mures, Romania, Gheorghe Marinescu street

no 38, 540136, (ROMANIA)


3 Department of Pediatrics, University of Medicine and Pharmacy Tîrgu Mures, Romania, Gheorghe Marinescu street no 38,

540136, (ROMANIA)
4 University of Medicine and Pharmacy Tîrgu Mures, Romania, Gheorghe Marinescu street no 38, 540136, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected], [email protected]

Abstract

Introduction
Heterotaxy syndrome, isomerism or ambiguous situs include any abnormal arrangement of the
thoracic or abdominal organs other than situs solitus or inversus and includes multiple
possibilities of abnormal organs position.

Material and method


The present study was performed in a tertiary diagnostic center for a period of 10 years
(February 2007-December 2017), on a group of 607 pregnant women assessed for the suspicion
of certain cardiac anomalies. We aimed to analyze the type of isomerism and the type of
associated anomalies.

Results
Among this group, 464 presented structural defects or pathological arrhythmias, and a number
of 13 fetuses (2.8%) presented echographic findings suggesting heterotaxy.
We assessed through fetal ultrasound the type of isomerism and the associated anomalies.
Therefore, we found 8 anomalies that were classified as left isomerism and 5 as right
isomerism. The series includes 9 complex anomalies of all 13 cases. Of the 6 cases with the
absence of inferior vena cava (IVC), only 3 did not present any association. These 3 represent a
particular subgroup, while the other 10 cases diagnosed with isomerism from our series presented
association of different anomalies.

Conclusions
The incidence of fetal hetorataxy in our series of congenital anomalies is similar with that
reported in the literature. The different associations of anomalies with the isomerism encountered
in our series indicates the wide variability of possibilities associated to these syndromes, most of
the cases being complex and with bad prognosis.
Keywords: fetal heterotaxy, cardiac anomalies

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Introduction

Situs solitus is defined by the right position of the structures: most of the liver, inferior and
superior vena cava, right atrium with the pyramidal appendix, the lung with three lobes, but also
structures situated normally on the left side: stomach, spleen, left atrium with the digitiform
atrium and pulmonary veins, but also the lung with two lobes [1].
Situs inversus is defined by a complete in mirror arrangement of the organs compared to the
solitus one. On the other hand, any arrangement of the thoracic or abdominal organs other than
situs solitus or inversus is defined as situs ambiguous, heterotaxic syndrome or isomerism [1].
This entity includes multiple possibilities of abnormal positioning of the organs, including
asplenia or polysplenia [1].
Of all cardiac congenital anomalies, heterotaxia can reach an incidence of up to 4.2% [2].
Heterotaxic syndrome or isomerism is divided into left and right. Left isomerism is the most
frequent in utero, while after birth, the right one is the most common. Left type isomerism
requires a visualization of IVC associated with an azygos continuity in both thoracic and
abdominal sections in order to establish the diagnosis [1, 3]. This type of heterotaxic syndrome
can present several associated anomalies, like: atrioventricular block (AVB), unbalanced atrial
septal defect (AVSD), double outlet right ventricle (DORV), aortic coarctation (AoCo), stenosis
or atresia of the pulmonary valve [1, 3], but is can also be diagnosed along with extracardiac
anomalies. Nevertheless, a normal heart cannot exclude a potential diagnosis of left isomerism
[1].
On the other hand, right isomerism supposes the position of the enlarged liver centrally, and
the stomach laterally, but also the inferior vena cava on the same side with the ascending aorta
and anteriorly, both vessels presenting the possibility to be on the left or right side of the spinal
cord [3]. This type of isomerism associates the following cardiac anomalies: unbalanced AVSD,
DORV, transposition of great arteries (TGA), stenosis or atresia of the pulmonary valve,
frequently left persistent superior vena cava (LPSVC) [1, 4, 5]. A visualization of a normal heart
is rarely associated with right isomerism [1].
The differential diagnosis of fetal isomerism involves situs inversus associated with levo- or
dextrocardia, simple AVSD, dextrocardia with corrected transposition of great arteries (cTGA)
[1], but also different types of isolated anomalies. The fetal death in utero is more frequently
encountered in case of left isomerism through AVB and unique atrioventricular valve, with
valvular incompetence and afterwards fetal hydrops. Familial heterotaxy is a disorder with an
autosomal, recessive or X-liked pattern of transmission that involves the defect of single gene
leading to a wide spectrum of heterotaxic variants [1, 2]. Øyen et al., found that the recurrence of
this condition in the future pregnancies of the same family can overpass 10% (recurrence risk
ratio for heterotaxy was 79.1) [6]. Among the genetic disorders that can be associated to this
condition we mention trisomy 18, as in case of common arterial trunk [7], microdeletions of the
22nd chromosome or rare translocations [3].

Material and method

The study was performed in a tertiary diagnostic center for a period of 10 years (February
2007-December 2017), o a group of 607 patients that were assessed for the suspicion of certain
fetal cardiac anomalies. Our aim was to analyze the type of isomerism and the association with
other anomalies.

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Results

Of all cases included in our study, 464 presented structural defects or pathological
arrhythmias, and a number of 13 fetuses (2.8%) presented suggestive ultrasonographic for
heterotaxy. The type of isomerism was established depending on the atrial morphology, and
where this could not be established, after the position of the great vessels and the stomach. As a
result of ultrasonographic assessments, we found 8 cases with left isomerism and 5 with right
isomerism. Each of the two groups of isomerism included 1 case that was hard to be classified in
a certain category due to its morphology and the associations (Table 1).

Table 1. The types of isomerism from our series


Numb Reason for referral, Isomerism Associations
er gestational age type
1 Cardiac anomaly, 36 weeks left The lack of IVC, azygos continuity, both great vessels
on the right, dextroposition of the heart, bicuspid Ao
2 Complex cardiac anomaly, right AVSD, TGA, severe hypoplasia of pulmonary trunk
32 weeks
3 Cardiac anomaly, 33 weeks left The lack of IVC, azygos continuity

4 Heterotaxy, 36 weeks right Hypoplasia of the Ao cross, AoCo, fetal bradycardia,


agenesis of biliary ducts
5 Anomaly of IVC, 21 weeks left The lack of IVC, azygos continuity
6 Cardiac anomaly, 23 weeks left The lack of IVC, azygos continuity, Fallot tetralogy,
hypoplasia of the thymus, dilation of the renal pelvis
7 Cardiac anomaly, 21 weeks right Severe bradycardia, cTGA, severe hypoplasia of Ao
arc, LPSVC
8 Cardiac anomaly, 25 weeks left The lack of IVC, azygos continuity
9 Complex cardiac anomaly, right? AVB 2:1, incomplete AVSD, ventricular inversion,
26 weeks DORV, Ao stenosis
10 Complex cardiac anomaly, right Unbalanced form of AVSD, severe form of ascending
21 weeks Ao and Ao arc hypoplasia, LPSVC
11 Complex cardiac anomaly, left? Complete and balanced, the lack of IVC, azygos
28 weeks continuity, LPSVC
12 Cardiac anomaly, 21 weeks left Incomplete AVSD, cTGA, Ao stenosis, LPSVC,
hypoplasia of the thymus
13 Cardiac anomaly, 24 weeks left The lack of IVC, azygos continuity, arterial duct with
sinuous trajectory
Table legend:
Ao – Aorta; AoCo – Aortic Coarctation; AVB atrioventricular block; AVSD – Atrio-ventricular septal defect; AVB –
atrioventricular block; cTGA – corrected transposition of great arteries; DORV – double outlet right ventricle; IVC
– inferior vena cava; LPSVC – left persistence superior vena cava; TGA (ROMANIA) transposition of great arteries

Discussions

Ideally the diagnosis of isomerism involves the establishment of both atria morphology. The
easiest diagnosis is a result of the assessment of the organs and vessels position in the upper
abdomen and thoracic cavity. The position of the stomach compared to the heart, complex cardiac
anomalies, atrioventricular block, and cardiac arrhythmias with or without fetal hydrops suggest a
potential heterotaxic syndrome [1]. Less than half of the patients (5/13) were examined in our
center under the age of 24 gestational weeks, even though the series includes 9 complex
anomalies of all 13 diagnosed. All our 13 cases associated similar anomalies as reported in the

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literature, such as complex cardiac anomalies, AVB, fetal bradycardia, but we also diagnosed
other associated conditions like hypoplasia of the thymus, dilation of the renal pelvis and agenesis
of biliary ducts. Of the 6 cases that associated the lack of IVC, only 3 did not present other
associations. These 3 cases represent a particular subgroup, while the other 10 cases of isomerism
from our series each presented different anomalies associated. Tridimensional (3D) ultrasound,
spacio-temporal image correlation (STIC) and Doppler techniques may improve our ability in
diagnosing atrioventricular septal defects [8-10].
Both types of isomerism were found to associate multiple cardiac and extracardiac anomalies
[1, 11, 12]. Similarly to the studies reported in the literature, the cases with left isomerism
diagnosed in our study associated the following cardiac anomalies: incomplete AVSD,
dextroposition of the heart, bicuspid Ao, corrected transposition of great arteries (cTGA),
LPSVC, Fallot tetralogy and arterial duct with sinuous trajectory. Extracardiac anomalies can
also occur along with left isomerism involving stomach on the right side, duodenal atresia, biliary
hypoplasia or the lack of the gallbladder, intestinal rotation, extrahepatic portal-systemic shunt, or
urinary anomalies [1, 3]. Our series of cases also presented different associations between left
isomerism and extracardiac anomalies, such as: hypoplasia of the thymus and dilation of the renal
pelvis. According to the data previously mentioned, hypoplasia of the thymus was not reported to
be frequently associated with this type of isomerism. Other studies stated that polysplenia can
also be commonly associated with this isomerism, but it is hard to be diagnosed in utero [13].
Nevertheless, none of our cases with left isomerism was encountered to present polysplenia.
On the other hand, regarding the associations between our cases with right isomerism and
other cardiac anomalies, we found: AVSD, TGA, severe hypoplasia of pulmonary trunk,
hypoplasia of the Ao cross, AoCo, Ao stenosis, fetal bradycardia, AVB, LPSVC, ventricular
inversion, DORV. Among these, hypoplasia of the pulmonary trunk, fetal bradycardia, AVB, and
Ao anomalies were not commonly reported in the literature to be associated with right isomerism
[1, 4, 14]. Nevertheless, LPSVC that was frequently reported in the literature and in our study to
be associated with right isomerism, was also found to be commonly associated with AoCo [5,
15].
Therefore, probably this fact may represent the explanation of our findings consisting in AoCo
associated with right isomerism. Certain studies report also an association of anomalies of
pulmonary veins connection, while other do not sustain this possibility [1, 4, 16]. Extracardiac
anomalies that can be encountered in cases of right fetal isomerism are: asplenia, bowel
malrotation, hiatal hernia with the stomach within the thoracic cavity, adrenal, genitourinary, or
anal anomalies [3]. Contrariwise, our cases with right isomerism associated only agenesis of the
biliary ducts as extracardiac anomaly, which was more frequently reported to be associated with
left isomerism by other studies.
Therefore, a part of the anomalies described by the specialty literature [1, 3, 4, 17] were also
present in our series, such as: complete and incomplete, balanced and unbalanced forms of
AVSD, TGA, LPSVC, AVB, stenosis of semilunar valves, Fallot tetralogy, DORV, hypoplasia of
Ao cross, agenesis of the biliary ducts, the lack of IVC.
The intrauterine and neonatal prognosis of fetal isomerism depends mostly on the presence of
different association. In case of left isomerism, its association with AVB can lead to fetal hydrops
and intrauterine death, representing another cause of cardiac-leading cause of fetal hydrops
besides tachyarrhytmias [18]. The inability to visualize the fetal gallbladder could suggest
agenesis of the biliary ducts that may result in neonatal death. Right isomerism has an even
worsen prognosis due to the associated severe cardiac anomalies. Therefore, generally, the
neonatal prognosis of left isomerism is better than of the right one [17, 19]. Nevertheless,

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independently of the isomerism type, multidisciplinary counselling regarding the prognosis of


heterotaxy is difficult and involves special communication skills with the parents and care-givers
[20, 21].
Even though this study which emphasize this rare anomaly is the first published in the south-
west Europe, its limitations consist mainly in the relatively small number of cases that were
assessed by a single center from our country and the inability to perform a screening all
pregnancies.

Conclusions

The incidence of fetal hetorataxy in our series of congenital anomalies is similar with that
reported in the literature. The different associations of anomalies with the isomerism encountered
in our series indicates the wide variability of possibilities associated to these syndromes, most of
the cases being complex and with bad prognosis.

Acknowledgements
This research was partially supported by the Collective Research Grants of the University of
Medicine and Pharmacy Tîrgu Mureş, Romania (“The role of mother’s genetic determinism in
child’s obesity correlated with bioimpedance and anthropometric parameters”
no.275/4/11.01.2017).

Listă abrevieri:
Ao – Aorta
AoCo – Aortic Coarctation
AVB – atrioventricular block
AVSD – Atrioventricular septal defect
AVB – atrioventricular block
cTGA – corrected transposition of great arteries
3D – tridimensional
DORV – double outlet right ventricle
IVC – inferior vena cava
LPSVC – left persistence superior vena cava
STIC – spacio-temporal image correlation
TGA – transposition of great arteries

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Type 1 Autoimmune Hepatitis, a Rare Condition in Children – A


Case Report and a Review of the Literature

MĂRGINEAN Cristina Oana1, MĂRGINEAN Claudiu2,


SĂSĂRAN Vlăduț Ștefănuț3, MĂRGINEAN Maria Oana1, ARMEAN Iulia1,
RĂCHITĂ Anca3, MELIȚ Lorena Elena1
1 Department of Pediatrics I, University of Medicine and Pharmacy Tîrgu Mureș, (ROMANIA)
2 Department of Obstetrics & Gynecology I, University of Medicine and Pharmacy Tîrgu Mureș, (ROMANIA)
3 University of Medicine and Pharmacy Tîrgu Mureș, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected], [email protected], [email protected]

Abstract

Autoimmune hepatitis (AIH) is a chronic, autoimmune condition of the liver, expressing a


progressive pattern in which the unbalanced immune system attacks the hepatocytes causing a
progressive, necrotizing, and fibrotic process affecting the liver. The incidence of this condition is
relatively rare in children, and undiagnosed, it can lead to end-stage liver disease. We report the
case of an 8-year-old female patient admitted in our clinic for elevated transaminase levels of
unknown etiology for approximately 1 year associated with a generalized, itchy rash. The
laboratory tests revealed both high levels of transaminases and IgG associated with positive anti-
SMA. The abdominal ultrasound showed mild enlarged liver. We also performed a hepatic
elastography, but fortunately, the parameters were within normal ranges. We ruled out viral
hepatitis (A, B, C), other infections (cytomegalovirus, toxoplasmosis, rubella, herpes viruses 1
and 2, Epstein-Barr virus), and Wilson’s disease. Based on all these specific features, we
established the diagnosis of type 1 AIH and we initiated steroid therapy and ursodeoxycholic
acid, postponing the liver biopsy when possible. After the first week of therapy, the transaminase
levels decreased by half, and the rash completely disappeared. The outcome of patients with AIH
depends mainly on the time and diagnosis and therapy initiation.
Keywords: type 1 autoimmune hepatitis, children, elastography

Abbreviations: AIH – autoimmune hepatitis, ANA – antinuclear antibodies, anti-SMA – anti-smooth muscle
antibodies, anti-LC1 – anti-liver cytosol type 1 antibodies, anti-LKM1 – anti-liver kidney microsomal type 1
antibodies, ALT – alanine-aminotransferase, AST – aspartate-aminotransferase, GGT – gamma-glutamyl transferase,
IgG – immunoglobulin G

Introduction

Autoimmune hepatitis (AIH) is a chronic, autoimmune condition of the liver, expressing a


progressive pattern. The immunologic feature of this condition is explained by the fact that the
unbalanced immune system attacks the hepatocytes causing a progressive, necrotizing, and
fibrotic process affecting the liver [1]. This condition was described for the first time in 1950 by
Waldenstrom, who noticed both increased levels of immunoglobulin G (IgG) and positive
antinuclear antibodies (ANA) in a group of women with progressive, severe hepatitis [2]. The

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pathogenesis of this autoimmune disorder remains unclear. Nevertheless, it seems that it is a


multifactorial disease involving a failed immune regulation, environmental factors, and host’s
genetic susceptibility [3]. The real incidence of AIH due to the lack of a precise standard method
of diagnosis. Therefore, The International Autoimmune Hepatitis Group conceived a standard
scoring system for diagnosing AIH in adults, which was adopted also for pediatric patients
worldwide [3]. Thus, Boberg calculated an incidence among white people from Europe and North
America of 0.1 to 1.9 per 100,000 individuals per year [4]. Regarding the incidence in children,
Verma et al., stated a worldwide prevalence of AIH between 2 and 17 per 100,000 children [5],
and it was reported to be more common in white children in comparison to Asian ones [6].
Regarding the age and gender, AIH was reported more frequently in females than males, with a
ration of 4:1, being diagnosed in people from infancy until the age of 75 years, with the highest
incidence between 10-30 years [3, 7].
There were described two types of juvenile AIH. The first type (AIH1) is defined by the
presence of ANA and/or anti-smooth muscle antibodies (anti-SMA), while type 2 (AIH2) is
diagnosed in patients who are seropositive for anti-liver kidney microsomal type 1 antibodies
(anti-LKM1), and/or anti-liver cytosol type 1 antibodies (anti-LC1) [8, 9]. The clinical picture
resembles with that of acute viral hepatitis involving symptoms such as: fatigue, fever, nausea,
vomiting, jaundice, dark urine and pale stools, and itching [3, 9]. In children, a subtler onset is
also possible, and unfortunately, in this form children are diagnosed with advanced disease [9].
In antithesis, patients can also be diagnosed in a ‘presymptomatic stage’, presenting increased
levels of transaminases, without any clinical symptoms [3]. The diagnosis of AIH is based on the
clinical symptoms, the laboratory tests, and the histopathological exam. Nevertheless, other
common causes of hepatitis should be ruled out before establishing the diagnosis of AIH.
Therefore, AIH comprises 3 main features: increased levels of transaminases and IgG
associated the presence of autoantibodies, inflammation at the histological exam, and the lack of
a known etiology for this condition [3]. Even though, a liver biopsy is required for the diagnosis,
in highly suspected individuals, the treatment should be initiated as soon as possible, delaying the
biopsy for a further possible moment [10]. The management of AIH in children involves the use
of corticosteroids and azathioprine as immunosuppressant drugs. The use of steroids, such as
Prednisone aims to reduce the levels of transaminases by 80% within the first 8 weeks of
treatment [11]. After the initiation of steroid therapy, the patients must benefit from weekly
monitoring of transaminase levels, with subsequently dosage adjusting. Azathioprine is usually
associated to steroids in order to decrease their side-effects, and it is introduced in the treatment
when severe steroids-associated side-effects appear or when no improvement of transaminase
levels is achieved using steroids alone [11]. Using the combination of these two drugs, the
remission rate will reach up to 80% [12].
We present this case report in order to underline the importance of pediatrician’s awareness of
this rare condition in children for establishing the diagnosis.
Informed consent was obtained from the patient’s mother (legal guardian) for the publication
of this case report.

Case report

Presenting concerns
We report the case of an 8-year-old female patient admitted in our clinic with elevated
transaminase levels of unknown etiology for approximately 1 year, and a generalized, itchy rash.

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Her personal history revealed the fact that approximately 1 year before the admission in our
clinic, the patient was found with highly elevated transaminase levels in a regional hospital
without any obvious etiology, being also diagnosed with cholestasis, gastritis and biliary reflux.
He underwent multiple treatments with liver protection drugs, but without any improvement.

Clinical findings
The clinical exam at the time of admission in our clinic revealed mildly enlarged liver,
approximately 1 cm under the right costal rib, and multiple generalized erythematous maculae
associated with lesions as a result of scratching, W: 26 kg.

Diagnostic focus and management


The laboratory tests revealed highly increased levels of transaminases (AST 441.5 U/L, ALT
467.6 U/L, GGT 238 U/L) with a normal level of bilirubin, and elevated levels of IgG 4052
md/dL. Therefore, we established the diagnosis of hepatitis. In order to identify the etiology, we
performed several tests. The urinary exam was normal. The serology for viral hepatitis (A, B, C)
were negative. We also ruled out cytomegalovirus infection, toxoplasmosis, rubella, herpes virus
infection (type 1 and 2), Wilson’s disease, and sclerotizing cholangitis. The abdominal ultrasound
revealed mildly enlarged liver. We also performed a liver elastography in order to identify a
potential degree of fibrosis, but fortunately, the parameters were within normal ranges.
Thus, we raised the suspicion of autoimmune hepatitis, and we identified positive anti-SMA
(1:160) and anti-double strained antibodies (66.6 U/ml). Based on all these findings and the
patient’s symptoms, the most-likely diagnosis was type 1 autoimmune hepatitis, and due to the
fact that we were not able to perform at the moment the liver biopsy, we initiated treatment with
steroids and ursodeoxycholic acid.

Follow-up and outcome


After approximately 1 week of treatment, the transaminase levels improved by half, and the
rash disappeared almost completely. The follow-up at 3 months from the diagnosis showed a
continuous improvement of the liver parameters (ALT 60.2 U/L, AST 27.8 U/L, GGT 75 U/L),
remaining on the same dose of Prednisone until the normalization of all parameters.

Discussions

AIH represents a rare cause of end-stage liver disease in pediatric patients. Despite its
multifactorial determinism (genetic, immunologic, environmental), the precise triggers of the
inflammatory process are not yet fully understood. Similarly, in the case presented above, we
were not able to identify the trigger of inflammation. In children, studies reported multiple genes
associated with the development of AIH, such as: DRB1*1301, DRB1*0301, DRB1*1401,
DRB1*0404, DRB1*0405, DRB1*0701, DRB1*0201[13,14]. This autoimmune condition affects
both children and adults, being most frequently diagnosed between 10 and 30 years of age, with a
predominance in females [3, 7]. Our patient was also a female, but her age was only 8 years. It
seems that the inflammatory process tends to be more severe in children, and that AIH can
overlap with primary sclerosing cholangitis [10]. This overlap syndrome is more common
encountered in pediatric patients than adult ones, comprising up to 50% of children diagnosed
with hepatitis. Therefore, a magnetic resonance of the biliary tract should be performed in
patients with persistent elevated levels of GGT and/or the unresponsiveness to
immunosuppressive treatment [15]. Fortunately, in our case, the level of GGT also decreased

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after the immunosuppressive treatment associated with ursodeoxycholic acid, and therefore we
ruled out the diagnosis of primary sclerotizing cholangitis. On the other hand, cholestasis can lead
to biliary reflux and secondary to gastroesophageal reflux, which can be assessed by pH-metry in
order to prevent associated esophagitis [16]. Besides this association, AIH can be also associated
with other autoimmune diseases [10]. Therefore, Deepak et al., reported a case of AIH associated
with autoimmune haemolytic anemia triggered by Varicella in an 18-year-old female [17].
Similarly, Jarasvaraparn et al., described another association between type 1 autoimmune
hepatitis and Evans syndrome in a 3-year-old female [18]. Nutritional disorders, like obesity can
lead to liver impairment regardless of the cause [19-22].
Both the incidence and the clinical course of AIH vary very much worldwide. Regarding the
outcome of AIH, it seems that adult Hispanic patients present a higher incidence of cirrhosis,
while the Asian ones have a poorer survival prognosis [5]. Despite the wide range of age at
diagnosis, the median age of diagnosis in white children was reported to be 12.9 years [12].
Regarding pediatric patients, AIH1 is diagnosed more frequently among adolescents, while
AIH2 affects especially younger children [3]. Nevertheless, our patient was presented AIH1 at a
young age, 8 years. Also, our patient presented a favorable clinical course at 3 months after the
initiation of steroids treatment. The quality of life for patients diagnosed with AIH can be
burdened by the progressive pattern of the disease itself, or by the side-effects of
immunosuppressive therapy. The clinical forms vary from asymptomatic to end-stage liver
disease at the time of diagnosis. Commonly, the clinical appearance resembles very much to that
of a viral hepatitis. We can state that our patient presented a ‘presymptomatic form’ of AIH
because she was encountered randomly with elevated transaminases, associated only an itchy,
generalized rash.
Pharmacological treatment improves survival in patients diagnosed with AIH. The treatment
of AIH involves mainly two types of immunosuppressant drugs, steroids and/or azathioprine.
The steroid therapy was reported to have a response rate of up to 90% [10]. In addition, the
response to steroid therapy is an essential feature of AIH, being a part of The International
Autoimmune Hepatitis Group revised diagnostic criteria [23]. The steroids dosage should be
initiated with 1-2 mg/kg/day, being adjusted according to the disease course. In our case, we
initiated the treatment with Prednisone at a dose of 1 mg/kg/day with a favorable evolution. After
3 months of the previously mentioned therapy, the patient presents only a mildly elevated level of
ALT and GGT. Treatment is mandatory to be initiated in patients with suggestive clinical
symptoms and severely increased biochemical markers, especially in children and adolescents
due to the aggressive course of the disease, even if liver biopsy can not be performed initially [10,
24]. Based on all these facts, we preferred to initiate the treatment with Prednisone even without a
histopathological exam. In addition, the responsiveness to steroid therapy indicated more towards
the diagnosis of type 1 autoimmune hepatitis in the case described above. Once remission is
achieved, the physician must administer the lowest possible dose in order to maintain a long-term
remission [25]. Despite the initial effectiveness of immunosuppressive therapy, disease relapse
can also occur [11]. The identification of different DRB alleles associated with AIH can lead to
the development of gene-related therapy in order to prevent the relapse in these patients [26]. If
untreated, AIH carries a poor prognosis.

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Conclusions

AIH is a relatively rare condition in children that requires an early diagnosis and treatment in
order to prevent the progression to an end-stage liver disease. Therefore, the pediatrician’s
awareness of this condition is essential for the outcome of these patients.

Acknowledgements
Funding/support: This research was partially supported by the UEFISCDI grant: “The
development of an innovative diagnostic guide of obese child through genetics, anthropometric,
bioimpedance and ultrasound assessment”, project number: 8159/27.07.2017 – PN-III-P4-ID-
PCE-2016-0766.

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Interrelation of Amniotic Fluid Volume with Parameters of Blood


Flow Dopplerometry in Labor

MIHALCEAN Luminita1, CAPROS Hristiana2, SURGUCI Mihai3


1, 2, 3
Moldova
Emails: [email protected], [email protected], [email protected]

Abstract

Introduction
The parameters of blood flow in the mother-placenta-fetus system in the onset of labor are
often changed depending by the presence of obstetric pathology, including the pathology of the
placenta and its components. In connection with this, it was of interest to study the relationship
between the amount of amniotic fluid (AF) and the dopplerometry of blood flow in the uterine
and umbilical arteries.

Methods
The study was prospective of 100 parturients with the pathology of amniotic fluid. All
pregnant women at the time of hospitalization were subjected to the ultrasound examination of
fetus, placenta and umbilical cord and the amount of AF.

Results
The results showed that the indexes of Doppler velocytometry curves during delivery were
different according to the gestation term. Thus, in premature births, all indicators of
dopplerometry were higher than in term births (p<0.01). In postterm births, the Doppler
velocimetry indices exceeded the indices of premature and urgent births (р<0.05). Analysis of the
relation between the dopplerometry data of the uterine artery and the amount of AF has shown
that, in case of oligohydramnios, all the parameters of the blood flow velocity curves were
significantly higher than those with the normal amount of fluid and polyhydramnios.
The difference was significant (р<0.05). A similar trend was observed in the changed
parameters of dopplerometry in the umbilical artery. All dopplerometry parameters were elevated
for premature and postterm birth, as well as in case of oligoamnios. Major changes in Doppler
velocytometry occurred in premature births at 28-31 weeks and in postterm after 42 weeks
(р<0.001). Therefore, the correlation between AF volume, fetal heart rate and uterine and
umbilical artery parameters is evident. Circulation resistance in these vessels increased as AF
volume decreased.

Conclusions
The term of gestation, amniotic fluid volume, cardiotocogram and dopplerometry parameters
during delivery are in close relationships.
Keywords: Doppler velocytometry curves, amniotic fluid volume, fetal heart rate

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Introduction

There have been written quite enough research papers in the modern scientific literature
referring to both low and excessive amniotic fluid volume during pregnancy. At the same time,
the impact of the amniotic fluid amount on the course of labor and the intrauterine development
of the fetus still remains unexplored. It is well known that the labor onset and particularly the first
stage of it leads to rapid changes within the utero-placental complex of the fetus [1]. The
development of compensatory-adaptive reactions depends on many factors, including the amount
and composition of the amniotic fluid surrounding the fetus [2]. Therefore, it is highly important
to determine the value of the amniotic fluid index in order to identify the biophysical profile of
the fetus during labor at various gestational stages, as well as their relationship during the
delivery and its outcomes [3]. The development of the most acceptable methods for diagnosing
and predicting perinatal abnormalities during labor will provide a qualitative medical assistance
as well as reduce the incidence of neonatal morbidity and mortality [4]. Purpose of the study was
to develop effective methods for detecting intrauterine fetal disorders in childbirth, as well as for
the prognosis of perinatal pathologies.

Methodology

There were examined 100 pregnant women within clinical settings, who were admitted to the
hospital with a labor onset. The average age ranged between 24.9+0.3 years old. Nulliparous
women made up 48%, women with recurrent births – 47%, and multiparious ones – 5%. Most
women gave birth at 38-41 weeks (85-59%) of the gestational period out of the total number of
cases. Late births occurred in 28 (28%), and premature births in 29 (29%) women. Women with
multiple pregnancies, pelvic presentation, fetal growth abnormalities and antenatal death cases
were not included in this study. All in-patient pregnant women underwent the ultrasonic biometry
of the fetus, placenta, umbilical cord, whereas the amount of amniotic fluid was revealed via an
ultrasound scanner called “АООСА-650-880” (Japan) equipped with a Doppler pulsating wave
unit (frequency filter 100 Hz, convection sensor 3,5 MHz). The echography determined the
biparietal diameter of the head (BPD), the average thoracic (TD) and abdominal diameter (AD) of
the fetus, the femur length (FL), the calf length (CL), and the abdominal circumference (AC).
Additionally, the degree of maturity, localization, thickness, presence of various inclusions of
the placenta and the state of the umbilical cord were determined. The amniotic fluid volume was
determined via two methods: by assessing the maximum vertical pocket (MVP) according to
Manning method (1981) and determining the amniotic fluid index (AFI) by Fellan method
(1987). MVP was measured in mm and in the most optimal assessment area such as between the
uterine wall and the minor parts of the fetus at a sensor angle of 90 degrees.
In order to determine the amniotic fluid index, the abdomen of a pregnant woman was divided
into 4 zones, by dividing it vertically along the white line of the abdomen and horizontally at the
level of the navel. In each quadrant, the height (mm) of the water space between the uterus wall
and the minor parts of the fetus or the umbilical cord was measured by applying an ultrasound
sensor perpendicularly to the floor. AFI consists of summing up these four measurements.
Assessment of the blood flow in the utero-placenta-fetal complex was performed in 52 women
in the first period of labor, taking into account the Dopplerometric basic rules. By means of a
qualitative analysis of the blood flow velocity curves in each vessel, the systolic-diastolic ratio
(SDR), pulsation index (PI), and resistance index (RI) were calculated. Cardiotocography (CTG)
via a biomonitor 80MSAYU “MESHSHA 800” was carried out in 100 pregnant women in the

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first stage of labor in order to assess the cardiac activity of the fetus. Furthermore, the duration of
the stable rhythm, the amplitude and frequency of the oscillations, the number of accelerations
and decelerations, their duration and amplitude were taken into account.

Results and Discussion

The assessment of amniotic fluid volume showed that the average ultrasound value in the
second half of pregnancy were 172.0+0.4 (101-250) mm, and the average AFI data were 77.9±0.4
(28-82) mm. Amniotic fluid volume index has progressively increased from 23 to 38 weeks of
pregnancy and has significantly decreased after 40 weeks of pregnancy. It has been observed that
the fastest rate of amniotic fluid volume increase occurred during the 23-33 weeks of pregnancy
(p<0.001), and kept on increasing until the 38-th week period (p<0.05), though more slowly.
There has been established a direct correlation (r=0.92) between the time of delivery and the
volume of amniotic fluid up to 38 weeks of gestation. At childbirth after 38 weeks there was a
sudden decrease in the indices of AFI and MVP. Thus, the mean AFI values decreased from 185
to 100 mm (p<0.001), whilst the mean MVP values from 100 to 50 mm (p<0-01). Moreover, an
inverse relationship between the duration of gestation and the volume parameters of the amniotic
fluid has been identified, AFI (g=-0.98) and MVP (g=-0.68). The incidence of low amniotic fluid
amount in women with delayed delivery was 45.7%.
We should draw attention to the fact that the change in the parameters of AFI was more
demonstrative, compared to the MVP indices throughout all gestational stages. This has been
proven both by the criteria of the reliability of the obtained results and by the correlational
relationship.
The indices of amniotic fluid volume were significantly less than the mean values for meconial
amniotic fluids (p<0.01), when related to intrauterine fetal growth restriction (IUGR) and delayed
delivery. A significant increase in these parameters with polyhydramnios (r<0.05) occurred only
in four cases. There were no cases of congenital fetal pathologies in this group, despite the
presence of a correlational relationship, whereas the changes in the AFI were more demonstrative
than in MVP indices. A through statistical analysis showed that the amount of amniotic fluid at
all gestational stages does not depend on the mother’s age and her anthropometric parameters, as
well as on the birth weight of the fetus (g>0.05). Furthermore, it has been established that the
parameters of the amniotic fluid volume as both the AFI and the MVP, were somewhat dependent
upon some parameters of the fetal biometry. Thus, the results of the correlation analysis have
shown that there is a direct correlation between the AFI and the transversal diameter of the fetal
chest cavity (g=0.65). A similar relationship, but less pronounced, was revealed between the AFI
and the transversal diameter of the fetal abdomen (g=0.61).
A study has been made on the dependence of the AFI and MVP indices upon various
parameters of the placenta. It has been found out that the thickness and perimeter of the placenta
had a less pronounced relationship with these parameters. However, the mass of the placenta
(g=0.70) and its overall area (g=0.68) were in direct correlation with the AFI. The latest data
indicates the involvement of the placenta in the production of amniotic fluid. Thus, both the mass
and the placenta area are important factors, However, there has not been revealed a correlation
between the AFI and the duration of labor, fetal assessment via the Apgar score, and other
biometric parameters of the fetus, namely the body weight, height at birth, the head
circumference.
In clinical settings, the relationship between the amniotic fluid volume and fetal
cardiotocography parameters (CTG) was evaluated. The results of the research showed that in 64

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parturient women out of the total number (100 patients) the fetal heart activity remained within
the normal range, having a heart rate of 138 ± 2.4. The oscillation amplitude was 9.3+0.3. The
oscillation frequency was 5-6 per minute. The frequency of the cardiac fetal accelerations
corresponded to the number of contractions and motion activity of the fetus during delivery. The
other patients presented certain disorders: bradycardia – in 7 cases; tachycardia in 23 cases;
deceleration in 7 women.
AFI parameters ranged within 120-220 ml, and MVP values ranged between 24 and 100 ml.
Therefore the parturient women were divided into three groups depending on the volume of
amniotic fluid: low-level, normal and high volume. All three groups presented cardiac disorders
in fetus. Assessment on the relationship of the amount of amniotic fluid with parameters of the
fetal cardiographs showed the following results. AFI higher than 150 mm is commonly followed
by normal CTG data. Same CTG data were revealed in MVP over 50 mm. Bradycardia and
deceleration of CTG commonly occurred in AFI over 150 and 180 mm, as well as in MVP less
than 30 mm. CTG disorders during labor more commonly occured in low amniotic fluid volume
rather than in normal or excessive ones. Regardless of the amount of the surrounding fluids, the
cardiotocography values were at the same level after the amniotomy or the self-rupture of the
amniotic sac. The blood flow parameters within the mother-placenta-fetus system may vary at an
early stage of delivery depending on the existing obstetric pathology, as well as due to placenta
pathologies and its elements. Therefore, the study showed interest in the relationship between the
amount of the surrounding amniotic fluids and Doppler values of the uterine and umbilical artery.
The study results showed that the CTG indicators in labor differ, depending on the gestational
period. Thus, in the preterm delivery, all Doppler indices were significantly higher than in normal
births (r<0.01). For delayed births, CTG indices were higher than in premature and urgent
deliveries, whereas the difference was quite a significant one (r<0.05). The analysis of the
dependence of the Doppler data of the uterine artery on the amount of amniotic fluid showed that,
in case of low amount of AFI, all the parameters of the CTG are significantly higher than in births
with normal AFV and polyhydramnios (r<0.05). A similar tendency has been revealed in the
Doppler parameters of umbilical artery. All Doppler parameters were elevated for premature and
delayed delivery, as well as a decrease in the amniotic fluid volume towards a lower level has
been detected. The most significant changes in CTG parameters occurred in premature births at
the gestational period over 28-31 weeks and in delayed deliveries after 42 weeks (r<0.001).
The indices of AFI and MVP compared to the Doppler data of the uterine and umbilical
vessels showed an inverse relationship with the SDR, PI, and RI parameters in the umbilical
artery, whereas the most obvious of which was the IR in cases of little amniotic fluid volume
(g=0.67). Undoubtedly, there is a relationship between the amount of amniotic fluid and the
parameters of cardiac fetal activity, as well as in the blood of uterine and umbilical artery. The
resistance to blood flow in these vessels increased as the amount of amniotic fluid decreased.
The term of delivery, the amount of amniotic fluid and CTG and Doppler parameters in
childbirth are closely interrelated.
All cases of childbirth outcomes were studied with no exceptions, according to the data of the
partographs, women’s health histories and of their newborns. Girls made up 51% and boys- 49%.
Of the total number of newborns, only 48% were in the early adaptation period, moderate and
severe injuries of central nervous system (CNS) occurred in 32% of newborns. The remaining
20% of newborns manifested different neonatal pathologies: intrauterine infections, hemolytic
jaundice, premature birth, post-term births, intrauterine growth retardation and others. Only 1
newborn died in the neonatal period (12.2% per 1,000 live births).

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Labor outcomes compared to clinical parameters showed that the most informative criteria for
assessing the fetus in labor was the amniotic fluid index. The accuracy of the method was 95%,
and sensitivity was 96%. The coincidence of low AFI and the rate of CNS involvement in
newborns was 92%. These results were confirmed by ultrasound indicators of the brain in
newborns.

Conclusions

The amniotic fluid volume presents a clinical significance in childbirth. The biophysical
profile of the fetus at the end of pregnancy and in labor, along with the fetal biometry parameters,
should identify the amniotic fluid index (AFI). In case if amniotic fluid index is less than 100
mm, particularly in delayed births, the fetal condition is critical. Of all the parameters for
determining the volume of the amniotic fluid in labor, the most reliable is the definition of the
AFI. The index of the maximally vertical pocket of the amniotic fluid in labor is less informative
due to the distortion of the amnion cavity under contractile activity of the uterus.
Assessment of amniotic fluid volume in labor is an acceptable and informative method for
both diagnosing fetal condition and predicting pathologies in newborns. The most informative
markers of the fetal condition in labor is AFI.

REFERENCES

1. Baron C, Morgan MA, Garite TJ. The impact of amniotic fluid volume assessed intrapartum on perinatal
outcome. Am J Obstet Gynecol. 2005 Jul; 193(1): pp. 167-74.
2. Ott WJ. Réévaluation of the relationship between amniotic fluid volume and perinatal outcome. Am J
Obstet Gynecol. 2005 Jun; 192(6): pp. 1803-9.
3. Sanderson M., Chauhan S.P., Hendrix N.W., Magann E.F., Devoe L.D. Perinatal outcome and amniotic
fluid index in the antepartum and intrapartum periods: A meta-analysis. Am J Obstet Gynecol. 2001 Dec;
191(6): pp. 1473-8.
4. Scharf, A., Seppelt, M., Sohn C. Doppler flow velocity to measure the redistribution of fetal cardiac output
in fetal stress/ Europ. J. Obstet & Gynecol and repr. Biolog. 2003; 110: SI 19-S126.

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Applications of Elastography in Cervical Pathology

MIHU Dan1, DICULESCU Doru1, MĂLUȚAN Andrei1, IUHAS Cristian1,


OANCEA Mihaela1, BUCURI Carmen1, DUDEA Marina1, CIORTEA Răzvan1
1Obstetrics Gynecology Clinic “Dominic Stanca”, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj-Napoca
(ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected], [email protected]

Abstract

Elastography is an ultrasound-based imaging technique that evaluates the rigidity of the


examined region. There are two types of elastography: dislocation elastography (strain) = real-
time elastography or sonoelastography; shear wave elastography. The better a cervix is softer
(extensible), the shear wave velocity is lower. In hard bodies the shear wave velocity is higher.
In recent years, elastography has become an ultrasound technique used in the study of cervical
pathology. It was attempted to define the “normal” cervical rigidity in order to be able to
objectify changes in its rigidity under various pathological conditions. Malignant lesions are
usually tougher and their extent in neighboring tissues is higher than that estimated by
conventional ultrasound. Physiological changes of the cervix during pregnancy affect its rigidity
and hence its elastographic properties. Elastography can play an important role in identifying
cervical insufficiency. It is considered that during the pregnancy the lower part of the cervix is
more extensible (soft) compared to the upper third. A low rigidity in the internal orifice during
pregnancy correlates with an increased risk of premature birth. An unresolved problem in
dislocation elastography is the inability to objectively standardize applied force to induce tissue
deformation. An ultrasonic probe integrated force sensor is a technical option to be developed and
tested. Alternatively, assessing the relative deformability of a specific region within the uterine
cavity compared to the rest of the organ, or evaluating the maximum tissue deformability,
indicates the possibility of obtaining additional information in the diagnosis of cervical affections.
Keywords: elastography, cervix, ultrasonography

Uterine cervical imaging assessments currently used are CT, MRI, ultrasound. MRI is the most
accurate examination of the cervix. Because MRI can not be routinely recommended,
ultrasonography is increasingly used.

The physical principles of elastography

Elastography is a non-invasive method that can be used in the diagnosis of cervical affections
by characterizing the consistency of the cervical component tissues. Tissues have an important
property, namely intrinsic elasticity, which can change under conditions of inflammatory or
tumoral processes. Rigidity is the resistance of tissues or structures to displacement and
deformation and is inversely proportional to the applied stress level [1]. Elastography is the only
objective way to highlight the hardness of a tissue through elastograms. The ultrasound image is

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composed of small, individual, punctual echoes. If a tissue is pressed with the transducer (up-
down movement), the echoes corresponding to the body structures will move in the sense that the
“up-down” compression force has been applied. At the end of this force the echoes return to the
original position (“up” movement). If a body is elastic (easily deformable) vertical movement of
the echoes is ample. If a body is rigid (undeformable) the echoes it represents will not move. In
cases where there is an alternation of elastic and rigid structures on the same line in space, the
elastic ones move (they are deformable) and the rigid ones do not move. The vertical deformation
of a resilient body (reduction in dimensions due to compression) is associated with the
deformation of the same body and in the transverse direction (perpendicular to the direction of
force application) in the direction of increasing the dimensions (the volume of the body remains
constant – if a diameter decreases, increase the other). The transversal increase in the dimensions
of an elastic body following a deformation results in the emergence of a transversal wave, which
propagates from near to near, called shear wave [2].

There are two types of elastography:


1. Strain – real-time elastography or sono-elastography, which describes the behavior of the
vertically echoes along the direction of application of the deformation force.
2. Shear wawe – which measures the propagation velocity of the wave in a transverse
direction (perpendicular to the direction of application of the initial force).
The more elastic the body is, the faster the shear wave velocity is, and the harder the speed is
higher in hard bodies. In shear elastography, the elasticity of a tissue is expressed by wave
velocity (m/sec) or by applying a direct conversion formula to rigidity units (Kilopascali – K Pa).
Displacement elastography represents the relative displacement of tissues from an ultrasound
image: the smallest depilation tissue is the hardest (colored blue), the one with the largest
displacement is the most elastic (soft) – (colored in red). There are no units of measure of
dislocation [3].
Information obtained through real-time elastography is color coded and overlapped with two-
dimensional echographic images. The software of the machine identifies the percentage of red
(soft), green (intermediate) and blue (hard) present in a particular region.
To define the hardness of a structure by dislocation elastography, we use the Strain Ratio in
which two areas of interest are compared to the same image:
- One area is the reference tissue (normal);
- An area represents the tissue to be analyzed (pathological).
By using the Strain Ratio value, the elasticity of the analyzed structures can be interpreted as
being less rigid (soft) or tougher than the reference area [4].

Applications of elastography in pre-neoplastic and neoplastic diseases of the uterine cervix

The cervix is composed of smooth muscle tissue (10%) and connective tissue (90%),
connective tissue consisting of collagen, elastin, macromolecular components, elements that
make up the extracellular matrix. It has been attempted to define the “normal” cervical rigidity in
order to quantify changes in its rigidity in obstetric (Premature delivery) or gynecological
pathologies (dysplasia and cancer) [5].
In he’s cervical study, Thomas et al., demonstrated the predominant presence of green color in
the normal cervical tissue (60%), its rigidity being intermediate regardless of the age of the
patient [6].
Other author has shown the utility of transvaginal elastography in finding endocervical lesions.

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Under these conditions there was predominantly the focal blue color at the level of the stroma
adjacent to the cervical canal. These changes in elastography can be identified early compared to
2D or Doppler ultrasound [7]. The management of invasive cervical carcinoma depends on the
initial clinical staging, which aims at establishing the extension – the depth of the stromal
invasion. In elastography, the tumor-damaged cervical stroma stains in blue, being easily
differentiated from the surrounding normal tissue. There is also information showing that when
the red area adjacent to the cervix disappears or is discontinuous, there is a parametric invasion.
Malignant lesions are usually tougher, affecting the elasticity of tissues [8].
In invasive cervical cancer, a significantly higher proportion of blue was seen compared to the
group of unaffected patients. In contrast to precancerous lesions of the uterine cervix,
sonoelastography showed no change in the blue color [9].
The results of elastography are usually analyzed and systematized using the proposed
classification by Veronika Gazhonova, according to which the elastic formations are
characterized by the coloring types 1 and 2, while the rigid formations are characterized by the
color types 3 and 4 [10].
- Type 1 – corresponds to liquid structures (contains the three colors)
- Type 2 – corresponds to elastic structures. It has 3 subtypes:
o 2a – characterizes highly elastic structures that contain large amounts of liquid.
o 2b – corresponds to less elastic structures of small size with rare rigid inclusions.
o 2c – the “mosaic” type that contains both high compressibility areas and rigid
inclusions.
- Type 3 – corresponds to rigid structures, which contain an equal number of areas with
increased and low compressibility.
- Type 4 – corresponds to extremely rigid structures that characterize malignant tumors
[10].

Staging of cervical cancer by elastography

Carcinoma in situ – no noticeable changes are noted.


• Stage I A – in most cases the images of the elastograms do not differ from the normal
ones.
Only 40% of cases with exophytic tumors can identify localized dark blue areas. Taking into
account the small size of the tumor invasion (up to 5-7 mm) at this stage, it is difficult to
distinguish the rigid areas of connective tissue inclusions, both of which are colored in dark blue.
Beginning with stage IB in the case of ˃1 cm tumors, characteristic images are mapped as near
dark blue (type 3 or 4), allowing a net differentiation from fibrous inclusions or inflammatory
processes[11].
• In Stages II – IV, the role of elastography is to estimate the levels of tumor extension and
its exact location.
Stage II A is characterized by tumor invasion in the uterus and vagina. The unaffected
miometer has the same elasticity as the cervix. In case of tumor invasion at the level of the
miometer, the dark blue color of the uterine body is detected, with a well-defined area between
the invaded area and the healthy, elastic miometer.
The main feature of differentiation between Stage IIA and Stage IIB is invasion of the
parametric tissue.
Elastography facilitates the assessment of tumor size and volume by visualizing its contours.

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Postradiotherapy has been shown to reduce the dark blue color, while at the same time
exhibiting changes in the stiffness of the tumor stroma compared to untreated tissue [12].

The limits of elastography

Elastography, like any other imaging examination method, has both strengths and weaknesses.
The limitation factor is reduced capacity in the detection of early stages of cervical cancer,
making it difficult to differentiate the early tumor invasion from fibrous inclusions, which leads
to increased rigidity. Elastography differentiates elastic formations from rigid, but not always
non-malignant lesions from malignant ones [13].
Elastography allows visualization of changes induced by tumor localized localizations at a
depth of between 5 and 50 mm.
Factors influencing elastography results are:
- Lack of standardization of oscillatory compression
- Reproducibility between examiners
- The voltage differences at the level of the examined areas.
The limit of dislocation elastography is the difficulty of objectively standardizing the applied
force to induce tissue deformation. A force sensor integrated with the US probe is a technical
option to be developed and tested. An useful feature of state-of-the-art devices is the possibility
of assessing the accuracy of the examination by a real-time analysis (QF) [14]. This technique
obviously reduces the error and subjectivism generated by the examiner’s different experiences
[15].
Shear elastography appears to be a promising method for assessing cervical rigidity, as this
technique allows for quantitative determination of tissue rigidity parameters in a manner
independent of the examiner [16].

REFERENCES

1. Thomas, A et al., (2007). Real-time sonoelastography of the cervix: tissue elasticity of the normal and
abnormal cervix. Acad Radiol 14, pp 193-200.
2. Frey, H. (2003). Realtime elastography. A new ultrasound procedure for the reconstruction of tissue
elasticity. Radiologe 43, pp 850.854.
3. Arda, K, Ciledag, N, Aktas, E. (2011). Quantitative assessment of normal soft-tissue elasticity using shear-
wave ultrasound elastography. Am J Roentgen 197, pp. 532-536.
4. Yamakawa, M, Shiina, T. (1998). Evaluation of a method for ultrasonic elastic imaging using 3-D tissue
model. J Acoust Soc Am pp. 923-924.
5. Molina, F, Gomez, L, Florido, J.(2012). Quantification of cervical elastography. A reproducibility study.
Ultrasound Obstet Gynecol 39, pp 685-689.
6. Thomas, A, Thomas F. (2007). Cervical elastography. Medix Supply pp. 58-62.
7. Shady, M, Abdel Latif, M, Nabil, H, El Sadda,W. (2015).Could trans-vaginal sono-elastography help
benign-malignant differentiation of cervical masses? The Egyptian Journal of Radiology and Nuclear
Medicine 46, pp. 1291-99.
8. Lu, R, Xiao, Y, Liu, M, Shi, D. (2014). Ultrasound elastography in the differential diagnosis of benign and
malignant cervical lesions. J Ultrasound Med 33(4), pp. 667-71.
9. Bakay, OA, Golovko, TS. (2015). Use of elastography for cervical cancer diagnostics. Exp Oncol 37, 2, pp.
139-145.
10. Gazhonova, V, Churkina, S, Lukyanova, E, et al., (2008). Clinical application of new method –
sonoelastography in gynaecology. Кremlin medicine. Clinical Herald 2, pp 18-23.
11. Akbayir, O, Corbacioglu, A, Numanoglu, C. (2011). Preoperative assessment of myometrial and cervical
invasion in endometrial carcinoma by transvaginal ultrasound. Gynecol Oncol 122, pp. 600-603.

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12. Yan, X, Lijing, Z, Baorui, L, Tong, R, Huanhuan, W, Jian, H, Song, L, et al., (2017). Strain elastography
imaging for early detection and prediction of tumor response to concurrent chemoradiotherapy in locally
advanced cervical cancer: feasibility study. Xu et al. BMC Cancer 17, p. 427.
13. Stoelinga, B, Hehenkamp, WJK, Brolmann, HAM , Hurine, JAF. (2014). Real-time elastography for
assessment of uterine disorders. Ultrasound Obstet Gynecol 43, pp. 218-226.
14. Ryo, E. (2014). Real time tissue elastography in gynecology and obstetrics. Donald School J Ultrasound-
Obstet Gynecol 8(4), pp. 428-436.
15. Thomas A. (2006). Imaging of the cervix using elastography. Ultrasound Obstet Gynecol 28, pp. 356-357.
16. Thomas, A et al., (2006). An advanced method of ultrasound real-time elastography. Ultrasound Obstet
Gynecol 28(3), pp 335-340.

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Agenesis of the Corpus Callosum

MITRACHE Dana1, PANTEA Manuela2, ANGELESCU-COPTIL Claudiu2,


EL GHAZI Ghita3
1 IInd Department of Obstetrics and Gynecology, “Pius Brânzeu” Emergency Clinical County Hospital Timisoara (ROMANIA)
2 Department of Neonatology “Pius Brânzeu” Emergency Clinical County Hospital Timisoara (ROMANIA)
3 IIIrd Discipline of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Faculty of Medicine, “Victor Babes”

University of Medicine and Pharmacy from Timisoara (ROMANIA)


Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Agenesis of corpus callosum is the most frequent cerebral malformations. Diagnosis is based
on brain imaging. It is most often asymptomatic. Craniosynostosis can be part of his clinical
picture. We present the case of a secundigravida, whose ultrasound revealed agenesis of corpus
callosum. After the baby was born physical examination showed facial dysmorphism, low-setears
and craniosynostosis. Brain imaging showed, in addition no other brain injuries but a corpus
callosum agenesis. This observation helped to highlight a disease whose clinical presentation is
specific. This malformation is to seek at prenatal, postnatal and even at the adulthood.
Keywords: corpus callosum agenesis, craniosynostosis, brain imaging

Introduction

The corpus callosum is a major axonal commissure of the brain connecting the two cerebral
hemispheres and providing communication between the cortical and subcortical neurons which
connect one hemisphere with the corresponding part of the other hemisphere. Agenesis of the
corpus callosum (ACC) is the failure of the callosal commissural fibres to cross the midline and
form the major connection between the two cerebral hemispheres [1]. The birth deffect can be
associated with other syndromes and conditions. The clinical findings differ greatly among
individuals, depending of the form – partial or complete of agenesia [2]. Ultrasound or Magnetic
Resonance Imaging are useful for prenatal diagnosis [3, 4].

Methodology

The study is a case report of a 27-years-old secundipara at 38 weeks of gestation presented


with uterine contractions in the Department of Obstetrics and Gynecology at the “Pius Brânzeu”
County Emergency Hospital in Timişoara. At the ultrasound of 36 weeks was established the
diagnosis of ACC. The patient had been counseled regarding mode of delivery and accepted the
surgical intervention. Patient had an uncomplicated caesarean section at 38 weeks.

Results

The gravida first visit at doctor was at 7 weeks of gestation. At first trimester of pregnancy she
presented nausea and vomiting. There was no maternal history of diabetes mellitus or

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hypertensive disease. She had no febrile illness in the course of pregnancy. The mother booked
pregnancy in the first trimester and had monthly antenatal visits before delivery. She had prenatal
ultrasound scan before delivery but could not recall the findings until 36 weeks when the
ultrasound revealed the indication of ACC and more other observations like small size ears,
craniosynostosis, cloverleaf skull.
Family history did not reveal similar ailment or any congenital deformity among his siblings.
There was no positive history of similar ailment in maternal or paternal family members. On
arrival in the Department of Obstetrics and Gynecology at the “Pius Brânzeu” County Emergency
Hospital in Timişoara at 38 weeks uterine contractions were noted every 5-6 minutes, she was
afebrile at 36,2 C, with a pulse rate of 97 bpm, blood pressure of 110/70, fetal heart tones noted to
be 126 bpm. Speculum examination had revealed a cloudy-white amniotic fluide and sterile
vaginal exam indicated cervical dilatation of 4 cm with 60% effacement. It was decided to
perform a cesarean delivery for the indication: fetal malformation – ACC. The weight of the baby
at birth was 3,650 g, with a cranial circumference of 34 cm and an Apgar score of 8/8.
The baby was admitted to the neonatal intensive care unit for ACC examination and then
referred for consultation to the Department of Neurology at “Louis Ṭurcanu” Hospital in
Timisoara for review the neurological anomalies. Physical examination showed psychomotor
retardation, low-setears, turricephaly, exophthalmia, craniosynostosis (Crouzon syndrome), facial
dysmorphism and feeding difficulties.

Fig. 1. The aspect of newborn in first day

No other malformation was found. Biological examination showed hypoproteinemia, mixed


anemia, blood clotting disorders and hidroelectrolytic disorders.
Craniectomy for sagittal craniosynostosis performed at age 2 months. The infant is doing well
with no permanent neurologic sequelae for the moment.

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Fig. 2. Sagittal craniosynostosis

Computed tomography scan of the head showed ACC with no other brain injuries. The
electroencephalogram test was normal.
Although the patient in question is presently growing without any major systemic problems, it
is considered quite possible that various complications may arise in the future, including those
related to the central nervous system, and it will be necessary to proceed with careful follow-up
observation.
ACC, a commissural (white matter) anomaly, is mostly congenital and occurs either in
isolation or in combination with other central nervous system (CNS) or systemic malformations.
The defect is more common in males than in females with a sex ratio approaching 2:1 [4, 5].
The index case is a female with ACC (completely absent) occurring in combination with
normal EEG and no other brain injuries.
The aetiology is extremely heterogeneous being attributed to disturbances of embryogenesis in
the first trimester of pregnancy. Its occurrence has been well documented in fetal alcohol
syndrome, inborn errors of metabolism, maternal diabetes and CNS infectious conditions [6, 7].
Biological examination of the index patient revealed errors of metabolism as hypoproteinemia,
mixed anemia, blood clotting disorders and hydroelectrolytic disorders.
The clinical manifestations of callosal agenesis have been described under two headings: non-
syndromic and syndromic. Non-syndromic forms are more common [8, 9]. Clinical signs and
symptoms in the non-syndromic variety vary widely from normal in some cases of isolated ACC
to diverse in the presence of other CNS abnormalities [8, 10]. Findings on physical examination
may include dysmorphic facial features (hypertelorism and a broad nose), hypotonia to severe
spasticity, ataxia, autistic behaviour, learning disabilities and behavioural disorders [11, 12]. The
index patient presented with psychomotor retardation and feeding difficulties.
Documented syndromes associated with ACC include Arnold-Chiari malformation, Dandy-
Walker syndrome, Aicardi’s syndrome, Andermann syndrome, Acrocallosal syndrome,
schizencephaly, holoprosencephaly and several of the trisomies [13, 14].
MRI remains the best modality for establishing the diagnosis of ACC and for delineating
associated anomalies of the CNS [1, 15]. Prenatal diagnosis of this malformation is now routinely
made by ultrasonography at 20th week and on MRI at 30th week of gestation [16-21].
In this case prenatal diagnosis of ACC was made by ultrasonography at 36 weeks.

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Treatment usually consists of learning to deal with specific symptoms and managing seizures
if they occur. Although the challenges of living with ACC are often significant and lifelong,
patients are frequently able to lead meaningful and productive lives. Patients may benefit from a
range of development therapies or educational support, and services.

Conclusion

Agenesis of corpus callosum is the most frequent cerebral malformations. Diagnosis is based
on brain imaging. It may be asymptomatic or reveled by a highly polymorphic and non-specific
clinical feature. It should be researched in prenatal, postnatal and even in adulthood.
In most cases, it is not possible to know what caused an individual to have ACC or another
callosal disorder. However, research suggests that some possible causes may include
chromosome errors, inherited genetic factors, prenatal infections or injuries, prenatal toxic
exposures, structural blockage by cysts or other brain abnormalities, metabolic disorders.
The prognosis depends on coexistence of other abnormalities. In association with cortical
disorders it is a poor prognosis. Normal or borderline intellectual development – in case of
isolated.

REFERENCES

1. Barbara, K.B., (2008). Agenesis of the corpus callosum. In: Kumar P, Burton BK, editors. Congenital
Malformations: Evidence Based Evaluation and Management. New York: McGraw-Hill Companies, Inc.
pp. 77-82.
2. Sung E.K., Hye-In, J., Kylie Hae-Jin C., Ji-Hee, S., et al., (2017). Clinical outcomes and
neurodevelopmental outcome of prenatally diagnosed agenesis of corpus callosum in single center of Korea
Obstet Gynecol Sci, 60(1), pp. 8-17.
3. Paladini, D., Pastore, G., Cavallaro, A., Massaro, M., Nappi, N., (2013). Agenesis of the fetal corpus
callosum: sonographic signs change with advancing gestational age. Ultrasound Obstet Gynecol, 42, pp:
687-690.
4. Craven, I., Bradburn, M.J., Griffiths, P.D., (2015). Antenatal diagnosis of agenesis of the corpus callosum.
Clin Radiol. 70(3), pp: 248-53.
5. Bernad, E.S., Bernad, S.I., Sargan, I., Craina, M.L., (2015). Saphenous vein graft patency after geometry
remodeling, Journal of Mechanics in Medicine and Biology, 2015, 16(2), 1540051.
6. Bookstein, F.L., Sampson, P.D., Connor, P.D., Streissguth, A.P., (2002). Midline corpus callosum is a
neuroanatomical focus of fetal alcohol damage. Anat Rec, 269, pp: 162-74.
7. Bernad, S.I., Bosioc, A.I., Bernad, E.S., Craina, M.L., (2015). Helical type coronary bypass graft
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8. Hetts, S.W., Sherr, E.H., Chao, S., Gobuty, S., Barkovich, A.J., (2006). Anomalies of the corpus callosum:
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14. Totorean, A.F., Bosioc A.I., Bernad, S.I., Susan-Resiga R., (2015). Critical flow regions in the coronary by-
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Amsterdam, pp: 745-747.

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Integrated System for Monitoring People with Diabetes.


Monitoring of Pregnant Women

ŞTEFAN Bogdan1, COSTACHE Ştefania-Bianca1, CRIŞAN-VIDA Mihaela1,


STOICU-TIVADAR Lăcrămioara1, MITRACHE Dana2
1Department of Automation and Applied Informatics, University Politehnica Timișoara (ROMANIA)
2“Pius Brinzeu” Emergency Clinic County Hospital Timisoara, IInd Department of Obstetrics and Gynecology, Timisoara
(ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

The paper presents an integrated system monitoring the behaviour of pregnant women
suffering of diabetes and tracks daily physical activities following how these influence the
pregnant woman’s health. Monitoring is done by both the clinician and the patient, observing the
generated reports and charts based on their physical activities and blood sugar recordings.
Observing these daily activities combined with the blood sugar recordings the specialist may
prescribe proper medication and behaviour for the patient to improve life during pregnancy. One
of the advantages of using this system by the patient is that she can follow the condition and take
proper measures in real time.
Keywords: physical activity, mobile application, blood sugar, web application, diabetes, pregnancy etc

Introduction

Obesity is one of the main factors causing various conditions and diseases. Due to obesity,
possibility of appearance of cardiovascular diseases, cancer, depression or type 2 diabetes is
drastically increased. Even though the medical research has made great progress, diabetes still has
no treatment and the only way to control it, is by monitoring the physical activity, diet and
medication. Diabetes represents a group of diseases. High blood glucose, also called high blood
sugar or hyperglycaemia, is present in individuals affected by diabetes.
The monitoring is crucial because the body changes dramatically, and the level of insulin
might change. Once the baby is born, the insulin will fall dramatically compared with the
pregnancy’s period [1].
The risk for a pregnant woman to develop gestational diabetes is between 5%-10% [2] and
increases if the person has a body mass index higher than 30. In most cases, the women with
diabetes who wanted to become pregnant, had pre-existing diabetes type 1, and a few had type 2.
In this case it is recommended [3] to perform at least 150 minutes of physical activity per
week, meaning 3-5 sessions, 30-45 minutes duration each. Gestational diabetes develops during
pregnancy. That means that the pregnant woman did not have diabetes before and generally the
condition disappears when the baby is born [3-4]. Safe physical activities during pregnancy are
walking, jogging, dancing, bicycling or swimming, but this should be firstly agreed with the
doctor [5]. During pregnancy, testing the blood glucose at least 4 times a day will help the

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pregnant woman to monitor her condition and the doctor to adjust the insulin level if it is
necessary [3].

State of the art

One of the main issues addressed in the relation patient-doctor, is the communication based on
which, often, a diagnostic is made or a treatment plan is established. Information is provided by
patient through a subjective manner to doctor. Additionally, the patient can observe his condition
through different charts and data from the application.
On the market there is an increased number of applications that are monitoring the daily
physical activities for people affected by diabetes, but only a reduced number of them can
provide information to the specialist [6]. Data useful for a specialist in a real-time communication
between doctor and patient is provided in applications Diabetes M, Diabetes UK, GlucoMe and
GlucoMan.
Diabetes M is developed for people suffering of diabetes. It monitors parameters as the blood
sugar, physical activity, carbohydrates amount and the rate diagram of the drip with blood sugar,
and provides reports, charts and statistics, sent to the specialist through email [7].
Diabetes UK registers and monitors the patient health state at different time periods and is
useful for patient when discussing with the doctor [8-12]. GlucoMe and GlucoMan are similar
with Diabetes M, but developed on a larger scale and thus incorporating more functionality useful
for both doctor and patient. GlucoMe provides alerts and reminders, continuous connection to
patient’s doctor, guidance on treatment plan, information logbook and charts, etc. [13].
GlucoMan, as main features, contains a logbook where patient can input relevant data for
doctor, charts, information about physical activity, e-mail notification, etc. [14, 15].

Integrated system for monitoring women suffering from gestational diabetes

The paper presents a digital healthcare solution for women dealing with diabetes during
pregnancy. We propose a system with 2 applications: for the patient we created a mobile
application to monitor routine activities and the corresponding blood sugar levels, and for the
doctor a web application to track the patient data and supporting prescription.
The patient application it was developed on an Android platform and tracks the user’s physical
activity. It recognizes three types of physical activities: walking, jogging and resting.
The data necessary to classify this type of activities are collected using the smartphone tri-axis
accelerometer.
User input data is transmitted to a database and it is checked by the healthcare specialist
evaluating the patient health state. The doctor searches the name of the patient and a table with
patient’s parameters in time will be displayed. After selecting the desired row from the table, two
charts with all recorded activities from the selected patient will pop on the screen. These consist
of blood sugar levels for each active day and the duration for each activity type. Based on these
values, the specialist will assist the pregnant woman, monitoring in real time her condition and
adjusting the medication if it is necessary.

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System architecture

Solution overview
The overall architecture of the proposed healthcare monitoring solution is shown in the block
diagram from Figure 1. Data is collected directly from the tri-axis accelerometer in real time,
using the smartphone device, it is processed, and the results are committed to Mongo Database.
The WEB Application is responsible for sending and receiving data through Node.js server to
and from Mongo Database. Mongo Database is a NoSQL database which uses JSON documents
[16].
Node.js represents a JavaScript run-time environment that executes code from server-side. It
produces dynamic web pages before the page is sent to the user’s browser [17-21]. Information is
accessed by doctor through this database and it is visible to be manipulated at any time by
specialist. Having a database which can store relevant data and group by categories, provides
means to have fast access to them.

Fig. 1. Information flow

Information Flow
The Android application can detect three types of physical activities based on the device’s
accelerometer data. In the first phase, the user has to calibrate the device for two types of
movement: running and walking, performing each for 1 minute. The values returned by the
accelerometer sensor on each axis are processed applying a cross-autocorrelation on these signals
in both calibration and detection phase.
The application is requiring between 60 to 200 samples to determine if the movement type is
running or walking. Each sample represents a set of data from accelerometer with the x, y and z
accelerations on the axes. The first 60 samples are necessary as accommodation time for the
detection phase. Boundaries for a physical activity is set as: lower limit is the score without the
error margin, upper limit is the score with the error margin.

Fig. 3. Hysteresis applied on a session Fig. 4. Walking pattern

The error margin for running activity is 3 and for walking activity is 10. These values have
been observed in field and they are reliable for 5 people on which it was tested. For a session of
continuous walking as presented in Figure 4, two types of invalid data were detected but they
were considered as walking, due to hysteresis threshold value 3. The threshold means that we
need at least three activities after the last one of the same type to have a valid type of activity.

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Based on the accelerometer data acquisition three different movements patterns were
identified. Figures 4, 5 and 6, present walking, running and sitting activities patterns with
accelerations on x, y and z axis. Data observed in the charts are depending on the movement and
direction of accelerometer. Computing the period between those peaks by applying
autocorrelation will result in a pattern recognized by the application.

Fig. 5. Running pattern Fig. 6. Sitting pattern

In Figure 4, 5 and 6 the blue colour represents the variation in acceleration on x axis, the red
colour on the y axis and the green colour on the z axis. On x axis is represented the sample
number and on y axis the accelerations (m/s^2).
The gravitational pull is acting on the accelerometer and the x, y and z values are not 0 while
sitting. Depending on the position of the phone, the accelerometer will provide different values.
Applying the autocorrelation, we can find the period distance between the peaks.
The WEB Application functionalities are: register a new patient, make an appointment and
visualize history of diabetes characteristics evolution. To register a new patient, the doctor needs
to fill the fields of a form.
The data is transmitted via Node.js server through Express framework to Mongo Database.
After the registration was performed, the patient has an account to login into the Android
application for monitoring her activities.
Figure 7 presents the fluctuation of blood sugar before and after daily activities are performed,
the pink bar representing the blood sugar value before activity and the orange bar the blood sugar
after that.
Figure 8 presents how much time the patient spent on each activity, the yellow bar
representing the resting duration, the light orange representing the walking and orange the
running time. In this situation the specialist will give a proper medication or recommendation for
the patient.

Fig. 7. Blood sugar chart Fig. 8. Physical activities chart

Conclusions

The application helps improving the health of the pregnant women suffering from diabetes
based on their daily physical activities and corelated with the levels of blood sugar. It monitors

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the fluctuation of blood sugar while the pregnant woman performs different kinds of activities
(resting, walking, easy running).
As the patient is monitor her state of health, she may improve her condition during pregnancy.
Another important benefit is the availability of the history in terms of data regarding her
activities and blood sugar over time.

REFERENCES

1. Tonic Digital Media Pty Ltd. Diabetes and getting pregnant (http://www.mydr.com.au/diabetes/diabetes-
and-getting-pregnant).
2. Society for Maternal-Fetal Medicine (2016). Gestational diabetes, https://www.smfm.org/, Accessed in
02.04.2018.
3. Thompson D., et al., “Diabetes and Pregnancy,” Canadian Diabetes Association 2013 Clinical Practice
Guidelines for the Prevention and Treatment of Diabetes in Canada. Canadian Journal of Diabetes, 37, pp:
S168-S183.
4. Petre, I., Bernad, E., Muresan, A., Bordianu, A., Bernad, S.I., Bacean, O., Folescu, R., Milulescu, A.,
Pantea, S., (2015). Choriocarcinoma developed in a tubal pregnancy – a case report, Rom J Morphol
Embryol, 56(2 Suppl), pp: 871-874.
5. Poiana, Catalina; Capatina, Cristina. Fracture Risk Assessment in Patients With Diabetes Mellitus.
JOURNAL OF CLINICAL DENSITOMETRY. Vol: 20 Issue: 3 Special Issue: SI, pp: 432-443 Published:
JUL-SEP 2017.
6. Bernad, S.I., Bernad, E.S., Barbat, T., Barbu, D., Albulescu, V., (2010). Assessment of the placental blood
flow in the developing and growth-restricted fetus, Proceedings of the 22th European Congress of Perinatal
Medicine, Granada, Spain, May 26-29, pp: 127-130.
7. Diabetes: M, https://www.diabetes-m.com/, Accessed in 05.04.2018.
8. Diabets UK Tracker, http://myhealthapps.net/app/details/26/Diabetes-UK-Tracker, Accessed in 05.04.2018
9. Petre, I., Barjica, D., Duta, C., Boglut, A., Bernad, E., Craina, M., Bolintineanu, S., Pantea, S., Radu, D.,
Ionita, I., (2016). Sclerotherapy for Varicose Veins, Materiale Plastice, 53(4), pp: 765-766.
10. Ionita, I., Grigorita, L., Miloicov, C.B., Petre, I., Bernad, E., Craina, M., Diaconu, M., Citu, C., Radu, F.,
Oros, D., Boglut, A., Furau, G., Enatescu, V., (2016). The Role of Thrombophilia in Pregnancy, Revista de
Chimie, 67(12), pp: 2643-2647.
11. Enatescu, V.R., Enatescu, I., Craina, M., Gluhovschi, A., Papava, I., Romosan, R., Marian, C., Oprea, A.,
Bernad, E., (2014). State and trait anxiety as a psychopathological phenomenon correlated with postpartum
depression in a Romanian sample: a pilot study, Journal of Psychosomatic Obstetrics and Gynecology,
35(2), pp: 55-61.
12. Bernad, E.S., Craina, M., Tudor, A., Bernad, S.I., (2012). Perinatal outcome associated with nuchal
umbilical cord, Clinical and Experimental Obstetrics & Gynecology, 39(4), pp: 494-497.
13. GlucoMe, https://www.glucome.com/solution/overview, Accessed in 05.04.2018.
14. Schmocker, K., Zwahlen, F., Denecke, K., (2018). Mobile App for Simplifying Life With Diabetes:
Technical Description and Usability Study of GlucoMan, JMIR Diabetes 3(1):e6.
15. Capatina, Cristina; Ghinea, Adela; Dumitrascu, Anda; et al., Concurrent onset of type 2 diabetes mellitus
and central diabetes insipidus in an adult male INTERNATIONAL JOURNAL OF DIABETES IN
DEVELOPING COUNTRIES Vol: 36 Issue: 4 Pages: 393-396 Published: DEC 2016.
16. Kerby, D. (2015). Why MongoDB is the Way to Go, https://dzone.com/articles/why-mongodb-is-worth-
choosing-find-reasons, Accessed in 10.04.2018.
17. Cuomo, J., (2013). JavaScript Everywhere and the Three Amigos,
https://www.ibm.com/developerworks/community/blogs/gcuomo/entry/javascript_everywhere_and_the_thr
ee_amigos?lang=en, (accessed in 15.04.2018).
18. Bernad, S.I., Totorean, A.F., Vekas, L., (2016). Particles deposition induced by the magnetic field in the
coronary bypass graft model, Journal of Magnetism and Magnetic Materials, 401, pp: 269-286.
19. Vida, M., Lupse, O., Gomoi, V., Stoicu-Tivadar, L., Stoicu-Tivadar, V., Bernad, E. (2014). Using Web
Services to support the interoperability between healthcare information systems and CDS systems. Control
Engineering and Applied Informatics, 16(1), pp: 106-113.
20. Bernad E., Bernad, S.I., Sargan I., Craina, M.L., (2015). Saphenous vein graft patency after geometry
remodeling, Journal of Mechanics in Medicine and Biology, 2015, 16(2), 1540051.

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21. Iovanescu, D., Frandes, M., Lungeanu, D., Burlea, A., Miutescu, B.P., Miutescu, E., (2016). Diagnosis
reliability of combined flexible sigmoidoscopy and fecal-immunochemical test in colorectal neoplasia
screening, OncoTargets and Therapy, 9, pp: 6819-6828.

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Meningitis During Pregnancy

MITRACHE Dana1, MOZA Andreea1,2, BURLICA Sorin1


1 IInd Department of Obstetrics and Gynecology of the “Pius Brânzeu” Emergency Clinical County Hospital Timisoara
(ROMANIA)
2 IIIrd Discipline of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Faculty of Medicine, “Victor Babes”

University of Medicine and Pharmacy from Timisoara (ROMANIA)


3 Ist Department of Obstetrics and Gynecology of the “Pius Brânzeu” Emergency Clinical County Hospital Timisoara

(ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Bacterial meningitis have been described during pregnancy in a few cases. Diagnosis is based
on lumbar puncture. We present the case of a primipara at 33 weeks of gestation, with fever,
mental status changes, neck stiffness and preterm contractions. The lumbar puncture revealed
gram positive cocci consistent with Streptococcus pneumoniae. During the pregnancy, the
ultrasound was normal. The patient had also other associated pathology: thrombophilia and B
hepatitis. Because the diagnose of Meningitis with Streptococcus pneumoniae was faster, the
mother and the baby are now alive, without neurological sequelae.
Keywords: meningitis, pregnancy, Streptococcus pneumoniae

Introduction

Few cases of bacterial meningitis have been described during pregnancy, and the causative
microorganisms and prognosis of bacterial meningitis during pregnancy are unclear. During
pregnancy, immunosuppressive cytokines are produced by the placenta and foetus to avoid
immunological attack by the mother [1]. This does not lead to increased susceptibility to most
infectious diseases, including pneumococcal disease, and usually infections in pregnant woman
are no more serious than in non-pregnant women [1].

Case report

The study is a case report of a 28-years-old primipara at 33 weeks of gestation presented with
mental status changes, fever, neck stiffness and preterm contractions. Lumbar puncture revealed
gram positive cocci consistent with Streptococcus pneumoniae. Patient was intubated and
admitted to intensive care unit where she was given antibiotics and adjunctive therapy with
dexamethasone. Throught her course of her hospitalization was utilized continous fetal
monitoring. Patient had an uncomplicated caesarean section at 36 weeks.

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Results and discussions

The gravida first visit at doctor was at 8 weeks of gestation. At first trimester of pregnancy she
presented nausea and vomiting. There was no maternal history of diabetes mellitus or
hypertensive disease. She had no febrile illness in the course of pregnancy.
Thrombophilia has been identified after her first miscarriage and thromboprophylaxis has been
suggested as an option of treatment (Clexane 0,4 ml). The test for B hepatitis was positive, but
the viral load was low, so physician didn’t recommend an oral antiviral drug in the third trimester
to reduce the risk of infecting the newborn at birth.
The mother booked pregnancy in the first trimester and had monthly antenatal visits before
delivery, she also took prenatal vitamins. The ultrasound was normal during pregnancy. First she
presented at intensive care unit at 33 weeks of gestation with mental status changes, fever, neck
stiffness and preterm contractions. She was intubated and she was given antibiotics and
adjunctive therapy with dexamethasone. The gravida was diagnosticated with Meningitis with
streptococcus pneumoniae.
The ultrasound revealed a gestational age of 33 weeks, with normal fetal measurement, normal
heart action, cephalic presentation, normal amniotic fluid, anterior high placenta and normal
structure and normal fetal blood flow.
On arrival in the Department of Obstetrics and Gynecology at the Pius Brânzeu County
Emergency Hospital in Timişoara she was afebrile at 36,2 C, with a pulse rate of 93 bpm, blood
pressure of 145/90. At 36 weeks uterine contractions were noted every 5-6 minutes, but fetal
heart tones noted to be 80 bpm. Speculum examination had revealed a cloudy-white amniotic
fluide and sterile vaginal exam indicated cervical dilatation of 2 cm with 80% effacement. After
repeated deceleration (under 100bpm), it was decided to perform a cesarean delivery for the
indications: acute fetal distress at the onset of labor, prematurity, premature rupture of
membranes and bacterial meningitis. The patient had been counseled regarding mode of delivery
and accepted the surgical intervention. She had a succesful C-section of a feminin infant
weighting 1990 gr with Apgar scores of 8 at 1 minute. Both she and the infant are doing well with
no permanent neurologic sequelae.
Meningitis-treatment failures attributed to cephalosporin resistance have been reported [2, 3].
The American Academy of Pediatrics recommends vancomycin (an antibiotic to which all S.
pneumoniae strains remain susceptible) in addition to an extended-spectrum cephalosporin for
treatment of suspected pneumococcal meningitis [4, 5] and this recommendation has also been
proposed for the treatment of adult patients with suspected pneumococcal meningitis [6]. The
index case received vancomycin 1gram at 12 hours and her evolution was better.
Early treatment with dexamethasone improves the outcome in adults with acute bacterial
meningitis. Adjunctive treatment with dexamethasone reduced the risks of both an unfavorable
outcome and death [7, 8]. In our case, the gravida received adjunctive therapy with
dexamethasone at the intensive care unit.
Alteration in level of consciousness and focal abnormalities like motor weakness and impaired
vision may be seen during acute phase of illness. Mental, retardation is seen in up to 4.2% of
cases [9, 10]. After the acute phase of illness the index case had no other neurolological sequelae.
In a recent prospective study, the clinical features and prognostic factors were described in
adults with bacterial meningitis. Risk factors for an unfavorable outcome were advanced age (>60
years), presence of otitis/sinusitis, absence of rash, low score on Glasgow coma score (<8),
tachycardia (>120 bpm), a positive blood culture, an elevated erythrocyte sedimentation rate
(>56), decreased platelet count (<180 000/mm3), low CSF white-cell count (<100/mm3), and

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causative species S. pneumoniae [11, 12]. In the current case, the likely mechanism for
transmission of the pathogen was through invasion of the central nervous system. Our gravida
met a minimum of four of these ten criteria (tachycardia, absence of rush, S. pneumoniae and
presence of otitis) placing her at low risk.
Otitis was found to be the most important risk factor in developing pneumococcal meningitis
in pregnant women [13, 17].
The main and important conclusion from the Dutch study is that meningitis in pregnancy and
postpartum has been historically underestimated in terms of frequency and mortality. The clinical
symptoms are frequently vague and not those of the classical meningitis triad, meaning that
healthcare workers need to consider the possibility of meningitis more proactively and diagnose it
faster.

Conclusion

Bacterial meningitis is a medical emergency in which early diagnosis and treatment is


imperative to prevent death and reduce long-term complications. Lumbar puncture is used to
confirm the diagnosis. A review of literature indicates only isolated cases of pneumococcal
meningitis being described during pregnancy. An extended period of time between onset of
maternal illness and delivery appears to reduce the risk of neonatal transmission and improve
both maternal and fetal outcomes.

REFERENCES

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remodeling, Journal of Mechanics in Medicine and Biology, 2015, 16(2), 1540051.
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flow patterns for straight and helical type graft, Bio-Medical Materials and Engineering, Volume 24(1), pp:
853-860.
11. van de Beek, D., de Gans, J., Spanjaard, L., Weisfelt, M., Reitsma, J.B., Vermeulen, M., (2004). Clinical
features and prognostic factors in adults with bacterial meningitis. New England Journal of Medicine,
351(18), pp: 1849-1859.
12. Bernad, S.I., Totorean, A., Bosioc, A., Crainic, N., Hudrea, C., Bernad E.S. (2015). Fluid mechanics in
stented arterial model, International Conference of Computational Methods in Sciences and Engineering
2015 (ICCMSE 2015), AIP Conf. Proc., vol. 1702, 080008-1-080008-4.

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13. Bernad, S.I., Totorean, A.F., Vekas, L., (2016). Particles deposition induced by the magnetic field in the
coronary bypass graft model, Journal of Magnetism and Magnetic Materials, 401, pp: 269-286.
14. Lucas, A.O., (1964). Pneumococcal meningitis in pregnancy and the puerperium. Br Med J 1964; 1: 92-95.
15. Bernad, E., Pantea, S., Boglut, A., Duta, C., Bernad, S.I., Petre, I., (2016). Investigation of Chorionic Artery
Bifurcation Using Micro Vascular Casting Model, Revista de Chimie, 67(2), pp: 339-343.
16. Totorean A.F., Bosioc A.I., Bernad, S.I., Susan-Resiga R., (2015). Critical flow regions in the coronary by-
pass graft anastomosis, Proceedings of the Romanian Academy, Series A, 16(2), pp: 201-208.
17. Totorean, A.F., Bosioc, A.I., Bernad, S.I., Susan-Resiga, R., (2014). Identification and visualization of the
vortices in by-pass graft flow, Proceedings of the Romanian Academy, Series A-Mathematics Physics
Technical Sciences Informational Science, 15(1), pp: 52-59.

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Evaluation of the Umbilical Cord Insertion

BERNAD I. Sandor1, MOZA Andreea2, MITRACHE Dana2


1Romanian Academy – Timişoara Branch, Centre for Fundamental and Advanced Technical Research (ROMANIA)
2“Pius Brinzeu” Emergency Clinic County Hospital Timisoara, IInd Department of Obstetrics and Gynecology, Timisoara
(ROMANIA)
Emails: [email protected], [email protected]

Abstract

The umbilical cord insertion to the placenta is divided into central/eccentric, marginal and
velamentous, as it relates to the chorionic plates. This observational study was conducted in the
Department of Obstetrics and Gynecology of the County Emergency Hospital Timisoara,
Romania. This study includes 134 pregnant women who delivered in our department from
January 2010 to December 2011. We have observed 134 specimens for the pattern of placental
attachment of umbilical cord as stated earlier in the materials and methods. Among the 134
specimens, 110 (82.09%) placentas showed the centrally and eccentrically presented umbilical
cords, which was considered as usual. Remaining 24 (17.91%) specimens showed the umbilical
cord attached to the placental mass less than 2 cm from the placental edge and were considered as
marginal insertions. In two specimen (1.49%) we found a velamentous cord insertion.
Keywords: umbilical cord insertion, risk factor, ultrasound, placenta

Introduction

Abnormal umbilical cord placental insertion is associated with poor perinatal and neonatal
outcomes [1]. Vascular flow interruptions can cause intrauterine death or severe fetal distress [1].
Variations of the insertion of the umbilical cord in the placenta site is a result of the process
known trophotropism [2] in which the chorionic frondosum or the early placenta “migrate” to
ensure a better blood supply from a more richly vascularised area [3].
The umbilical cord inserts typically to the central portion of the placenta, well away from the
placental edge [2, 4-5]. The umbilical cord insertion to the placenta is divided into
central/eccentric, marginal and velamentous, as it relates to the chorionic plates.
If the umbilical cord is inserted within two cm from the placental edge, it is considered as
marginal insertion [5-7]. This is associated with IUGR [2], preterm labor [8] and development of
velamentous type insertion [5]. In velamentous type, cord inserts to the chorio-amniotic
membranes of placenta instead on to the placental mass [9-11].
This anomaly is associated with a series of events/pathology like low birth weight, growth
retardation, low APGAR scores, abnormal fetal heart patterns [12-15], single umbilical artery,
bilobed placenta and trisomy 21 [2, 11]. In literature, the velamentous cord insertion has
correlated with advanced maternal age and multiparity [8, 16-17]. Vasa Previa is the most
common complication of the velamentous umbilical cord insertion [18-19].
This study aimed to determine the association between umbilical cord insertion at the delivery
and the cord insertion detected using ultrasound technique.

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Patients and method

This observational study was conducted in the Department of Obstetrics and Gynecology of
the County Emergency Hospital Timisoara, Romania. This study includes 134 pregnant women
who delivered in our department from January 2010 to December 2011.

Fig. 1. Umbilical cord placental insertions: a) central insertion, b) eccentric insertion, c) marginal insertion,
d) velamentous insertion

After all vaginal and cesarean deliveries, the placenta was checked clinically and measured
(insertion of the umbilical cord, weight of placenta and length of the umbilical cord).
Gestational age was defined based on the date of the last menstrual period, and by ultrasound,
if there was a disparity of more than three days on the first-trimester measurement or 7 days on
the second-trimester measurement.

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Results

We have observed 134 specimens for the pattern of placental attachment of umbilical cord as
stated earlier in the materials and methods. Among the 134 specimens, 110 (82.09%) placentas
showed the centrally and eccentrically presented umbilical cords, which was considered as usual
(Figure 1 A and C). Remaining 24 (17.91%) specimens showed the umbilical cord attached to the
placental mass less than 2 cm from the placental edge and were considered as marginal insertions
(Figure B). In two specimen (1.49%) we found a velamentous cord insertion (Figure 1D).

Fig. 2. Sonographic evaluation of the umbilical cord, placental insertion: a) velamentous insertion, b)
velamentous insertion using color Doppler evaluation, c) marginal insertion

Discussions

Interruptions in the umbilical cord blood flow, whether arising from cord compression,
torsion, or insertion, confer significant risk to the fetus. Umbilical cord abnormal insertion plays
an essential role in fetoplacental circulation evolution [10], but the reasons for the associated
dysfunction are not clear.
In our unpublish research we investigated using sonography 36 pregnancies which included 36
singletons for a total of 36 placental cord insertions. In this study we observed that 32 (88.88%)

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regular insertions (central and eccentric insertions), 4 (11.11%) marginal and 1 (2.77%)
velamentous insertions (Figure 2).

Conclusions

Our study produces several conclusions:


- umbilical cord insertion anomalies are with other congenital anomalies;
- anomalies of the umbilical cord placental insertion are one of the causes of intrauterine
death of fetus;
- in conclusion, the early prenatal diagnosis of umbilical cord insertion can give an insight
into other congenital anomalies.

Acknowledgment
For S.I. Bernad this work was supported by the CFATR/LHC 2016-2020 research programme.

REFERENCES

1. Lacro, R.V., Jones, K.L., Benirschke, K., (1987). The umbilical cord twist: origin, direction, and
relevance. Am J Obstet Gynecol 157, p. 833.
2. Robinson, L.K., Jones, K.L., Benirschke, K. (1983). The nature of structural defects associated with
velamentous and marginal insertion of the umbilical cord. Am J Obstet Gynecol 146, pp: 191-193.
3. Monie, I.W., (1965). Velamentous insertion of the cord in early pregnancy. Am J Obstet Gynecol 93,
pp: 276-281.
4. Mclennan, J.E., (1968). Implications of the eccentricity of Human Umbilical Cord. Am J Obstet
Gynecol 101, pp: 1124-1130.
5. Bernad, E., Pantea, S., Boglut, A., Duta, C., Bernad, S.I., Petre, I., (2016). Investigation of Chorionic
Artery Bifurcation Using Micro Vascular Casting Model, Revista de Chimie, 67(2), pp: 339-343.
6. Pretorius, D.H., Chau, C., Poeltler, D.M. et al., (1996). Placental cord insertion visualization with
prenatal ultrasonography. J Ultrasound Med 15, pp :585-593.
7. Petre, I., Barjica, D., Duta, C., Boglut, A., Bernad, E., Craina, M., Bolintineanu, S., Pantea, S., Radu,
D., Ionita, I., (2016). Sclerotherapy for Varicose Veins, Materiale Plastice, 53(4), pp: 765-766.
8. Liu, C.C., Pretorius, D.H., Sciascia, A.I., Hull, A.D. (2002). Sonographic prenatal diagnosis of marginal
placental cord insertion: clinical importance. J Ultrasound Med 21, pp: 627-632.
9. Brody, S., Frenkel, D.A., (1953). Marginal insertion of the cord and premature labor. Am J Obstet
Gynecol 65, p. 1305.
10. Kouyoumdjian, A. (1980). Velamentous insertion of the umbilical cord. Obstet Gynecol 56, pp: 737-
742.
11. Paavonen, J., Jouttunpaa, K., Kangaslucoma, P., et al., (1984). Velamentous insertion of the umbilical
cord and vasa previa. lnt J Gynaecol Obstet 22, pp: 207-211.
12. Bernad, S.I., Bosioc, A., Bernad, E.S., Craina, M.L., (2014). Comparison between experimentally
measured flow patterns for straight and helical type graft, Bio-Medical Materials, and Engineering,
Volume 24(1), pp: 853-860.
13. Elena S. Bernad, Sandor I. Bernad, Izabella Sargan, Marius L. Craina, (2015). Saphenous vein graft
patency after geometry remodeling, Journal of Mechanics in Medicine and Biology, 2015, 16(2),
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14. Bernad, S.I., Bosioc, A.I., Bernad, E.S., Craina, M.L., (2015). Helical type coronary bypass graft
performance: Experimental investigations, Bio-Medical Materials and Engineering, 26(s1), pp. 477-
486.
15. Bernad, E.S., Frantescu, A., Bernad, S.I., Vernic, C., (1998). WEB-MO – A Computer Aided Learning
on WWW, Proceedings of The 9th World Congress on Medical Informatics, MedInfo’98 In Studies in
Health Technology and Informatics, vol 52, Editors: B. Cesnik, A.T. McCray, J.-R. Scherrer, IOS Press
Amsterdam, pp: 745-747.

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16. Ionita, I., Grigorita, L., Miloicov, C.B., Petre, I., Bernad, E., Craina, M., Diaconu, M., Citu, C., Radu,
F., Oros, D., Boglut, A., Furau, G., Enatescu, V., (2016). The Role of Thrombophilia in Pregnancy,
Revista de Chimie, 67(12), pp: 2643-2647.
17. Vida, M.M., Lupse, O.S., Stoicu-Tivadar, L., Bernad, E., (2012). Flexible Solution for Interoperable
Cloud Healthcare Systems. Proceedings of the 24 th Medical Informatics in Europe Conference (MIE),
AUG 26-29, 2012, Pisa, Italy. QUALITY OF LIFE THROUGH QUALITY OF INFORMATION,
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18. Bjoro, K.Jr., (1983). Vascular anomalies of the umbilical cord. Obstetrical implications. Early Hum
Dev 8, p. 119.
19. Enatescu, V.R., Enatescu, I., Craina, M., Gluhovschi, A., Papava, I., Romosan, R., Marian, C., Oprea,
A., Bernad, E., (2014). State and trait anxiety as a psychopathological phenomenon correlated with
postpartum depression in a Romanian sample: a pilot study, Journal of Psychosomatic Obstetrics and
Gynecology, 35(2), pp: 55-61.

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Anatomopathological Diagnostic Possibilities in Perinatal Infection

STOICESCU Silvia-Maria1,2, BIZINICHI Mădălina2, IONESCU Mioara2,


CHIRCULESCU Raluca2, MOHORA Ramona1,2
1“Carol Davila” University of Medicine and Pharmacy, Bucharest (ROMANIA)
2“Alessandrescu-Rusescu” National Institute for Mother and Child Health, Polizu Maternity, Neonatology Clinic, Bucharest
(ROMANIA)
Email: [email protected]

Abstract

Fetal inflammatory response as a result of infectious injury of umbilical cord is histologically


manifested as umbilical vasculitis and funisitis, predicting a possible early neonatal infection.
We conducted an analytic study over 18 months on the histological findings in fetuses and
newborns affected by perinatal infection. Among the neonates, 81.54% were term and 18.45%
preterm infants. There were 44% perinatal infections defined by using the diagnosis-related group
system (DRG) and using histological exam in a few cases. The pregnancies were of natural
conception and in-vitro fertilization. The newborns needed invasive resuscitation techniques in
4% of cases. The macroscopic aspect revealed a withered, hypocoiled or meconium stained
umbilical cord. Microscopic examination of the umbilical cord showed perivascular and Wharton
jelly inflammatory neutrophil infiltrate who was also found in amniotic membranes and in the
placenta. Anatomopathological diagnosis of perinatal infection guides the practice of the medical
team and represents a tool in the legal medicine.
Keywords: umbilical cord, preterm, term newborn, perinatal infection

Introduction

Intra-amniotic inflamation is considered to be the cause of acute histologic changes in the


umbilical cord, referred as vasculitis and funisitis [1].
Acute chorioamnionitis is evidence of a maternal response, funisitis and chorionic vasculitis
are fetal inflammatory responses [2].
Intra-amniotic infection has been generally considered to be the cause of acute histologic
chorioamnionitis and funisitis; but, recent evidence indicates that “sterile” intra-amniotic
inflammation, which occurs in the absence of demonstrable microorganisms and can be induced
by “danger signals”, is frequently associated with these lesions [2].
Funisitis and chorionic vasculitis are the manifestation of the fetal inflammatory response
syndrome (FIRS) [2], associated with severe neonatal morbidity [3] (congenital sepsis, severe
retinopathy of prematurity, periventricular leukomalacia when severe inflammation occurs [4]).
Fetal inflammatory neutrophilic response originates initially from the umbilical vein and later
from the arteries leading to umbilical cord vasculitis and funisitis [1].
Recent evidence suggests that amniotic fluid bacteria can form biofilms (communities of
sessile organisms that attach to a substratum or to each other), with an altered phenotype and
resistant to antibiotic treatment [2]. Once microbial invasion of the amniotic cavity leads to an

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intra-amniotic cytokine storm clinically manifested by preterm labor, parturition is largely


irreversible, and eradication of such infection has not been possible with antibiotic treatment [2].
In previous reports, there was a significant relationship between the duration of rupture of
membranes (term or preterm) and the risk of histologic chorioamnionitis. However, we were not
able to demonstrate a significant association between the duration of rupture of memebranes and
funisitis or histologic chorioamnionitis, this might result from longer duration of labor [8].
Moreover, in a recent study performed in patients with preterm rupture of membranes, the
duration of the rupture of membranes did not affect the rate of intra-amniotic inflammation. This
evidence might suggest that the suction-like effect of uterine contractions be the necessary
condition for the funisitis or histologic chorioamnionitis, rather than ruptured membranes [8].
The frequency with which microorganisms invade the human fetus is difficult to ascertain;
however, studies in which amniocentesis and cordocentesis have been performed in patients with
preterm rupture of membranes indicate that 30% of patients with microbial invasion of the
amniotic cavity have positive fetal blood cultures for microorganisms (i.e. bacteremia).
Therefore, the frequency of congenital microbial invasion of the fetus is likely to be higher
than that reported in the pediatric literature – the reasons for this are multiple (e.g. bacteremia
may not be continuous in the neonatal period; the inoculum size may be small, leading to a high
rate of negative blood cultures; and the lack of detection of the most common microorganisms,
genital mycoplasmas, may reflect that cultures for these organisms require special media, and
such cultures are not routinely performed in neonatal intensive care units) [2].
Bacteria associated with intrauterine infection are: group B Streptococcus, Escherichia coli,
Fusobacterium or Bacteriodes species, Listeria monocytogenes; fungi (Candida species); less
common causes are Actinomyces species, herpes simplex virus, Treponema pallidum [9].
An acute fetal inflammatory response is most often a response to bacterial infection, occurring
after the maternal inflamatory response and suggesting a more well-established infection [5].
Furthermore, funisitis at term appears to have a different clinical significance from funisitis in
the preterm gestation - funisitis at term has not been associated with cerebral palsy [6].
A high rate of funisitis in preterm placentas and a robust inflammatory response of preterm
babies with funisitis suggest that the presence of funisitis might have more significance in
preterm fetuses and their intrauterine environment than in term fetuses and their intrauterine
environment [10].
The presence of both funisitis and histologic chorioamnionitis was associated with a greater
reduction in the occurrence of respiratory distress syndrome than histologic chorioamnionitis
alone, compared to the absence of all placental inflammation (OR 0.20 vs. OR 0.44 after
adjusting for gestational age at delivery) [10].

Methods

We conducted an analytic study over 18 months in “Alessandrescu-Rusescu” National


Institute for Mother and Child Health – Neonatology Clinic, which included histological findings
from fetuses and neonates affected by perinatal infection risk.

Results

Funisitis was present in 4% of the term pregnancies. Microscopic examination of the umbilical
cord showed perivascular and Wharton jelly inflammatory neutrophil infiltrate (Fig. 1).

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Funisitis occurred in 1% of the cases with intact membranes and in the absence of labor, but
the incidence was rising with the presence of labor or ruptured membranes.
In our study, no pregnant woman presented clinical signs of chorioamnionitis, but
anatomopathologic assessment identified cases of chorioamnionitis (Fig. 2). Neutrophilic
inflammatory infiltrate was found in amniotic membranes and in the placenta.

Fig. 1. Vascular wall with inflamatory cells, Fig. 2. Amniotic membranes with massive inflamatory
extending to Wharton jelly (funisitis) response, with neutrophils and diffuse ulceration
(chorioamnionitis)
Discussions

The early (prenatal) diagnosis of funisitis is difficult because it requires invasive procedures,
such as cordocentesis and placenta examination. Routine anatomopathologic examination of the
umbilical cord and placenta after birth should be a standard procedure. Being a fetal inflamatory
response, funisitis can be a valuable marker for early-onset neonatal sepsis [3].
Amnion cells and placental villous tissues from preterm placenta have a more pronounced
cytokine response than those from term placenta, which lead to different clinicopathologic
significance of acute funisitis in term versus preterm pregnancies [7].
In our study, funisitis occurred with rising incidence in the presence of labor or ruptured
membranes compared to the cases with intact membranes, in accordance with the studies that
indicate that the longer the duration of labor, the higher the risk of funisitis and histologic
chorioamnionitis [8].

Conclusions

Fetal inflammation can occur in the absence of any clinical sign of infection, leading to
inflammatory histologic changes, with great impact on the neonatal outcome. Perinatal infection
using anatomopathological diagnosis has implications in legal medicine.

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REFERENCES

1. Buhimschi, C.S., Buhimschi, I.A, Abdel-Razeq, S., Rosenberg, V.A., Thung, S.F., Zhao, G., Wang, E.,
Bhandari, V. Proteomic Biomarkers Of Intra-Amniotic Inflammation: Relationship With Funisitis And
Early-Onset Sepsis In The Premature Neonate, Pediatric Research volume 61, pages 318-324 (2007),
doi:10.1203/01.pdr.0000252439.48564.37.
2. Kim, C. J., Romero, R., Chaemsaithong, P., Chaiyasit, N., Yoon, B. H., & Kim, Y. M. (2015). Acute
Chorioamnionitis and Funisitis: Definition, Pathologic Features, and Clinical Significance. American
Journal of Obstetrics and Gynecology, 213(4 0), S29-S52. http://doi.org/10.1016/j.ajog.2015.08.040.
3. Lee, S.Y., Park, K.H., Jeong, E.H., Oh, K.J., Ryu, A., Park, K.U. Relationship between Maternal Serum C-
Reactive Protein, Funisitis and Early-Onset Neonatal Sepsis. J Korean Med Sci. 2012 Jun;27(6):674-680.
https://doi.org/10.3346/jkms.2012.27.6.674.
4. Kowalski, P.J. Umbilical vasculitis and funisitis. PathologyOutlines.com website.
http://www.pathologyoutlines.com/topic/placentaacutefunisitis.html. Accessed April 12 th, 2018.
5. Mussen, D. (2017). Fetal Inflammatory Response Of Umbilical And Chorionic Plate Vessels. available at
https://www.mussenhealth.us/during-pregnancy/fetal-inflammatory-response-of-umbilical-and-chorionic-
plate-vessels.html.
6. Lee,S.E., Romero, R., Kim, C.J., Soon-Sup Shim & Bo Hyun Yoon (2006). Funisitis in term pregnancy is
associated with microbial invasion of the amniotic cavity and intra-amniotic inflammation, The Journal of
Maternal-Fetal & Neonatal Medicine, 19:11,693-697, DOI:10.1080/14767050600927353.
7. Chong, J.K., Bo, H.Y., Sung-Shin, P., Mi, H.K., Je G.C. Acute Funisitis Of Preterm But Not Term Placentas
Is Associated With Severe Fetal Inflammatory Response. Human pathology, volume 32, issue 6, 623-629,
DOI: https://doi.org/10.1053/hupa.2001.24992.
8. Lee, S. M., Romero, R., Lee, K. A., Yang, H. J., Oh, K. J., Park, C.-W., & Yoon, B. H. (2011). The
frequency and risk factors of funisitis and histologic chorioamnionitis in pregnant women at term who
delivered after the spontaneous onset of labor. The Journal of Maternal-Fetal & Neonatal Medicine : The
Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania
Perinatal Societies, the International Society of Perinatal Obstetricians, 24(1), 37-42.
http://doi.org/10.3109/14767058.2010.482622.
9. Paul J. Kowalski, M.D., Placenta – Umbilical cord – Umbilical vasculitis and funisitis, available from
http://www.pathologyoutlines.com/topic/placentaacutefunisitis.html
10. J. Lee, K.J. Oh, C.-W. Park, J.S. Park, J.K. Jun, B.H. Yoon ;The presence of funisitis is associated with a
decreased risk for the development of neonatal respiratory distress syndrome; J. Lee et al.,/Placenta 32
(2011) 235e240. doi:10.1016/j.placenta.2010.11.006

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Bilateral Ovarian Neoplasia with Negative Roma Score: A Case


Report

MOISEI Cristina1, LESNIC Anca1, SIMA Romina-Maria1,2,


STĂNESCU Anca-Daniela1,2
1Clinical Hospital “Sf. John”, “Bucur” Maternity Bucharest, (ROMANIA)
2UMF “Carol Davila”, Bucharest, Bucur Clinic Bucharest, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Introduction
Ovarian cancer is one of the most common cancers. It is a leading cause of cancer death, after
lung and bronchus, breast, colorectal, and pancreatic cancers, as it causes more deaths than any
other cancer of the female reproductive system, but it accounts for only about 3% of all cancers in
women. When ovarian cancer is found in its early stages, treatment works best.

Material and methods


We present the case of a 46 year old woman diagnosed with bilateral ovarian neoplasia with
negative ROMA score results.

Results
A 46 year old woman was admitted in our clinic for chronic lower abdominal pain. The
transvaginal ultrasonographic exam showed two transonic images situated lateral to the uterus,
the right one 80 mm in diameter, and the left one 45 mm in diameter, as well as 2 small
intramural leiomyomas. The MRI exam confirmed the ultrasonographic findings. A ROMA
SCORE exam was performed with negative results and the chest x-ray came back normal. The
patient also performed a Pap smear that showed no malignant lesions, only inflammatory cervical
lesions. A total hysterectomy with bilateral salpingo-oophorectomy was performed in our clinic
with general anesthesia in June 2016, with no post-surgery complication occuring. The
histopathologic exam came back as bilateral ovarian neoplasia (papillary cystadenocarcinoma of
the ovary) with right fallopian tube serosal invasion, immunohistochemistry (IHC) was
recommended. The pacient was referred to a surgical oncology clinic, where in July 2016 she
underwent a second surgery: omentectomy, mesenteric adenopathy resection, anterior abdominal
wall adenopathy resection as well as interaortocaval lymph node resection. In December 2016 the
patient performed an MRI that showed no evolutive lesions. The TNM staging was T2N0M0,
with negative prognostic factors being T2, and G2, as well as post-surgery elevated CA 125
levels. The patient received 6 cycles of chemotherapy (Taxol 175 mg/sqm with 260 mg/day and
Carboplatin 600mg/day), with Osetron, Dexamethasone and Metoclopramid administration with
good tolerance. The whole body MRI scan performed in January 2017 showed complete
remission, with regular check-ups required as well as another chemotherapy round.

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Conclusions
The peculiarity of this case is represented by the fact that there were no clinical, paraclinical or
imagistic indications that the ovarian masses would in fact be malignant, as the ROMA SCORE
was negative and the MRI did not point out any abnormal characteristics of the ovarian cysts.
Keywords: ovarian neoplasia, surgery, ROMA score

Background

Ovarian cancer is one of the most common cancers. It is a leading cause of cancer death, after
lung and bronchus, breast, colorectal, and pancreatic cancers, as it causes more deaths than any
other cancer of the female reproductive system, but it accounts for only about 3% of all cancers in
women [1]. It results from abnormal cells that have the ability to invade or migrate to other parts
of the body. When this process begins, symptoms become more noticeable as the cancer
progresses, but the majority of them are not specific ([1], [2]). Symptoms vary and may include
bloating, pelvic pain, abdominal swelling, and loss of appetite, among others. Common
metastasis areas the peritoneum, lymph nodes, lungs, and liver, as well as the brain, bone, spleen
etc. ([2], [3], [4]). Ovarian cancers are histologically and genetically divided into type I or type II.
Type I cancers are of low histological grade, and include endometrioid, mucinous, and clear-
cell carcinomas. Type II cancers are of higher histological grade and include serous carcinoma
and carcinosarcoma [5]. Three explanations as to the origin of serous ovarian adenocarcinomas
have been put forward. The first one points towards the ovarian surface epithelium (OSE) as
tissue of origin. Second, remnants of the embryologic Müllerian duct, the secondary Müllerian
system, have been suggested as possible tissue of origin. The third is the Fallopian tube inner
surface epithelium (TSE) (=oviduct epithelium) [6].

Fig. 1. [7]

Incidence of ovarian cancers by histopathology

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A screening method for ovarian cancer has proven to be difficult to be perfected. Currently, a
method using hysteroscopy to obtain cell samples obtained for histological examination is being
developed, similar to the current pap smear (Babes-Papanicolau test), that is used to detect
cervical cancer [8]. The UK Collaborative Trial of Ovarian Cancer Screening is testing a
screening technique that combines CA-125 blood tests with transvaginal ultrasound.
ROMA (Risk of Ovarian Malignancy Algorithm), is a score that utilizes the combination of
human epididymis protein 4 (HE4) and CA125 values to assess the risk of epithelial ovarian
cancer (EOC) in women with a pelvic mass. Studies have shown that the ROMA is a simple
scoring system which shows excellent diagnostic performance for the detection of EOC in post-
menopausal women, but not in pre-menopausal women. Moreover, the dual marker combination
of HE4 and CA125 (ROMA) does not show better performance than HE4 alone [9].
Once it is determined that ovarian, fallopian tube, or primary peritoneal cancer is present,
treatment is scheduled by a gynecologic oncologist, who can recommend surgery and give
chemotherapy to women with ovarian cancer. A treatment plan is developed by a
multidisciplinary team. Treatment usually involves surgery and chemotherapy, and sometimes
radiotherapy, regardless of the subtype of ovarian cancer [10]. Surgical treatment may be
sufficient for well-differentiated malignant tumors and confined to the ovary. Addition of
chemotherapy may be required for more aggressive tumors confined to the ovary. For patients
with advanced disease, a combination of surgical reduction with a combination chemotherapy
regimen is standard. Borderline tumors, even following spread outside of the ovary, are managed
well with surgery, and chemotherapy is not seen as useful [11]. Second-look surgery and
maintenance chemotherapy have not been shown to provide any benefits.
Chemotherapy in ovarian cancer typically consists of platins, a group of platinum-based drugs,
combined with non-platins. Common therapies can include paclitaxel, cisplatin, topotecan,
doxorubicin, epirubicin, and gemcitabine. Carboplatin is typically given in combination with
either paclitaxel or docetaxel; the typical combination is carboplatin with paclitaxel [12], [13].
Chemotherapy can be given intravenously or in the peritoneal cavity [13].
As of 2013, even though it is an active area of research, immunotherapy hasn’t been shown to
be effective [12]. Trials of the antibody and VEGF inhibitor bevacizumab, which can slow the
growth of new blood vessels in the cancer, have shown promising results, especially in
combination with pazopanib, which also slows the process of blood vessel growth. Bevacizumab
has been particularly effective in preliminary studies on stage-III and -IV cancer and has been
cited as having at least a 15% response rate [14].
Radiation therapy does not improve survival in people with well-differentiated tumors [13].
Dysgerminomas are most effectively treated with radiation, though this can cause infertility
and is being phased out in favor of chemotherapy [13].
Even though 60% of ovarian tumors have estrogen receptors, ovarian cancer is only rarely
responsive to hormonal treatments. Estrogen alone does not have an effect on the cancer, and
tamoxifen and letrozole are rarely effective [12].
Complementary and alternative medicine (CAM) use is common in women receiving
chemotherapy for EOC. A study from 2018 that analyzed the anticancer activity of toxins from
bee and snake venom, noted that natural toxins from bee and snake venom could become
potential candidates for the future treatment of different types of cancer, especially ovarian cancer
[15]. Increasingly, interactions between CAM and prescribed medication are being identified, and
oncologists should be aware and actively inquire about CAM use [16]. Similarly, a study from
2016 noted that the effects of combinations of dietary phytochemicals (like polyphenols) with

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chemotherapy and radiotherapy used in the treatment of cervical cancer, showed results in the
resistance of cervical tumor cells to chemo- and radiotherapy [17].
Ovarian cancer usually has a relatively poor prognosis. It is disproportionately deadly because
it lacks any clear early detection or screening test, meaning most cases are not diagnosed until
they have reached advanced stages [12].

Case presentation

A 46 year old woman was admitted in our clinic for chronic lower abdominal pain. The
transvaginal ultrasonographic exam showed two transonic images situated lateral to the uterus,
the right one 80 mm in diameter, and the left one 45 mm in diameter, as well as 2 small
intramural leiomyomas. The MRI exam confirmed the ultrasonographic findings. A ROMA
SCORE exam was performed with negative results and the chest x-ray came back normal. The
patient also performed a Pap smear that showed no malignant lesions, only inflammatory cervical
lesions. A total hysterectomy with bilateral salpingo-oophorectomy was performed in our clinic
with general anesthesia in June 2016, with no post-surgery complication occuring. The
histopathologic exam came back as bilateral ovarian neoplasia (papillary cystadenocarcinoma of
the ovary) with right fallopian tube serosal invasion, and a immunohistochemistry (IHC) exam
was recommended.

Fig. 2.

Hematoxylin and eosin staining of the ovarian and fallopian tissue

The pacient was referred to a surgical oncology clinic, where in July 2016 she underwent a
second surgery: omentectomy, mesenteric adenopathy resection, anterior abdominal wall
adenopathy resection as well as interaortocaval lymph node resection. In December 2016 the
patient performed an MRI that showed no evolutive lesions. The TNM staging was T2N0M0,
with negative prognostic factors being T2, and G2, as well as post-surgery elevated CA 125
levels. The patient received 6 cycles of chemotherapy (Taxol 175 mg/sqm with 260 mg/day and
Carboplatin 600mg/day), with Osetron, Dexamethasone and Metoclopramid administration with
good tolerance. The whole body MRI scan performed in January 2017 showed complete
remission, with regular check-ups required as well as another chemotherapy round.

Discussions

A study from 2016 stressed out that sonography is a clinically important imaging modality for
assessing whether an adnexal mass is likely benign or possibly malignant, and that most ovarian
surgeries are for benign disease and can be performed laparoscopically [18]. Only 1 patient had
ovarian carcinoma (1.4%), and 1 patient a borderline tumor (1.4%), revealing a strong correlation
between the ultrasound findings and the pathological results for adnexal tumors [18].

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Another study reported a similar rate of unexpected ovarian malignancy resected by


laparoscopy of 1.5%, and that the presence of an early-stage unexpected ovarian malignancy did
not alter the patient prognosis [19].
A similar case of syncronous bilateral ovarian carcinoma was reported in 2017 in the Romania
Journal of Morphology and Embriology [20].

Conclusions

The peculiarity of this case is represented by the fact that there were no clinical, paraclinical or
imagistic (sonographic) indications that the ovarian masses would in fact be malignant, as the
ROMA SCORE was negative and the MRI did not point out any abnormal characteristics of the
ovarian cysts.

REFERENCES

1. National Cancer Institute. (February 20, 2018). Ovarian Epithelial, Fallopian Tube, And Primary Peritoneal
Cancer Treatment (PDQ)-Patient Version. Retrieved from
https://www.cancer.gov/types/ovarian/patient/ovarian-epithelial-treatment-pdq
2. Ebell, M.H., Culp, M,B.,& Radke, T.J .(2016). A Systematic Review of Symptoms for the Diagnosis of
Ovarian Cancer. American journal of preventive medicine. 50 (3): pp. 384-94.
doi:10.1016/j.amepre.2015.09.023. PMID 26541098.
3. Ruddon, R. W. (2007). Cancer biology (4th ed.). Oxford: Oxford University Press. p. 223. ISBN
9780195175431.
4. Marcu, M.L., Neacsu, A., Stoica, C., Bacalbasa, N., Cotolenco, A., &Radu, E. (2017). Clinical and
pathological features of splenic metastasis from cervical squamous cell carcinoma. Rom J Morphol
Embryol, 58(4): pp. 1157-1164 ISSN (print) 1220-0522 ISSN (online) 2066-8279.
5. Jayson, G.C., Kohn, E.C., Kitchener, H.C., &Ledermann, J.A.(2014). Ovarian cancer. Lancet. 384(9951):
pp. 1376-88. doi:10.1016/S0140-6736(13)62146-7.
6. Piek, J.M., van Diest, P.J., &Verheijen, R.H. (2008). Ovarian carcinogenesis: an alternative hypothesis.
Adv. Exp. Med. Biol. Advances in Experimental Medicine and Biology. 622:79-87. doi:10.1007/978-0-387-
68969-2_7.
7. Häggström, M. (2014). Medical gallery of Mikael Häggström 2014. WikiJournal of Medicine
1(2).DOI:10.15347/wjm/2014.008. ISSN 2002-4436. Public Domain.
8. Gizzo, S., Noventa, M., Quaranta, M., Vitagliano, A., Saccardi, C., Litta, P., & Antona, D. (2017). A novel
hysteroscopic approach for ovarian cancer screening/early diagnosis. Oncology Letters, 13(2), pp. 549-553.
http://doi.org/10.3892/ol.2016.
9. Montagnana, M., Danese, E., Ruzzenente, O., et al., (2011). The ROMA (Risk of Ovarian Malignancy
Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it
really useful?. Clinical Chemistry and Laboratory Medicine, 49(3), pp. 521-525. Retrieved 8 Jun. 2018,
from doi:10.1515/CCLM.2011.075
10. Cancer research UK. (April 27, 2016). Types of ovarian cancer. Retrieved from
http://www.cancerresearchuk.org/about-cancer/ovarian-cancer/types.
11. Cancer research UK. (April 6, 2016). Treatment decisions. Retrieved from
http://www.cancerresearchuk.org/about-cancer/ovarian-cancer/treatment/treatment-decisions
12. Jayson, G.C., Kohn, E.C., Kitchener, H.C., &Ledermann, J.A. (2014). Ovarian cancer. Lancet. 384(9951):
pp. 1376-88. doi:10.1016/S0140-6736(13)62146-7. PMID 24767708.
13. Seiden, M.V. (2012). Gynecologic Malignancies. In Longo DL, Kasper DL, Jameson JL, Fauci AS, Hauser
SL, Loscalzo J. Harrison’s Principles of Internal Medicine (18th ed.). McGraw-Hill. ISBN 978-0-07-
174889-6.
14. Leffers, N., Daemen, T., Helfrich, W., Boezen, H.M., Cohlen, B.J., Melief, C.J., & Nijman, H.W. (2014).
Antigen-specific active immunotherapy for ovarian cancer. The Cochrane Database of Systematic Reviews.
9:CD007287. doi:10.1002/14651858.

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15. Moga, M.A., Dimienescu, O.G., Arvătescu, C.A., Ifteni, P., Pleş, L. (2018).Anticancer Activity of Toxins
from Bee and Snake Venom-An Overview on Ovarian Cancer. Molecules. 19; 23(3). pii: E692. doi:
10.3390/molecules23030692.
16. Helpman, L., Ferguson, S.E., Mackean, M., Rana, A., Le, L., Atkinson, M.A., Rogerson, A., &Mackay, H
(2011). Complementary and alternative medicine use among women receiving chemotherapy for ovarian
cancer in 2 patient populations.Int J Gynecol Cancer. 21(3): pp. 587-93. doi:
0.1097/IGC.0b013e31820fa24a.
17. Moga, M.A., Dimienescu, O.G., Arvatescu, C.A., Mironescu, A., Dracea, L., & Ples, L. (2016). The role of
natural polyphenols in the prevention and treatment of cervical cancer-an overview. Molecules. Aug 17;
21(8). pii: E1055. DOI: 10.3390/ molecules 21081055.
18. Ples, L., Sima, R.M., Burnei, A., Albu, D.F., Bujor, M.A., Conci, S., &Teodorescu, V. (2016). The
experience of our Clinic in laparoscopy for adnexal masses and the correlation between ultrasound findings
and pathological results. Rom J Morphol Embryol. 57(4): pp. 1337-1341.
19. Matsushita, H., Watanabe, K., Yokoi, T., Wakatsuki, A. (2014). Unexpected ovarian malignancy following
laparoscopic excision of adnexal masses. Human Reproduction, Volume 29, Issue 9, pp. 1912-1917.
https://doi.org/10.1093/humrep/deu162.
20. Ionescu, C.A., Vladareanu, S., Ples, L., Dimitriu, M.C.T., Furau, G.O., Vladescu, T.C., Calin, A.M., &
Oprescu, N.D (2017). Synchronous bilateral primary ovarian carcinoma-case presentation. ROMANIAN
JOURNAL OF MORPHOLOGY AND EMBRYOLOGY. Volume: 58 Issue: 1, pp. 219-223.

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Hypoechoic Abdominal Mass: Case Report


MOISEI Cristina1, LESNIC Anca1, SIMA Romina-Maria1,2,
BĂLĂLĂU Denisa-Oana1,2
1Clinical Hospital “Sf. John”, “Bucur”Maternity Bucharest, (ROMANIA)
2UMF “Carol Davila”, Bucharest, Bucur Clinic Bucharest, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Introduction
The incidence of fetal tumors has been steadily increasing due to prenatal evaluation and
improvement of imaging techniques. The early detection of a fetal tumor and understanding of its
imaging features are very important for fetal, maternal, and neonatal care. Usually,
ultrasonography is used for the detection and differential diagnosis of fetal tumors, and magnetic
resonance imaging is increasingly being used as a complementary study.

Material and methods


We present the case of a fetal abdominal mass detected at 17 weeks of pregnancy during an
ultrasonography, most likely a liver hemangioma.

Results
We report a case of a supervised pregnancy in which a fetal abdominal mass was first detected
at 17 weeks of pregnancy as a hypoechoic mass 22/14 mm, with thick hyperchoic septa, no
Doppler signal present, located in the right fetal iliac fossa, consequently intestinal anomaly
suspicion arose. At the second trimester ultrasonographic morphologic exam the hypoechoic
mass was located in the right abdominal fetal flank, near the abdominal wall, apparently situated
in the liver, with thick septa, no Doppler signal, half the initial size, and the suspicion shifted to
liver hemangioma. The 3rd semester ultrasonographic morphologic exam showed a hypoechoic
elongated liver mass 24/5 mm, with no other anomalies present. At 37 weeks of pregnancy
another ultrasonography was performed, and the liver mass was reduced to a 20 mm hyperchoic
band, with no other anomalies present. The entire pregnancy was supervised by a qualified obgyn
specialist, and the gravida performed usual blood work (moderate anemia, ABO incompatibility
OI/AII with isoimmunization, titre 1/8), Double Marker test-Kryptor, 2nd and 3rd trimester
morphologic exams, as well as cervical cultures, which came back negative. The gravida had
been diagnosed wit Basedow’s disease 2 years before the pregnacy, and was treated with
propylthiouracil. A female fetus was delivered via caesarean at 39 weeks, 2850 grams, Apgar
score of 9, with normal postpartum development.

Conclusion
The peculiarity of this case is represented by the early detection of the fetal abdominal mass,
the evolution of the mass in size and in echogenicity, and as well as anatomical placement.
Keywords: fetal ultrasonography, hypoechoic abdominal mass, pregnancy, hemangioma

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Background

the prevalence of the majority of congenital tumors has been reported by many studies as 1.7-
13.5 per 100,000 live births, but the rate might be much higher by including the cases of stillborn
and aborted fetuses [1]. The detection of these tumors has increased due to the expansion of better
prenatal care, fetal morphology ultrasound exams (Ultrasound and Color Doppler Ultrasound, as
well as Doppler spectrum analysis) and improvement of imaging techniques [1], [2]. The
diagnosis is usually difficult to make, but resonance imaging (MRI) is increasingly being used as
a complementary study, the challenging problem is deciding which case may be appropriate to
ultrasonography (US) monitoring and may be referred to postnatal surgery [3], [4].
The prognosis of fetal tumor is generally poor, and it depends on the the location and size of
the fetal tumors, as well as the histological type, both the malignant and benign tumors may be
fatal, the latter by causing cardiovascular compromise or airway obstruction due to their size [1].
The genesis of fetal tumors has not been completely elucidated, many authors blame both
genetic and environmental agents (chemical and physical agents) for causing tumorgenesis and
tumor growth, but more studies need to be conducted. Usually, exposure to pesticides and
different types of radiation of the parents before conception, or in the first trimester of pregnancy,
has been known to cause different metabolic changes both in the parents, as well as the fetus,
leading to complex cellular damage [1], [5], [6].
Hepatic tumors comprise approximately 5% of all congenital tumors, both benign and
malignant growths, including hemangioendothelioma, mesenchymal hamartoma, hepatoblastoma,
hepatocellular adenoma, and metastases [1], [7].

Case presentation

We report a case of a supervised pregnancy in which a fetal abdominal mass was first detected
at 17 weeks of pregnancy using ultrasonograpy. The mass was hypoechoic, 22/14 mm, located in
the right fetal iliac fossa, with thick hyperchoic septa, with no Doppler signal present;
consequently intestinal anomaly suspicion arose. At the second trimester ultrasonographic
morphologic exam, the hypoechoic mass was located in the right abdominal fetal flank, near the
abdominal wall, apparently situated in the liver, with thick septa, no Doppler signal, half the
initial size, and the suspicion shifted to liver hemangioma. The 3rd semester ultrasonographic
morphologic exam showed a hypoechoic elongated liver mass 24/5 mm, with no other anomalies
present. At 37 weeks of pregnancy another ultrasonography was performed, and the liver mass
was reduced to a 20 mm hyperchoic band, with no other anomalies present. The entire pregnancy
was supervised by a qualified obgyn specialist, and the gravida performed usual blood work
(which found moderate anemia, ABO incompatibility OI/AII with isoimmunization, titre 1/8),
Double Marker test-Kryptor with normal range results (except a higher than normal risk of
developing fetal growth restriction), 2nd and 3rd trimester morphologic exams, as well as cervical
cultures, which came back negative. The gravida had been diagnosed with Basedow’s disease 2
years before the pregnacy, and was treated successfully with propylthiouracil (PTU). A female
fetus was delivered via caesarean at 39 weeks, 2850 grams, Apgar score of 9, with normal
postpartum development, theindication for caesarean section being acute fetal distress.

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Fig. 1.

The fetus at 13 weeks of gestation (no abdominal mass is observed)

Fig. 2.

The hypoechoic abdominal mass at 32 and 34 weeks of gestation

Discussion

On prenatal ultrasonography, liver hemangiomas usually are presented as well-defined


abdominal masses, ranging in diameter from 1 to 10 cm. The internal structure is in most cases
heterogeneous, with hypoechoic central areas, but both hypo- and hyperechogenicity may be
observed. Color Doppler ultrasonograpy may show vascular flow with low resistive index. The
reported death rate in infantile hepatic hemangioma has been reported as 12%-90%, with
complications including congestive cardiac failure, thrombocytopenia, and intra-abdominal
hemorrhage as a consequence of rupture of the tumor [8].
Mentaining a balanced thyroid function in pregnancy is very important for the developement
of the fetus, recent studies have shown that even subclinical forms of thyroid disfunction can lead
to intrauterine growth restriction (IUGR) and low Apgar score [9]. In our case the patient was
diagnosed 2 years prior to the pregnancy with autoimmune thyroid disease and was treated
successfully with PTU. The Double Marker test-Kryptor performed for our patient showed a
higher than normal risk for IUGR, consequently the patient received a low dose aspirin treatment
until 36 weeks of gestation, the benefit of this treatment being outlined in recent studies [10].
A study from 2016 stressed out the fact that the diagnosis of foetal distress is imprecise and a
surprinsingly poor predictor of foetal outcome leading to a tendency for unnecessary caesarean
sections. But on the contrary, lack of adverse outcome could reflect the fact that usually
physicians make decisions at a precise time, avoiding clinically significant fetal compromise [11].

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Conclusions

The peculiarity of this case is represented by the early detection of the fetal abdominal mass,
the evolution of the mass in size and in echogenicity, as well as anatomical placement.
The initial diagnosis was of a intestinal malformation, followed by liver hemangioma, which
was the most probable diagnosis (the exact and correct diagnosis is obtained by histopathologic
examination of the sample, which was not the case in this situation, because surgery was not
performed). After birth, ultrasonographic exams were performed at 0,6 and 12 months, with no
significant changes observed. The baby had normal somatic and neurological development, and
resonance imaging (MRI) was not performed. The mother recovered well after the procedure, no
immediate and late complications were observed, only treatment with Euthyrox 50 ug a day was
neccessary, after a check up with the endocrinologist. Contraception with birth control pills was
initiated after 6 weeks.

REFERENCES

1. Cho, J. Y., & Lee, Y. H. (2014). Fetal tumors: prenatal ultrasonographic findings and clinical
characteristics. Ultrasonography, 33(4), pp. 240-251. http://doi.org/10.14366/usg.14019.
2. Ples, L., Sima, R. M., Stanescu, A. D.; & Olaru, O. G. (2017). The Importance of a National Congenital
Anomalies Registry – the Role of the Prenatal Diagnosis. Proceeding paper for the 5TH ROMANIAN
CONGRESS OF THE ROMANIAN SOCIETY OF ULTRASOUND IN OBSTETRICS AND
GYNECOLOGY.pp. 505-510.
3. Borsellino, A., Zaccara, A., Nahom, A., Trucchi, A., Aite, L., Giorlandino, C., et al., (2006). False-positive
rate in prenatal diagnosis of surgical anomalies. J Pediatr Surg;41: pp. 826-829.
4. McEwing, R., Hayward, C., & Furness, M. (2003). Foetal cystic abdominal masses. Australas Radiol.; 47:
pp. 101-110.
5. Moga, M.,Ples, L., Bigiu, N.,& Manitiu, I. (2011). An Overview Of The Risk Of Adverse Reproductive
And Developmental Disorders Due To Exposure To Pesticides.Journal Of Environmental Protection And
Ecology. 12(3A), pp. 1311-1319.
6. Comandasu, D.E.,Bratila, E., Stanculescu, E., Carstoiu, M.M., Miricescu, D., Lixandru, D. (2015). Adverse
Fetal Metabolic Phenotyope Programming Induced by Maternal Obesity a New Concept. PROCEEDINGS
OF THE 49TH ANNUAL SCIENTIFIC MEETING OF THE EUROPEAN SOCIETY FOR CLINICAL
INVESTIGATION. Pp. 133-138.
7. Isaacs, H. Jr. (1997). Tumors of the fetus and newborn. Philadelphia, PA: WB Saunders;. pp. 1-38, 244-297.
8. Fishman, S.J., & Mulliken, J.B. (1993). Hemangiomas and vascular malformations of infancy and
childhood. Pediatr Clin North Am. 40: pp. 1177-1200.
9. Saki, F., Dabbaghmanesh, M. H., Ghaemi, S. Z., Forouhari, S., Ranjbar Omrani, G., & Bakhshayeshkaram,
M. (2014). Thyroid Function in Pregnancy and Its Influences on Maternal and Fetal Outcomes. International
Journal of Endocrinology and Metabolism, 12(4), e19378. http://doi.org/10.5812/ijem.19378
10. Stanescu, A.D., Banica, R., Sima, R.M., & Ples, L. (2018). Low dose aspirin for preventing fetal growth
restriction: a randomised trial. J Perinat Med. Retrieved 8 Jun. 2018, from doi:10.1515/jpm-2017-0184.
11. Gangwar, R., & Chaudhary, S. (2016). Caesarean Section for Foetal Distress and Correlation with Perinatal
Outcome. Journal of Obstetrics and Gynaecology of India, 66(Suppl 1), pp. 177-180.
http://doi.org/10.1007/s13224-015-0831-5.

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Management of a Case with Anencephaly

MOZA Andreea1,2, BRISAN Cosmin1, VRINCEANU Luminita3


1 “Pius Brinzeu” Emergency Clinic County Hospital Timisoara, IInd Department of Obstetrics and Gynecology, Timisoara
(ROMANIA)
2 University of Medicine and Pharmacy Victor Babes Timisoara, Department of Functional Sciences, Timisoara (ROMANIA)
3 Medline, Tirgu Jiu (ROMANIA)

Email: [email protected]

Abstract

Anencephaly appears due to lack of closure of the anterior neuropore in the forth gestational
week. We present the case of a 25 years old patient with 20 weeks gestational pregnancy who
presented in the Emergency Department Of Obstetrics with uterine contractions and ruptured
membranes. The ultrasound exam established the diagnosis of anencephaly. No other
morphological abnormalities were evidentiated. Labour started spontaneously and the patient
aborted a female fetus of 260 grams with the one minute Apgar Score of 2 and the 5 and 10
minute Apgar Score of 0. Anencephaly is an unfortunate pathology, due to homogenous fatal
prognosis. The brigth side of this matter is that this condition is easely detected in the first
trimester of pregnancy, when termination of pregnancy implies the lowest risck of complications.
When facing a case with anencephaly, the practitioner should explain the family all the
consequences of continuing a pregnancy with an anencephalic fetus. All women with a prior
pregnancy with anencephaly should start at least 3 months before conception 4 mg of folic acid
per day.
Keywords: anencephaly, neural tube defects, folic acid

Introduction

Anomalies of the central nervous sistem are the most common anomalies found in the fetus. It
includes: neural tube defects, ventriculomegaly, holoprosenchephaly, agenesis of corpus
callosum, intracranial tumors, hidrancephaly and Dandy Walker malformations. Anencephaly,
encephalocele and spina bifida are the most common neural tube defects [1]. Worldwide the
incidence of anencephaly varies from 0.2 in 10.000 births in USA to 124 in 10.000 deaths in
Pakistan [2, 3].
Low serum levels of acid folic were incriminated in the development of anencephaly since
1980, however in Europe the incidence of this malformation is quite high (5 in 10000 birth in
UK, with overall incidence of 9.1 in 10000 births) due to failure of implementing
periconceptional supplementation with folic acid [4].

Case presentation

We present the case of a 25 years old, gesta II, para I, with a 20 weeks pregnancy that
presented in the Emergency Department of Obstetrics for uterine contractions and vaginal
leakage. She had no significant family history. As far as the obstetrical past is concerned, she

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reported a first trimester miscarriage that took place 1 year ago. She had only one antenatal
consult at 5 gestational weeks when intrauterine pregnancy was confirmed, when 5 mg of folic
acid/day was prescribed. She had no history of infection or drug intake during pregnancy. So far
she reported an uneventful pregnancy.
The clinical examination revealed the distended abdomen by the gravid uterus with uterine
fundus two centimeters above the level of the ombillicus. The uterine tonus was normal. Rare
uterine contractions were clinical percepted. Spculum exam identified a closed cervix, however
the pooling sign was present.
Ultrasound examination diagnosed a single intrauterine live fetus in pelvic presentation with
anencephaly, amniotic fluid index in normal range, fundal posterior placenta. No other
morphological abnormalities were evidentiated. The 3D ultrasound confirmed the diagnosis.

Fig. 1. Bidimensional ultrasound appearance of the fetus

Fig. 2. Tridimensional ultrasound aspect of the fetus

The patient was admitted with the diagnosis: 20 weeks pregnancy, single live fetus in pelvic
presentation, ruptured membranes. Imminence of abortion. High risk obstetrical pregnancy:
malformation of the fetus: anenchepahly. Blood test were taken, and cervical swabs were take for
culture. Two grams of Ampicillin two times a day were administered for prophylactic reasons.

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Labour started spontaneously and the patient aborted a female fetus of 260 grams with the one
minute Apgar Score of 2 and the 5 and 10 minute Apgar Score of 0. Both fetus and placenta were
sent to histopathology exam.

Discussions

Anencephaly is a consequence of lack of closure of the anterior neuropore in the forth


gestational week. According to the literature it can be diagnosed on ultrasound as early as 11-12
weeks of gestation. Anencephaly and acrania although associated most of the time are not similar.
Anencephaly refers to absence of cortical tissue and cranial vault, whereas in acrania there the
clavaria is absent but the cortical hemispheres are covered by a thin membrane, the meninges [5,
7]. It is considered that if anacephaly is isolated amniocentesis is not required [8].
When it is not isolated, anencephaly has been asociated with many findings including:
sirenomelia, complete ectopia cordis or craniospinal rachischisis [9, 11]. Also, twin prengnancy
with anencephaly has been reported. If sporadic, the recurrence risk for future pregnancies is 2-
5% [12-14]. Our patient had four years later an uneventful prengnancy. She gave birth to a 3020g
female with one minute Apgar Score of 9. Preconceptual supplementation with folic acid may
reduce the recurrence risk by up to 70%. WHO recommends administrating 400μg/day, 3 months
before conception.

Fig. 3. Macroscopic aspect of the fetus

Common ultrasound features in anencephaly are:


a) absence of cortical tissue above the orbits and absent calvarium, however parts of the
occipital bone and mid brain may be present,
b) “frog eyes” or “mickey mouse” appearance due to bulging orbits and lack of cranial
bone and brain,
c) polyhidramnios may be seen in 15% of cases because of difficulties of swallowing,
d) the crown rump length is less than the expected value.
A 10 years study on pregnancies complicated with anencephaly identified that out of the 53
cases when families decided to continue the pregnancy, in 38% there was in utero demise, most

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of the deaths occurred intrapartum. Despite literature, in this study, in the group of live births
34% were born premature. The mode of delivery was vaginal delivery. The median postnatal
survival time was 51 minutes in this study, and 94% of deaths occurred in the first day [15-17].
Rarely, newborn with anencephaly live more than expected period, because of less severe
imvolvement of the brain stem. Their autonomous system works, however they can’t fell pain and
cannot interact with the external environment.

Conclusions

Anencephaly is an unfortunate pathology, due to homogenous fatal prognosis. The brigth side
of this matter is that this condition is easely detected in the first trimester of pregnancy, when
termination of pregnancy implies the lowest risck of complications. When facing a case with
anencephaly, the practitioner should explain the family all the consequences of continuing a
pregnancy with an anencephalic fetus. All women with a prior pregnancy with anencephaly
should start at least 3 months before conception 4 mg of folic acid per day.

REFERENCES

1. Copp, A.J., Stanier, P., Greene, N.D., (2013). Neural tube defects: Recent advances, unsolved questions, and
controversies. Lancet Neurology, 12(8), pp: 799-810.
2. Persad, V.L., Van Den Hof, M.C., Dube, J.M., Zimmer, P, (2002). Incidence of open neural tube defects in
Nova Scotia after folic acid fortification. CMAJ, 167, pp. 241-245.
3. Zaganjor, I., Sekkarie, A., Tsang, B.L., (2016). Describing the Prevalence of Neural Tube Defects
Worldwide: A Systematic Literature Review. PLoS One, 11(4), pp. e0151586.
4. Khoshnood, A., Loane, M., de Walle, H., Arriola, L., (2015). Long term trends in prevalence of neural tube
defects in Europe: population based study. BMJ, 351, pp. h5949.
5. Dudar, J.C., (2010). Qualitative and quantitative diagnosis of lethal cranial neural tube defects from the fetal
and neonatal human skeleton, with a case study involving taphonomically altered remains. Journal of
Forensic Sciences, 55(4), pp. 877-883.
6. Bernad, S.I., Bosioc, A., Bernad, E.S., Craina, M.L., (2014). Comparison between experimentally measured
flow patterns for straight and helical type graft, Bio-Medical Materials and Engineering, Volume 24(1), pp.
853-860.
7. Bernad, E.S., Bernad, S.I., Craina, M.L., (2014). Hemodynamic parameters measurements to assess severity
of serial lesions in patient specific right coronary artery, Bio-Medical Materials and Engineering, 24(1), pp.
323-334.
8. Sepulveda,W., Corral, E., Ayala, C., (2004). Chromosomal abnormalities in fetuses with open neural tube
defects: prenatal identification with ultrasound. Ultrasound Obstet Gynecol, 23, pp: 352-356.
9. Theofanakis, C., Theodora, M., Sindos, M., (2017). Prenatal diagnosis of sirenomelia with anencephaly and
craniorachischisis totalis: A case report study Medicine (Baltimore), 96(50), pp. e9020.
10. Bernad, E.S., Frantescu, A., Bernad, S.I., Vernic, C., (1998). WEB-MO – A Computer Aided Learnig on
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Amsterdam, pp. 745-747.
11. Totorean, A.F., Bosioc, A.I., Bernad, S.I., Susan-Resiga, R., (2014). Identification and visualization of the
vortices in by-pass graft flow, Proceedings of the Romanian Academy, Series A-Mathematics Physics
Technical Sciences Informational Science, 15(1), pp. 52-59.
12. Bianchi, D.W., Crombleholme, T.M., D’Alton, M.E., Malone, F.D., (2010). Management of fetal conditions
diagnosed by sonography. Fetology: Diagnosis and Management of the Fetal Patient, Second Edition.
McGraw-Hill Companies; pp. 77-82.
13. Totorean, A.F., Hudrea, C.I., Bosioc, A.I., Bernad, S.I., (2017). Flow field evolution in stented versus
stenosed coronary artery, Proceedings of the Romanian Academy, Series A-Mathematics Physics Technical
Sciences Informational Science, 18(3), pp. 248-255.

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14. Bernad, E.S., Craina, M., Tudor, A., Bernad, S.I., (2012). Perinatal outcome associated with nuchal
umbilical cord, Clinical and Experimental Obstetrics & Gynecology, 39(4), pp. 494-497.
15. Machado, I.N., Martinez, S.D., Barini R., (2012). Anencephaly: Do the Pregnancy and Maternal
Characteristics Impact the Pregnancy Outcome? ISRN Obstet Gynecol, pp. 127490.
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vortices in a curved pipe. 11th International Conference of Numerical Analysis and Applied Mathematics,
2013, ICNAAM 2013, 21 – 27 September 2013, Rhodes, Greece. AIP Conference Proceedings, vol. 1558,
pp. 172-175.

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Diagnosis and Management in Placenta Praevia Accreta

MOZA Andreea1,2, BERNAD Elena1,3, PANTEA Stelian4


1 “Pius Brinzeu” Emergency Clinic County Hospital Timisoara, IInd Department of Obstetrics and Gynecology, Timisoara
(ROMANIA)
2 University of Medicine and Pharmacy Victor Babes Timisoara, Department of Functional Sciences, Timisoara (ROMANIA)
3 The University of Medicine and Pharmacy Victor Babes Timisoara, Department of Obstetrics and Gynecology (ROMANIA)
4 The University of Medicine and Pharmacy Victor Babes Timisoara, Department of Surgery (ROMANIA)

Email: [email protected]

Abstract

Introduction
The pathology of the placenta can be investigated using ultrasound or magnetic resonance
imaging which can sometimes offer more details. Cases that associate adherent placenta imply a
careful attention in order to lower life threatening complications. The objective of this paper is to
present a study of the management of a case with placenta praevia and accreta.

Case presentation
The article is a case presentation of a secundipara with a 29 weeks pregnancy that was
admitted for uterine contractions and metrorrhagia. The ultrasound identified central placenta
praevia, however on some areas invasion of the placenta in the myometrium was suspected.
Despite tocolysis, the symptoms persisted and the mother became hemodynamically instable
so emergency Caesarean section was performed with transverse fundal histerotomy and
extraction of the newborn. Decollation of the placenta failed. Hysteroraphy was performed for
haemostasis followed by interanexial hysterectomy. Although the end result is still hysterectomy,
maternal blood loss was markedly reduced compared to the cases where transverse incision of the
segment was performed. The mother and the newborn had a faster recovery.

Conclusions/Discussion
There are many techniques that have been reported in the last ten years each with its advantage
and drawbacks, although none of them are standard. What is clear is that transplacental incision,
in case of suspicion of invasive placenta is no longer an option and when dealing with a case of
with this type of pathology is mandatory to have a mix surgical team.
Keywords: placenta praevia, adherent placenta, bleeding in pregnancy

Introduction

Invasive placenta is a life threatening condition in which a part of the placenta or the whole
placenta grows into the walls of the uterus leading to failure of detachment during delivery
consequently severe bleeding. In relation to the depth of placental invasion in the myometrium
there are 3 types of placental invasion: placenta accreta, increta and percreta [1].
Ultrasound has an important role in diagnosing adherent placenta [1]. Magnetic resonance
imaging can sometimes offer more details [2, 3]. The management of cases with adherent

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placenta praevia is a current topic nowadays. Despite optimal antenatal care, surgical treatment
can have life threatening consequences [4, 5]. The objective of this paper is to provide different
possibilities of diagnosis and recent surgical techniques in cases of invasive placenta.

Case presentation

We present the case of a 31 years secundipara with a 29 weeks pregnancy that was admitted in
our clinic with uterine contraction and metrorrhagia. She had experience metrorrhagia since the
beginning of the pregnancy, and in the late second trimester she was diagnosed with central
placenta Praevia. Her obstetrical past includes one Caesarean section (3 years ago), and 2
abortions.
At the admission she was afebrile, blood pressure and pulse in normal range. The local
inspection identified a gravid uterus, with a fundal height of 29 cm, normal uterine tonus, uterine
contractions at 7 minutes that lasted 30 seconds, active fetal movements, fetal heart rate within
normal range. The vaginal exam was not done, however the speculum exam identified active
minimal to moderate metrorrhagia. At the admission, the patient had an ultrasound that
evidentiated a live fetus with biometry that corresponded to 28 weeks and 4 days. The
morphology of the fetus was in normal range. On ultrasound, placenta Praevia was confirmed,
however on a limited area the aspect pleaded for placental invasion of the myometrium. Blood
tests were taken. The patient started the prophylaxis of hyaline membrane disease with
corticosteroids (4 doses of 6 mg of Dexamethasone) in accordance with the National Guidelines.

Fig. 1. The appearance of the uterus after histeroraphy

Also tocolysis was initiated with Hexoprenalium as per National Protocole of Tocolysis, and
the mother and the fetus were permanently monitored. Despite all efforts, the uterine contractions
did not remise and metrorrhagia persisted, moreover the general state of the patient worsened. A
new set of blood test were taken that showed a decrease of the hemoglobin with 2 mg/dl since
admission. Blood pressure was 75/33 mmHg at the right hand and 100/60 mmHg at the left hand.
Pulse was 130 bpm.
The protocole for placenta Praevia was followed and a complex interdisciplinary team
(obstetrician, general surgeon, neonatologist and anesthesiologist) was formed that opted for

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emergent delivery of the baby through Caesarean section. The indication was: placenta Praevia
and risk of uterine rupture at a gravida in labor. A transverse hysterectomy was performed at the
level of the anterior uterine wall between the uterine horns, and a male newborn of 1360g was
extracted. The one minute Apgar Score was 4. Decollation of the placenta was tempted, however
it proved to be adherent to the myometrium. Soon the inferior segment of the uterus developed a
barrel shape. In order to stabilize the hemostastatic histeroraphy was performed (Figure 1),
followed by total hysterectomy. The adnexa were left in place.
The patient’s and the newborn’s evolution was favourable; she was discharged 7 days post-
surgery. The newborn’s admission was uneventful; he was discharged 6 weeks later, when he
gained the proper weight.

Discussion

Predisposing factors for invasive placenta are advanced maternal age, multiparity, smoking,
prior uterine curettage, uterine irradiation, endometrial ablation, Asherman syndrome, manual
delivery of the placenta, postpartum endometritis, hysteroscopic surgery, endometrial ablation,
and uterine artery embolization [6-8]. However, Fitzpatrick et al., (2012) concluded that previous
caesarean-section in women with previous uterine surgery; in-vitro fertilization pregnancy and
placenta praevia diagnosed antepartum increased the risk independently [9]. Some suggest the
caesarean section technique can be a factor in determining the appearance of adherent placenta
(continuous locked suture of the caesarean incision may be associated with thinner residual
myometrium) [10], however until present time there is no clear data that can confirm it.
In sporadic cases, adherent placenta developed in nuliparous women who had uterine
anomalies such as bicornuate uterus, adenomyosis, submucous fibroids, and myotonic dystrophy
[11].
Due to close association of invasive placenta to previous caesarean section and placenta
praevia/placenta covering the uterine scar, ROCG (Royal College of Obstetrics and
Gynaecology) recommend that all women who fit in this category should be managed as if they
have placenta acreta [11, 12]. Due to the continuous increase of the rate of invasive placenta, and
the potential catastrophic complications to the mother and the newborn, new techniques have
been imagined in order to lower the complication rates as well as to preserve the mother’s
fertility.
All guidelines advise that a case when invasive placenta is suspected should be managed by a
complex team formed of: gynaecologist, urologist, general surgeon, and/or vascular surgeon [13].
Recent literature [14] advises against transplacental incision because usually there is profuse
bleeding from the placental blood, the placenta can’t visualize and it is associated to fetal
anaemia. Also, in case of lower uterine incision hysterectomy is more difficult especially when
the bleeding cannot be controlled thus intraoperative complications (bladder injuries) are more
likely to happen [15].
ROCG recommends that the incision should be made at least 2 cm away from the placental
margin in case of invasive placenta is suspected [4, 16]. In his study Polat (2017) removes the
placenta with the attached myometrium, practicing hysteroplasty. The approach describes two
techniques: the single segmental ellipsoid incision with extraction of the newborn and ulterior
removal of the myometrium with the adherent placenta. If wide adherent placenta is suspected,
the author recommends extraction of the newborn through a transverse fundal incision with
ulterior removal of the placenta and the attached myometrium (double incision technique) [17].

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Even during metroplasty, the severe bleeding can obscure the view of the surgeon so Kurtser
proposes temporary ceasing the blood supply of the uterus through balloon occlusion of the
common iliac arteries [18]. Other studies opted for single transverse incision at the level of the
uterine fundus with extraction of the fetus, followed by manual extraction of the placenta. As
complementary surgical steps, Kotsuji recommends dissection the bladder from the anterior wall
of the uterus and placing a rubber tourniquet around the cervix in order to control bleeding. This
technique helps in direct observation of the placenta. Also with the aid of the tourniquet, bleeding
from the placental bed can be controlled and sutures can be made in order to achieve haemostasis.
If there are macroscopic signs of uterine invasion, the author recommends leaving the placenta
in situ with ulterior hysterectomy [19].
When fertility is mandatory and if there is no bleeding from the placenta, conservative
management can be taken into consideration. This includes bilateral embolization of the uterine
arteries, parenteral methotrexate or both. In all cases when methotrexate was used, the studies
recommend leaving the placenta in situ and due to the great risk of bleeding and infection, one
must start broad spectrum antibiotics and uterotonic drugs. Also, frequent blood test should be
made in order to exclude any complications. Dinamic decrease of serum βhCG and vascular
indices of the placenta can predict the favourable evolution of the case [20]. In cases when
Metrotrexate was administered the expulsion of the placenta varied from 7 days to 6 months [21].
In respect with uterine artery embolization, there are many techniques described in the
literature: prophylactic embolization of the left uterine artery followed by caesarean section,
removal of the placenta and embolization of the right uterine artery, or embolization of both
uterine arteries after manual extraction of the placenta (curative embolization) [22]. Some cases
report successful results when the placenta was left in utero, embolization of the uterine arteries
was performed and methotrexate administration [23-26].

Conclusions

There are many techniques that have been reported in the last ten years each with its advantage
and drawbacks, although none of them are standard. What is clear is that transplacental incision,
in case of suspicion of invasive placenta is no longer an option and when dealing with a case of
with this type of pathology is mandatory to have a mix surgical team.

REFERENCES

1. Oyelese Y, Smulian J.C., (2006). Placenta praevia, placenta accreta, and vasa praevia. Obstet Gynecol 107,
pp. 927-41.
2. Nunes, C., Carvalho, M.R., Araújo, C., et al., (2014). Diagnosis of placenta accreta by ultrasonography: a
“gold standard”? Acta Obstet Ginecol Port, 8(2), pp. 136-140.
3. Bernad, S.I., Bernad, E.S., Barbat, T., Barbu, D., Albulescu, V., (2010). Assessment of the placental blood
flow in the developing and growth-restricted fetus, Proceedings of the 22th European Congress of Perinatal
Medicine, Granada, Spain, May 26-29, pp. 127-130.
4. Placenta Praevia, Placenta Praevia Accreta and Vasa Praevia: Diagnosis and Management Green-top
Guideline No. 27 (2011).
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Pantea, S., (2015). Choriocarcinoma developed in a tubal pregnancy – a case report, Rom J Morphol
Embryol, 56(2 Suppl), pp. 871-874.
6. Wu, S., Kocherginsky, M., Hibbard, J.U., (2005). Abnormal placentation: twenty-year analysis. Am J
Obstet Gynecol, 192, pp. 1458-61.

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7. Petre, I., Barjica, D., Duta, C., Boglut, A., Bernad, E., Craina, M., Bolintineanu, S., Pantea, S., Radu, D.,
Ionita, I., (2016). Sclerotherapy for Varicose Veins, Materiale Plastice, 53(4), pp. 765-766.
8. Ionita, I., Grigorita, L., Miloicov, C.B., Petre, I., Bernad, E., Craina, M., Diaconu, M., Citu, C., Radu, F.,
Oros, D., Boglut, A., Furau, G., Enatescu, V., (2016). The Role of Thrombophilia in Pregnancy, Revista de
Chimie, 67(12), pp. 2643-2647.
9. Fitzpatrick, K.E., Sellers, S., Spark. P., (2012). Incidence and Risk Factors for Placenta
Accreta/Increta/Percreta in the UK: A National Case-Control Study, Plos One, 7(12), pp. 528-93.
10. Jurkovic J.E.D., (2016). Long-term complications after caesarean section. In: Jauniaux E, Grobman W, eds.
A textbook of caesarean section. Oxford: Oxford University Press, pp. 129-144.
11. Bhide J.E.A., Burton, G.J., (2017). Pathophysiology of accreta. In: Silver R, ed. Placenta accreta syndrome.
Portland: CRC Press, pp. 13-28.
12. Enatescu, V.R., Enatescu, I., Craina, M., Gluhovschi, A., Papava, I., Romosan, R., Marian, C., Oprea, A.,
Bernad, E., (2014). State and trait anxiety as a psychopathological phenomenon correlated with postpartum
depression in a Romanian sample: a pilot study, Journal of Psychosomatic Obstetrics and Gynecology,
35(2), pp. 55-61.
13. Wu, S., Kocherginsky, M., Hibbard, J.U., (2005). Abnormal placentation: twenty-year analysis. Am J
Obstet Gynecol, 192, pp. 1458-61.
14. Comstock, C.H., Love, J.J. Jr, Bronsteen, R.A., et al., (2004). Sonographic detection of placenta accreta in
the second and third trimesters of pregnancy. Am J Obstet Gynecol, 190, pp. 1135-40.
15. Bernad, E.S., Craina, M., Tudor, A., Bernad, S.I., (2012). Perinatal outcome associated with nuchal
umbilical cord, Clinical and Experimental Obstetrics & Gynecology, 39(4), pp. 494-497.
16. Ionita, I., Grigorita, L., Miloicov, C.B., Petre, I., Bernad, E., Craina, M., Diaconu, M., Citu, C., Radu, F.,
Oros, D., Boglut, A., Furau, G., Enatescu, V., (2016). The Role of Thrombophilia in Pregnancy, Revista de
Chimie, 67(12), pp. 2643-2647.
17. Polat, I., Yücel, B., Gedikbasi A., et al., (2017). The effectiveness of double incision technique in uterus
preserving surgery for placenta percreta. MC Pregnancy and Childbirth An international Journal of
Obstetrics and Gynecology, 17, pp. 129-132.
18. Kurtser, M.A., Breslav, I.Yu., Latyshkevich, O.A., et al., (2017). Temporary balloon occlusion of the
common iliac arteries in patients with post-cesarean uterine scar and placenta accreta: Advantages and
possible complications. Scientific and Practical Journal Obstetrics and Gynecology, 12, pp. 70-75.
19. Kotsuji, F., Nishijima, K., Kurokawa, T., Yoshida, Y., (2013). Transverse uterine fundal incision for
placenta praevia with accreta, involving the entire anterior uterine wall: a case series. An International
Journal of Obstetrics & Gynaecology, 120(9), pp. 1144-1149.
20. Lin, K., Qin, J., Xu, K., Hu, W., Lin, J., (2015). Methotrexate management for placenta accreta: a
prospective study. Arch Gynecol Obstet, 291(6), pp. 1259-64.
21. Tong, S.Y., Tay, K.H., Kwek, Y.C., (2008). Conservative management of placenta accreta: Review of three
cases. Singapore Med, J 49, pp: 156-9.
22. Diop, A.N., Chabrot, P., Bertrand, A., Constantin, J.M., et al., (2010). Placenta accreta: management with
uterine artery embolization in 17 cases. J Vasc Interv Radiol, 21(5), pp. 644-8.
23. Achou, A.N.R., Ashram, M., Mokbel M., (2017). Uterine artery embolization for management of placenta
accreta, a single-center experience and literature review. The Arab Journal of Interventional Radiology,
1(1), pp. 37-42.
24. Bernad, S.I., Totorean, A.F., Vekas, L., (2016). Particles deposition induced by the magnetic field in the
coronary bypass graft model, Journal of Magnetism and Magnetic Materials, 401, pp: 269-286.
25. Totorean, A.F., Bernad, S.I., Susan-Resiga, R.F., (2016). Fluid dynamics in helical geometries with
applications for by-pass grafts, Applied Mathematics and Computation, 272 part 3, pp: 604-613.
26. Totorean, A.F., Hudrea, C.I., Bosioc, A.I., Bernad, S.I., (2017). Flow field evolution in stented versus
stenosed coronary artery, Proceedings of the Romanian Academy, Series A-Mathematics Physics Technical
Sciences Informational Science, 18(3), pp: 248-255.

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Sonographic Evaluation of the Umbilical Cord Vessel Number

BERNAD Elena1, MOZA Andreea2


1The University of Medicine and Pharmacy Victor Babes Timisoara (ROMANIA)
2“Pius Brinzeu” Emergency Clinic County Hospital Timisoara, IInd Department of Obstetrics and Gynecology, Timisoara
(ROMANIA)
Emails: [email protected], [email protected]

Abstract

A single umbilical artery is associated with congenital anomalies and increased perinatal
morbidity and mortality. Umbilical cord accident (UCA) is a type of Sudden antenatal death
syndrome SADS which can be managed with established obstetrical practices and can be detected
with ultrasound. This study was conducted in the Department of Obstetrics and Gynecology of
the County Emergency Hospital Timisoara, Romania. After deliveries, the placenta was checked
clinically and measured (insertion of the umbilical cord, weight of placenta and length of the
umbilical cord). Presence of the single umbilical artery (SUA) is frequent in twins, diabetic
pregnancies, and in association with long cords and small placentas. Screening by Doppler
velocimetry of the umbilical cord length, cord artery pairs, and umbilical cord helical types
suggested some differences which may be essential to fetus development.
Keywords: ultrasound, single umbilical artery, umbilical cord accident

Introduction

A single umbilical artery is associated with congenital anomalies and increased perinatal
morbidity and mortality. Several abnormalities of the umbilical cord are associated with perinatal
morbidity and mortality [1, 2].
The three vessels of the umbilical cord form a helix (Figure 1). Nine weeks’ gestation well
establishes this helix, and coiling keeps pace with cord growth. In an umbilical cord of regular
length, approximately 11 coils (turns of 360º) are found [3].
The goal of the obstetrics is to successfully deliver an infant and also to do so without an
outcome. Sudden antenatal death syndrome SADS is an essential national policy issue. Umbilical
cord accident (UCA) is a type of SADS which can be managed with established obstetrical
practices and can be detected with ultrasound [4, 5].
Umbilical cords of normal and abnormal fetuses present essential biochemical differences [6].
In the literature, the human umbilical cord has a reported with an average diameter of 2.5 cm.
The ultrasound average vein diameter reported is 8mm with an average artery diameter of 4
mm at term [7].

Patients and method

This study was conducted in the Department of Obstetrics and Gynecology of the County
Emergency Hospital Timisoara, Romania.

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Fig. 1. Three-vascular umbilical cord: a) longitudinal ultrasound images, b) sectional ultrasound


images; c) and d) gross digital images of the umbilical cord vessels distributions

After deliveries, the placenta was checked clinically and measured (insertion of the umbilical
cord, weight of placenta and length of the umbilical cord). As part of an examination of the
placentas, all investigated placentas are photographed, and the umbilical cord coils are counted
and recorded. A diagnosis of the normocoiled, hypocoiled or hypercoiled umbilical cord was
made based on the gross sample measurements indicating that the umbilical cord had more than
three coils per 10 cm segment or less than three coils per 10 cm. The gross digital images of all
investigated placentas were collected and examined. Placenta, where the umbilical cord was too
short for analysis (<10 cm), were excluded.

Results

Presence of the single umbilical artery (SUA) has been reported with a variety of outcomes [8-
12]. SUA is associated with disturbance of fetal blood flow, and there are two forms: a helical
form, and a straight form (Figure 2). SUA is common in twins, diabetic pregnancies, in
association with long cords and small placentas. Finding an SUA on ultrasound screening should
place the pregnancy on alert for associated developments [12].

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Fig. 2. Single umbilical artery: a) sonographic image; b)


gross image after delivery

There are differences in umbilical cord shape which may predispose the fetus to UCA. A
screening by Doppler velocimetry of the umbilical cord length, cord artery pairs, and umbilical
cord helical types suggested some differences which may be essential to fetus development.

Conclusions

Different characteristics in umbilical cord structure may predispose a given fetus to UCA.
Umbilical cord properties like diameter, length, circumference, Wharton's jelly content, may
be determined genetically, but umbilical cord development and growth may depend on the sex of
the fetus. Umbilical cord compression has varying effects on fetal physiology depending on the
degree of the stimulus and duration of the interruption of blood flow. Gestational age of the fetus
also determines the response to umbilical blood flow changes.

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Acknowledgment
For Elena Bernad this work was supported by the grant of the Romanian National Authority
for Scientific Research and Innovation, CNCS/CCCDI-UEFISCDI, project number PN-III-P2-
2.1-PED-2016-0293, within PNCDI III.

REFERENCES

1. Kouvalainen, K., Pynnonen, A.l., Makarainen, M., Peltonen, T., (1971). Weights of placenta membranes
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2. Moinian, M., Meyer, W.W., Lind, J., (1969). Diameters of umbilical vessels and the weight of the cord in
relation to clamping time. Am J Obstet Gynecol 105, pp: 604-611.
3. Oudesluys-Murphy, H.M., (1990). The Human Umbilical Cord and its Separation. PediaBoek: Oud-
Beijerland. 1990.
4. Bjoro, K. Jr., (1983). Vascular anomalies of the umbilical cord. Obstetrics implications. Early Hum Dev, 2,
pp: 119-27.
5. Bernad, S.I., Totorean, A., Bosioc, A., Stanciu, R., Bernad, E.S. (2013). Numerical investigation of Dean
vortices in a curved pipe. 11th International Conference of Numerical Analysis and Applied Mathematics,
2013, ICNAAM 2013, 21-27 September 2013, Rhodes, Greece. AIP Conference Proceedings, vol. 1558, pp:
172-175.
6. Franc, S., Rousseau, J.C., Garrone, R., van der Rest, M., Moradi-Ameli, M., (1998). Microfibrillar
Composition of Umbilical Cord Matrix: Characterization of Fibtillin, Collagen VI, and intact Collagen V.
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7. Weissman, A., Jakobi, P., Bronshtien, M., Goldstein, I., (1994). Sonographic measurement of the umbilical
cord and vessels during normal pregnancies. J Ultrasound Med, 13, pp: 11-14.
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Association of single umbilical artery with congenital malformations of vascular etiology. Pediatr Dev
Pathol, 6, pp: 487-93.
9. Bernad, S.I., Totorean, A.F., Vekas, L., (2016). Particles deposition induced by the magnetic field in the
coronary bypass graft model, Journal of Magnetism and Magnetic Materials, 401, pp: 269-286.
10. Totorean, A.F., Bernad, S.I., Susan-Resiga, R.F., (2016). Fluid dynamics in helical geometries with
applications for by-pass grafts, Applied Mathematics and Computation, 272 part 3, pp: 604-613.
11. Totorean, A.F., Bosioc A.I., Bernad, S.I., Susan-Resiga R., (2015). Critical flow regions in the coronary
bypass graft anastomosis, Proceedings of the Romanian Academy, Series A, 16(2), pp: 201-208.
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outcome following fetal single umbilical artery diagnosis. J Matern Fetal Med 10, pp: 59-63.

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Umbilical Cord Sonographic and Numerical Investigation

BERNAD I. Sandor1, MOZA Andreea2, BERNAD Elena3


1 Romanian Academy – Timişoara Branch, Centre for Fundamental and Advanced Technical Research (ROMANIA)
2 “Pius Brinzeu2 Emergency Clinic County Hospital Timisoara, IInd Department of Obstetrics and Gynecology, Timisoara
(ROMANIA)
3 The University of Medicine and Pharmacy Victor Babes Timisoara (ROMANIA)

Emails: [email protected], [email protected], [email protected]

Abstract

Sonography was used to visualize and measure the umbilical cord coiling during the second
trimester of pregnancies. In the present study, the adverse pregnancy outcome was associated
with both hypo- and hyper-coiled umbilical cords. The primary effort is to provide a
comprehensive understanding of the characteristics of the flow fields through the umbilical cord.
In this work, the flow fields in the umbilical cord vascularization (umbilical artery) was
numerically studied in detail for the patient-specific umbilical cord. Hyper-coiled cords showed
slower blood flow, comparatively with a normo-coiled cord. This may lead to the insufficient
blood supply to the placenta, pregnancy complications like IUGR.
Keywords: umbilical cord insertion, risk factor, ultrasound, placenta

Introduction

Abnormality of the umbilical cord coiling induces several perinatal outcomes. In literature, the
hypercoiled umbilical cord is associated with the decreased pressure of the umbilical vein, and
also place the fetus at higher risk for a cord accident [1]. In the other study, evaluation of the
umbilical cord undulating pattern, describe that the wider spreading of coils had less thrombosis
than the linked patterns of coiling [2].
The undercoiled umbilical cord (or straight cord) can increase the incidence of intrauterine
growth restriction, fetal anomalies, preterm labor [3, 4].
Elevated wall shear stresses or significant umbilical cord compression can produce thrombosis
in fetal vessels, stasis of fetal blood flow, and ultimately fetal death. Also, the literature describes
that hypercoiled umbilical cord is more highly associated with placental histologic features of
chronic umbilical cord obstruction and stillbirth [5-7]. A computational model to study the effects
of umbilical cord coiling on arterial blood flow, and numerical analysis of the blood flow showed
that the number of coils has an effect on wall shear stresses, but that more extensive spreading of
the coils reduced wall shear stresses (corresponding to the normocoiled umbilical cord) [8].

Patients and method

The purpose of the present study is to evaluate the flow pattern and flow characteristics for
hypo- and normocoiled umbilical cord.
This observational study was conducted in the Department of Obstetrics and Gynecology of
the County Emergency Hospital Timisoara, Romania. The study used placenta obtained from two

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normal pregnancy of vaginal delivery (ages: P1=29 and P2=33 years old, parity 1 and 2
respectively, and gestation weeks are 37 and 39 weeks). Birth weight 2920g and 3150g.

Fig. 1. Different type of umbilical cord: a) sonographic image of the hypocoiled umbilical cord; c)
sonographic evaluation of the normocoiled umbilical cord. b) and d) gross examination at the delivery
of the hypocoiled and normocoiled umbilical cord

Ultrasound examination of the umbilical cord structure and umbilical cord evolution before
labor is the practices to evaluate and predict the perinatal outcomes [4, 5]. Ultrasonic examination
of the umbilical cord was performed in the late third trimester because of a relative lack of
amniotic fluid compared to the fetal size. Gestational age was defined based on the date of the
last menstrual period, and by ultrasound, if there was a disparity of more than three days on the
first-trimester measurement or 7 days on the second-trimester measurement. After deliveries, the
placenta was checked clinically and measured (insertion of the umbilical cord, weight of placenta
and length of the umbilical cord).

Results

During the numerical simulation the blood is assumed to be incompressible, and Newtonian,
with a dynamic viscosity (μ) of 0.00408 Pa and a density (ρ) of 1050 kg/m3. Several recent works
investigated the effect of blood rheology assumptions on the axial velocity profiles in bifurcation
models founding a satisfactory agreement between the non-Newtonian viscosity and Newtonian
viscosity flow based on a characteristic shear rate [9, 10].

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Fig. 2. Numerical reconstruction of the umbilical cord: a) normocoiled; b) hypocoiled

The primary effort is to provide a comprehensive understanding of the characteristics of the


flow fields through the umbilical cord. In this work, the flow fields in the umbilical cord
vascularization (umbilical artery) was numerically studied in detail for the patient-specific
umbilical cord (Figure 2). The streamline reveals the dynamics of the flow, velocity, pressure and
wall shear stress (WSS) fields (Figures 3).

Fig. 3. Numerical reconstruction of the umbilical cord: a) normocoiled; b) hypocoiled

Pressure distribution is uniform along each type of cord and shows a vital variation depending
on the numbers of the coil.
Hyper-coiled cords showed slower blood flow, comparatively with a normo-coiled cord. This
may lead to the insufficient blood supply to the placenta, pregnancy complications like IUGR.
This is in line with the finding of IUGR fetuses with hyper-coiling and altered venous system
hemodynamics to present a higher risk of hypoxia.

Conclusions

The hemodynamic analysis demonstrated that energy losses due to pressure gradients in the
umbilical cord are dependent on the umbilical cord type (normo- or hypo-coiled umbilical cord).
The clinical application of simulation-based medical planning techniques is a fundamentally
new approach to treatment planning. In the case of placenta disease, these methods could enable
physicians to develop the patient-specific treatment plans to improve blood flow.

Acknowledgment
For S.I. Bernad this work was partially supported by the CFATR/LHC 2016-2020 research
programme. For Elena Bernad this work was supported by the grant of the Romanian National

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Authority for Scientific Research and Innovation, CNCS/CCCDI-UEFISCDI, project number


PN-III-P2-2.1-PED-2016-0293, within PNCDI III.

REFERENCES

1. Ezimokhai M, Rizk DE, Thomas L. Maternal risk factors for abnormal vascular coiling of the umbilical
cord. Am J Perinatol 2000; 17(8): pp. 441-5.
2. Strong TH. Factors that provide optimal umbilical protection during gestation. Contemp Obstet Gynecol
1997; 42: pp. 82-105.
3. Strong TH, Jarles DL, Vega JS, Feldman DB. The umbilical cord coiling index. Am J Obstet Gynecol 1994;
170(1pt1): pp. 29-32.
4. Degani S, Leiborich Z, Shapiro I, Gonen R, Ohel G. Early second-trimester low umbilical coiling index
predicts small for gestational age fetuses. J Ultrasound Med 2001 (Nov); 20(11): pp. 1183-8.
5. Machin GA, Ackerman J, Gilbert Barness E. Abnormal umbilical cord coiling is associated with adverse
perinatal outcomes. Pediatr Dev Pathol 2000 (Sep-Oct); 3(5): pp. 462-71.
6. Totorean, A.F., Hudrea, C.I., Bosioc, A.I., Bernad, S.I., (2017). Flow field evolution in stented versus
stenosed coronary artery, Proceedings of the Romanian Academy, Series A-Mathematics Physics Technical
Sciences Informational Science, 18(3), pp. 248-255.
7. Bernad, S.I., Totorean, A., Bosioc, A., Stanciu, R., Bernad, E.S. (2013). Numerical investigation of Dean
vortices in a curved pipe. 11th International Conference of Numerical Analysis and Applied Mathematics,
2013, ICNAAM 2013, 21-27 September 2013, Rhodes, Greece. AIP Conference Proceedings, vol. 1558, pp.
172-175.

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Extreme Preterm Delivery Under 32 Weeks. Which is the Best


Approach?

MUREȘAN Daniel1,*, STAICU Adelina*, ROTAR Ioana Cristina1,


NASTASE Diana, BONDOR Cosmina, ZAHARIE Gabriela2
1 1st Department of Obstetrics and Gynaecology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca,
(ROMANIA)
2 Departement of Neonatology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, (ROMANIA)
3 Department of Medical Informatics and Biostatistics, Iuliu Hațieganu University of Medicine and Pharmacy, 6 Pasteur Street,

400349 Cluj-Napoca, (ROMANIA)


* Muresan Daniel and Staicu Adelina have equally contributed to this work
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected]

Abstract

The aim
Of the study was to evaluate the impact of the delivery mode on the extreme preterm neonatal
outcome.

Methods
Between 1.01.2014-12.31.2015, a retrospective study was conducted in a tertiary center of
Obstetrics and Gynecology in Cluj-Napoca, Romania including all patients that give birth prior to
32 weeks of gestation (WG). A total of 96 singleton extreme preterm pregnancies fulfilled the
inclusion criteria. The cases were divided in two groups, first group was formed by 27 singleton
extreme preterm births between 24-28 WG and the second group were included 69 singleton
preterm births 29-32 WG. In the first stage of the research main maternal, fetal and adnexal
preterm birth risk factors were correlated with the delivery mode, infants birth weight, neonatal
morbidity and early mortality. The two groups were compared using Pearson's chi-squared test.
A value of p<0.05 was considered significant. In the second stage obstetrical parameters and
delivery modes and main immediate neonatal outcomes were assessed using multivariate
analysis.

Results
During the study period, 30.96% of all preterm birth (PB) occurred before 32 WG. In the first
group 24-29 WG was registered a high rate of complication of 70.37% (19 cases) and a mortality
of 11.11%. A high complication rate was registered also in the second group of 46.37% (32
cases) with 10.29% mortality. Prelabour caesarean section (CS) for medical indications was
performed in 22.91% (22 cases), 30.2% (29 cases) presented spontaneous unexplained preterm
labor with intact membranes, but almost half of the patients presented idiopathic preterm
premature rupture of membranes 46.86% (45 cases). 61.45% (59 cases) had a vaginal births
compared to 38.54% (37 cases) that required a CS. In the first group the rate of CS was 33.3%
and in the second group 42%. Children born vaginally had a better postpartum evolution than

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singleton born by CS. A higher mortality rate was registered after delivery by CS. The delivery
path had no statistical influence on the type of respiratory distress syndrome (RDS) developed.
Gestational age and birth weight were statistical significant correlated with the need of
Synchronized Intermittent-Mandatory Ventilation (SIMV) requirements (p=0.001 and p<0.0082
respectively) and the occurrence of neonatal complications.

Conclusion
Current study results do not support a policy of routine CS for preterm delivery infants.
Keywords: preterm birth, delivery mode, CS, neonatal outcome, neonatal morbidity

Introduction

Globally, prematurity is the main cause of neonatal death and the second most common cause
of death in children under the age of 5 years [1]. It is estimated that about 15 million children are
born prematurely each year. Nearly 1 million children die each year due to complications of
premature birth [1].
If in 1960 the gestational age at which at least half of newborns survived at birth was 30-31
weeks, nowadays it has reached 23-24 weeks. In 2012, the American College of Obstetricians and
Gynecologists (ACOG) set the accepted viability limit between 22-25 weeks of gestation.
Survival as well as long-term morbidity of external premature babies has improved over the past
few years, and the acceptable limit of viability has decreased [2].
Although the preterm birth and preterm infants have an almost widely accepted management,
there are controversial regarding the preferred mode of delivery: vaginal delivery versus CS [3].
There are disputes on CS recommendations in preterm delivery and its impact upon neonatal
outcome. CS is supposed to be the safest delivery mode in preterm, especially in breech
presentation [3]. Still, CS increases the risk of maternal morbidity, higher risk for future
pregnancies, and hospital costs [4]. Moreover, neonatal RDS occurs more frequently after CS
compared to vaginal delivery (VD) [5]. Also recent studies associates CS with the incapacity to
activate the immune defense system at birth [6].
Overall the main risk factor for poor neonatal outcome regardless the delivery mode is
prematurity of low birth weight infants [7], therefore some studies still recommend vaginal
delivery for preterm breech presentation.
Thus, the question results whether CS is the recommended delivery mode of extreme preterm
babies after carefully considering maternal preconditions.
The aim of the study was to investigate the risk maternal and fetal risk factors and their impact
of the delivery mode on the extreme preterm neonatal outcome.

Methods

A retrospective study was conducted in 1st Obstetrics and Gynecology Clinic of Cluj-Napoca,
Romania between 1.01.2014 to 12.31.2015. Were included in the study all patient that give birth
in our department before 32 weeks of gestation.
The gestational age was confirmed by early ultrasound examination during the first trimester
of pregnancy. Patients with an uncertain gestational age, multiple pregnancies or antepartum fetal
death were excluded from the study. Nighty six singleton extreme preterm pregnancies fulfilled
the inclusion criteria. Depending on the gestational age, the cases were divided in two groups. In

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the first group were included 27 singleton delivered between 24-28 GW. In the second group
were included 69 singleton preterm births between 29-32 weeks of gestation. The term good
evolution during the neonatal hospitalization defines a newborn that has been discharge without
any neuro-motors impairments.
The local ethics committee was approved the study protocol.
Data was analyzed using SPSS software package 17.0®.
In the present study, main maternal, fetal and adnexal parameters were correlated with the
delivery modes, infants’ birth weight, immediate, 5 minutes Apgar score, neonatal morbidity and
early mortality. The two groups were compared using Pearson's chi-squared test (p<0.05).

Results

Between 1.01.2014-12.31.2015 in 1st Clinic of Obstetrics and Gynecology, Cluj-Napoca,


Romania were recorded a total number of 3711 births: 310 (8.35%) occurred before 37 WG
resulting in 357 premature infants. From the preterm newborns 30.96% occurred before 32 WG.
In the first group, median gestational age was 26.66 WG and median birth weight was 1024 g
(500; 1600g). This particular group had the higher rate of complications- 70.37% (19 cases) with
a mortality of 11.11%.
In the second group, median gestational age was 31.45 WG with a median birth weight was
1602 g (ranging from 700 to 2300g), 46.37% (32 cases) of complications and 10.29% mortality.
Prelabour CS for medical reasons was performed in 22.91% (22 cases), 30.2% (29 cases)
presented spontaneous unexplained preterm labor with intact membranes, but almost half of the
patients presented idiopathic preterm premature rupture of membranes (PPROM) 46.86% (45
cases). The main medical and obstetrical indications for preterm birth in the study population
were severe preeclampsia 14.58% (14 cases) and intrauterine growth restriction IUGR 6.25% (6
cases).
In table one the cumulative antecedents and risk factors for preterm birth are analyzed.

Risk Factor Number of cases (%) Observations


Prior Preterm Birth 10 (10.41%) 1-2 prior preterm births
Anemia 37 (38.54%) Hemoglobin level ≤10mg%
Cervical infection 9 (9.37%) E.Coli, Staphylococcus aureus
and bacterial vaginosis Gardnerella, Trichomonas vaginalis,
No: streptococcus B
Insufficient prenatal care 21 (21.87%) Less than 3 prenatal consultations
Associated maternal pathologies 23 (23.95%) Cardiac thrombophilias, chronic
cardiac, respiratory or infectious
pathology
Obstetrical history with more than three 13 (13.53%) Spontaneous or voluntary
abortions
Obstetrical history with more than two births 8 (8.33%)
regardless the delivery route
Table 1. Antecedents and risk factors/cumulative

In the study cohort, 61.45% (59 cases) had a vaginal births compared to 38.54% (37 cases)
that required a CS. In the first group the rate of CS was 33.3% (5 cephalic presentation, 3 breech,
1 transverse) and in the second group 42% (23 cephalic presentation, 5 breech, 1 transverse).

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In table 2 is compared the type of delivery mode and immediate neonatal outcome in the two
groups. In both groups children born vaginally had a better postpartum evolution than those born
by CS (results not statistically significant, p=0.302).

Delivery mode by presentation Group 1 Group 2


24-28 WG (%) 29-32 WG (%)
Cephalic delivered spontaneous 86.7 96.3
Cephalic delivered by CS 60 88.7
Breech delivered spontaneous 50 89.2
Breech delivered by CS 100 87
Table 2.Comparison between the type of delivery and good neonatal outcome

Also, overall 8.5% of singletons born spontaneously died in postpartum, compared to 13.5 %
of singletons born that died in postpartum after delivery by CS (p=0.501). The delivery mode
does not seem to impact upon RDS type developed by the infants included in the study, p=0.351
(Table 3).

Respiratory distress syndrome (RDS) Spontaneous vaginal birth CS

Mild RDS 25.5% 19.4%


Moderate RDS 41.5% 35.5%
Severe RDS 29.4% 45.2%
Table 3. Influence of the delivery path and type of RDS

Comparing the two groups, a higher mortality rate was noted after delivery by CS, 12.5% in
first group and 13.08 in the second group.
Antenatal corticosteroids therapy (ACT) was administered in 20 cases (70.07 %) from group 1
and respectively 51 cases (73.91 %) from group 2. Despite the administration of ACT, 61.53%
(16 infants) of the infants from group 1 developed severe respiratory distress syndrome.
There were no cases without RDS in group 1. In group 2, only 26.66% (16 cases) developed
severe RDS with complete dose of ACT being received in 10 cases. Almost half of the infants in
group 2 presented moderate RDS (48.7%). Factors that had an important influence on the type of
RDS developed were gestational age and birth weight as presented in Table 4.

Gestational age (WG) Birth weight (g)

Mild RDS 30.21+/-1.78 1612+/-444.91


Moderate RDS 29.88+/-1.81 1522+/- 542.732
Severe RDS 28.48+/- 2.31 1066.5+/-373.66
P value <0.005 <0.001
Table 4. Influence of gestational age and birth weight on the type of RDS

In the second part of the study was assessed the influence of the delivery path on the
immediate neonatal outcome. The delivery mode did not influence the need of Synchronized
Intermittent-Mandatory Ventilation (SIMV) between the two groups (p=0.925). Gestational age
and birth weight were statistical significant correlated with the SIMV requirements (p=0.001 and
p<0.0082 respectively) and the occurrence of neonatal complications (Tabel 5).

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Gestational age (WG) Birth weight (g)

Neonatal complications 28.82+/- 2.24 1256.25+/-515.68


No neonatal complications 30.37+/- 1.72 1650+/- 558.23
P value <0.001 0.001
Table 5. Parameters that correlate with neonatal complications
* neonatal complications include neonatal sepsis, intracerebral hemorrhage, anemia,
necrotic ulcerative enter colitis,, gastrointestinal hemorrhage, neonatal death

Discussions

Sometimes can be very difficult to decide the delivery route for a preterm birth; the choice has
to be individual based on associated maternal condition (eg preeclampsia), associated fetal
condition (eg IUGR), fetal presentation (cephalic, breech, transverse lie), parity and Bishop
Score. Overall the current study did not find any statistical significant difference regarding
perinatal outcomes in preterm neonates born vaginally versus infants borne by CS.
Bergenhenegouwen et al., consider that cesarean delivery may reduce hemodynamic stress
during labor, therefore CS for obstetrical indication after viability limit (23 weeks) may improve
neonatal outcome compared with a vaginal birth [7].
Main medical indications for premature delivery were severe preeclampsia and intrauterine
growth restriction. Preeclampsia is one of the most important obstetric complications, with an
overwhelming impact upon maternal and fetal morbidity and mortality worldwide and in our
country [8], therefore thorough follow-up by reliable non-invasive methods is required [9].
Studying the risk factors involved in the etiopathogenesis of premature births is still a
sustained effort across the world [10-13]. In the present study, the most important risk factors
outlined for premature delivery were anemia, maternal pathologies and insufficient maternal care.
As expected, the rate of complications during the NICU hospitalization was bigger in the 24-
28 WG group regardless the delivery mode. Still, for both groups, better neonatal outcome at
discharge had the infants born spontaneously.
In contrast, a recent systematic review and meta-analysis of non-randomized studies that
assessed the association between mode of delivery and neonatal mortality in women with preterm
breech presentation found that neonatal mortality is significantly reduced by 37% (pooled RR
0.63; 95% CI 0.48-0.81) with a CS as compared to VD in preterm breech presentation at
gestational age 25+0 till 36+6 weeks [14], stressing the importance of larger studies to confirmed
the findings.
Also in the present study the mortality rate of singleton born spontaneously was lower than
singletons born by CS. Furthermore, the second group 29-32 WG registered a higher mortality
rate after CS delivery.
Obviously, neonates from the 24-28 WG registered a mortality baseline risk higher than in
neonates born between 29-32 WG. As highlighted by other authors, the relative benefit of a CS
can be more obvious in neonates born late preterm [3].
After CS, in both groups was encountered a higher rate of severe RDS, moreover all neonates
with incomplete ACT have developed moderate or severe type of RDS. As anticipated, most
cases of severe RDS were registered in the first group 24-28 WG. Comparing the results of both
groups can be concluded that each day or desirable week of in utero life brings an improvement
in RDS severity. All infants required some type of respiratory assistance in the delivery room, but

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intubation and need of Synchronized Intermittent-Mandatory Ventilation (SIMV) were more


frequent in the first group 24-28 WG.
The results obtained have highlighted 30.4 WG as a cut-off value for improve neonatal
outcome, good neonatal outcome being correlated with increasing of gestational age and birth
weight, in correspondence with other published studies [15].
In the EXPRESS study, infants born before 27 WG in Sweden 2004-2007 the risk of death
within 24 h after birth was demonstrated to decrease with the gestational age [odds ratio (OR)
0.3], administration of antenatal corticosteroids (OR 0.3), and cesarean section (OR 0.4; 95) and
increased with multiple birth (OR 3.0;), vaginal breech delivery (OR 2.3;), 5-min Apgar score <4
(OR 50.4), and birth at a level II hospital (OR 2.6) [14]. We cannot comment about hospital level
since all our data are based on birth that took place in a tertiary center.
In conclusion, the data obtained do not support a policy of routine CS for preterm delivery
infants. Large randomized controlled trial studies are necessary to confirm the results, but are
unlikely to be performed in the near future, due to inevitable bias derived from a common sense
impossibility of randomizing the birth path of all premature births.

REFERENCES

1. Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde
S, Say L, Lawn JE. (2012). National, regional and worldwide estimates of preterm birth rates in the year
2010 with time trends since 1990 for selected countries: A systematic analysis and implications. Lancet
379(9832): pp. 2162-72.
2. Seri I, Evans J. (2008). Limits of viability: definition of the gray zone. J Perinatol 28: pp. S4-8.
3. Golfier F, Vaudoyer F, Ecochard R, Champion F, Audra P, Raudrant D. (2001). Planned vaginal delivery
versus elective caesarean section in singleton term breech presentation: a study of 1116 cases. Eur J Obstet
Gynecol Reprod Biol 98(2): pp. 186-92.
4. Su M, McLeod L, Ross S, Willan A, Hannah WJ, Hutton EK, Hewson SA, McKay D,Hannah ME. (2007.
)Factors associated with maternal morbidity in the Ter Breech Trial. J Obstet Gynaecol Can 29: pp. 324-30.
5. Krantz ME, Wennergren M, Bengtson LG, Hjalmarson O, Karlsson K, Sellgren.(1986) Epidemiological
analysis of the increased risk of disturbed neonatal respiratory adaptation after caesarean section. Acta
Paediatr Scand 75: pp. 832-9.
6. Huurre A, Kalliomaki M, Rautava S, Rinne M, Salminen S, Isolauri E. (2008). Mode of delivery–effects on
gut microbiota and humoral immunity. Neonatology 93: pp. 236-240
7. Bergenhenegouwen LA, Meertens LJ, Schaaf J, Nijhuis JG, Mol BW, Kok M, Scheepers
HC.(2014).Vaginal delivery versus caesarean section in preterm breech delivery: a systematic review. Eur J
Obstet Gynecol Reprod Biol 172: pp. 1-6.
8. Procopciuc LM, Caracostea G, Zaharie G, Puscas M, Iordache G, Popa M, Colcear D, Olteanu I, Stamatian
F.(2011). Maternal/newborn genotype contribution of the renin-angiotensin system (Met235Thr,
Thr174Met, I/D-ACE, A2350G-ACE, A1166C-AT2R1, C3123A- AT2R2, 83A/G-REN) to the risk of pre-
eclampsia: a Romanian study. J Renin Angiotensin Aldosterone Syst 12(4): pp. 539-48.
9. Mureșan D, Rotar IC, Stamatian F. (2016). The usefulness of fetal Doppler evaluation in early versus late
onset intrauterine growth restriction. Review of the literature. Med Ultrason 18(1): pp. 103-9.
10. Procopciuc LM, Caracostea G, Zaharie G, Stamatian F. (2014). Maternal/newborn VEGF-C936T interaction
and its influence on the risk, severity and prognosis of preeclampsia, as well as on the maternal angiogenic
profile. J Matern Fetal Neonatal Med 27(17): pp. 1754-60.
11. Muresan D, Staicu A, Zaharie G, Marginean C, Rotar IC. (2017). The influence of seasonality and weather
changes on premature birth incidence. Clujul Med. 90(3): pp. 273-278. doi: 10.15386/cjmed-744. 2017;
90(3): pp. 273-278.
12. Muresan D, Ona D, Cruciat G, Rotar I, Stamatian F. (2008). Recurrent intrahepatic cholestasis of
pregnancy. A case report. J Gastrointestin Liver Dis. 17(3): pp. 323-5.
13. Goidescu I, Goidescu CM, Eniu DT, Micu R, Stamatian F. (2017). Preterm birth, preeclampsia, prematurity
and subsequent breast cancer risk. Obstetrica si Ginecologia LXV(2): pp. 73-78.

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14. Vidovics M, Vidovics VR, Fischer T, Maier B. (2014). Comparison of fetal outcome in premature vaginal
or cesarean breech delivery at 24-37 gestational weeks. Arch Gynecol Obstet 290(2): pp. 271-813.
15. Källén K, Serenius F, Westgren M, Maršál K; EXPRESS Group. Impact of obstetric factors on outcome of
extremely preterm births in Sweden: prospective population-based observational study (EXPRESS). Acta
Obstet Gynecol Scand 94(11): pp. 1203-14.

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Possibilities and Limitations of First Trimester Fetal Heart


Ultrasound Examination

MUREȘAN Daniel1, ROTAR Ioana Cristina1, MĂRGINEANU Claudiu2,


TUDORACHE Ștefania3, MIHU Dan4, SCHITCU Cristina1, ZAHARIE Gabriela4
1 1st Department of Obstetrics and Gynaecology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca,
(ROMANIA)
2 Department of Obstetrics and Gynecology I, University of Medicine and Pharmacy of Targu Mures, (ROMANIA)
3 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, (ROMANIA)
4 Departement of Neonatology, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca, (ROMANIA)

Emails: [email protected], [email protected], [email protected],


[email protected], [email protected], [email protected], [email protected]

Abstract

Congenital heart diseases (CHD) is an important contributor to perinatal mortality. Incidence


of CHD has been estimated to 8/1000 live births. The standard of care in sonographic evaluation
of the fetal heart is undertaken at midgestation; however important advances in technology
permitted the shifting of the examination towards the end of the first trimester. It is performed
between 11 to 13 GW+6 days during the early morphological scan of the fetus. Visualization
rates increase linearly with gestational age. Using both transvaginal and transabdominal approach
with the aid of color Doppler, standard sections used in midgestational evaluation can be
obtained. Added to these standard examination tools, spatiotemporal image correlation and
tomographic ultrasound imaging can aid the detection of most important CHD. Early diagnosis
provides an opportunity to ensure a better management of these cases, thus improving neonatal
outcomes.
Keywords: cardiac activity, crown-rump length measurement, Colour Flow map, first trimester, pregnancy, transvaginal
sonography

Introduction

Congenital heart diseases (CHD) is an important contributor to the perinatal mortality.


According to the European Congenital Surveillance Anomalies (EUROCAT) population based
registries, 22.6% of neonates that die perinatally have a structural heart defect. Rates are higher in
countries where therapeutic termination of pregnancy (TTOP) is not legal, such as Malta
(3.34/1000 live births) [1].
Overall prevalence of CHD reported by Mitchell et al., estimated to be 8/1000 live births [2].
Considering varied legislation regarding TTOP among countries in nonviable fetal heart
malformations, nowadays-prenatal diagnosis provides an opportunity to diagnose early in
gestation the presence of a CHD, which enables the search for other possibly associated structural
defects or chromosomal anomalies. When completing the process of diagnosis parents can be
informed about the prognosis, treatment options before and after delivery.
Moreover, according to a meta-analysis published by Holland et al., prenatal diagnosis of
CHD improves neonatal outcomes of children with critical congenital heart disease [3]. Prenatal

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diagnosis has allowed an early intrauterine detection of a variety of CHD ensuring a better
management of these cases.

Screening for CHD: where do we stand now?

In the dawn of fetal sonography, in 1987 Copel et al., proposed the inclusion of the four-
chamber view in all routine obstetrical examinations, claiming that both positive and negative
predictive values are higher than 95% in detecting CHD [4]. One year later, Allan et al., already
applying this approach prove the feasibility of routine screening of the fetal heart [5].
Unfortunately, four chamber view is not reliable for the detection of transposition of the great
vessels, tetralogy of Fallot, double-outlet right ventricle, truncus arteriosus, and outlet septal
defects, therefore the evaluation of three vessel section is mandatory [6]. By adding the three
vessel view the sensitivity of detection of CHD from approximately 30% to 69%-83% [7].
Traditionally heart evaluation is performed at midgestation between 16 to 22 gestational weeks
(GW) [8] but the recent advances in technology permitted the shift from second trimester to the
end of first trimester [6]. In addition, given the psychological burden of late TTOP, the increasing
complications involving it and the tremendous advances in technology it was proposed that the
set off for CHD screening should be in the late first trimester (11-13 weeks of gestation). In a
prospective study published by Becker and Wegner in 2006 analyzing 3094 unselected fetuses
but from pregnancies where the mother’s median age was 35 years the detection rate of CHD was
84%. They concluded that most of the severe CHD can bet detected at this gestational age by an
experienced sonographer [9] thus extending the first trimester NT screening to a more complex
evaluation [10]. In the daily practice in most services in case of a suspicion of CHD the
ultrasound is repeated in the second trimester and usually is confirmed/infirmed by a fetal
cardiologist.

Indications for CHD screening

Ideally, fetal heart should be examined in the first trimester between 11 to 13GW+6days in
every fetus in so-called early morphological scan. In particular situations, fetal heart should be
examined in the as soon as possible as depicted in table number 1. The existence of a personal
history or family history of CHD imposes an early heart evaluation. Abnormal findings during
the first trimester ultrasound such as increased NT, abnormal ductus venosus flow, tricuspid
regurgitation or the detection of other morphological anomalies impose a detailed heart
examination [12,13]. Previous studies have indicated that euploid fetuses with abnormally high
NT have a higher CHD rate [14], but the performance of NT alone for CHD screening is poor
[15]. Consanguinity is known to be associated with a high prevalence of CHD, data reconfirmed
by a recent systematic review [16] therefore early heart examination is recommended. In addition,
pregnant women with presentational diabetes or phenylketonuria should also be carefully
screened for fetal cardiac malformations. The prevalence of of CHD in the diabetic population is
reported to be two fold increased [17], [18] in direct correlation with poor glycemic control [19].
Also, maternal exposure to teratogenic drugs such as lithium, anticonvulsivants, retinoic acid,
indometacin, angiotensin-converting enzyme inhibitors are associated with moderate to increased
risk for developing CHD in the fetus [20]. A rare but important condition is monochorionic twin
where early examination not only allows an early diagnosis of CHD known to be increased [21]
but also the early evaluation of the pathological circulation permit and early diagnosis and
treatment of particular complications such as TTTS and TRAP sequence [22].

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Indications for fetal heart examination in the first trimester


1. previous infant with CHD
2. family history of CHD
3. abnormal basic fetal heart examination during first trimester scan
4. indirect markers such as high nuchal translucency (NT)
5. abnormal ductus venosus flow, tricuspid regurgitation
6. detection of chromosomal anomalies
7. detection of other structural defects
8. fetuses from assisted reproduction techniques (ART)
9. monochromic twins
10. consanguinity
11. diabetes mellitus
12. phenylketonuria
13. maternal teratogenic exposure
Table 1. Indications for early fetal heart examinations [10-20]

Sonographic examination reference points

The stepping-stone of prenatal ultrasound imaging is the accurate knowledge of embryonic


heart developmental stages. Cardiac development reaches the 4-chamber stage at the end of the
8th week of gestation while formation of the foramen ovale is completed by the 9th week. At the
same gestational age heart rate reaches the highest values (approximately 175 beats/minute)
encountered during pregnancy, presumably concurring with the completion of morphological
development. Heart size is linearly correlated with crown rump length (CRL). At 12 WG the
mean heart diameter is about 5.6-8.2 mm [23]. The cardiac activity has to be documented as soon
as the embryo reaches 3.5 mm, the lack of cardiac pulsations at a CRL > or = 3.5 mm having a
100% positive predictive value for a nonviable pregnancy [24].
With the shifting of sonographic assessment of the fetal heart towards the end of the first
trimester, several techniques were undertaken for a better visualization of the cardiac structures.
Transvaginal examination seems to be the logical approach in the first trimester bearing in
mind that embryonic cardiac activity was visualized for the first time by this route in 1967 by
Kratochwil and Eisenhut [25]. In case of high maternal body, mass index (BMI) or extroverted
uterus transvaginal route can facilitate better examination [26, 27]. Complete evaluation of the
fetal heart structures was obtained by Vimpelli et al., using a transvaginal 5-7 MHz probe in
58%-62%, visualization rates increased linearly with gestational age [28]. Gembruch et al.,
concluded in a prospective cross-sectional study comparing transabdominal vs transvaginal
examination of the fetal heart that the latter is superior before 14 weeks of gestation. The study
also concluded that in a more anteriorly or higher positioned uterus transabdominal evaluation is
more helpful [29].
Added to these standard examination tools, in the modern era of technology spatiotemporal
image correlation (STIC) was developed to help visualize both 2D and 3D image sequences. 3
and 4 D ultrasound techniques can improve the examination of the heart, as they have optimized
and facilitate the examination of the cerebral structures [30]. For the examination of the heart in
the first trimester, 3 and 4 D techniques must be associated with Doppler examination for the best
resolution. As underlined by DeVore et al., it provides a temporal resolution to a B Mode
sequence of 80 frame rates per second and it allows the revision of an unlimited number of
images thus reducing the time needed for image acquisition [31]. Also, by using tomographic
ultrasound imaging (TUI), another novel addition, it helps displaying several cross-sectional
images from a specific distance from the 4 chamber view [32].

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Practical points

The most important objectives during the first trimester cardiac scan as Carvalho J.S said in a
paper published in Perinatal Diagnosis are defining what is considered “normal” at this stage of
gestation (11+0-13+6 gestation weeks) and establishing what can be visualized during this period
[33]. In order to certified that a heart is normal in the first trimester the following structures need
to be assessed: normal situs, cardiac connections, atrioventricular junction, right-, left-sided
symmetry and septo-aortic continuity [34]. The CHD detection rate varies according to the
gestational age from 20% at 11 GW up to 92% at 13 GW.
The examination starts in the 2D (B-mode). Doppler examination is extremely important in the
first trimester allowing the evaluation of the cardiac axis and more important great vessels
evaluation. At the end of the first trimester the examination can be performed using
transabdominal probes, linear probes can also be used. The transvaginal probe is particularly
useful in obese patients.
Examination should start by upper abdominal section with the visualization of the stomach and
later by the four chamber view. The position of the fetal heart and cardiac axis should be noted.
In the four chamber view ventricular and atrial septum needs to be assessed; the lack of the cross
of the heart can be seen in atrioventricular septal defect (AVSD) known to be frequently
associated with Down syndrome. Mitral and tricuspid valve can be assed in the four chamber
view. Doppler ultrasound CFM mode is particularly useful for the evaluation of aortic and
pulmonary ejection. The examination of heart should include ductal arch and aortic arch.
The visualization of systemic venous drainage should be tried in all fetuses in the first
trimester.
Quarello proposed simplified a evaluation between 11-13+6 GW for low-risk population that
has to include two sections: four-chambers view and the three vessels and trachea using color or
directional Doppler ultrasound [6], In the above mentioned study the visualization of four
chambers view was possible in 86% and respectively 79% for three vessels and trachea.
Moreover, the gestational age does not seem to influenced the visualization of four chamber
view. Instead the three vessels and trachea was better visualized when the crown-rump length was
>75 m [6]. Using the same methods Wiechec reported a sensitivity of a sensitivity of 88.7% for
cardiac defects, with an improved detection rate when color Doppler was applied [35].

Performance first trimester CHD detection

Visualization rates are higher as we approach to 14 weeks of gestation [36]. Dolkart et al.,
showed a 100% visualization rate by transvaginal route by 13 weeks of gestation only of the four-
chamber view. The aorta in a short axis was seen in 70% of cases by 12 weeks as a bright ring in
the center of the heart [37]. Overall visualization success rates are > 85% for each by 14 weeks of
gestation (Table 1).
Another mitigated aspect to consider when counselling parents, is the risk of intrauterine fetal
demise (IUFD). The overall risk of stillbirth in the general population is 0,6% while among CHD
fetuses (with no other structural or genetic anomalies) a 2-fold increase was observed. IUFD is
more frequent in fetuses with severe valve regurgitation [38, 39].
Not all CDH can be identified in the first trimester. Volpe et al., had classified CHD taking
into account the natural history and the limitation of first trimester scan into cardiac defects can
be detected in the first trimester (transposition of great arteries, double outlet right ventricle,
hypoplastic left heart), cardiac defects that might be detected (coartation of aorta, tetralogy of

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Fallot, Canal AV, truncus arteriosus) and cardiac defects that are unlikely to be detected
(ventricular septal defects, Ebstein’s anomaly, mild aortic or pulmonary stenosis, cardiac tumors,
myocardial hypertrophy, fibroelastosis, abnormal pulmonary venous return) [40].

Conclusions

The performances of the new ultrasound machine has allowed an early diagnosis of the CHD.
Initial heart evaluation at 11-14 GW it is recommended to be performed in the first trimester in
the meanwhile with NT measurement. The fact that CHD are six time more prevalent in fetuses
than chromosomal abnormalities represents a good argument. Sonographers need to train in CHD
detection in the first trimester. One should bare in mind that not all CHD can be diagnosed in the
first trimester, due to the small dimensions of the fetal heart, fetal position, maternal obesity but
also because of their evolutivity. In most of the cases one a CHD suspicion is made the case is
reexamined later buy an experienced sonographer and a fetal cardiologist where available. Once a
diagnosis of CHD is made a scrupulous detailed fetal examination is done. Classic karyotyping
by CVS or fetal DNA is performed. In particular situations 22q11 microdeletion can be
performed. The early diagnosis of a fetal CHD allows a TOP in case of severe cardiac
malformation. Moreover, CHD is less severe, the fetus can be born in a obstetrical center close to
a specialized cardiac pediatric center with a better outcome for the newborn.

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11. Donofrio MT, Moon-Grady AJ, Hornberger LK, Copel JA, Sklansky MS, Abuhamad A, et al., (2014)
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12. Coquel P, Balut J-P, Ville Y (2010).Pratique de l’ecographie obstetricale au premier trimestre 2:239-47.
13. Navolan Dan, Vladareanu Simona, Ciohat Ioana, Carabineanu Adrian, Craina Marius, Nemescu Dragos,
Birsasteanu Bogdan, Onofriescu Alina, Boia Marioara, Tepetzikiotis Efstathios, Craciunescu Mihaela,

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Birsasteanu Florin. Distribution of Biochemical and Ultrasound Markers Values in the First Trimester
Screening Program in Timisoara. Revista de Chimie. 2017 68(7):1636-1639.
14. Hyett J, Moscoso G, Papapanagiotou G, et al., (1996). Abnormalities of the heart and great arteries in
chromosomally normal fetuses with increased nuchal translucency thickness at 11-13 weeks of gestation.
Ultrasound Obstet Gynecol 7(4):245-50.
15. Westin M, Saltvedt S, Bergman G, et al., (2006).Is measurement of nuchal translucency thickness a useful
screening tool for heart defects? A study of 16,383 fetuses. Ultrasound Obstet Gynecol 27(6):632-9.
16. Shieh, JTC., Bittles, AH, Hudgins, L (2012). Consanguinity and the Risk of Congenital Heart Disease.
American Journal of Medical Genetics. Part a, 158A(5), 1236-1241.
17. Macintosh MC, Fleming KM, Bailey JA et al., (2006). Perinatal mortality and congenital anomalies in
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18. Persson M, Norman M, Hanson U (2009). Obstetric and perinatal outcomes in type 1 diabetic pregnancies: a
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19. Lisowski LA, Verheijen PM, Copel JA, et al., (2010). Congenital heart disease in pregnancies complicated
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39. Divanovic, Allison, et al., (2016) Intrauterine fetal demise after prenatal diagnosis of congenital heart
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Vaginal Microbiome Analysis: Clinical Applications

URSU Ramona Gabriela1, IANCU Luminița Smaranda1


1University of Medicine and Pharmacy “Grigore T. Popa”, Discipline of Microbiology, Iași,
(ROMANIA)
Emails: [email protected], [email protected]

Abstract

Background
Vaginal microbiome is characterized by 5 different community state types (CSTs); CST I, II,
III, and V are dominated by Lactobacillus crispatus, L. gasseri, L. iners, and L. jensenii
respectively, and CST IV (characteristic for bacterial vaginosis) and conversely, is a
heterogeneous group typified by depletion of Lactobacillus spp. with presence of strictly
anaerobic species. Vaginal dysbiosis and L. iners was recognized to be implicated in preterm
birth delivery and in Human papilloma Virus (HPV) persistence and Cervical Intraepithelial
Neoplasia (CIN) severity.

Aim
This minireview wants to analyse the interaction between vaginal microbiome and an
increased risk for preterm delivery, assessed by short cervical lenght at transvaginal
ultrasonography, and also the vaginal microbiome in relation HPV status, in women with
normal/abnormal Pap test, respectively.

Methods
A brief review of scientific literature focused on two study groups of patients: first group
referred to pregnant women at risk for preterm birth (short cervical lenght at transvaginal
ultrasonography). The second group, related to women with different abnormal results of Pap
smear. We were focused to analyse the presence of Lactobacillus spp in both groups of patients,
detected by a new developed assay of multiplex TaqMan qPCR, in order to underline the
potential role of these species in the mentioned pathologies.

Results and conclusions


The vaginal microbiome characterisation can be useful to appreciate differences between
individuals so they can be taken into account in risk assessment, disease diagnosis and
progression. Using appropriate molecular assays for vaginal microbiome analysis will facilitate
better characterisation of favoring factors for patients at risk for preterm birth and for CIN
persistence.
Keywords: Lactobacillus spp, qPCR multiplex, preterm birth, HPV multiplex genotyping, CIN progression

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VM (Vaginal Microbiome)

The vaginal microbiota is unique in that it undergoes major compositional changes throughout
women’s lifespan, from birth, to puberty, reproductive age, and menopause. Lactobacilli are
known to be predominant normal flora in young women vagina and they play a key role in
promoting a healthy vaginal environment. Commensal vaginal Lactobacillus spp. are thought to
defend against pathogens and sexually transmitted infections through maintenance of a hostile
pH, production of species-specific metabolites, bacteriocins and through adherence to mucous
and disruption of biofilms [1]. Next generation sequencing (NGS) based studies have facilitated
detailed characterisation of the “healthy” vaginal microbiome and shown that 5 major
community-state types (CSTs) exist; CST I, II, III and V are dominated by Lactobacillus
crispatus, L. gasseri, L. iners and L. jensenii respectively, whereas IV has characteristically low
numbers of Lactobacillus spp. and increased diversity of anaerobic bacteria, such as Gardnerella,
Megasphera, Sneathia, and Prevotella [1]. The stability and composition of the vaginal
microbiome (VM) may play an important role in determining host innate immune response and
susceptibility to infection. Depletion of Lactobacilli and the prevalence of fastidious anaerobic
bacteria in the vaginal enviroment are considered a hallmark of bacterial vaginosis (BV), a
disorder associated with an elevation of the vaginal pH and symptoms, such as vaginal discharge
and fishy odor, although a large percentage of women with BV can be asymptomatic. Since most
of the BV-associated microorganisms are difficult to culture, culture-independent molecular
methods, qPCR (quantitative Polimerase Chain Reaction) in particular, are becoming widely
accepted for diagnosis of vaginal health. Recently, many authors developed qPCR techniques for
Lactobacilli detection, the sequences of Lactobacilli being well established [2-4] (Table 1).

Table 1. The sequences of VM Lactobacilli – single primers [2, 3]


Lacto_tuf-S14, CGT GGT TCA GCW TTG AAG GC 20
Lacto_tuf-AS20, CTT CAA CTG GCA TYA AGA ATG GC
L. iners-TM, /5HEX/AG GCG ATC C/ZEN/A GAA CAA GAA GCA G
L. crispatus-TM, /56-ROXN/AG GCG ACA AGG AAG CTC AAG AAC
L. gasseri-TM, /56-FAM/AG GTG ACC C/ZEN/A GAA CAA CAA GAC G
L. jensenii-TM, /5Cy5/AG GTG ACC C/TAO/A GAA CAA GAA AAG GT

Even more, in 2015, Kusters JG et al., [5], evaluated a semi-quantitative multiplex PCR assay
for the diagnosis BV in a prospective study in a population of Dutch women. A ratio of L.
crispatus over L. iners of ˂1 (as calculated from the quantification cycle value (Cq)) was present
in women with a NS (Nugent Score) of 7-10 in 66% versus 33% in women with a NS of 1-3
(P˂0.001). The BV-PCR displayed a sensitivity of 92% and specificity of 96% with a positive
predictive value of 94% and a negative predictive value of 95%. The Lactobacillus-index
improved the correct classification of samples where only one of the other bacterial species was
detected, multiplex qPCR being evaluated like a convenient tool for performing observer
independent diagnosis of BV [5].
The Lactobacillus-index improved the correct classification of samples where only one of the
other bacterial species was detected, multiplex qPCR being evaluated like a convenient tool for
performing observer independent diagnosis of BV (5). Beside the commnon association of
lactobacilli with BV, recent articles revealed the Lactobacillus association with other two clinical
entities: cervical intraepithelial neoplasia (CIN) and with preterm labor in pregnant women.

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VM-HPV (Human Papilloma Virus)

It is very well known that persistent infection with oncogenic human papillomavirus (HPV) is
necessary but not sufficient for the development of cervical cancer. The factors promoting
persistence as well those triggering carcinogenetic pathways are incompletely understood (Fig.
1). Rapidly evolving evidence indicates that the VM may play a functional role (both protective
and harmful) in the acquisition and persistence of HPV, and subsequent development of cervical
cancer. Relatively little is known about the mechanisms associated with clearance or persistence
of HPV infection. Along with higher rates of HPV infection, BV has been associated with
delayed clearance of the virus and with CIN, suggesting that a diverse, Lactobacillus-depleted
microbiome may play a mechanistic role [6, 7]. In 2015, Mitra A et al., [8] has detected that L.
iners is associated with HSIL, and L. iners dominant VM’s are most likely to transition to CST
IV. In addition, L. iners has been implicated in depletion of reduced glutathione, unlike L.
crispatus and L. jensenii, which are both seen to be associated with increased levels of reduced
glutathione, indicating L. iners colonization results in higher levels of oxidative stress. The same
author found that a Lactobacillus spp.-depleted, Atopobium spp. enriched (CST IV) community
structure is associated with slowest regression of HPV whereas a Lactobacillus gasseri-
dominated microbiome (CST II) is associated with the most rapid regression rates for HPV.
These results are sustained also by other recent research papers [9, 10]. Regarding the structure
of the VM correlated to the HPV status and genotype, Mitra A. et al., founded that CST IV was
most frequently observed in high-risk HPV (HR-HPV) positive as compared to HRHPV negative
women [8]. Recently, new HPV multiplexing HPV assay were developed, having the advantage
of high-throughput screening, being sensitive, accurate and easy to clinic validate [11, 12].

Fig. 1. Evolution of HPV infection to invasive carcinoma

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VM-PTB (preterm birth)

Each year, PTB, defined as delivery before 37 weeks of gestation, causes more than 1 million
deaths worldwide [13]. Vaginal Lactobacilli are known to be central to reproductive health, as it
is known that in pregnancy, their increase quantity offer stability, and their decrease leads to
dysbiosis. Also, ascending vaginal infection is considered an important cause of PTB. The major
risk for spontaneous PTM is short cervical lenght [14], but recent papers published that vaginal
dysbiosis & L. iner are implicated in preterm birth. The evaluation of risk of preterm birth found
that L. iners was the dominant microbe < 24 weeks gestations, and also in women with previous
PTB <37 weeks, with a RR 2.4 (95% CI 1.2 – 9.1). In case of women with short cervix ≤25 mm,
the RR for L. iners increased at 2.7 (95% CI 1.6 – 14.1) [8]. VM (L. iners and dysbiosis) is
known to be implicated in spontaneouus PTB, as interaction between the cervix and vagial
microbiome contributes to preterm birth risk, and L. iners being considered pathogenic and L.
crispatus protective. The absence of vaginal Lactobacillus species and any bacterial colonisation
increases the risks of preterm delivery and low birth weight in women with intermediate vaginal
flora in early pregnancy. A recent paper revealed that a significant number of pregnant women
with British population had a L. jensenii – dominated microbiome. L. jensenii was predominantly
observed in women of Asian and Caucasian ethnicity whereas L. gasseri was absent in samples
from Black women [15]. It will be useful to perform a study in order to reveal new insights into
Romanian female population regarding biogeographical and ethnic effects upon CIN progression
and upon the pregnancy and postpartum vaginal microbiome which can have important
implications for future studies exploring relationships between the vaginal microbiome, host
health and pregnancy outcomes.
Having these scientific data very well established by published papers [16-21], we propose to
be used a validated molecular assay (e.g., multiplex Taqman multiplex qPCR) for Lactobacillus
detection and quantitation and multiplex genotyping of HPV using a bead-based multiplex assay,
in order to evaluate the relation of vaginal microbiome with the risk of spontaneous premature
birth and of CIN progression [22-24]. It is recognized that human microbiome was associated
lately with other disease conditions also [25].

Conclusions

For analysing the VM classical culture techniques are limited, as >90% bacteria can’t be
cultured in vitro, methods are largely qualitative and microbiology is still very important. The
next generation sequencing (culture independent techniques) can identify all bacteria in a given
sample. It provides quantitative data, permits measurements of bacterial diversity and richness,
and is expesive. We propose a target multiplex TaqMan qPCR assay for specific bacteria
considered being involved in these two clinical situation: CIN and PTB. This will allow a local
characterization of VM distridution in women with CIN/abnormal Pap test or with an increased
risk for preterm delivery. We will evaluate in this way if vaginal microbiome community state
predict preterm labour or HPV persistence. Although the development of HPV vaccines will be
the main prevention strategy for this disease, its implementation in many settings can be
challenging due to financial, cultural barriers and lack of infrastructure. Microbiome modulation
with pre- and probiotics towards stable Lactobacillus-dominant vaginal community structure that
promotes HPV clearance, could represent low-cost future therapeutic strategies.

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Rare Case of Mechanical Dystocia by Previa Ovarian Cyst – Case


Report

NOUR Corina Madalina1, CRISTUREAN Constantin Viorel2,3, CARDON Iuliana1,


TICA Vlad2
1 County Emergency Clinical Hospital “Sf Apostol Andrei” Constanta (ROMANIA)
2 “Ovidius” University of Constanta – Faculty of Medicine (ROMANIA)
3 Prosana Medical Center Constanta (ROMANIA)

Email: [email protected]

Abstract

The incidence of ovarian tumors diagnosed during pregnancy is between 0.3 and 5.4%. The
most common ovarian tumors diagnosed during pregnancy are functional cysts diagnosed
incidentally during the first trimester ultrasound and spontaneous regression is often observed.
Dermoid cysts and cystadenoma are the most frequent organic benign ovarian tumors
diagnosed during pregnancy. We have presented the case of a 33-year-old pregnant woman which
has been ultrasound diagnosed with left ovarian tumor during the first trimester of pregnancy. At
the subsequent ultrasounds we found the previa localization of the cyst. The previa position of the
cyst was maintained until the end of pregnancy, so that the patient gave birth by cesarean section.
Mechanical dystocia by previa ovarian cyst is a rare situation described in the literature, of
pregnancy associated with previa tumors.
Keywords: pregnancy, ovarian tumor, cesarean section

Introduction

The liberal use of prenatal ultrasound for evaluation of the fetus has also resulted in increased
detection of asymptomatic adnexal masses during pregnancy. Prior to the widespread use of
ultrasound, most adnexal masses in pregnant women remained unrecognized until cesarean
delivery or until they became symptomatic, usually in the postpartum period. Now, many
asymptomatic masses are recognized in the first half of pregnancy when they are identified
incidentally during an antenatal ultrasound performed for obstetrical indications [1, 2, 3, 4].
Adnexal masses that have not been diagnosed antepartum may be identified at cesarean
delivery. In a retrospective study of over 46,500 term cesarean deliveries performed for
obstetrical indications, 151 women (0.3 percent) underwent concurrent surgery of an adnexal
mass, which was an incidental finding at surgery in just over half of the women (83 of 151; 55
percent) [5].
Most adnexal masses identified in pregnant women are benign simple cysts less than 5 cm in
diameter. Most of these are functional ovarian cysts, either follicular or corpus luteum cysts, that
occur as part of the normal physiological function of the ovary. Approximately 70 percent of all
adnexal cystic masses detected in the first trimester spontaneously resolve by the early part of the
second trimester, which is consistent with the natural history of functional cysts [3]. The majority

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of persistent adnexal masses 5 cm or greater in diameter are mature teratomas, followed by chist
adenoma. [1]
A mature cystic teratoma (dermoid cyst) is a benign germ cell tumor and is the most common
ovarian neoplasm in the second and third decades of life [7]. Mature teratomas can contain
elements differentiated to all three germ cell layers: ectodermal (eg, skin, hair follicles, sebaceous
glands), mesodermal (eg, muscle, urinary), and endodermal origin (eg, lung, gastrointestinal. [7].
Serous and mucinous cystadenomas are among the most common benign ovarian tumors.
They are thin walled, uni- or multilocular, and range in size from 5 to <20 cm.
Compared with serous cystadenomas, mucinous cystadenomas occur less frequently, are more
likely to be multiloculated, are larger (they can attain an enormous size), and are less often
bilateral (less than 5 versus 20 to 25 percent). A definitive diagnosis depends on pathologic
evaluation to determine the cell type lining the cysts. Serous lining is similar to fallopian tube
lining, and mucinous lining cells collect mucin in their cytoplasm and resemble either
endocervical or gastrointestinal epithelium. Many of these tumors are asymptomatic and found
incidentally on pelvic examination or with ultrasound. As the masses grow, they can cause
pressure or pain, bloating, and urinary symptoms and can present with ovarian torsion. [8]
The main complication of presumed benign ovarian tumor during pregnancy is adnexal torsion
and is estimated at around 8%, especially at the end of the first trimester and during the second
trimester. Tumor markers are not reliable during pregnancy to assess the risk of malignancy of
ovarian tumor. Ultrasound remains the gold standard for characterizing an ovarian tumor during
pregnancy, but with a lower specificity for the diagnosis of malignancy. [9]
Ultrasound-guided aspiration of ovarian tumors is not recommended during pregnancy (grade
C). Expectation is recommended in cases of presumed benign ovarian tumors during pregnancy,
which does not enlarge (grade C). Whatever the gestational age, surgery is recommended in
patients with symptoms suggesting an adnexal torsion (grade C). The route of delivery should not
be modified by the ovarian tumor, except in case of previa cyst requiring a cesarean section, a
complication or suspicion of malignancy (grade C). Surgical treatment of presumed benign
ovarian tumors during pregnancy may be performed during a cesarean section indicated for
another reason. The risk of torsion is increased during the postpartum period. [9]

Case report

The 33-year-old pregnant woman in the first trimester, from the urban, tertigesta
secondiparaos has presented for pregnancy monitoring. In the ultrasound we detected an ongoing
pregnancy of 11 weeks and left ovary turned in to a cyst about 98/89mm (Fig. 1).
Ultrasound appearance of adnexal tumor was rotund- oval anechoic formation, well defined,
unilocular, without intracystic vegetation, which stand up for benignity, which is why it was
decided to monitor the dynamic evolution of the cyst.

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Fig. 1. Obstetrical ultrasound at 11 weeks of gestation

In subsequent periodic scans we notice increase in size of left ovarian cyst (Fig. 2.). At the
same time the previa location of the tumor is maintained throughout pregnancy. (Fig. 3.)

Fig. 2. Obstetrical ultrasound at 20 weeks of gestation

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Fig. 3. Previa position of the ovarian cyst

Pregnancy evolution was uncomplicated, with normal parameters of fetal development located
in cranial presentation. At 39 weeks of amenorrhea ultrasound reveals dystocia position of cyst
which reached approximate dimensions of 244/91mm, which is why we decided delivery by
elective caesarean section. (Fig. 4.)

Fig. 4. Obstetrical ultrasound at 39 weeks of gestation

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During surgery we found left ovary turned in a tumor with safely surface, gray-violet, without
external vegetation, of oval shape, inclavated in the pelvis, with dimensions of 240/130mm,
normal right ovary as appearance (Fig. 5).

Fig. 5. The left ovary during surgery

We practiced anexectomy left with extemporaneous examination which revealed the absence
of malignancy. Postsurgery evolution of patient and newborn (3200 g weight and Apgar Index
10) were favorable without complications. In three days postpartum mother and baby were
discharged.
The histological paraffin examination has established the diagnosis of mucinous adenoma cyst
with focal epithelial stratification.

Conclusions/discussions

Usually, the adnexal masses associate with pregnancy which persists after first trimester had
abdominal development due to increase in size of the uterus.
Mechanical dystocia through previa ovarian cyst is a rare situation described in the literature
of pregnancy associated with previa tumors.

REFERENCES

1. Schmeler KM, Mayo-Smith WW, Peipert JF, Weitzen S, Manuel MD, Gordinier ME.(2005).Adnexal
masses in pregnancy: surgery compared with observation. Obstet Gynecol May, pp. 1098-1103.
2. Palmer J, Vatish M, Tidy J. Epithelial ovarian cancer in pregnancy: a review of the literature. (2009) BJOG
116(4), pp. 480-491.
3. Giuntoli RL 2nd, Vang RS, Bristow RE. (2006) Evaluation and management of adnexal masses during
pregnancy. Clin Obstet Gynecol Sept, pp. 492-505.
4. Machado F, Vegas C, Leon J, et al., (2007) Ovarian cancer during pregnancy: analysis of 15 cases. Gynecol
Oncol May, pp. 446-450.

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5. Baser E, Erkilinc S, Esin S, et al., Adnexal masses encountered during cesarean delivery.(2013) Int J
Gynaecol Obstet 2013 Nov; pp. 124-126.
6. Webb KE, Sakhel K, Chauhan SP, Abuhamad AZ. Adnexal mass during pregnancy: a review.(2015) Am J
Perinatol 2015, pp. 1010-1016.
7. Killackey MA, Neuwirth RS.(1988) Evaluation and management of the pelvic mass: a review of 540 cases.
Obstet Gynecol 1988, pp. 311-322.
8. Froyman W, Landolfo C, De Cock B, et al., (2017)Risk of complications in conservatively managed
adnexal masses initially thought to be benign at subjective impression by the ultrasound examiner.
Ultrasound Obstet Gynecol 2017; p. 1
9. O. Tariel, C. Huissoud, R.C. Rudigoz, G. Dubernard, (2013) Tumeurs ovariennes présumées bénignes lors
de la grossesse, Journal de Gynécologie Obstétrique et Biologie de la Reproduction 2013, pp. 842-855.

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The Importance of the Prenatal Detection of Umbilical Cord


Abnormalities for Antenatal and Intrapartum Management

NOVAC Liliana1, DIJMĂRESCU Anda Lorena1, MANOLEA Maria Magdalena1,


VRABIE Sidonia Cătălina1, TUDORACHE Stefania1, ILIESCU Dominic Gabriel1,
TUDOR Adriana2, STOENESCU Manuela2, NOVAC Marius Bogdan3
1 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy Craiova, (ROMANIA)
2 Department of Obstetrics and Gynecology, PhD Student, University of Medicine and Pharmacy of Craiova, (ROMANIA)
3 Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy of Craiova, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Introduction
Umbilical cord (UC) is the vital link between the placental and fetal well-being in the fetomaternal
interface. A complete fetal ultrasonographic study includes umbilical cord assessment because
abnormalities related to morphology, coiling, placental insertion, number of vessels, presence of
primary masses can contribute to perinatal complications. These conditions may be associated with
other fetal abnormalities and aneuploidy, that may require karyotyping and echocardiography.

Material and Methods


The study analyzes 52 pregnancies diagnosed with umbilical cord abnormalities detected by the
second trimester scan at the “Filantropia” Clinical Hospital, Craiova. The umbilical cord structure
was demonstrated by conventional real-time ultrasound and the umbilical blood flow patterns were
analyzed by color (power) and pulsed Doppler ultrasound. Neonatal outcome was evaluated by the
Department of Neonatology.

Results
Of the 52 cases, vascular abnormalities were: single umbilical artery-3 cases; cases, unusual
persistence of the right umbilical vein-1 case; hypoplastic umbilical artery- 2 cases. The presence of
aneuploidy was diagnosed in 2 cases. Systematic ultrasound evaluation of cases with isolated cordon
abnormalities led to a good neonatal outcome, the main complications were the intrauterine growth
restriction and the need of emergency cesarean for acute fetal distress in 5 cases.As insertion
abnormalities, velamentous insertion was diagnosed in 4 cases, with vasa praevia in one case,
requiring repeat cardiotocographic and echographic follow-up in the last trimester and elective
extraction of the fetus at 35 weeks in the case of a patient with vasa praevia. Hypercoiled umbilical
cord was present in 15 cases resulted in intrapartum heart rhythm abnormalities and Apgar score
below 8, one case being complicated by fetal demise at 32 weeks.
Hypercoiled umbilical cord was present in 15 cases resulted in intrapartum heart rhythm
abnormalities and Apgar score below 7 at 1 and 5 minute in 3 cases, one case being complicated by
fetal demise at 32 weeks. 22 cases presented single or multiple loops of nuchal cord, 4 cases with
multiple loops and macrosomia required birth by emergency cesarean.
Keywords: umbilical cord, fetal outcome, ultrasound

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Introduction

The umbilical cord provides a stable interconnection between the well-being of the fetus and
the placenta at the level of the fetal-maternal interface. Umbilical cord ultrasound evaluation can
diagnose important congenital and functional abnormalities of this structure, improving
pregnancy outcome by orientated intrapartum management. Altered structure of umbilical cord
can be associated in some cases with fetal anomalies and aneuploidies. Using ultrasound, we can
depict various congenital abnormalities associated of the umbilical cord related to morphology,
placental insertion, number of vessels and primary tumors.

Material and method

The study analyses 52 pregnancies diagnosed with umbilical cord abnormality detected by the
second trimester scan at Filantropia Clinical Hospital, Craiova. The study group included
primigravida and multigravida with singleton pregnancies only. All pregnant women were
informed about the study using the patient information sheet and were appropriately counselled.
Second trimester scan documented the presence or absence of umbilical cord complications
placental lie and placental umbilical cord insertion.
Four characteristics of the umbilical cord were evaluated: measuring the area of the umbilical
cord, assessing the number of vessels, assessment of the umbilical cord placental insertion site,
determining spiral pattern. Fetal karyotyping was carried out by amniocentesis.
Each antenatal visit included fetal heart rate monitoring for five minutes. Prolonged non-stress
tests were used in third trimester. Patients were managed according to obstetrical principles and
interventions were undertaken for obstetric indications, after informed consent.
We defined an adverse perinatal outcome as Apgar score of <7 at 1 and 5 minutes and
admission to Neonatal Intensive Care Unit (NICU). Neonatal outcome was evaluated by the
Department of Neonatology.

Results

Of the 52 cases, vascular abnormalities such as single umbilical artery (SUA) were found in 3
cases. Invasive testing for chromosome analysis was recommended in 2 cases of SUA associated
with structural anomalies, oligohydramnios and intrauterine growth restriction(IUGR). Trisomy
18 was found in both cases (Fig. 1, Fig. 2).

Fig. 1. SUA – 2D and Doppler ultrasound, transverse section

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Fig. 2. SUA – identifying just one umbilical artery a long the fetal bladder

One case of persistent right umbilical vein (PRUV) was diagnosed with positive karyotyping
for trisomy 18 followed by therapeutic abortion.
The hypoplastic umbilical artery was diagnosed in 2 cases, without other associated
malformations of the fetal urinary tract. Both pregnancies have developed small for gestational
age fetuses (SGA) with Apgar score <7 and respiratory distress (Fig. 3).

Fig. 3. Hypoplastic umbilical artery

Second trimester scan diagnosed true cord cysts in 4 cases, one having large, persistent
dimensions without any associated fetal abnormalities (Fig. 4). These cases did not require
special management in labor with good neonatal status, Apgar score 8 at 1 minute and 9 at 5
minutes.

Fig. 4. Cord cyst – 2D and 3D evaluation

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There was a case of congenital umbilical hernia. The presence of aneuploidy was diagnosed
followed by therapeutic abortion (Fig. 5).

Fig. 5. Congenital umbilical hernia

Systematic ultrasound evaluation of cases with isolated cord abnormalities led to a good
neonatal outcome, the main complications were the intrauterine growth restriction (IUGR) and
the need of emergency cesarean for acute fetal distress in 5 cases.
As insertion abnormalities, velamentous insertion (VCI) was diagnosed in 4 cases, with vasa
praevia in one case, requiring repeat cardiotocographic and echographic follow-up in the last
trimester and elective extraction of the fetus at 35 weeks in the case of a patient with vasa praevia
(Fig. 6, Fig. 7).

Fig. 6. Velamentous insertion

Fig. 7. Vasa praevia

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Hypercoiled umbilical cord was present in 15 cases resulted in intrapartum heart rhythm
abnormalities and Apgar score below 7 at 1 and 5 minute in 3 cases, one case being complicated
by fetal demise at 32 weeks (Fig. 8).

Fig. 8. Umbilical coiling index (UCI) – hypercoiling

22 cases presented single or multiple loops of nuchal cord. 4 cases with multiple loops and
macrosomia required birth by emergency cesarean (Fig. 9).

Fig. 9. Multiple loops of nuchal cord

Discussions

Detection of single umbilical artery is important for prenatal diagnosis because it can be
associated with congenital anomalies and aneuploidy. In two-thirds of cases asociated with fetal
malformations there is an increase risk of antepartum fetal demise [1]. Hypoplastic umbilical
artery has a better fetal prognosis than SUA and karyotyping is not indicated in isolated forms
because there is no evidence of increased risk of chromosomal defects. Pathological conditions
like IUGR, placental infarction, polyhydramnios, congenital heart disease, umbilical cord
hematoma and abnormal umbilical cord insertion can influence pregnancy evolution [2].PRUV
occurs in 0.1%-0.3% of pregnancies and results in an abnormal course of blood flow in the fetal
liver [3]. Nonisolated forms associates genitor-urinary, gastrointestinal, cardiac and skeletal
developmental disorders [4]. During routine ultrasound screening umbilical cord cysts can be
easily overlooked. In our study the neonatal outcome was favourable for isolated cysts. It is

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recommended to conduct a detailed ultrasound examination for other associated malformations


when an umbilical cord cyst is diagnosed and to evaluate the need to carry out a karyotype if
other anomalies are found [5]. A nuchal cord may be the result of increased fetal activity or
reduced amniotic fluid but can resolve spontaneously. There are important dilemmas regarding
the appropriate clinical management. Antepartum identification of a nuchal cord did not affect
our intrapartum management. As discussed above, there is no strong evidence of a clinically
significant increase in adverse pregnancy outcome. Cases with changes in the tightness of a
nuchal cord were managed as labor with fetal heart rate decelerations. Short-term outcomes of
neonates with a history of a tight nuchal cord were favorable. In a large retrospective study, term
neonates with a tight nuchal cord were slightly more likely to be admitted to a neonatal intensive
care unit [6]. Prenatal identification of pregnancies with velamentous insertion can influence the
perinatal outcome. Velamentous insertion is associated with an increased rate of vasa previa,
incidence being estimated at 0.04 %. These fetal vessels may break and the result is fetal
exsanguination. Intrapartum diagnosis is very difficult [7]. What is important and highlights the
progress of prenatal sonography is that in a small percentage of cases, subsequent findings have
led to another fetal diagnosis and parental counseling for the future pregnancy [8].

Conclusions

A complete second trimester ultrasound examination includes umbilical cord evaluation


because abnormalities related to morphology, coiling pattern, placental insertion, number of
vessels, presence of nuchal cords may contribute to perinatal complications. These conditions
may be associated with other fetal anomalies and aneuploidy.
Targeted examination can improve neonatal prognosis by identifying risk pregnancies
requiring close monitoring and intrapartum specific management.

REFERENCES

1. Hua, M, Odibo AO. (2010). Single umbilical artery and its associated findings. Obstet Gynecol. 115(5), pp.
930-934.
2. Petrikovsky, B. (1996). Prenatal diagnosis and clinical significance of hypoplastic umbilical artery. Prenat
Diagn.16(10), pp. 938-940.
3. Weichert, J. (2011). Persistent right umbilical vein: a prenatal condition worth mentioning? Ultrasound
Obstet Gynecol, 37, pp. 543-548.
4. Wolman, I., Gull, I., Fait, G., Amster, R., Kupferminc, MJ., Lessing, JB., Jaffa, AJ. (2002). Persistent right
umbilical vein: incidence and significance. Ultrasound Obstet Gynecol. 9(6), pp. 562-564.
5. Ruiz Campo, L., Saviron Cornudella, R., Gamez Alderete, F., Martinez-Payo, C., Perez Perez, P., Garrido
Fernandez, P., Lerma Puertas, D. (2017). Prenatal diagnosis of umbilical cord cyst: Clinical significance and
prognosis. Taiwan J Obstet Gynecol. 56(5), pp.622-627.
6. Henry, E., Andres, RL., Christensen, RD. (2013). Neonatal outcomes following a tight nuchal cord. J
Perinatol. 33, pp. 231-234.
7. Catanzarite V. (2001). Prenatal sonographic diagnosis of vasa previa: ultrasound findings and obstetric
outcome in ten cases. Ultrasound ObstetGynecol. 8, pp. 109-115.
8. Şorop-Florea, M., Ciurea, RN., Ioana, M., Stepan, AE., Stoica, GA., Tănase, F., Comănescu, MC., Novac,
MB., Drăgan, I., Pătru, CL., Drăguşin, RC., Zorilă, GL., Cărbunaru, OM., Oprescu, ND., Ceauşu, I.,
Vlădăreanu, S., Tudorache, Ş., Iliescu, DG. (2017). The importance of perinatal autopsy. Review of the
literature and series of cases. Rom J Morphol Embryol. 58(2). pp. 323-337.

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Doppler Change in Middle Cerebral Artery and Umbilical Artery –


Predictor for Perinatal Outcome in Intrauterine Growth-Restricted
Fetuses

NOVAC Maria Violeta1, TUDORACHE Stefania2, ILIESCU Dominic Gabriel2,


MANOLEA Maria Magdalena2, DIJMARESCU Lorena Anda2, VRABIE Sidonia2,
ȘOROP-FLOREA Maria2, ALEXANDRU Dragos5, TABACU Carmen6,
GHEONEA Ioana Andreea4, NOVAC Marius3
1 Department of Radiology and Medical Imaging, PhD Student, University of Medicine and Pharmacy of Craiova, (ROMANIA)
2 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy Craiova, (ROMANIA)
3 Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy of Craiova, (ROMANIA)
4 Department of Radiology and Medical Imaging, University of Medicine and Pharmacy of Craiova, (ROMANIA)
5
Department of Medical Informatics and Biostatistics,University of Medicine and Pharmacy of Craiova, (ROMANIA)
6 Department of Obstetrics and Gynecology, PhD Student, University of Medicine and Pharmacy of Craiova, (ROMANIA)

Emails: [email protected], [email protected]

Abstract

Objective
To estimate the role of the middle cerebral artery (MCA) and umbilical artery (UA) Doppler
parameter in predicting the fetal outcome in intrauterine growth restriction (IUGR).

Material and Methods


The prospective study was conducted on 126 single pregnancy with small for gestational age
(SGA) fetuses, which were evaluated by the middle cerebral artery and umbilical artery
velocimetry between 30-32 weeks of gestation.

Results
Mean gestational age at the inclusion was 32.2 weeks, mean estimated fetal weight (EFW) at
study inclusion was 10 percentile and mean birth growth was 8 percentile. Pregnancy with
abnormal velocimetry (UA-PI> 95 percentiles, UA Absent/Reversed EDF and MCA-PI <5
percentiles, MCA Absent/Reversed EDF) had a high percentage of Apgar score ≤ 7 to 1 and 5
minutes, admission of NICU and of premature birth, than those with normal velocimetry.

Conclusions
There is enough evidence that Doppler indexes from the fetal circulation can predict the
perinatal outcome in an IUGR pregnancy.
Keywords: IUGR, Doppler velocimetry, perinatal outcome

Introduction

Detecting the fetus with growth restriction that presents an increased risk of adverse perinatal
outcome was a challenge in obstetrics. In pregnancies affected by IUGR, a number of progressive

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and predictable placental and fetal Doppler modifications have been described as an adaptive
mechanism for intrauterine stress [1]. But the clinical and ultrasound measurements establish the
diagnosis of IUGR at a late stage when the fetus can already be compromised, while Doppler
velocimetry can detect IUGR at an early stage so that the affected fetus can be born without
significant impairment. The color Doppler ultrasound provides information on vascular and blood
flow resistance. The introduction of Doppler velocimetry in obstetrics has provided a non-
invasive method of indirect assessment of fetal and uteroplacental circulation [2].
The umbilical artery is the most commonly studied vessel in Doppler velocimetry due to its
accessibility and association with fetal outcomes. Umbilical artery Doppler has first been seen as
a possible ability to monitor fetal compromise. In normal pregnancies, umbilical artery resistance
shows a continuous decline, unlike fetuses with uteroplacental insufficiency. With the evolution
of IUGR, end-diastolic velocity is lost (AEDF) and, finally, reversed (REDF). The middle
cerebral artery is the most studied fetal cerebral artery and can detect cerebral blood flow and
direction, which is why it has been selected for examination in this context [3]. MCA Doppler
recordings are commonly included in the management of fetuses at risk of developing placental
and of course fetal compromise.
Doppler velocities are useful as a specific clinical tool if a placental insufficiency may lead to
IUGR [4]. It seems that the umbilical and middle cerebral artery velocimetry can be a good
predictor of risk of antenatal compromise in growth restricted fetus [5, 6]. The combination of
fetal and fetal placental parameters is an important method of investigation for both the placental
function and the hemodynamic adaptation of the fetus. [7].

Material and method

The study population includes 126 singleton pregnancies with small for gestational age fetuses
(birth weight <10th percentile of gestational age), conducted over two years, from October 2015
to November 2017 in the Department of Obstetrics and Gynecology of the Municipal Clinic
Hospital “Filantropia” Craiova. These pregnant women were examined for the prenatal Doppler
of the umbilical artery and the middle cerebral artery between 30-32 and 36-38 weeks of
gestation. The diagnosis of growth restriction was established on the basis of the ultrasonographic
evaluation of fetal growth and birth growth. We have eliminated pregnancies with fetal
congenital malformations and stillbirths. We defined an adverse perinatal outcome as Apgar score
of ≤7 at 1 and 5 minutes, admission to NICU, birth weight of <10th percentile at delivery,
premature birth (gestational age <37 weeks at delivery).

Results

A total of 126 patients were selected into the study, and who were detected to have an IUGR
suspicion at the time of study inclusion. Mean gestational age at the inclusion was 32.2 weeks,
mean estimated fetal weight (EFW) at study inclusion was 10 percentile and mean birth growth
was 8 percentile. The Doppler parameters of the umbilical and middle cerebral artery, the
Resistance Index (RI), the Pulsatility Index (PI) and the systolic/diastolic ratio (S/D) showed
modified values, especially on the umbilical artery (Table 1).

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Table 1. Baseline feature in pregnancies with IUGR


Parameter Mean±SD
GA at study inclusion (weeks) 32.2±0.45
EFW at study inclusion (percentile) 10±2.07
Birth growth (percentile) 8±1.26
Umbilical artery Resistance index 0.74±0.11
Pulsatility index 1.22±0.23
S/D ratio 3.65±2.09
Middle cerebral artery Resistance index 0.85±0.07
Pulsatility index 1.77±0.24
S/D ratio 6.28±1.47
Data are expressed in Mean±SD; GA: Geastational age; EFW: estimated fetal weight

Umbilical artery flow shows the degree of placental damage. Absent or reversed end diastolic
flow indicates a reduction in placental blood flow and induction of a severe fetal distress (Fig. 1).
An abnormal UA Doppler assessment was defined as a PI > 95 percentile, AEDF or REDF.

Fig. 1. AEDF in UA. 32.5 week of gestation; SGA=9 percentile

The evaluation of cerebral blood flow in middle cerebral artery of the fetuses was an important
part of the assessment of IUGR pregnancies. MCA abnormalities were defined as a PI<5
percentile, AEDF or REDF. MCA resistance index values gradually decrease to AEDF fetuses,
indicating a continued reduction in cerebral vascular resistance during chronic fetal hypoxia and
the installation of the brain-sparing phenomenon (Fig. 2, 3).

Fig. 2. REDF in MCA. 32.5 week of gestation; SGA=9 percentile

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Fig. 3. AEDF in MCA. 30.5 week of gestation; SGA=4 percentile

The fetal outcomes were analyzed in terms of a percentile of birth weight, Apgar score ≤7 at 1
and 5 minutes, admission to NICU and premature birth (Table 2).
UA-PI> 95 percentiles were associated with a low Apgar score ≤7 at 1 minute (32.53%) and 5
minutes (24.6%), with an admission to NICU at 30.15% of cases and premature birth in 22.22%
of cases.
Concerning another parameter, MCA-PI <5 percentiles (24.60% of cases), 23.80% and
16.66% had an Apgar score of ≤7 at 1 minute and 5 minutes, respectively. Admission to NICU
occurred in 21.42% of cases and premature birth in 15.87% of cases.
In the case of UA Absent/Reversed EDF and MCA Absent/Reversed EDF, almost all cases,
6.34% and 11.90% respectively, showed a low Apgar score ≤7 to 1 and 5 minutes, admission to
NICU and premature birth. We mention that these modified Doppler parameters were present as
associates, at both AU and MCA level.

Table 2. Neonatal outcome in relation to abnormal umbilical and middle cerebral artery indices
Doppler indices Neonatal outcome
No. of % 1 minute ≤7 5 minutes ≤7 Admission to Premature
cases Apgar score Apgar score NICU birth
(%) (%) (%) (%)
UA Doppler
UA-PI >95 percentile 46 36.5 32.53 24.6 30.15 22.22
UA Absent/Reversed EDF 8 6.34 6.34 5.55 6.34 6.34
Normal UA Doppler 80 63.49 24.6 1.58 3.17 16.66
MCA Doppler
MCA-PI < 5 percentile 31 24.60 23.80 16.66 21.42 15.87
MCA Absent/Reversed EDF 15 11.90 11.90 11.11 11.90 9.52
Normal MCA Doppler 95 75.39 31.74 4.76 11.11 20.63
UA: umbilical artery; MCA:middle cerebral artery; PI:pulsatility index; NICU:neonatal intensive care unit;
EDF:end diastolic flow

Discussions

The information obtained by prenatal ultrasonography of high risk pregnancy has become
essential in the routine pregnancy care [8]. Doppler velocimeters can detect altered blood flow
velocity in the middle cerebral artery and umbilical artery and show changes in placental
resistance, so it can make decisions about the appropriate timing of delivery. It is known that
perinatal morbidity and mortality were significantly higher in small for gestational age babies

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with abnormal Doppler than those with normal Doppler, and it seems that the association between
smoking and IUGR increases even more the risk of stillbirth [9].
Arduini and Rizzo [10] in a cross-sectional study demonstrated that the ratio of Doppler
indices to the cerebral and umbilical arteries provided the best predictive method of perinatal
outcome. This report reflected hemodynamic changes better than the doppler index of the
umbilical and cerebral arteries, studied individually. So, the combination of Doppler parameters
in the umbilical artery and the middle cerebral artery would reflect the best way of early detection
of fetal compromise and monitoring of IUGR high risk pregnancies.
The UA Doppler is a method that specifically evaluates the placental function [11].
Deterioration of placental function, which is manifested by increased resistance to blood flow
and consequent reduction of the diastolic velocity of the umbilical artery, is a factor that may
influence neonatal prognosis [12]. This was shown in our study by demonstrating that changes in
the Doppler UA were associated with high percentages of adverse perinatal outcomes. The fetal
Doppler in the third trimester is an important tool for predicting negative fetal outcome.
The present study showed that only MCA Absent/Reversed EDF manifested an increased
percentage of a low Apgar score, admission to NICU and premature birth. We recommend the
use of Doppler in all patients of an IUGR, and pregnancy could be continued even in the presence
of AEDF for 7 to 10 days, with intensive fetal surveillance. By this, you can also gain time for
steroids to improve fetal lung maturity, increase gestational age and fetal transfer “in utero” to a
tertiary center where adequate neonatal care can be provided.

Conclusions

There is enough evidence that Doppler indexes from the fetal circulation can predict the
perinatal outcome in the IUGR pregnancy.

REFERENCES

1. Unterscheider, J., Daly, S., Geary, MP., Kennelly, MM., McAuliffe, FM., O'Donoghue, K,, Hunter, A.,
Morrison, JJ., Burke, G., Dicker, P., Tully, EC., Malone, FD. (2013). Predictable progressive Doppler
deterioration in IUGR: does it really exist? Am J Obstet Gynecol. 209(6), pp. 539.e1-7.
2. Khanduri, S., Parashari, UC., Bashir, S., Bhadury, S., Bansal, A. (2013). Comparison of diagnostic efficacy
of umbilical artery and middle cerebral artery waveform with color Doppler study for detection of
intrauterine growth restriction. J Obstet Gynaecol India. 63(4), pp. 249-255.
3. Aditya, I., Tat, V., Sawana, A., Mohamed, A., Tuffner, R., Mondal, T. (2016). Use of Doppler velocimetry
in diagnosis and prognosis of intrauterine growth restriction (IUGR): A Review. J Neonatal Perinatal Med.
9(2), pp. 117-126.
4. Moldoveanu (Said), A. L., Oprescu, DN., Catanescu Novac, V., Dragan, I., Novac M. (2017). The Role of
Fetal Doppler Monitoring in Preeclampsia with/without Intrauterine Growth Delay. Proceedings, 5 th
Congress of The Romanian Society of Ultrasound in Obstetrics and Gynecology, Targu Mures, Romania,
20-22 April 2017, pp. 401-405.
5. Novac, L., Niculescu, M., Iliescu, D., Manolea, M., Dijmarescu, L., Comanescu, A., Tudorache, S., Cernea,
N., Căpitănescu, R., Novac, M. (2010). Chorial villositary vasculogenesis correlated with ultrasound
morpho-functional markers of the trophoblast. Advance in Perinatal Medicine, Conference Proceedings,
XXII European Congress of Perinatal Medicine, Granada, Spain, May 26-29, 2010, Monduzzi Ed. p. 143-
148.
6. Dhand, H., Kansal, HK., Dave, A. (2011). Middle cerebral artery Doppler indices better predictor for fetal
outcome in IUGR. J Obstet Gynaecol India. 61(2), pp. 166-171.
7. Lerner, JP. (2004). Fetal growth and well-being. Obstet Gynecol Clin N Am. 31, pp. 159-176
8. Şorop-Florea, M., Ciurea, RN., Ioana, M., Stepan, AE., Stoica, GA., Tănase, F., Comănescu, MC., Novac,
MB., Drăgan, I., Pătru, CL., Drăguşin, RC., Zorilă, GL., Cărbunaru, OM., Oprescu, ND., Ceauşu, I.,

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Vlădăreanu, S., Tudorache, Ş., Iliescu, DG. (2017). The importance of perinatal autopsy. Review of the
literature and series of cases. Rom J Morphol Embryol. 58(2), pp. 323-337
9. Ionescu, AC., Popescu, I., Banacu, M., Matei, A., Bohîltea, R., Dimitriu, M. (2017). Is it Possible to Predict
Stillbirth in the Third Trimester?. Proceedings, 5th Congress of The Romanian Society of Ultrasound in
Obstetrics and Gynecology, Targu Mures, Romania, 20-22 April 2017, pp. 194-198.
10. Arduini, D., Rizzo, G. (1992). Prediction of fetal outcome in small for gestational age fetuses: comparison
of Doppler measurements from different vessels. J Perinat Med. 20, pp. 29-38.
11. Cruz-Martinez, R., Figueiras, F. (2009). The role of Doppler and placental screening. Best Pract Res Clin
Obstet Gynaecol.23, pp. 845-855.
12. Nomura, RM., Niigaki, JI., Horigome, FT., Francisco, RP., Zugaib, M. (2013). Doppler velocimetry of the
fetal middle cerebral artery and other parameters of fetal well-being in neonatal survival during pregnancies
with placental insufficiency. Rev Assoc Med Bras.59(4), pp. 392-399.

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Role of Pre-Natal Diagnosis of Congenital Heart Defects – Case


Study

OANCEA Mihaela1, BLAGA Ligia1, BALTOAICA Razvan2, CIORTEA Razvan1,


BUCURI Carmen1, DICULESCU Doru1, VIDRA Camelia2,
POIENAR Alexandra-Andreea2, MIHU Dan1
1Iuliu Hatieganu University of Medicine and Pharmacy (ROMANIA)
2Dominic Stanca Clinic, Cluj-Napoca (ROMANIA)
Email: [email protected]

Abstract

Introduction
Interrupted aortic arch is a rare congenital heart disease (1% of congenital heart diseases), very
rarely diagnosed in the fetus. Of the three types, B type (aortic arch interrupted between left
common carotid artery and left subclavian artery) is the most frequent (55% of cases). It is
associated with ventricular septal defect (VSD) in 90% of cases and Di George Syndrome in 50%
of cases.

Methodology
We present a new-born antenatally diagnosed with interrupted aortic arch and VSD. Amniotic
fluid genetic testing revealed the deletion of 22q11.2 (Di George Syndrome). Spontaneously born
at term, with good postnatal adaptation, he was transferred in a pediatric cardiac surgery unit,
under prostaglandin treatment.
Echocardiography confirmed type B interrupted aortic arch, VSD, bicuspid hyperplasic aortic
valve, patent foramen ovale and patent ductus arteriosus. Surgical intervention in the 5th day of
life reconstructed the aortic arch and closed the VSD, atrial septal defect and ductus arteriosus.
After surgery the new-born was hemodynamically stable with moderate inotrope support. The
evolution was slowly favourable, in the 19th postoperative day he was transferred to the pediatric
cardiology unit.
3 weeks after surgery he developed a Staphilococcus epidermidis sepsis, which resolved under
antibiotic treatment.
The final postoperative echocardiography revealed a good cardiac function.

Results
The short and long term cardiac prognosis is good, but in this new-born it is encumbered by
the association of 22q11.2deletion.

Conclusions/Discussion
The antenatal diagnosis and prompt surgical intervention in a specialised unit offers a good
survival chance for children with rare congenital heart disease.
Keywords: antenatal diagnosis, interrupted aortic arch, echocardiography

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Introduction

Interrupted aortic arch (IAA) is a rare cardiac malformation. This anomaly occurs in 3/10000
live births [1], it represents almost 1% of critical congenital heart diseases [2] and it accounts for
5% off all cases of aortic arch disruptions [3].
Interrupted aortic arch is characterised by a disruption in the continuity of the ascending aorta
and the descending intra-thoracic aorta. The disruption may be complete or incomplete in which
case, a nonpatent fibrotic band is formed [4].
It was classified in 1959 in three categories: type A (IAA-A): interruption between the left
subclavian artery and the descending aorta; type B (IAA-B): interruption between the left
subclavian artery and the left common carotid artery; type C (IAA-C): interruption between the
innominate and the left carotid artery [5]. IAA-B is the most common form, with an incidence of
84% of the total of IAA cases [6].
IAA can be associated with intracardiac defects or other conotruncal anomalies. The
association with ventricular septal defect or other complex cardiac malformations is present in
more de 95% of cases [7].
The pre-natal detection rate is approximately 50% [8].
Prenatal diagnosis is difficult to detect, but its importance is vital, due to the rapid degradation
of the new-borne and the immediate necessity for neo-natal treatment and preparation for
corrective surgery [1].
Preoperative management relies on the administration of prostaglandins to allow lower body
perfusion from the right ventricle, via the arterial duct [3].

Methodology

Maternal Data
We examined a 24 year old woman, G1, P0, Caucasian ethnicity, without significant medical
history. The patient’s height is 158 cm, and weighs 55.6kg. The pregnancy was obtained
spontaneously and she took Folic acid, 400 micrograms per day, until the twelfth week of
gestation.

First trimester screening


The first trimester scan was performed at 12 week ad 5 days. The embryo was 63.3mm, with a
nuchal fold of 1.2mm. The fetal heart rate was 140bpm. The blood level of betaHCG was 0.57
MoM and of PAPP-A was 1.09 MoM, The combined risk was 1/6596 for trisomy 21 and 1/12183
for Trisomy 13 and 18.

Second trimester scan


The second trimester scan was performed at 23 weeks and 3 days of gestation. The biometry
was within normal range: head circumference 220.5mm (59th percentile); abdominal
circumference 195mm (67th percentile); femoral length 41.1 mm (35th percentile); estimated fetal
weight 543g (21st percentile). The placenta was anterior, with normal structure, with central
insertion of the umbilical cord. The amniotic fluid was elevated, with a deepest vertical pouch of
8.2 cm (hidramnios). The umbilical cord was normal, with 3 vessels. Active fetal movements
were observed.
The foetal anatomy is normal, except for the cardio-vascular system. Foetal sex: female.

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Doppler studies of the uterine arteries registered a PI a 1.23 and a Vmax of 75.8 cm/s for the
right uterine artery and a PI of 1.02 and V max 93.1 cm/s for the left artery. No notch was
identified on either one of them.
The transvaginal ultrasound didn’t show any vasa praevia and the distance between the
internal cervical orifice and the lower margin of the placenta was 35mm. the cervical length was
30mm.

Fetal echocardiography
The situs was normal, solitus (Fig. 1), with the stomach on the left and the fetal heart axis
oriented at a 40° angle. The cardio-thoracic index was 0.5. The venous systemic drainage
appeared normal. The pulmonary venous drainage appeared normal. The interatrial septum
appeared normal, with the foramen ovale valve in the central third of the septum, opening in the
left atrium (Fig. 2). The blood flow at the level of the foramen ovale was normal, from right to
left.
The atrio-ventricular valves were normally placed, mobile, of similar dimensions, with atrio-
ventricular concordance. No atrio-ventricular regurgitation was noticed at colour flow mapping or
pulse wave Doppler.
A moderate ventricular septum defect was found in the perimembranous area (Fig. 3), with
normal biventricular kinetics.
We highlighted a normal ventriculo-atrial concordance, without regurgitation at the valve
level.
The pulmonary artery had a normal trifurcation: left arterial artery, right arterial artery and
arterial duct.
The arterial duct was of normal size and placing (left of the trachea) and no aliasing was
noticed.
The transverse portion of the aortic arch could not be seen on three vessels view (Fig. 4).
On long axis view of the aortic arch we highlighted the ascending aorta that did not continue
with the aortic arch and split into the brachiocephalic truck and the common carotid artery. The
left subclavian artery emerges from the descending aorta, after the junction with the arterial duct
(Fig. 5).
The described findings advocated for the diagnosis of interrupted aortic arch type B.
The heart rhythm was 145 bpm. No pericardial effusion was found.

Cardiac biometry
The diameter of the aorta at the valve level was 2.3 mm (z-score 3.39).
The pulmonary artery diameter was 4 mm (z-score 0.55).
The diameter of the aortic arch was 2.8 mm (z-score 0.08).

Cardiac Doppler
The pulmonary veins had a normal pattern.
The ductus venosus had a positive a wave and a PIV 0.776.
E/A of mitral valve was 0.56.
Velocity of the aorta was 45 cm/s.
Velocity of the pulmonary artery was 42 cm/s.

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Aditional investigations
A amniocentesis was performed + FISH (the association between the elevated amniotic fluid
level and the cardiac defect indicated a chromosomal examination). The result showed a 22q11.2
deletion and the diagnosis of DiGeorge syndrome was made.

Management
The couple were informed about the prognosis of the cardiac defect and its association with
the chromosomal anomaly.
The patient was referred to a fetal cardiac department where she received information about
the possibility of surgical correction of the cardiac defect. She was re-evaluated at 28 weeks of
gestation.
The fetal growth and the amniotic fluid were periodically evaluated.
A in utero transfer was made in a third degree centre where the immediate post-partum
surgical correction was possible.

Outcome
A vaginal birth of a 3000g female baby took place at 39 weeks and 5 days. The APGAR score
of the new-borne was 7/8/8.
The surgical correction was performed in day 5. The surgical team managed to reconstruct the
aortic arch, close the ventricular defect and ligature the arterial duct.
The post operatory recovery was slow due to some episodes of infection.

Follow up
The child was re-evaluated in a pediatric cardiology unit. The investigations showed good cardiac
function.
She was given specific treatment for the hypoparathyroidism and the prophylactic mesures to
prevent infectious endocarditis were taken.

Discussions

Indications for prenatal testing for the 22q11.2 deletion are: a previous child with a 22q11.2
deletion or a DiGeorge/velocardiofacial syndrome, an affected parent with 22q11.2 deletion and
in utero detection of a fetus with a conotruncal cardiac defect [9].
Deletion at the level of the long arm of chromosome 22 is involved in many congenital heart
defects through the disruption of rostral neural crest cells [10].
DiGeorge syndrome is present in 30% of patients with IAA. The risk of this chromosomal
anomaly is higher in patients with posterior ventricular septal defect and IAA-B [3].

Conclusions

The antenatal diagnosis and management in a specialised unit offers a good survival chance
for children with rare congenital heart disease.

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Fig. 1. situs normal, solitus (vena cava inferior Fig. 2. interatrial septum with foramen
and aorta on same view as the stomach) ovale visible

Fig. 3. ventricular septal defect in the Fig. 4. three vassels view: aortic arch not
perimembranous area visible

Fig. 5. left subclavian artery emerges from the descending aorta, after the junction with the arterial duct

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REFERENCES

1. Slodki M. et al., (2011). The three-vessel view in the fetal mediastinum in the diagnosis of interrupted aortic
arch. Ultrasound in Med & Biol (37)11, pp.1808-1813.
2. Knudson JD. Et al. (2012). Type B Interrupted Left Aotic Arch with Isolated Right Subclavian Artery.
Congenit Heart Dis 7, pp. E25-E30.
3. Friedman K. (2018). Preoperative Physiology, Imaging, and Management of Interrupted Aortic Arch.
Seminars in Cardiothoracic and Vascular Anesthesia 00(0), pp. 1-5.
4. Axt-Fliendner R. et al., (2011). Fetal and Neonatal Diagnosis of Interrupted Aortic Arch: Associations and
Outcomes. Fetal Diagn Ther 30, pp. 299-305.
5. Celoria CC. Patton RB. (1959). Congenital absence of the aortic arch. Am Heart J 58, pp. 408.
6. Schreiber C. et al., (1997). The interrupted aortic arch: an overview after 20 years of surgical treatment. Eur
J Cardiothorac Surg 12, pp. 466-469.
7. Allen HD. Driscoll DJ. Shaddy RE. Feltes TF. (2008). Moss and Adam’s Heart Disease in Infants, Children
and Adolescents. 7th ed. Lippincott Williams & Wilkins.
8. Vogel M. et al., (2010). Fetal diagnosis of interrupted aortic arch. Am J Cardiol 105, pp. 727-734.
9. Driscoll DA. (2001). Prenatal diagnosis of the 22q11.1 deletion syndrome. Genetics in Medicine 3(1), pp.
14-18.
10. Volpe P. Gentile M. Marasini M. (2002). Interrupted aortic arch type A with 22q11 deletion: prenatal
detection of an unusual association. Prenat Diag 22, pp. 371-374.

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Pulmonary Ultrasound in the Differential Diagnosis of Acute


Neonatal Respiratory Failure – Case Report

OGNEAN Maria Livia1,2, ZGARCEA Corina2, BOANTA Oana2, GROSU Florin1,3,


COTARLA Viorela4, CHICEA Radu1,5
1 Faculty of Medicine, University Lucian Blaga, Sibiu, (ROMANIA)
2 Neonatology Dept., Clinical County Emergency Hospital Sibiu, (ROMANIA)
3 Radiology and Medical Imaging Dept., Clinical County Emergency Hospital Sibiu, (ROMANIA)
4 Clinical Hospital of Pediatrics Sibiu, (ROMANIA)
5 Obstetrics and Gynecology Dept., Clinical County Emergency Hospital Sibiu, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected], [email protected]

Abstract

Acute neonatal respiratory failure may have different etiology and evolves with hypoxia,
persistent pulmonary hypertension, and often with cardiac failure. Ultrasonography, including
cardiac and pulmonary ultrasound, have acquired, in recent years, an extremely important role in
the diagnosis and management of neonatal respiratory distress.

Objective
The authors are presenting an illustrative case for the importance of pulmonary and Doppler
echocardiography in the diagnosis and management of the newborn with acute respiratory failure.

Methods
Case report of a near term infant with persistent pulmonary hypertension secondary to
transient tachypnea, complicated with right pleural effusion and acute hypoxic respiratory failure.

Results
C.S.C., female, BW 2550g, GA 35 weeks, was delivered in a lower level maternity hospital by
C-section for hemorrhagic placenta praevia, Apgar score 4/8, and presented early onset
respiratory distress syndrome. The infant was submitted to our unit with severe respiratory
failure, pallor, generalized cyanosis, peripheral oxygen saturations of 70-75%, tachypnea,
intercostal and subcostal retractions, apnea, tachycardia, systolic murmur grade II/6. Mechanical
ventilation was initiated, Doppler echocardiography revealed persistent foramen ovale and ductus
arteriosus, grade II tricuspid insufficiency, while thoracic x-ray showed right pulmonary
atelectasis while pulmonary ultrasound visualized anterior-lateral pleural fluid collection on the
right side up to the pulmonary apex. Invasive respiratory support was continued under
sonographic and radiologic monitoring with resolution of the pleural effusion in 72 hours,
extubation on CPAP after 6 days and discharge of the newborn after 16 days.

Conclusions
Pulmonary ultrasound helped clarifying the origin of the right lung atelectasis and serial
examinations helped avoiding pleural drainage, allowing a more conservative management of the

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case and lowering the risk for more complications. Bedside ultrasonography – cardiac,
pulmonary, cerebral – allows a rapid differential diagnosis in the acute neonatal respiratory and
cardiac failure and rapid, focused therapeutic interventions.
Keywords: sonography, echocardiography, pulmonary ultrasound, acute cardiac failure, acute neonatal respiratory
failure, pleural effusions, newborn

Introduction

The ability of the newborn to adapt to extrauterine life is essential for neonatal survival. Of all
the physiological changes occurring after birth, the most critical for survival is pulmonary
adaptation, the transition from fluid-filled to air-filled lung. Therefore, respiratory distress
syndrome (RDS) is the most frequent condition in newborns.
Careful evaluation of the neonate, complete pregnancy and birth history and investigations as
pulse oximetry, chest x-ray, blood tests (blood count with differentials, inflammatory tests, blood
gas analysis, etc.) are necessary in order to establish the etiology and complications of neonatal
RDS. Lung ultrasound has become, more and more, an useful and efficient tool in diagnosing
RDS and its complications during neonatal period, proving in many instances that is superior to
x-ray and allowing follow-up of the disease course. Pleural effusions are rarely occurring in
neonates, have various etiology, may evolve asymptomatic or with acute respiratory failure but
can be diagnosed rapidly and monitored using lung ultrasound. Also, interventions as
thoracocentesis can be performed under sonographic guidance.

Case report

We are reporting the case of a female newborn, C.S.C, delivered by emergency Cesarean
section at 35 weeks gestation for bleeding placenta praevia in a level I maternity hospital. The
newborn weighted at birth 2550 g, and had an Apgar score of 4 at 1 minute, 8 at 5 minutes,
needing manual bag and mask ventilation and stimulation. The parents were adolescents, the
mother, at the first pregnancy, had 15 years, the father 17 years, living in rural area. The newborn
presented signs of respiratory distress – tachypnea, grunting, nasal flaring, costal retractions –
immediately after birth and the newborn was submitted at two hours after birth to our unit (level
III, regional neonatal intensive care unit). At admission, the newborn was diagnosed with severe
RDS, severely altered general condition, pallor, cyanosis, peripheral oxygen saturations of 70-
75% in room air, tachypnea interrupted by short apneas requiring bag and mask ventilation,
intercostal and subcostal retractions, nasal flaring, grunting, tachycardia, and a systolic murmur,
grade II/6. In these conditions the decision was made to start mechanical ventilation on
endotracheal tube. Targeted volume, pressure-controlled ventilation was the ventilatory strategy
used in this case. The preterm infant was placed on a radiant warmer, pulse oximetry, blood
pressure, respiratory and heart rate were monitored. Considering hypoxia at birth we also
monitored diuresis, amplitude electroencephalography (aEEG) monitoring was started and fluid
restriction was instituted. Umbilical vein line was used initially for parenteral nutrition, fluids and
electrolytes. Prophylactic antibiotics – Penicillin G and Amykacin – were also administered
intravenously. In the same time, investigations were started to establish the etiology of RDS.
Hypoxemia was revealed by blood gas analysis (paO2 40 mmHg) after one hour of mechanical
ventilation. Anemia was diagnosed by blood count-hemoglobin 13,3g/dL.

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Creatinphosfokinase and lactic dehydrogenase were elevated, confirming birth hypoxia. On


cranial ultrasound, mild cerebral edema was seen while Doppler echocardiography showed
persistent pulmonary hypertension (persistent foramen ovale and ductus arteriosus and grade II
tricuspid valve regurgitation, and grade II pulmonary valve regurgitation) and mild pericardial
effusion. Chest radiography revealed thymus hypertrophy, enlarged heart, air bronchogram, and a
homogenous opacity on the lateral side and apex of the right lung. The opacity was interpreted as
pleural effusion (Fig. 1). Lung ultrasound confirmed simple pleural effusion but with a larger
extension than seen on x-ray, situated on the lateral side of the whole right lung up to the apex
(Fig. 2).

Fig. 1. Chest x-ray: homogenous opacity on the lateral side of the right lung, air bronchogram

Fig. 2. Pleural effusions on lung ultrasound in the first day of life

Since the newborn was rapidly stabilized with mechanical ventilation, a decision was made for
non-invasive management of the fluid correction, at least in the next few hours, and to monitor
the evolution of the pleural effusion with lung ultrasound. At 24 hours, sildenafil was used to

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treat persistent pulmonary hypertension. Resolution of the fluid collection was noted after 72
hours, concomitant with favorable clinical course (Fig. 3). Umbilical line was removed after 5
days since the newborn tolerated enterally well all the fluids and nutrients. In the 7th day of life
both heart and lung ultrasound were normal and the infant was extubated on nasal CPAP
(continuous positive airway pressure) for another 3 days. At this moment, all blood tests and
aEEG (slightly higher voltage initially) were normal.

Fig. 3. Normal lung aspect on ultrasound in the third day of life

The newborn was discharged at 16 days of life, with all tests normal, including standard EEG,
ophthalmologic and auditive screening tests, breastfed on demand, constantly growing, with
normal tone and reflexes and indication to return for follow-up of the neurodevelopment.

Discussions

Neonatal ability to adapt to extrauterine life is essential for survival. Of all the physiological
changes occurring at birth, pulmonary adaptation is the most critical for survival. Therefore, RDS
is frequently diagnosed in newborns [1, 2, 3]. Many of the neonatal respiratory conditions are
unique to neonatal period, occurring as a consequence of a delayed or abnormal adaptation to
extrauterine life. Respiratory distress occurs in almost 15% of term neonates, 29% of late preterm
infants, and the percentages are increasing under 34 weeks gestation as the gestational age
decreases [4, 5]. Transient tachypnea of the newborn, meconium aspiration, persistent pulmonary
hypertension, pneumonia, pneumothorax, aspiration syndromes, pleural effusions, and congenital
pulmonary malformations are the main causes of respiratory distress in term and late preterm
infants but in preterm infants surfactant deficiency is, by far, the most important cause of RDS [1,
6]. The most important risk factor for RDS are prematurity, meconium stained amniotic fluid,
delivery by Cesarean section, maternal diabetes and chorioamnionitis, and pulmonary congenital
abnormalities [4-7]. The clinical picture of RDS reflects increased work of breathing (tachypnea,
retractions, nasal flaring, grunting). But in term and near term neonates, without prompt
treatment, RDS may evolve rapidly with persistent pulmonary hypertension, and acute cardio-
respiratory failure. Respiratory failure is defined by the inability to maintain either oxygen
delivery to the tissues or the removal of carbon dioxide from the tissues, occurring when an
imbalance exists between the respiratory workload and ventilatory strength and endurance.

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Detailed history of pregnancy and birth, careful physical examination, laboratory tests (blood
count and differential, inflammation tests, blood gas analysis, etc.), and chest radiography are
needed for a more specific diagnosis of RDS and for targeted and timely interventions [4].
Differential diagnosis includes all possible causes of RDS and is important for treatment. In
our case, prematurity seemed the main cause of respiratory failure but perinatal hypoxia
complicated the initial course. Also, inadequate respiratory support at birth and during
transportation contributed to the occurrence of persistent pulmonary hypertension and, most
probably to pleural effusions, that aggravated respiratory failure and precipitated cardiac failure.
Pleural effusions defined as fluid accumulation in the pleural space, are rarely diagnosed in
newborns – 5.5/10.000 to 2.2% live births [8, 9] –. Pleural effusions are produced by changes in
venous pulmonary hydrostatic pressure, lymphatic pressure, oncotic blood pressure, local tissue
trauma, or inflammation [10]. Symptoms vary form no symptoms to aggravation of the
respiratory difficulties and acute respiratory failure. Depending on fluid type, there are serous
collections (hydrothorax), blood collections (hemothorax), lymph collection (chylothorax), and
purulent collections (pyothorax or empyema) [11]. In the presented case, we speculate, based on
imaging, lab tests, and evolution, that pleural effusion was serous, secondary to congestive heart
failure, same as the small pericardium collection seen on the first day of life. The usual
recommended treatment is thoracocentesis but serial lung ultrasound gave us the advantage of
trying a non-invasive approach.
Lung ultrasound has gained, recently, a lot more attention and a definite place in neonatal
intensive care units. The neonate has the advantage of a small chest that allows an indirect but
optimal lung visualization. Also, all the sonographic signs – normal or pathologic – described in
adults are found similarly in neonates [12, 13]. Linear probes are offering the best images [13].
Lung ultrasound is offering also other important advantages as lack of ionizing radiation,
simplicity, ease of use, bed side use, so that the method can be used to monitor lung diseases [11,
13, 14]. Lung ultrasound has been proved to be more sensitive than chest radiography [12, 15]
and almost as accurate as computer tomography [12] in the diagnosis of pleural effusions, being
able to detect small volumes of 3-5 ml of fluid[15]. Also, lung ultrasound can be used to guide
pleural fluid drainage [11]. Limitations of lung ultrasound are mostly related to the experience of
the examinator but authors are suggesting that a standardized protocol of examination may
alleviate this limitation [12]. Pleural effusions are seen on lung ultrasound as anechoic or cloudy
hypoechogenic aspect between the echogenic pleural line and roughly parallel lung surface, a
sign described as quaid sign [12, 14, 16]. Dynamic examination, with changing patient position,
shows that fluid flows about pleural space according to patient position [11]. Sinusoid sign
indicates the movement of the lung towards the pleural line [12]. Complex collections – as in
hemothorax, empyema – are seen as thicker fluid collections with internal septa [11]. Lung
consolidation – as in pneumonia – is more dense and contains multiple aeric spaces (internal
bronchogram) and can be easily differentiated from pleural effusions on lung ultrasound. The
volume of the collection can be measured using a simple index [12]. In our case, lung ultrasound
allowed us to refine the radiological suspicion of pleural effusion, a better estimation of the
volume and extension, and, most of all, trough serial examinations, a non-invasive management
could be performed, avoiding thoracocentesis.

Conclusions

Point-of-care ultrasonography has become a standard in modern neonatal intensive care units.

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Cardiac, pulmonary, cerebral, and even abdominal ultrasonography allow a rapid differential
diagnosis in acute respiratory and cardiac failure of the newborn enabling rapid therapeutic
interventions, aiming the etiology and identified complications, and increasing the chances for a
better recovery, without sequellae. In the described case, use of serial lung ultrasound allowed a
non-invasive management, avoiding thoracocentesis. The newborn recovered uneventfully,
without relapse, only with careful targeted volume, pressure-controlled mechanical ventilation.
Conservative management of small to medium simple pleural collections can become a
therapeutic strategy under close lung ultrasound monitoring.

REFERENCES

1. Gallacher, DJ, Hart, K, Kotecha, S. (2016). Common respiratory conditions of the newborn. Breathe 12, pp.
30-42.
2. Hillman, NH, Kallapur, SG, Jobe, AH. (2012). Physiology of transition from intrauterine to extrauterine
life. Clin Perinatol 39, pp. 769-783.
3. Sinha, SK, Donn, SM. (2006) Fetal-to-neonatal maladaptation. Semin Fetal Neonatal Med 11, pp. 166-173
4. Reuter, S, Moser, C, Baack M. (2014). Respiratory Distress in the Newborn. Pediatrics in Review 35, pp.
147-429.
5. Hibbard, JU, Wilkins, I, Sun, L, et al., Consortium on Safe Labor. (2010). Respiratory morbidity in late
preterm births. JAMA 304(4), pp. 419-425.
6. Natile, M, Ventura, ML, Colombo M, et al., (2014). Short-term respiratory outcomes in late preterm infants.
Italian Journal of Pediatrics 40, p. 52.
7. Bak, SY, Shin, YH, Jeon, JH, et al., (2012). Prognostic factors for treatment outcomes in transient
tachypnea of the newborn. Pediatr Int 54(6), pp. 875-880.
8. Rocha, G, Fernandes, P, Rocha, P. (2006). Pleural effusions in the neonate. Acta Paediatr 95, pp. 791e8.
9. Long, WA, Lawson, EE, Harned, JRHS, Kraybill, EN. (1984). Pleural effusions in the first days of life: a
prospective study. Am J Perinatol 1, pp 190e4.
10. Shih, Y-T, Su, P-H, Chen, J-Y, et al., (2011). Common Etiologies of Neonatal Pleural Effusion. Pediatrics
and Neonatology 52, pp. 251-255.
11. Ferreira, AC, Mauad, FF, Braga, T, et al., (2006). The role of ultrasound in the assessment of pleural
effusion. Radiologia Brasileira 39(2), pp. 145-150.
12. Lichtenstein, DA, Mauriat P. (2012). Lung Ultrasound in the Critically Ill Neonate. Current Pediatric
Reviews 8, pp. 217-223.
13. Gargani L, Volpicelli G. (2014). How I do it: Lung ultrasound. Cardiovascular Ultrasound 12, p. 25.
14. Cucerea, M, Rusneac, M, Suciu, L, et al., Ultrasound Contribution in the Neonatal Emergencies. 5 th
Congress Of The Romanian Society Of Ultrasound In Obstetrics And Gynecology. Ed. Vlădăreanu, S,
Mărginean, C, Vlădăreanu R. Filodiritto International Proceedings 2017, pp. 203-207.
15. Gryminski, J, Krakowa, P, Lypacewicz, G. (1976). The diagnosis of pleural effusion by ultrasonic and
radiologic techniques. Chest 70, pp. 33-37.
16. Simon, M, Gall, Z, Suciu, L, et al., The Role of Ultrasound Screening in the Neonatal Period – The
Detection and Monitoring of Neonatal Pathology with Prenatal, as well as of Postnatal Onset. 5th Congress
Of The Romanian Society Of Ultrasound In Obstetrics And Gynecology. Ed. Vlădăreanu, S, Mărginean, C,
Vlădăreanu R. Filodiritto International Proceedings 2017, pp. 334-339.

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Maternal Thrombophilia – Risk Factor for Fetal Cerebral


Hemorrhage?

OGNEAN Maria Livia1,2, ZGÂRCEA Corina Laura2, DUMITRA Raluca Elena2,


BOANTĂ Oana2, CHICEA Radu1,3
1 Faculty of Medicine, University Lucian Blaga, Sibiu, (ROMANIA)
2 Neonatology Dept., Clinical County Emergency Hospital Sibiu, (ROMANIA)
3 Obstetrics and Gynecology Dept., Clinical County Emergency Hospital Sibiu, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected], [email protected]

Abstract

The impact of maternal thrombophilia, both for the mother and the fetus, is controversial.
Early during pregnancy thrombophilia may cause abortions while placental vascular
abnormalities may induce problems towards the end of the pregnancy (fetal loss, preeclampsia,
placental abruption, intrauterine fetal retardation). Perinatal intraventricular hemorrhages and
cerebral vascular stroke were observed in the latest years in newborns delivered after pregnancies
complicated by thrombophilia, and hemorrhagic and ischemic events were seen in the absence of
a predisposing or causal context and without symptoms during neonatal period.

Objective
Given these observations, the authors wanted to evaluate the incidence of this type of perinatal
pathology using ultrasonography screening of the newborns from mothers with thrombophilia.

Methods
Cerebral and renal ultrasonography scans were performed between January 1, 2016 and
December 31, 2017 in term newborns delivered by mothers with thrombophilia admitted in the
Neonatology I Dept. of the Clinical County Emergency Hospital Sibiu. Data were collected
prospectively for neonates and maternal data were retrieved from the hospital charts.

Results
232 newborns delivered by mothers diagnosed with thrombophilia (gestational ages 37-40
weeks, birth weight 2620-3860 g) were evaluated through cerebral and renal ultrasound scans
during the study period (prevalence of 3.96% of all the 5853 deliveries during the study period;
91 cases in 2016, 3.23%, 141 cases in 2017, 4,64%). 17 of the 232 newborns had abnormalities
on the sonographic screening: 16 on the head ultrasonography and 1 on the renal scan (right
hypoplastic kidney – with possible vascular pathogenesis). 7 of the 16 newborns with abnormal
head ultrasound had intraventricular hemorrhages, choroid plexus cysts being observed in the
other 9 cases (maximum size 3 mm). Intraventricular hemorrhages were all minor - 4 grade I,
limited to the germinal matrix and 3 grade I/II, extended in the lateral ventricle but without
ventricular dilatation). In all the cases the sonographic aspect was typical for old hemorrhage,
with antenatal onset. All neonates with abnormal cerebral scans were delivered by Cesarean
section, only in 3 cases the surgical delivery being performed after labor onset. No correlation

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was observed between the severity of the cerebral hemorrhage and the maternal thrombophilia
type (minor/major). None of the neonates with intraventricular hemorrhage identified during
screening presented symptoms suggestive for cerebral hemorrhage during hospitalization, all had
an uneventful adaptation to the extrauterine life.

Conclusions
The results of the postnatal cerebral and renal sonographic screening of the newborns
delivered from pregnancies complicated with thrombophilia are raising more questions: are these
abnormalities related to maternal thrombophilia?, if maternal thrombophilia is a hereditary one
can this be the reason of the hemorrhages identified postnatally, is a more careful antenatal
sonographic evaluation more cost-efficient than the postnatal screening?, which is the long term
impact of these cerebral hemorrhages and if these neonates can be classified as at risk for
developmental and neurological abnormalities?
Keywords: maternal thrombophilia, pregnancy, newborn, prenatal ultrasound, head ultrasound, intraventricular hemorrhage

Introduction

The impact of maternal thrombophilia, both for the mother and the fetus, is controversial.
Early during pregnancy thrombophilia may cause abortions while placental vascular
abnormalities may induce problems towards the end of the pregnancy (fetal loss, preeclampsia,
placental abruption, intrauterine fetal retardation) [1]. Controversial is, also, the role of fetal
thrombophilia, in the case of the inherited disease, in the pathogeny of perinatal thrombosis
leading to perinatal ischemic stroke of cerebral sinovenous thrombosis [2, 3]. Perinatal
intraventricular hemorrhages and cerebral vascular stroke were observed in the latest years in
newborns delivered after pregnancies complicated by thrombophilia, and hemorrhagic and
ischemic events were seen in the absence of a predisposing or causal context and without
symptoms during neonatal period [3, 4]. There is an increased concern related to these
hemorrhagic and thrombotic perinatal events due to long term impact on neurodevelopment:
increased risk of cerebral palsy, epilepsy, cognitive disabilities, motor retardation, behavioural
problems, functional visual disturbances [1, 5].

Material and methods

Cerebral and renal ultrasonography scans were performed between January 1, 2016 and
December 31, 2017 in term newborns delivered by mothers with thrombophilia admitted in the
Neonatology I Dept. of the Clinical County Emergency Hospital Sibiu. The scans were performed
usually a day before discharge or in the day the newborns were discharged, using sectorial and
linear probes, using Logiq e ultrasound machine (General Electric). Neonatal data –
anthropometric characteristics, type of birth, Apgar score, clinical evolution, and scan results –
were collected prospectively for neonates and maternal data – number of pregnancies, births,
spontaneous abortions, thrombophilia type, concurrent illnesses, coagulation – were obtained
from the hospital charts.

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Results

During the study period, 5853 deliveries were registered in our level III regional unit. Of these
232 newborns were delivered by mothers diagnosed with thrombophilia, comprising the study
group. The gestational ages of the newborns in the study group varied between 37 and 40 weeks
(Table 1). Infants in the study group had birth weights between 2620 and 3860 g (Table 1). The
prevalence calculated for the two years of study was 3.96%, 91 infants were born in the first year
of study (2016) – prevalence 3.23% – and 141 cases were noted in the second year of study
(2017) – increased prevalence, 4.64% -. 17 of the 232 newborns had abnormalities on the
sonographic screening: 16 on the head ultrasonography and 1 on the renal scan (one case of right
hypoplastic kidney - with possible vascular pathogenesis). 7 of the 16 newborns with abnormal
head ultrasound had intraventricular hemorrhages. Choroid plexus cysts were diagnosed in the
other 9 cases (maximum size 3 mm, 2 cysts in one case). Intraventricular hemorrhages seen on
ultrasound scans were all minor – 4 cases with grade I according to Volpe classification [4],
limited to the germinal matrix (Fig. 1.A) and 3 cases with grade I/II, extended in the lateral
ventricle but without ventricular dilatation). In all the cases the sonographic aspect was typical for
old hemorrhage, with antenatal onset (Fig. 1.B). The hemorrhage was bilateral, limited to
germinal matrix in 2 cases, on the left or right side in the other cases. All neonates with abnormal
cerebral scans were delivered by elective, planned Cesarean section. The surgical delivery was
elective, planned in 11 cases and performed after labor onset in 3 cases (spontaneous rupture of
the membranes). No correlation was observed between the severity of the cerebral hemorrhage
and the maternal thrombophilia type (minor/major) (Table 1). None of the neonates with
intraventricular hemorrhage identified during screening presented clinical symptoms suggestive
for cerebral hemorrhage during hospitalization, all had an uneventful adaptation to the
extrauterine life. Maternal data retrieved from the hospital charts were scarce, we observed
missing data even about the preventive treatment of thrombophilia, and coagulation studies were
incomplete, therefore this data could not be analyzed. Concurrent maternal conditions, prior or
during pregnancy are presented in the Table 1.

Table 1. Neonatal and maternal data of the cases included in the study
Maternal Other
Case Year BW1 GA2 AS3 Symptoms thrombop maternal Birth HUS4 RUS5
hilia conditions
S.A. 2016 3875 38 10 none major IVF C-section CPC normal
Grade I
C.A.M. 2016 3090 38 10 none minor - C-section IVH, normal
right
Grade
M.A.I. 2016 3500 39 10 none minor - C-section I/II IVH, normal
right
Grade I
D.M. 2016 3480 40 10 none minor - C-section IVH normal
bilateral
Femoral
Grade
thrombosis
G.I. 2016 3330 38 9/10 none major C-section I/II IVH, normal
prior
left
pregnancy
Diabetes
R.T.N. 2016 2730 37 10 none minor C-section CPC Normal
mellitus
B.I.M. 2016 3450 39 10 none major - C-section CPC Normal

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Hashimoto
R. A. 2017 3500 38 10 none minor C-section CPC normal
thyroiditis
Paraplegia
S.A. 2017 3480 39 10 none minor prior to C-section CPC Normal
pregnancy
N.R.L. 2017 2620 39 10 none minor - C-section CPC normal
Unilater
al
B.A. 2017 2910 39 10 none major - C-section normal kidney
hypoplas
ia
G.D. 2017 3860 38 10 none minor - C-section CPC normal
Bilateral
Grade I mild
G.S 2017 3690 38 10 none major - C-section IVH, pelvic
bilateral dilatatio
n
Grade I
B.D.C 2017 3820 38 10 none minor - C-section
IVH, normal
right
S.V.N. 2017 3190 39 9 none major - C-section CPC (2) normal
Grade
G.M.M. 2017 3100 38 10 none minor - C-section I/II IVH, Normal
left
T.D. 2017 3090 39 10 none major - C-section CPC Normal
Legend: BW – birth weight, GA – gestational age, AS v Apgar score, HUS – head ultrasonography, RUS – renal
ultrasound, IVH – intraventricular hemorrhage, CPC – choroid plexus cysts

Fig. 1A. Intraventricular hemorrhage limited to germinal matrix. B. Grade I/II intraventricular hemorrhage

Discussions

Long debates are still existing in the literature as regards maternal thrombophilia: its impact on
pregnancy and fetus, the risks related to possibly inherited fetal thrombophilia, different risks
related to different thrombophilic factors, need for maternal and neonatal screening for
thrombophilia, management of thrombophilia during pregnancy [1, 5-7]. All these debates started
with data published in the literature associating maternal thrombophilia with increased risks for
spontaneous abortion and pregnancy complications (preeclampsia, intrauterine growth

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retardation, abruptio placentae, fetal death) [1, 6, 7] and continued with reports associating
hereditary thrombophilia with perinatal ischemic stroke, cerebral sinovenous thrombosis,
perinatal hypoxic-ischemic encephalopathy, and cerebral hemorrhage [2-4, 6, 8, 9] with long term
impact on neurodevelopmental outcome of the infant [1, 5]. It is generally admitted today that
maternal and fetal thrombophilia are not direct, causal factors for pregnancy and perinatal
thrombotic events but it can act as a trigger in a context of risk factors for thrombosis [1, 3, 5, 6,
8].
Neonatal hemostasis is unique, with qualitative and quantitative abnormalities of coagulation
and fibrinolysis (compared to children and adults) complicated by hereditary and acquired defects
of coagulation and fibrinolysis [4]. Liver immaturity is associated with a natural deficit of protein
C, S, and antithrombin. Platelet function, the concentration of procoagulant and anticoagulant
proteins is age dependent in newborns, as well as the concentration of the proteins of the
fibrinolysis pathway [10]. Also, blood vessels are more fragile in neonates, especially in preterm
infants [10], with smaller caliber, and the blood is thicker due to increased hematocrit.
The etiology of neonatal intraventricular hemorrhage is multifactorial, the role of genetic
polymorphism is unclear [4]. Hemorrhages are significantly more often seen in preterm infants,
usually starting from the veins of the germinal matrix [4, 9]. Venous stasis and thrombosis of the
germinal matrix microvasculature may increase local pressure, followed by red blood cell
transudate and rupture of the veins and blood tunneling along perivenous space, distortion and
traction of the small tributary venules [4, 11]. Clinical signs may be obvious in preterm infants
but may be absent in term ones, mostly in those without serious illnesses [5].
Studies have demonstrated an increased incidence of factor V Leiden mutations and
prothrombine gene G2021A in preterm [4, 12, 13] and term infants [4, 9, 13] with intraventricular
hemorrhage compared to controls but the pathogenic mechanism remains unknown [4]. But there
are also authors suggesting that these mutations, especially those of the factor V Leiden may
exert a protective effect against severe cerebral bleeding [1]. A case of intrauterine cerebral
bleeding, limited to the matrix, resolved in utero, followed by ventriculomegaly and normal
development has been described by Ramenghi [9] in an infant with 2 mutations (in factor V
Leiden and methyltetrahydrofolatreductase) inherited from the father, underlining that hereditary
thrombophilia can be inherited by the fetus from the paternal side also. Still, reports on
intraventricular hemorrhage in term neonates related to maternal thrombophilia are rare [1, 9].
We weren’t able to find any study in the literature involving screening in term newborns
delivered by mother with thrombophilia to compare our results. Also, we weren't able to make
connections between maternal thrombophilia and the occurrence of such an increased incidence
of choroid plexus cysts compared to a normal population nor with the presumed etiology of these
cysts [14]. We have found that fetal thrombophilia has been associated with liver lesions,
intestinal atresia, heart abnormalities, oligoamnios [15] but not with hypoplastic kidney.
However, we can not exclude a vascular pathogenic mechanism for the case with hypoplastic
kidney identified in our study.

Conclusions

The results of the postnatal cerebral and renal sonographic screening of the newborns
delivered from pregnancies complicated with thrombophilia are not answering to the current
debate in the literature as regards the effects of maternal and fetal thrombophilia on pregnancy
and neonatal outcome but they are raising some other questions as: are these abnormalities related

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to fetal or maternal thrombophilia? is a sonographic screening justified in newborns delivered by


mothers with thrombophilia?

REFERENCES

1. Torresa, VM, Saddi, VA. (2015). Systematic review: hereditary thrombophilia associated to pediatric
strokes and cerebral palsy. J Pediatr (Rio J) 91(1), pp. 22-29.
2. Simioni, P, Spiezia, L, Suppiej, A, et al., (2016). Thrombosis in children and neonates: data from the RITI
registry (Registro Italiano Trombosi Infantili). Hematologia, 20, pp. 83-90.
3. Simchen, MJ, Goldstein, G, Lubetsky, A, et al., (2009). Factor V and Antiphospholipid Antibodies in Either
Mothers or Infants Increase the Risk for Perinatal Arterial Ischemic Stroke. Stroke 40, pp. 65-70.
4. Ramenghi, LA, Fumagalli, M, Groppo, M, et al., (22011). Germinal Matrix Hemorrhage: Intraventricular
Hemorrhage in Very-Low-Birth-Weight Infants The Independent Role of Inherited Thrombophilia. Stroke
42, pp. 1889-1893.
5. O’Brien, SH (2015). Perinatal thrombosis: implications for mothers and neonates. Hematology, pp 48-52
6. Curtis, C, Mineyko, A, Massicotte, P, et al., (2017). Thrombophilia risk is not increased in children after
perinatal stroke. Blood 129(20), pp. 2973-2978.
7. Roozbeh, N, Banihashemi, F, Mehraban, M, Abdi, F. (2017). Potential role of Factor V mutation in adverse
pregnancy outcomes: An updated systematic review. Biomed Res Ther 4(12), pp. 1832-1846.
8. AbdelAziz, NHR, AbdelAzeem, HG, Monazea, EMM, Sherif, T. (2017) Impact of Thrombophilia on the
Risk of Hypoxic-Ischemic Encephalopathy in Term Neonates. Clinical and Applied Thrombosis/Hemostasis
23(3), pp. 266-273.
9. Ramenghi, LA, Fumagalli, M, Righini, A, et al., (2005) Thrombophilia and fetal germinal matrix-
intraventricular hemorrhage: does it matter? Ultrasound Obstet Gynecol 26, pp. 574-576.
10. Haley, KM (2017) Neonatal venous Thromboembolism. Front Pediatr 5, p. 136.
11. Ghazi-Birry, HS, Brown, WR, Moody, DM, et al., (1997) Human germinal matrix: venous origin of
hemorrhage and vascular characteristics. AJNR Am J Neuroradiol18, pp. 219-229.
12. Komlosi, K, Havasi, V, Bene, J, et al., (2005) Increased prevalence of factor V mutation in premature but
not in full-term infants with grade I intracranial haemorrhage. Biol Neonate 87, pp. 56-59.
13. Harteman, JG, Nikkels, PGJ, Kweec, A, v (2012) Patterns of placental pathology in preterm infants with a
periventricular haemorrhagic infarction: Association with time of onset and clinical presentation. Placenta
33, pp. 839e844.
14. Ognean, ML, Silaghy, N, Olariu, E, et al., (2010). – Chisturile de plex choroid – aspecte epidemiologice în
perioada neonatală, In Ognean, ML. Medicina bazată pe dovezi în neonatologie, pp. 82-90.
15. UK Neonatal Screening Committee. (2016) Neonatal and general adult populations screening for
thrombophilia. Solutions for Public Health.

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Accuracy of Tumor Size Measurements During Mammography and


Breast Ultrasonography in Breast Cancer Patients

OPREA Adela-Luciana1, GEORGESCU Rareș2, IONESCU Paul2,


MĂRGINEAN Claudiu1
1 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy Tîrgu Mureș, Gheorghe Marinescu street no
38, 540139, (ROMANIA)
2 Department of Surgery, University of Medicine and Pharmacy Tîrgu Mures, Romania, Gheorghe Marinescu street no 38,

540139, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Background
In breast cancer, the tumor size influences the treatment decision.

Material and method


The study was planned as a retrospective cohort and was performed between September 2017
and May 2018. 90 patients who underwent surgical complete resection of their breast cancer were
included for the analysis. The aim of our study was to determine which imaging method,
ultrasound or mammography, determines the tumor diameter of a breast cancer patient in
comparison with the golden standard the histological result. We collected data about patient’s
gender, age, findings of sonography and mammography such as microcalcifications and spicules,
tumor grade, histological type and molecular type of the tumor. We selected the largest tumor
diameter as the sizing reference for every case.

Results
Among the 90 cases included in our study we observed that the mean difference between
ultrasound measurements and histological dimensions was -0.304mm, with a minimum
underestimation of -32 mm and a maximum overestimation of 23 mm, while the mean difference
between mammographic measurements and histological dimensions was -1.93mm (-33 mm to 35
mm), (p=0,29). There was no significant difference between measurements of the two imaging
methods.

Connclusions
With the conventional methods such as sonography and mammography, tumor measurements
were similar to the actual tumor size which is determined by gold standard, the histological
assessment.
Keywords: sonography, mammography, tumor size, breast cancer, histological size

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Introduction

In breast cancer the tumor size influences the treatment decision. That’s why tumor sizing
using different imagistic methods plays a central role. The relationship between breast size and
the tumor influences the surgical treatment allowing to do or not to do breast conserving surgery.
It has been shown that the best imaging methods to measure the size of a tumor are
mammography (MM), sonography (US) and magnetic resonance imaging (MRI). According to
German guidelines for breast cancer treatment and diagnosis, mammography is the standard
imaging tool [1]. An ultrasound should be added to achieve higher sensitivity in case of high
breast density [2]. Both mammography and ultrasound are standard diagnostic tools for breast
cancer assessment [3, 4]. The role of breast MRI is controversial. Houssami and colleagues in a
meta-analysis of 9 clinical studies, found that MRI doesn’t reduce re-excisions but significantly
increased the rate of modified radical mastectomies (MRM) [5, 6]. They suggest that it could do
more harm than good, a routine MRI [5].
The aim of our study was to determine which imaging method, ultrasound or mammography,
determines the tumor diameter of a breast cancer patient in comparison with the golden standard,
the histological result.

Material and method

The study was planned as a retrospective cohort. 90 patients who underwent surgical resection
for breast cancer treatment in the Surgical Department from Tîrgu Mureș, Romania at any stage
between September 2017 and May 2018 were included in this study.
The inclusion criteria were having both mammography and breast ultrasound preoperatively
undergoing complete cancer resection. We selected the largest tumor diameter as the sizing
reference for every case. All the patients were diagnosed with breast cancer after undergoing a
core needle biopsy. Data was retrieved from patient records. Patients with involved surgical
margins at initial resection were excluded. Also any patient with an imaging report which didn’t
include tumor size measurement was excluded.
The outcomes of this study are to assess the accuracy of mammography and ultrasound
imaging in tumor size measurement. The measurements were compared with the actual tumor
size measured at permanent pathological assessment.
Ultrasound was done using a linear array transducer with 12 to 4 MHz extended operating
frequency range. It was used a Phillips ClearVue 650 model. Mammography was performed
using a Flat III Metaltronica, Mammograph. Only doctors who were certified in breast imaging
and diagnosis performed every imaging.
We collected data about patient’s gender, age, findings of ultrasonography and mammography
such as presence of microcalcification and spicules, tumor grade, histological type and molecular
type of the tumor.
Regarding defining the breast cancer subtypes, Luminal A breast cancer was defined as ER-
positive>1% and/or PR- positive>1%, Her 2-negative, and low KI -67(≤25). Luminal B breast
cancer was defined as ER-positive>1% and/or PR- positive>1%, Her 2- negative and high Ki -
67(>25%). Her 2-positive breast cancer was defined as ER-negative, PR-negative, Her-2 positive
confirmed by CISH. Triple negative breast cancer (TNBC) was defined as ER, PR- negative,
HER-2 negative and high Ki-67.

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Statistical analysis

For the statistical evaluation we performed a Bland-Altman plot (Bland & Altman, 1986 and
1999), or difference plot, which is a graphical method. The comparison of mammography and
ultrasound reading with histological size were made separately. For every case we picked the
largest tumor size. In this graphical method the differences (or alternatively the ratios) between
the two techniques are plotted against the averages of the two techniques. Alternatively
(Krouwer, 2008) the differences can be plotted against one of the two methods, if this method is a
reference or “gold standard” method, in our case the histological result. Horizontal lines are
drawn at the mean difference, and at the limits of agreement, which are defined as the mean
difference plus and minus 1.96 times the standard deviation of the differences. If the differences
within mean ±1.96 SD are not clinically important, the two methods may be used
interchangeably. The plot is useful to reveal a relationship between the differences and the
averages, to look for any systematic biases and to identify possible outliers. The Bland and
Altman plot may also be used to assess the repeatability of a technique by comparing repeated
measurements using one single method on a series of subjects. In this case, the graph can also be
used to check whether the variability or precision of a method is related to the size of the
characteristic being measured.

Results

All of the 90 patients with primary breast cancer were evaluated in this retrospective study.
Every patient was female (100%), the median age was 60 years (range 36-87). 50% of the
tumors presented spicules on the mammographies assessment and 33.3% calcifications. We
classified the pathological subtypes into: ductal carcinoma in situ (DCIS), invasive ductal
carcinoma (IDC) and ductal carcinoma in situ + invasive ductal carcinoma (DCIS+IDC). 80% of
the cases were IDC, 5.55% pure DCIS and 14.44% DCIS +IDC. The molecular subtypes Luminal
A(53.3%), Luminal B(17.77%), Human epidermal growth factor receptor 2(HER 2+), (20%) and
triple negative breast cancer (TNBC) (8.88%) were classified according to immunohistochemical
staining of estrogen receptor (ER), progesteron receptor (PR), HER-2/neg, and KI 67 values. We
classified also the histological types into: lobular cancer (6.66%), ductal cancer (90%), and others
(metaplastic carcinoma, apocrine, neuroendocrine, mucinous breast cancer) (3.33%). Concerning
tumor grading, we found that 33.33% of the cases were grade 1, 45.55% grade 2 and 21.11%
grade 3 (Table 1).
The median of ultrasonography measurements was 18 mm with a minimum of 3.9 mm and a
maximum of 78 mm. The median of measurements obtained by mammography was 20 mm (0-
90), while the median dimension obtained by histopathology was 19 mm (0-60). By applying the
Kruskal Wallis test the results were not statistically significant between the three measurements
(p=0.37) (Table 2)

Table 1. Batch characteristics


Mean age 60 years (min 36 – max
87)
Gender Female 100%(90/90)
Mammography Spicules present 45/90 (50%)
features Calcification present 30/90 (33.33%)
Histological IDC 72/90 (80%)
subtypes DCIS 5/90 (5.55%)

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DCIS+IDC 13/90 (14.44%)


Molecular type Her+ 18/90 (20%)
Luminal A 48/90 (53.3%)
Luminal B 16/90 (17.77%)
Triple - 8/90 (8.88%)
Histopathological Ductal 81/90 (90%)
type Lobular 6/90 (6.66%)
Others 3/90 (3.33%)
Tumor grade I 30/90 (33.33%)
II 41/90 (45.55%)
III 19/90 (21.11%)
*IDC-invasive ductal carcinoma, DCIS-ductal carcinoma in situ, DCIS+IDC- invasive ductal carcinoma with in situ
component, others(metaplastic carcinoma, apocrine, neuroendocrine, mucinous breast cancer)

Table 2. Tumor size assessment using ultrasound, mammography and histology


Number of values Ultrasound tumor Mammography Histological tumor
size (n=90) tumor size (n=90) size (n=90)
Minimum 3,900 0,0 0,0
Median 18,00 20,00 19,00
Maximum 78,00 90,00 60,00
Mean 18,55 20,79 18,86
Std. Deviation 10,58 12,55 10,51
Std. Error 1,115 1,323 1,108
*n-number of patients; dimensions are expressed in mm

Using Bland-Altman method we have compared the ultrasound measurement with the
histological dimensions. We settled limits of agreement (LOA) from -17.7 to 17.07. Therefore the
size of the two measurements should be between these intervals. If for a case the maximum size
of the tumour was higher than 17.07 or lower than-17.7 then the measurement was over or
underestimated. We didn’t find a significant difference between ultrasound and the histological
result. Out of 90 patients there were 4 cases in which the ultrasound overestimated the size of the
tumour versus the histological result, (LOA: 34 mm vs 22 mm; 69 mm vs 18 mm, 22 mm vs 20
mm) and in 4 patients the ultrasound image of the largest diameter of the tumour was
underestimated by the histological result (LOA: 24 mm vs 32 mm; 20.5 vs 21 mm, 20.5 mm vs
21 mm; 18.5 mm vs 23 mm). (Fig. 1)
Then we used the Bland-Altman Method to compare the difference between the
mammography result and the histological findings. Limits of agreement 95% were settled from -
21.2 to 17.34. In 3 cases out of 90 patients we found that the mammography overestimated the
histological result (35 mm vs 20 mm, 29.5 mm vs 29 mm, 75 mm vs 30 mm) and in 3 cases the
maximum diameter of the tumor using mammography underestimated the histological result (25
mm vs 30 mm, 32.5 mm vs 35 mm, 23.5 mm vs 33 mm). (Fig. 2)

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30

20 +1.96 SD
17,3

10
DIM ECHO - DIM H

Mean
0
-0,2

-10

-1.96 SD
-20 -17,7

-30

-40
0 20 40 60 80
Mean of DIM ECHO and DIM H
Fig. 1. Bland Altman Test illustrating the difference between ultrasound tumor size versus the histological result

40

30

+1.96 SD
20 21,2
DIM MAMO - DIM H

10

Mean
0 1,9

-10
-1.96 SD
-20 -17,3

-30

-40
0 20 40 60 80 100
Geometric mean of DIM MAMO and DIM H
Fig. 2. Bland Altman Test illustrating differences between mammography tumor size versus the histological result

The mean difference between ultrasound measurements and histological dimensions was -
0.304mm (-32mm to 23 mm) while the mean difference between mammographic measurements
and histological dimensions was -1.93mm (-33mm to 35 mm). By applying the Student test, the
results between the two imaging methods were not statistically significant. (p=0.29) (Table 3).
As the secondary outcome of the study, we also compared the measurements in each breast
cancer subtype separately. The readings were also similar in Luminal A, B, Her2 enriched and
triple negative cancers (Table 4).

Table 3. The mean differences using ultrasound and mammography tumour size versus the histological finding
Number of values Ultrasound tumor size versus Mammography tumor size
Histology tumor size versus Histology tumor size
Minimum -32,00 -33,00
25% Percentile -4,000 -6,000
Median 0,0 -1,000
75% Percentile 4,000 2,000
Maximum 23,00 35,00
Mean -0,3044 -1,933
Std. Deviation 8,868 9,834
*dimensions are expressed in mm

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Table 4. Tumor size measurement in each breast cancer subtype


Molecular Variables Sonography Mammography Histological P value
subtypes tumor size tumor size tumor size
Luminal A Median (Min-Max) 16.7 (5-40) 19.5 (3-45) 19 (2-45) 0.26*
Luminal B Median (Min-Max) 19.5 (7-31) 20 (8-33) 18 (9-33) 0.53*
HER + Median (Min-Max) 21 (4-35) 23.5 (0-50) 21.5 (0-50) 0.97*
Triple Median (Min-Max) 12.5 (3.9-78) 10 (6-90) 14.5 (0-60) 0.98*
negative
*Kruskal Wallis test; dimensions are expressed in mm

Discussion

In this study we didn’t find any statistical differences between the two imaging methods,
mammography and sonography for the tumor size of breast cancer patients in comparison with
the golden standard, histological result. The strength of this study is that even though the data we
collected were not read by the same person, we still achieved a good correlation with the
pathological size.
In line with Grueber et. al., [7] we had 4 cases in which ultrasound underestimated the
histological tumor size (Fig. 1). Hieken et. al., [8], Shoma et al., [9] and Bosch et. al., [10]
confirmed the sonographic underestimation of the histological tumor size. Hieken et. al., [8]
atributted this to the unclear margins of sonographic results from extensive intraductal in-situ
component. Bosch et. al., [10] linked the underestimation with tumor size, with the image
presentation exceeding what is possible with the transducer. Dummin and colleagues [11], found
that ultrasound underestimates breast cancer size. They said that mammography is the most
precise tool for predicting histological tumor size. However, different biological cancer
subgroups have not been compared regarding the correlations between histological, sonographic
and mammographic tumor.
Regarding mammography, we found in 3 cases an underestimation of the histological result
with a mean of -1.93mm. Hieken et. al., [8] attributed the underestimation using mammography
to the high compression of the breast during the examination.
Even though we did not use MRI in our study as an imaging modality, other studies show that
MRI is superior to both mammography and sonography in the diagnosis of DCIS and ILC [12-
15]. In a study by Kuhl et. al., [13] MRI showed better sensitivity for all DCIS cases, whether
with or without microcalcification of 98%. For mammography, which relies on the interpretation
of suspicious microcalcification and therefore does not detect all DCIS cases, the sensitivity was
only 52% [13]. Berg et. al., [12] also show that MRI exhibited a sensitivity of 89% compared to
55% sensitivity for mammography and 47% for ultrasound.
In a retrospective study is important to ask all the clinicians if they interpreted the malignancy
criteria in the same way. [16, 17]. Dorsal acoustic attenuation, margins who are blurred,
infiltrated vessels in Doppler sonography, could cause a different interpretation of the tumour
size. [18, 19] Isermann et. al.,didn’t find a significant advantage in breast lesion sizing using
sonoelastography, even though it has a lower interobserver variability, than conventional B-mode
imaging. [20]
Georgescu et. al., [21] said that tumour size is a prognostic factor for breast cancer patients
therefore, tumor size measurement using ultrasound and histological assessment should be
crucial. Regarding our study, the number of patient collected for our study was moderate in
comparison with other studies and there weren’t significant variations among different readers

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throughout the study. We had superior results using sonography and mammography therefore we
think MRI wouldn’t have brought any significant information in our study.

In conclusion, although we didn’t use imagistic methods such as MRI we used conventional
methods, sonography and mammography to appreciate the tumor size they were similar with the
histological result which is the golden standard. Mammography and ultrasound before surgery
seem to give adequate information for planning the surgical management in breast cancer
patients.

Acknowledgements
We thank Prof. Dr. Bahadir M. Gulluoglu for his kind help in revising the context of the study.

REFERENCES

1. Kreienberg RAU, Follmann M, Kopp I, Kühn T, Wöckel A, Zemmler T. Diagnosis and Treatment of
Patients with Primary and Metastatic Breast Cancer. Interdisciplinary S3 Guideline. Berlin: German Cancer
Socienty; 2012. http://www.leitlinienprogramm-onkologie.org.
2. Nothacker M, Duda V, Hahn M, Warm M, Degenhardt F, Madjar H, et. al., Early detection of breast cancer:
benefits and risk of supplemental breast ultrasound in asymptomatic women with mammographically dense
breast tissue. A systematic review. BMC Cancer. 2009; 9: p. 335.
3. (NICE) NNIfCE. Early and locally advanced breast cancer: diagnosis and treatement. 2009.
4. Shoma A, Mouramed A, Ameen M, Abdelwahab A. Ultrasound for accurate measurement of invasice breast
cancer tumor size. Breast J. 2006; 12(3): pp. 252-6.
5. Houssami N, Turner R, Morrow M. Preoperative magnetic resonance imaging in breast cancer: meta-
analysis of surgical outcomes. Ann Surg. 2013; 257(2): pp. 249-55.
6. Houssami N, Ciatto S, Macaskill P, Lord SJ, Warren RM, Dixon JM, et. al., Accuracy and surgical impact
of magnetic resonance imaging in breast cancer staging: Systematic review and meta-analysis in detection
of multifocal and multicentric cancer. J Clin Oncol. 2008; 26(19): pp. 3248-58.
7. Gruber IV, Rueckert M, Kagan KO, Staebler A, Siegmann KC, Hartkopf A, et. al., Measurement of tumour
size with mammography, sonography and magnetic resonance imaging as compared to histological tumour
size in primary breast cancer. BMC Cancer. 2013; 13: p. 328.
8. Hieken TJ, Harrison J, Herreros J, Velasco JM. Correlating sonography, mammography and pathology in
the assessment of breast cancer size. Am J Surg. 2001; 182(4): pp. 351-4.
9. Shoma A, Moutamed A, Ameen M, Abdewahab A: Utrasound for accurate measurement of invasive breast
cancer tumour size. Breasst J 2006, 12: pp. 252-256.
10. Bosch AM, Kessels AG, Beets GL, Rupa JD, Koster D,van Engelshoven JM, Von Meyenfeldt MF:
Preoperative estimation of pathological breast tumour size by physical examination, mammography and
ultrasound: a prospective study on 105 invasive tumours. Eur J Radiol 2003; 48: pp. 285-292.
11. Dummin LJ, Cox M, Plant L. Prediction of breast tumor size by mammography and sonography – A breast
screening experience. Breast. 2007; 16(1): pp. 38-46.
12. Berg WA , Gutierez L, NessAiver MS, Carter WB, Bhargavan M, Lewis RS, Ioffe OB: Diagnostic accuracy
of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer,
Radiology 2004, 233: pp. 830-849.
13. Kuhl, CK, Schrading S, Bieling HB, Wardelmann E, Leutner CC, Koenig R, Kuhn W, Schild HH: MRI for
diagnosis of pure ductal carcinoma in situ: a prospective observational study, Lancet 2007: 370: pp. 485-
492.
14. Schelfout K, Van Goethern M, Kersschot E, et. al., Preoperative breast MRI in patients with invasive
lobular breast cancer, Eur Radiol 2004, 14: pp. 1209-1216.
15. Weinstein SP, Orel SG, Heller R, et. al., MR imaging of the breast in patients with invasive lobular
carcinoma, AJR Am J Roentgenal 2001, 176(2)399-406.
16. Lenz S: Breast ultrasound in office gynecology-ten years of experience Ultraschall Med 2011, 32(Suppl 1):
pp. 3-7.

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17. Varga D, Woeckel A, Wagner J, Koretz K, Kreinberg R, Sauer G: Value of ultrasound in preoperative local
staging in early breast cancer. Ultraschall Med 2011, 32: pp. 387-392.
18. Madjar H, Sauerbrei W, Hansen L: Multivariate analysis of flow data in breast lesions and validation in a
normal clinical setting. Ultraschall Med 2011, 32: pp. 511-517.
19. Oblinger R, Frese H, Paepke, S, Heyer, Kohler G, Schwesinger G, Grunwald S: Ultrasonographic:
compared to histological sizing of bening and malignant breast lesions, Geburts Frauenheilk 2006, 66: pp.
373-376.
20. Isermann R, Grundwald S, Hatzung G, Konsgen-Mustea D, Behrndt PO, Geaid AA, Jager B, Ohlinger R:
Breast Lesions Sizing by B-Mode Imaging and sonoelastography in Comparison to Histopathological
Sizing-a prospective study. Ultraschall Med 2011, 32: pp. 21-26.
21. R. Georgescu, MF Coroș, Simona Stolnicu, Daniela Podeanu, S Sorlea, Anca Roșca, C. Copotoiu:
Prognostic factors in breast cancer, Revista medico-chirurgicală a Societății de Medici și Naturaliști din Iași,
2012, Vol.116, Nr. 1: pp. 262-267.

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Necrotizing Fasciitis of the Thoracolumbar Posterior Area


(Type 1) in a Newborn

OSAKWE Henry1, CRISAN Carmen1,2, DUMITRA Simona1,2,


TRAILESCU Maria1,2, PAVEL Adrian1,2, PAVEL Nicoleta3, CRISAN Adrian1,2
1 County Emergency Hospital Arad, (ROMANIA)
2 West University “Vasile Goldis” Arad, (ROMANIA)
3 Medlife Arad, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected], [email protected], [email protected]

Abstract

Background
Necrotizing fasciitis is a rare challenging and life threatening infection of the skin and the
under lying tissues. Prompt diagnosis and rapid aggressive treatment determines patient’s
survival. A three weeks old newborn was seen at the ER with a giant thoracolumbar hunchback
like mass and a history of back fall 7 days ago.

Method
Musculoskeletal Ultrasound: Showed a thoracolumbar transonic area of about 16/12 cm.
Thoraco-abdominal x-ray: Normal. Thoracolumbar x-ray: Showed absence of facture and a
large volume of subcutaneous collection on the lateral view x-ray. A thorough history and
physical examination provided some clues to the pathogens involved. Thoraco-lombar cut down
incision of about 1 cm, a large volume of purulent secretion (300 ml) with foul smell, surgical
debridement, flushing and placement of drainage tube. Collection of purulent discharge from
lesion for culture prior to initiating antimicrobial therapy and results of bacteriologic studies
(Gram stain and culture) guided therapeutic decisions.

Result
The main pathogens involved in these infections are Staphylococcus aureus and group A β-
hemolytic streptococci, but enteric organisms also play a role especially in nosocomial infections.
In our case culture revealed that E. Coli was the unexpected cause of infection. Pus culture
was sensitive for ampicilin+sulbactam, ceftriaxone, cefuroxime, ceftazidime etc. Patient was
initially placed on empiric antibiotics (clindamycin and gentamicin) but later switched to
ceftriaxone in accordance with sensitivity result.

Conclusion
Patient responded well to treatment and was discharged in due time. E. Coli was unexpected
sensitivity result, the cause of infection usually being staphilococcus aureus/streptococcus beta
hemolitic infection.
Keywords: Newborn, necrotizing fasciitis, E. Coli, thoracolumbar area

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Introduction

Necrotizing fasciitis is a bacterial infection with intestinal aerobe/anaerobe or mixed flora such
as proteus, clostridium, E. Coli, bacteroides, enterobacteriacea, or by a single organism such as
group A streptococci (1). Necrotizing fasciitis is a rapidly progressive inflammatory infection of
the fascia, with secondary necrosis of the subcutaneous tissues (2). Necrotizing fasciitis is not a
chronic disease and it is often caused by a minor lesion (3). The prevalence is extremely low in
pediatric cases (0.02%) Infections of the skin and soft tissues can be broadly classified based on
the extent of tissue involvement (5). Necrotizing fasciitis is often misdiagnosed as cellilitis due to
its rarity so physicians should always keep this in mind (4).
Evolution of the disease is severe due to the involvement of a strain of bacteria with increased
virulence and direct cytotoxic effect (6). Delay in the first 24 hours doubles the mortality rate.
This disease rarely occurs in children. Pediatric cases were reported mainly in resource-poor
nations where poor hygiene is prevalent (2). Increasing antibacterial resistance is becoming a
major problem in the treatment of these infections worldwide. Specifically, the rise of methicillin-
resistant S. aureus and glycopeptide-resistant S. aureus are major challenges for the future (7).
Surgery plays a key role in the treatment of abscesses (pus release) and the debridement of
necrotic tissue in deep infections (8). Intravenous immunoglobulin, as an adjunctive therapy, can
be helpful in treating necrotizing fasciitis (9). Antistaphylococcal β-lactam antibacterial is the
first-line therapy for most infections. Third-generation cephalosporins and β-lactam/β-lactamase
inhibitor antibacterial medications as well as clindamycin or metronidazole often require broad-
spectrum coverage for polymicrobial infections (9).

Case presentation

A 3 weeks old newborn caucasian male was seen in the ER with a massive fluctuant
hunchback like thoracolumbar mass. Mum narrated a previous bed fall 7 days ago. Indicative
findings: low grade fever, pain, restlessness, frequent cries, tachycardia, edema, erythema, purple
discoloration of the skin and crepitation covering almost the whole back mimicking a large
tumor, axillar and inghinal lymphadenitis, absence of bleeding and absence of purulence or
suppuration on gentle palpation. Clinical investigation upon admission: elevated WBC, ESR,
Neutrophils, C-reactive protein, mild thrombocytopenia, mild anemia which gradually led to a
severe infectious anemia and sever thrombocytopenia. Musculoskeletal Ultrasound: Showed a
thoracolumbar transonic area of about 16/12 cm. Thoracoabdominal x-ray was normal.
Thoracolumbar x-ray: Showed absence of facture and a large volume of subcutaneous
collection on the lateral view x-ray. Thoraco-lombar cut down incision of about 1 cm, a large
volume of purulent secretion (300 ml) with foul smell, surgical debridement, flushing and
placement of drainage tube. Culture and sensitivity: E. Coli, sensitive for ampicilin+sulbactam,
ceftriaxone, cefuroxime, ceftazidime etc. Patient was initially placed on empiric antibiotics
(clindamycin and gentamicin), but later switched to ceftriaxone in accordance with sensitivity
result. Patient responded well to treatment and was discharged accordingly.

Aim

Our aim is to create awareness of this rapidly disappearing disease especially in the newborn.

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Material and method

The clinical management of this immune-deficient newborn from a poor social background
was challenging. Mum narrated a previous bed fall 7 days earlier. Indicative findings: edema,
erythema, purple discoloration of the skin and crepitus covering almost the whole of the back
mimicking a large hunchback like tumor (see Fig. 1). Chest x-ray was normal (see Fig. 2).
Clinical investigation upon admission: increased WBC, ESR, Neutrophils, C-reactive protein,
mild thrombocytopenia, mild anemia which gradually advanced to sever infectious anemia and
sever thrombocytopenia.

Fig. 1. Thoracolumbar x-ray: Showed absence of facture and a large volume of subcutaneous collection on the lateral
x-ray view

Fig. 2. Musculoskeletal Ultrasound: Showed a thoracolumbar transonic area of about 16/12 cm.
Thoraco-abdominal x-ray: Normal.

Results

Thoraco-lombar cut down incision of about 1 cm helped evacuated a large volume of purulent
secretion (300 ml) with foul smell this was followed by surgical debridement, flushing and
placement of drainage tube (see Fig. 3, 4, 5, 6). Culture and sensitivity: E. Coli, sensitive for
ampicilin+sulbactam, ceftriaxone, cefuroxime, ceftazidime etc. Based on our clinical findings we
concluded that this is a case of necrotizing fasciitis type 1 with E.coli. Patient was initially placed
on clindamycin and gentamicin but later switched to ceftriaxone in accordance with sensitivity

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result. The evolution of this case was favorable without complication and baby was discharged
after 3 weeks.

Fig. 3. – dorsal incision (cut down), debridement, pus release approximately 300ml shown on the blue drape

Fig. 4. – Debridement and verification of residual pus was followed by repeated wound flushing

Fig. 5. – Seventh day after cut down and pus realease (repeated flushing image).
Removal of drainage tube.

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Fig. 6. –two weeks after treatment. Good wound healing (no more pus) but skin discoloration and erythema persists

Discussion

• Necrotizing fasciitis is a severe and dangerous infection with a very high mortality and
morbidity rate. It is rare in children and often misdiagnosed (1).
• Necrotizing fasciitis with E, Coli infection is very rare (2).
• Pediatric cases were reported mainly in resource-poor nations where poor hygiene is
prevalent. These patients are usually immune-suppressed (3).
• The major differential diagnosis confusion is often between cellulitis, superinfection and
necrotizing fasciitis (4).
• Clinical signs of swelling edema, erythema are nonspecific while crepitation is regarded
as more typical clinical sign, it is as a result of gas produced by bacteria (5).
• Pain in a newborn is associated with restlessness and frequent cries (6).
• A simple mosquito bite can cause necrotizing fasciitis so sign of bites or trauma should be
sort (7).
• Optimal diagnoses and early surgical exploration remains the gold standard (8).
• Empiric broad spectrum antibiotics should be continued until the culture and sensitivity
result is obtained (9).

Conclusions

Though the onset of illness according to mum was a back fall, it was difficult to collaborate
this story after 7 days. The immunodeficiency of the patient was a factor that could not be over
looked. Infection may also take place at the trauma site affecting the soft tissues, even in the
absence of a skin bruise. The poor social status of parents was another negative factor for the
onset of disease. Though E.coli was unexpected sensitivity result because of its rarity, the cause
of infection usually being staphilococcus aureus/streptococcus beta hemolitic infection. The rapid
recovery of patient was a surprise as these cases are mostly life threatening and sometimes with
associated complications or even death.

REFERENCES

1. Bisno AL, Stevens DL. Streptococcus infections of skin and soft tissues. N Engl J Med, 1996; 334: pp. 240-
245.

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2. Cha JY, Releford BJ Jr, Marcarelli P. Necrotizing fasciitis: a classification of soft tissue infections. J Foot
AnkleSurg, 1994; 33: pp. 148-155
3. File TM Jr, Tan JS. Group A streptococcus necrotizing fasciitis. Compr Ther, 2000; 26: pp. 73-81.
4. Harisson – Principiile medicinei interne Ed. 14, pp. 976-983.
5. Hsich WS, Yang PH, Chao HC, Lai YJ. Neonatal necrotizing fasciitis. A report of three cases and revew of
the literature. Pediatric, 1999; 103:e53.
6. Paya K, Hayek BF, Rebhandl W, et al., Retroperitoneal necrotizing fasciitis in a 4-year-old girl. J Pediat
Surg 1998; 33: pp. 778-780.
7. Seal DV. Necrotizing fasciitis. Curr Opin Infect Dis, 2001; 14: pp. 127-132.
8. V. Rusu, Dictionar Medical, Ed. Medicala, 2001.
9. Wong CH, Chang CH HC, Pasupathy S, et al., Necrotizing fasciitis: clinical presentation, mycrobiology and
determinants of mortality. J Bone Joint Surg Am, 2003; 85: pp. 1454-1460.

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Management of Prenatally Diagnosed Foetal Goitre

PANAITESCU Anca-Maria1
1Filantropia Clinical Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest (ROMANIA)
Email: [email protected]

Abstract

A foetal goitre is usually diagnosed in relation to maternal known Graves’ disease and results
from the transplacental passage of high levels of thyroid stimulating antibodies, thyroid inhibiting
antibodies or of anti-thyroid drugs. The goitre can grow during the foetal life and can cause
compression on the foetal neck structures. Foetal goitres can be associated with either
hypothyroidism or hyperthyroidism. Prenatal ultrasound examination allows easy recognition of
the goitre but is not reliable in distinguishing between foetal hypo- and hyperthyroidism.
Assessment of the maternal condition and, in some cases, cordocentesis can provide adequate
diagnosis of the foetal thyroid function. First-line treatment is addressed to adjusting the dose of
maternal anti-thyroid drugs. Delivery is aimed at term. In cases with large goitres, caesarean-
section is indicated because of the high risk of head dystocia. An EXIT (ex utero intrapartum
treatment) procedure may be required to access and stabilize neonatal breathing while
maintaining placental flow through the mother.
Keywords: foetal goitre; Graves’ disease, methimazole; carbimazole; propylthiouracil, EXIT procedure

Introduction

Foetal thyroid goitre is a rare finding with a reported incidence of about 1 in 5,000 births and
is found usually in association with maternal Graves’ disease. [1, 2] Graves’s disease is among
the commonest endocrine problems associated to pregnancy along with gestational diabetes and
hypothyroidism [3] and it is an autoimmune disorder characterised by the presence of
immunoglobulins that bind the TSH receptors and usually stimulate the production of thyroid
hormones leading to hyperthyroidism, the occurrence of inhibiting autoantibodies being
extremely rare. Affected individuals are treated by radioiodine therapy or surgical removal of the
gland followed by the administration of the synthetic thyroid hormone levothyroxine. Some
patients are treated by anti-thyroid drugs, such as propylthiouracil, carbimazole and methimazole;
these drugs inhibit the enzyme thyroperoxidase which facilitates the addition of iodine to tyrosine
in the production of thyroglobulin, an essential step in the formation of thyroid hormones. Other
causes of foetal goitre are insufficient or excessive iodine availability [4] or congenital thyroid
dyshormonogenesis [5] due to defects in genes involved in the pathway of thyroid hormone
production. [6]
During pregnancy, thyroid stimulating immunoglobulins can cross the placenta by using the
physiological maternal-foetal antibody transfer pathways and can act on the foetal thyroid gland
resulting in the development of foetal hyperthyroidism and in some cases to a foetal hyperthyroid
goitre. Indications for testing for thyroid stimulating immunoglobulins in pregnant women with
Graves’ disease include (a) mothers with untreated or drug-treated hyperthyroidism in pregnancy,

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(b) a previous history of Graves’ disease with past treatment with radioiodine or total
thyroidectomy, (c) a previous history of delivering an infant with hyperthyroidism, or (d) a
known history of thyroidectomy for the treatment of hyperthyroidism in pregnancy. A level of
antibodies of 3 times the upper limit of normal is an indication for establishing close follow-up of
the foetus. [7] However, most cases of foetal thyroid goitre are the consequence of foetal
hypothyroidism due to trans placentally derived anti-thyroid drugs used for the treatment of
maternal hyperthyroidism. [8, 9, 10] Development of foetal goitre, with either hypothyroidism or
hyperthyroidism has been reported in about 10% of mothers with Graves’ disease on anti-thyroid
medication. [8-11]

Prenatal diagnosis

The prenatal diagnosis of goitre can be achieved by the demonstration of cervical, usually,
echogenic mass at the level of the anterior neck. Large foetal goitres could cause obstruction of
foetal swallowing and lead to polyhydramnios; the neck is usually hyperextended. As with other
causes of obstructive polyhydramnios (duodenal stenosis, oesophageal atresia) the associated
polyhydramnios in cases of goitre becomes evident usually after 24 weeks and places the
pregnancy at risk for preterm birth. It is for this reason that serial scans for measuring cervical
length are required in these cases. A shortening cervix may be a hint that preterm birth can ensue
and may be an indication of amniodrainage. With large foetal goitres birth dystocia may be a
complication because of the impossibility of the foetus the perform the normal head flexion
during labour. Another problem is related to breathing after delivery: the goitre can compress the
trachea and lead to intubation failure. It is for this reason that in some of the goitre cases an EXIT
(ex utero intrapartum treatment) procedure is arranged at the time of the caesarean section.
Another potential complication of foetal goitre relates to the thyroid dysfunction that can be
associated with it. Ultrasound is a good tool for diagnosing the goitre and appreciating the size, it
is not however reliable to distinguish between foetal hyper and hypothyroidism. With foetal
hyperthyroidism there may be associated intrauterine growth restriction, accelerated bone
maturation, tachycardia, oligohydramnios, intrauterine death by cardiac failure or thyrotoxicosis
and craniosynostosis. [12, 13] In foetal hypothyroidism delayed bone maturation [14] may be
noted and there may also be impaired growth and bradycardia.
A foetal goitre is usually an isolated finding, with no other associated structural anomalies
demonstrable. The incidence of chromosomal or genetic anomalies is similar to that in the general
population and not increased by the presence of the foetal goitre. When the foetal goitre is the
result of thyroid dyshormonogenesis, this is a genetic condition inherited as an autosomal
recessive fashion and therefore there is a 25% risk of recurrence.

Management

The management depends on the size of the goitre and its associated foetal thyroid
dysfunction. In most cases assessment of the maternal thyroid status will help decide whether
there is foetal hypothyroidism or hyperthyroidism. In uncertain cases, cordocentesis and
measurement of foetal blood thyroid hormones and TSH can help distinguish between
hypothyroidism, with low thyroid hormones and high TSH, due to anti-thyroid drugs or
congenital dyshormonogenesis, and hyperthyroidism, with high thyroid hormones and low TSH,
due to thyroid stimulating immunoglobulins. [8, 15]

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Foetal hypothyroidism
In foetal hypothyroid goitre the first-line of treatment is to reduce or even discontinue maternal
anti-thyroid medication aiming to maintain maternal blood thyroxine levels in the upper level of
the gestational age-specific normal range. [7] It should be noted that Graves’ disease, like most
other autoimmune disorders, improves during pregnancy and consequently requires less
medication. [16, 17] The second-line of treatment is intra-amniotic injection of levothyroxine, at
a recommended dose of 100 μg/kg every 1-2 weeks until delivery at term. [8, 18]
The goitre usually decreases in size within a few days after the first course of treatment.
Subsequent injections are given depending on sonographic evidence of re-enlargement of the
gland or serial measurements of levels of thyroid hormones in amniotic fluid or foetal blood. [8,
19, 20]

Foetal hyperthyroidism
In foetal hyperthyroid goitre the treatment of choice is administration of anti-thyroid drugs to
the mother. [21] These drugs will cross the placenta and act on the foetal thyroid gland. The
challenge in this case is to maintain the euthyroid state for the mother and it may be that the
mother should receive levothyroxine, as the dose of anti-thyroid drug can be appropriate for the
foetus but could lead to hypothyroidism in the mother. [11] The foetal goitre usually decreases in
size within a few days after the initiation of treatment, but if this does not occur measurement of
levels of thyroid hormones in foetal blood [22] may be needed and the dose of anti-thyroid drugs
given to the mother adjusted as necessary.

Follow-ups
Follow-up should be arranged depending on the clinical context, but generally at every 4
weeks to monitor foetal growth, size of the tumour, foetal heart rate, amniotic fluid volume and
cervical length. In pregnant women with known Graves’ disease, treated or untreated, thyroid
stimulating immunoglobulins should be determined in the beginning of pregnancy and later in the
second and third trimester. If the level is 3 times the normal range, close follow-up should be
initiated from the second trimester onwards with targeted ultrasound for the foetal neck. [7]

Delivery

Delivery in the case of foetal goitre should take place in a hospital with neonatal intensive care
capacities and paediatric surgery facilities, ideally around 38 weeks. Depending of the size of the
goitre we can aim for a vaginal delivery. With large goitres, where there is hyperextension of the
neck, caesarean section is the preferred method of delivery. An EXIT (ex utero intrapartum
treatment) procedure may be required to access and stabilize neonatal breathing while
maintaining placental flow through the mother.

REFERENCES

1. Panaitescu AM, Nicolaides K. Maternal autoimmune disorders and fetal defects. J Matern Fetal Neonatal
Med 2017; 18: pp. 1-9.
2. Panaitescu AM, Nicolaides K. Fetal Goitre in Maternal Graves’ Disease. Acta Endo (Buc) 2018 14: pp. 85-
89 doi: 10.4183/aeb.2018.85
3. Panaitescu AM, Peltecu G. Gestational Diabetes. Obstetrical Perspective. Acta Endo (Buc) 2016, 12 (3): pp.
331-334.

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4. Sasaki Y, Kikuchi A, Murai M, Kanasugi T, Isurugi C, Oyama R, Sugiyama T. Fetal goiter associated with
preconception hysterosalpingography using an oil-soluble iodinated contrast medium. Ultrasound Obstet
Gynecol 2016; 49: pp. 275-276.
5. Rosenfeld H, Ornoy A, Shechtman S, Diav-Citrin O. Pregnancy outcome, thyroid dysfunction and fetal
goitre after in utero exposure to propylthiouracil: a controlled cohort study. Br J Clin Pharmacol 2009; 68:
pp. 609-617.
6. Rubio IG, Medeiros-Neto G. Mutations of the thyroglobulin gene and its relevance to thyroid disorders.
Curr Opin Endocrinol Diabetes Obes 2009; 16: pp. 373-378.
7. The American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum,
Stagnaro-Green A, Abalovich M, et al., Guidelines of the American Thyroid Association for the Diagnosis
and Management of Thyroid Disease During Pregnancy and Postpartum. Thyroid 2011; 21: pp. 1081-1125.
8. Bliddal S, Rasmussen AK, Sundberg K, Brocks V, Feldt-Rasmussen U. Antithyroid drug-induced fetal
goitrous hypothyroidism. Nat Rev Endocrinol 2011; 7: pp. 396-406
9. Burrow GN. Neonatal goiter after maternal propylthiouracil therapy. J Clin Endocrinol Metab 1965; 25: pp.
403-408.
10. Volumenie JL, Polak M, Guibourdenche J, Oury JF, Vuillard E, Sibony O, et al., Management of fetal
thyroid goitres: a report of 11 cases in a single perinatal unit. Prenat Diagn 2000; 20: pp. 799-806.
11. Luton D, Le Gac I, Vuillard E, Castanet M, Guibourdenche J, Noel M, Toubert ME, Léger J, Boissinot C,
Schlageter MH, Garel C, Tébeka B, Oury JF, Czernichow P, Polak M: Management of Graves’ disease
during pregnancy: the key role of fetal thyroid gland monitoring. J Clin Endocrinol Metab 2005; 90: pp.
6093-6098.
12. Daneman D, Howard NJ. Neonatal thyrotoxicosis: intellectual impairment and craniosynostosis in later
years. J Pediatr 1980; 97: pp. 257-259.
13. Heckel S, Favre R, Schlienger JL, Soskin P. Diagnosis and successful in utero treatment of a fetal goitrous
hyperthyroidism caused by maternal Graves’ disease. A case report. Fetal Diagn Ther 1997; 12: pp. 54-58.
14. Avni EF, Rodesch F, Vandemerckt C, Vermeylen D. Detection and evaluation of fetal goitre by ultrasound.
Br J Radiol 1992; 65: pp. 302-305.
15. Kilpatrick S. Umbilical blood sampling in women with thyroid disease in pregnancy: Is it necessary? Am J
Obstet Gynecol 2003; 189: pp. 1-2.
16. Momotani N, Noh J, Oyanagi H, Ishikawa N, Ito K. Antithyroid drug therapy for Graves’ disease during
pregnancy. Optimal regimen for fetal thyroid status N Engl J Med 1986; 315: pp. 24-28.
17. Smyth PP, Wijeyaratne CN, Kaluarachi WN, Smith DF, Premawardhana LD, Parkes AB, Jayasinghe A, de
Silva DG, Lazarus JH. Sequential studies on thyroid antibodies during pregnancy. Thyroid 2005; 15: pp.
474-477.
18. Bliddal S, Rasmussen ÅK, Sundberg K, Brocks V, Skovbo P, Feldt-Rasmussen U. Graves’ disease in two
pregnancies complicated by fetal goitrous hypothyroidism: successful in utero treatment with levothyroxine.
Thyroid 2011; 21: pp. 75-81.
19. Munoz JL, Kessler AA, Felig P, Curtis J, Evans MI. Sequential Amniotic Fluid Thyroid Hormone Changes
Correlate with Goiter Shrinkage following in utero Thyroxine Therapy. Fetal Diagn Ther 2016; 39: pp. 222-
227.
20. Nachum Z, Rakover Y, Weiner E, Shalev E. Graves’ disease in pregnancy: prospective evaluation of a
selective invasive treatment protocol. Am J Obstet Gynecol 2003; 189: pp. 159-165.
21. Polak M. Thyroid disorders during pregnancy: impact on the fetus. Horm Res Paediatr 2011; 76 Suppl 1:
pp. 97-101.
22. Polak M, Leger J, Luton D, Oury JF, Vuillard E, Boissinot C, Czernichow P. Fetal cord blood sampling in
the diagnosis and the treatment of fetal hyperthyroidism in the offsprings of a euthyroid mother, producing
thyroid stimulating immunoglobulins. Ann Endocrinol (Paris) 1997; 58: pp. 338-342.

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Differential Diagnosis of Body Stalk Anomaly and Limb-Body Wall


Complex by Ultrasound in the First Trimester of Pregnancy

PANAITESCU Anca-Maria1
1Filantropia Clinical Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest (ROMANIA)
Email: [email protected]

Abstract

The introduction of routine screening for chromosomal abnormalities at 11 to 14 weeks’


gestation by the combined test has made it possible to also perform a detailed fetal structural
evaluation at this stage and to identify fetuses with major structural anomalies early in pregnancy.
Body stalk anomaly and limb-body wall complex are two major, sporadic, severe and lethal
fetal structural anomalies that can be easily diagnosed in the first trimester, at the time of the
routine 11 to 14 weeks assessment. Body stalk anomaly has sometimes been included in the
heterogeneous group of limb-body wall complex, however many authors consider it a separate
entity. The aim of this short communication is to discuss the differential diagnosis of these two
fetal defects by ultrasound in the first trimester of pregnancy at 11 to 14 weeks’ gestation.
Keywords: abdominal wall defects; body stalk anomaly; limb-body wall complex; amniotic band syndrome; amniotic band
sequence; first-trimester ultrasound

Introduction

The introduction of routine screening for Down syndrome and other chromosomal
abnormalities at 11 to 14 weeks’ gestation by the combined test has become a standard of
antenatal care in many countries worldwide. [1, 2] At this stage, a detailed fetal structural
evaluation can also be performed with the aim of identifying fetuses with major structural
anomalies earlier in pregnancy. [3, 4] An early accurate diagnosis allows families reproductive
choice and optimal counselling about postnatal outcome. Body stalk anomaly (BSA) and limb-
body wall complex (LBWC) are two major, severe and lethal structural anomalies that can be
easily diagnosed in the first trimester, at the time of the routine 11 to 14 weeks assessment. [5]
The terms BSA and LBWC are often used interchangeable, however, these conditions are
different in regards to their development and features. The aim of this short paper is to discuss the
differential diagnosis of BSA and LBWC by ultrasound in the first trimester of pregnancy at 11 to
14 weeks gestation.

Ultrasound features of body stalk anomaly and limb-body wall complex

Body stalk anomaly (BSA) is a rare condition that has been reported with an incidence of 1 in
7500 pregnancies in antenatal series. [6] The condition is sporadic and is thought to result from
abnormal embryonic folding and defective closure of body wall very early in embryogenesis. [7]
In BSA abdominal organs are herniated outside the abdominal cavity, they are covered by an
amnioperitoneal membrane and are attached to the placenta. The umbilical cord is absent or very

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short. Reported ultrasonographic features of BSA include a large abdominal wall defect, severe
kyphoscoliosis and a short umbilical cord [6, 8-10]. The nuchal translucency is increased in about
half of the affected fetuses at 11 to 14 weeks. [5] The amniotic membrane appears intact on its
entire surface apart from the level of abdominal wall defect. The abdominal organs are herniated
into the celomic cavity and the rest of the fetus is contained in the amniotic sac within a normal
amount of amniotic fluid. The abdominal-placental attachment is easily recognized in the first
trimester as compared to later in pregnancy. Eventhough the umbilical cord is short or absent, the
umbilical vessels can be demonstrated with the use of colour Doppler running from the placenta
to the fetus, marginal to the eviscerated abdominal content. Affected fetuses appear fixed to the
placenta with severe kyphoscoliosis and an abnormal position of the legs. [5]
Limb-body wall complex (LBWC) is a term used to describe a very heterogeneous group of
fetal conditions characterised by the presence of amniotic bands and secondary fetal limb
amputations and body-wall defects. The definition of LBWC has been meeting two of the
following three criteria: (1) thoraco-abdominoschisis or abdominoschisis, (2) limb defects and (3)
craniofacial defects such as cleft lip/palate and encephalocele [7]. Many of the anomalies of
LBWC are found in amniotic band sequence including the craniofacial and limb defects and the
two conditions are considered to overlap. [11, 12] Most authors consider LBWC to result from
early amnion rupture. [12, 13]
Body stalk anomaly and limb-body wall complex can be diagnosed in the first trimester at 11
to 14 weeks [6, 8-9]. Accurate differentiation from other abdominal wall defects is important for
optimal counselling as BSA and LBWC are both lethal conditions. Other abdominal wall defects
that have been diagnosed at 11 to 14 weeks’ gestation and are important in the differential
diagnosis are exomphalos, gastroschisis, extrophy of the cloaca and OEIS complex (omphalocele-
extrophy-imperforate anus-spinal defect), pentalogy of Cantrell and abdominoschisis due to
amniotic bands. In exomphalos, the herniated viscera appear in the base of the umbilical cord,
covered by the cord membrane and a free-floating cord is visible in the amniotic cavity. In
gastroschisis the herniated viscera are freely floating in the amniotic cavity, uncovered and the
long normal umbilical cord can be seen. With pentalogy of Cantrell, there is a large abdominal
wall defect extending upwards in the chest and the herniated viscera are both from the abdominal
and thoracic content. With cloaca extrophy, the defect is downwards, under the level of the
umbilical cord and it involves the bladder. In abdominoschisis due to amniotic bands, the
amniotic membrane continuity is lost, but the umbilical cord is free-floating. In early amnion
rupture, deformation and disruption of other structures, including craniofacial and limbs, can be
demonstrated [11-13].

Differential diagnosis between body stalk anomaly and limb-body wall complex

Body stalk anomaly has sometimes been included in the very heterogeneous group of fetal
conditions known as limb-body wall complex (LBWC), however many authors consider BSA a
separate entity [14, 15]. The most accepted definition of LBWC has been meeting two of the
following three criteria: (1) thoraco-abdominoschisis or abdominoschisis, (2) limb defects and (3)
craniofacial defects such as cleft lip/palate and encephalocele [7]. While with BSA the cord is
absent, the abdominal organs are herniated and attached to the placenta, there is kyphoscoliosis
and positional abnormalities of the lower limbs. Many of the anomalies of LBWC are found in
amniotic band sequence including the craniofacial and limb defects and the two conditions are
considered to overlap [11, 12]. Most authors consider LBWC to result from early amnion rupture
[12, 13] while BSA is thought to be a consequence of abnormal embryonic folding [16]. In a

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series of 17 cases of BSA diagnosed in the first and early second trimester [5], none had clefts,
anencephaly or limb amputations. These features help in the ultrasonographic differential
diagnosis of BSA and amniotic band sequence/limb-body wall complex in the first trimester. The
differential diagnosis is presented in Table 1.

Table 1. Differential diagnosis of body stalk anomaly and limb-body wall complex
Body stalk anomaly Limb-body wall complex
Herniated viscera Liver, bowel Liver, bowel
Herniation site Coelomic cavity Amniotic cavity
Umbilical cord Absent/very short Free-floating
Amniotic membrane Interrupted at the level of the Ruptured/evidence of amniotic bands
herniated abdominal organs
Coelomic space Contains abdominal organs Obliterated
Fetal mobility Stuck through abdominal-placental Normal
attachment
Spine Kyphoscoliosis Normal/defects at various levels
Limbs Normal/talipes Amputations
Head/face Normal Defects

Conclusions

Accurate prenatal diagnosis of BSA and LBWC is feasible from at least as early as the 11
weeks’ gestation and the conditions can be easily distinguished in between them and from other
abdominal wall defects. In BSA the cord is absent, the abdominal organs are herniated and
attached to the placenta, there is kyphoscoliosis and positional abnormalities of the lower limbs,
however, there amniotic membrane is continuous, there are no clefts or wall defects. In LBWC
the amniotic membrane is ruptured, there is evidence of amniotic bands, there is abdominoschisis
due to these bands and there are limbs or craniofacial defects. Both BSA and LBWC are lethal
and sporadic, therefore the counselling for the affected pregnancies is similar. It is however
important to be able to make a distinction between these two entities especially if we want to
understand their different etiologies. [12]

REFERENCES

1. Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn 2011; 31: pp. 7-15.
2. Nicolaides KH. A model for a new pyramid of prenatal care based on the 11 to 13 weeks’ assessment.
Prenat Diagn 2011; 31: pp. 3-6.
3. Syngelaki A, Chelemen T, Dagklis T, Allan L, Nicolaides KH. Challenges in the diagnosis of fetal non-
chromosomal abnormalities at 11-13 weeks. Prenat Diagn 2011; 31: pp. 90-102.
4. Vayna AM, Veduta A, Duta S, Panaitescu AM, Stoica S, Buinoiu N, Nedelea F, Peltecu G. Diagnosis of
Fetal Structural Anomalies at 11 to 14 Weeks. J Ultrasound Med. 2018. doi: 10.1002/jum.14561.
5. Panaitescu AM, Ushakov F, Kalaskar A, Pandya PP. Ultrasound Features and Management of Body Stalk
Anomaly. Fetal Diagn Ther. 2016; 40(4): pp. 285-290.
6. Daskalakis G, Sebire NJ, Jurkovic D, Snijders RJ, Nicolaides KH. Body stalk anomaly at 10-14 weeks of
gestation. Ultrasound Obstet Gynecol 1997; 10: pp. 416-418.
7. Van Allen MI, Curry C, Gallagher L. Limb-body wall complex: I Pathogensesis. Am J Med Genet 1987; 28:
pp. 529-548.
8. Smrcek JM, Germer U, Krokowski M, Berg C, Krapp M, Geipel A, Gembruch U. Prenatal ultrasound
diagnosis and management of body stalk anomaly: analysis of nine singleton and two multiple pregnancies.
Ultrasound Obstet Gynecol 2003; 21: pp. 322-328.

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9. Murphy A, Platt LD. First-trimester diagnosis of body stalk anomaly using 2-and 3-dimensional
sonography. J Ultrasound Med 2011; 30: pp. 1739-1743.
10. Pakdaman R, Woodward PJ, Kennedy A. Complex Abdominal Wall Defects: Appearances at Prenatal
Imaging. Radiographics 2015; 35: pp. 636-649.
11. Hunter AG, Seaver LH, Stevenson RE. Limb-body wall defect. Is there a defensible hypothesis and can it
explain all the associated anomalies? Am J Med Genet A 2011; 155A: pp. 2045-2059.
12. Kruszka P, Uwineza A, Mutesa L, Martinez AF, Abe Y, Zackai EH, Ganetzky R, Chung B, Stevenson RE,
Adelstein RS, Ma X, Mullikin JC, Hong SK, Muenke M. Limb body wall complex, amniotic band
sequence, or new syndrome caused by mutation in IQ Motif containing K (IQCK)? Mol Genet Genomic
Med 2015; 3: pp. 424-432.
13. Halder A. Amniotic band syndrome and/or limb body wall complex: split or lump. Appl Clin Genet 2010; 3:
pp. 7-15.
14. Russo R, D’Armiento M, Angrisani P, Vecchione R. Limb body wall complex: a critical review and a
nosological proposal. Am J Med Genet 1993; 47(6): pp. 893-900.
15. Craven CM, Carey JC, Ward K. Umbilical cord agenesis in limb body wall defect. Am J Med Genet 1997;
71(1): pp. 97-105
16. Romero R, Pilu G, Jeanty P, Ghidini A, Hobbins JC. Prenatal Diagnosis of Congenital Anomalies. Norwalk:
Appleton and Lange, pp. 226-227.

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Chronic Hypertension in Pregnancy and the Risk of Superimposed


Preeclampsia

PANAITESCU Anca-Maria1
1Filantropia Clinical Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest (ROMANIA)
Email: [email protected]

Abstract

Chronic hypertension (CH) is among the most frequent medical conditions encountered in
pregnant women. Pregnancy in women with CH is associated with increased risk for a wide range
of adverse pregnancy outcomes, including stillbirth, preeclampsia, small for gestational age,
gestational diabetes, iatrogenic preterm birth and the need for elective caesarean section.
Superimposed preeclampsia (sPE) complicates about 1 in 4 of these pregnancies and it is often
challenging to diagnose. Preeclampsia is a major contributor to preterm birth and caesarean
delivery in these women and women with CH with superimposed preeclampsia have worse
pregnancy outcomes than women with CH without superimposed preeclampsia. Medical
interventions to reduce the risk of PE development in women with CH have been proposed
however the extent to which they really work remains to be determined.
Keywords: chronic hypertension; pregnancy; preeclampsia; sFLT-1; PLGF; aspirin

Introduction

Chronic hypertension (CH) is one of the most common medical conditions we encounter in
pregnant women and is defined by the presence of blood pressure (BP) ≥140 mm Hg systolic
(SBP) and/or 90 mm Hg diastolic (DBP) before pregnancy or before 20 weeks’ gestation, use of
antihypertensive medications before pregnancy, or persistence of hypertension for >12 weeks
after delivery. [1] Chronic hypertension needs to be differentiated from other hypertensive
conditions that may arise during pregnancy (Table 1). In gestational hypertension the BP rises at
≥140 mm Hg or DBP ≥90 mm Hg after 20 weeks of gestation in a previously known
normotensive woman. In preeclampsia there is association of increased BP (SBP ≥140 mm Hg or
DBP ≥90 mm Hg) after 20 weeks’ gestation with proteinuria (demonstration of ≥0.3 g protein in
a 24-h urine collection) or with other systemic manifestations in a previously normotensive
woman.

Table 1. Classification of hypertension in pregnancy [1]


Gestational hypertension Elevated BP (SBP ≥140 mm Hg or DBP ≥90 mm Hg)
after 20 weeks’ gestation in a previously normotensive
woman
Preeclampsia After 20 weeks’ gestation, SBP ≥140 mm Hg or DBP
≥90 mm Hg in a previously normotensive woman.
Proteinuria (excretion of ≥0.3g protein in a 24h urine
collection) or with other systemic manifestations.
Chronic hypertension SBP ≥140 mm Hg and/or DBP ≥90 mm Hg before

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pregnancy or before 20 weeks’ gestation


Chronic hypertension with superimposed New onset of proteinuria in the setting of hypertension
preeclampsia before 20 weeks’ gestation
An increase in proteinuria (if present earlier)
An increase in blood pressure
Onset of HELLP syndrome
BP – blood pressure; DBP – diastolic blood pressure; HELLP – haemolysis, elevated liver enzymes, low
platelets; SBP – systolic blood pressure.

Depending of the studied population, CH is found in 1 to 3% of the pregnant population. In a


cohort study that included a multiracial inner-city population of 109,932 pregnancies in Great
London, Great Britain there were 1,417 (1.3%) cases of CH. [2] The incidence of CH was found
to increase with maternal age and weight and was three-times higher in women of Afro-
Caribbean racial origin and twice as high in those of South Asian origin, compared to Caucasian
women. Presence of metabolic syndrome or other risk factors for gestational diabetes also
increases the incidence of CH. [3, 4]
Pregnancy in women with CH is associated with increased risk for a wide range of adverse
pregnancy outcomes, including stillbirth, preeclampsia, small for gestational age, gestational
diabetes, iatrogenic preterm birth and the need for elective caesarean section. [2, 5]

Superimposed preeclampsia

Superimposed PE is very frequent in women with CH. In a recent prospective cohort study of
women with CH, superimposed PE complicated 23% of these pregnancies. The incidence of
preterm PE (PE developing before 37 weeks’ gestation) was 8.5% and term PE (PE developing
after 37 weeks’ gestation) 14.3%. After adjustment for confounding factors the risk of both
preterm and term PE was 5-6 times higher in women with CH than in those without CH. [2] The
risk of PE in all pregnancies increased with the level of mean arterial pressure (MAP) at 11-13
weeks’ gestation. [2, 5]
The diagnosis of superimposed preeclampsia in women with CH is challenging because the
blood pressure may already be elevated, and proteinuria may be present before pregnancy in
association with latent kidney disease. Therefore, in this population of pregnant women,
superimposed preeclampsia should be considered if blood pressure increases, if especially there is
new-onset proteinuria or worsening of pre-pregnancy proteinuria or if there is an increase in the
required medication to achieve control of blood pressure. Laboratory abnormalities
(thrombocytopenia, elevated liver function tests, and increasing serum creatinine) will also often
distinguish preeclampsia from worsening of underlying hypertension. Biomarkers of placental
origin as placental growth factor (PLGF) and sFLT-1 (soluble fms-like tyrosine kinase 1) have
been used to predict and diagnose onset of sPE in women with CH [6, 7] however, more studies
are required to include these markers for clinical use at this time. [1]
Preeclampsia is an important contributor to preterm birth and caesarean delivery in women
with CH and pregnant women with chronic hypertension with superimposed preeclampsia have
worse birth outcomes than women with chronic hypertension without superimposed
preeclampsia. [2, 8, 9] However, there currently are no effective preventive measures to decrease
these risks. In the general pregnant population, aspirin 150 mg from 11-13 weeks’ gestation in
those of high risk for preterm PE has been proven to reduce the risk of development of PE with
onset before 37 weeks’ gestation. [10] Unfortunately, aspirin has not been proven to be effective
in women with CH. [11] Other prevention strategies as administration of pravastatin or

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metformin have been proposed for prevention of PE or types of PE such as term PE. [12-15]
Perhaps, these drugs will prove more effective than aspirin in preventing sPE in the population of
women with CH.
Tight control of BP values during pregnancy has also been proposed as a potential intervention
to reduce the risk of developing PE. In patients with CH, as in those with gestational hypertension
or PE it is recommended that severe hypertension (SBP of 160 and/or DBP of 110 mmHg or
higher) should be controlled to reduce the risk of maternal death and morbidity. [1, 16]
However, in the case of mild (140/90 to 149/99 mmHg) to moderate hypertension (150/100 to
159/109 mmHg) it is uncertain whether normalization of blood pressure is beneficial and whether
such therapy would reduce the associated increased risk of PE. A meta-analysis of trials
evaluating antihypertensive treatment vs. placebo or no treatment in pregnancies with CH
reported no significant differences between the groups in risk of superimposed PE. [17] Another
recent meta-analysis examined the evidence of whether in patients with CH and mild to moderate
hypertension the level of control of BP during pregnancy has a beneficial or adverse effect on the
risk of PE. The finding of this study suggested that lowering the MAP by antihypertensive
medication in women with mild to moderate hypertension in the context of CH has no significant
effect on risk of PE. [18]

Conclusions

Chronic hypertension (CH) is among the most frequent medical conditions encountered in
pregnant women and it significantly increases the risk of adverse pregnancy outcomes.
Superimposed PE will eventually develop in 1 of 4 women with CH. Strategies to reduce the
risk of sPE development have been tried but found to be ineffective. Current research is focused
on finding new interventions that would potentially reduce the risk of PE and improve pregnancy
outcomes for these women.

REFERENCES

1. Committee on Hypertension in Pregnancy. Hypertension in Pregnancy. Washington, DC: American College


of Obstetricians and Gynecologists; 2013.
2. Panaitescu AM, Syngelaki A, Prodan N, Akolekar R, Nicolaides KH. Chronic hypertension and adverse
pregnancy outcome: a cohort study. Ultrasound Obstet Gynecol. 2017; 50(2): pp. 228-235.
3. Spaan JJ, Sep SJ, van Balen VL, Spaanderman ME, Peeters LL. Metabolic syndrome as a risk factor for
hypertension after preeclampsia. Obstet Gynecol. 2012; 120 (2 Pt 1): pp. 311-7.
4. Panaitescu AM, Peltecu G. Gestational Diabetes. Obstetrical Perspective. Acta Endo (Buc) 2016, 12 (3): pp.
331-334.
5. Panaitescu AM, Baschat AA, Akolekar R, Syngelaki A, Nicolaides KH. Association of chronic
hypertension with birth of small-for-gestational-age neonate. Ultrasound Obstet Gynecol. 2017; 50(3): pp.
361-366.
6. Bramham K, Seed PT, Lightstone L, Nelson-Piercy C, Gill C, Webster P, Poston L, Chappell LC.
Diagnostic and predictive biomarkers for pre-eclampsia in patients with established hypertension and
chronic kidney disease. Kidney Int. 2016; 89(4): pp. 874-85.
7. Verlohren S, Herraiz I, Lapaire O, Schlembach D, Moertl M, Zeisler H, Calda P, Holzgreve W, Galindo A,
Engels T, Denk B, Stepan H. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders
and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012; 206(1): pp. 58.e1-8.
8. Sibai BM, Lindheimer M, Hauth J, Caritis S, VanDorsten P, Klebanoff M, MacPherson C, LandonM,
Miodovnik M, Paul R, Meis P, Dombrowski M. Risk factors for preeclampsia, abruptio placentae, and
adverse neonatal outcomes among women with chronic hypertension: National Institute of Child Health and
Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med.1998; 339: pp. 667-671

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9. Panaitescu AM, Akolekar R, Kametas N, Syngelaki A, Nicolaides KH. Impaired placentation in women
with chronic hypertension who develop pre-eclampsia. Ultrasound Obstet Gynecol. 2017; 50(4): pp. 496-
500.
10. Rolnik DL, Wright D, Poon LC, O’Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S,
Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K,
Meiri H, Gizurarson S, Maclagan K, Nicolaides KH. Aspirin versus Placebo in Pregnancies at High Risk for
Preterm Preeclampsia. N Engl J Med. 2017; 377(7): pp. 613-622.
11. Poon LC, Wright D, Rolnik DL, Syngelaki A, Delgado JL, Tsokaki T, Leipold G, Akolekar R, Shearing S,
De Stefani L, Jani JC, Plasencia W, Evangelinakis N, Gonzalez-Vanegas O, Persico N, Nicolaides KH.
Aspirin for Evidence-Based Preeclampsia Prevention trial: effect of aspirin in prevention of preterm
preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history.
Am J Obstet Gynecol. 2017; 217(5):585.e1-585.e5.
12. Romero R, Erez O, Hüttemann M, Maymon E, Panaitescu B, Conde-Agudelo A, Pacora P, Yoon BH,
Grossman LI. Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention
of preeclampsia and cancer, and the promotion of longevity. Am J Obstet Gynecol. 2017; 217(3): pp. 282-
302.
13. Costantine MM, Cleary K, Hebert MF, Ahmed MS, Brown LM, Ren Z, Easterling TR, Haas DM, Haneline
LS, Caritis SN, Venkataramanan R, West H, D’Alton M, Hankins G; Eunice Kennedy Shriver National
Institute of Child Health and Human Development Obstetric-Fetal Pharmacology Research Units Network.
Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant
women: a pilot randomized controlled trial. Am J Obstet Gynecol. 2016; 214(6):720.e1-720.e17.
14. Huluta I, Panaitescu AM. Prediction of preeclampsia developing at term. Ginekol Pol. 2018;89(4): pp. 218-
221.
15. Panaitescu AM, Wright D, Militello A, Akolekar R, Nicolaides KH. Proposed clinical management of
pregnancies after combined screening for pre-eclampsia at 35-37 weeks’ gestation. Ultrasound Obstet
Gynecol. 2017; 50(3): pp. 383-387.
16. NICE. Hypertension in pregnancy: The management of hypertensive disorders during pregnancy. NICE
Clinical Guideline 107. Manchester, UK: National Institute for Health and Clinical Excellence, 2011: pp. 1-
53.
17. Webster LM, Conti-Ramsden F, Seed PT, et al., Antihypertensive treatment on maternal and perinatal
outcomes in pregnancy complicated by chronic hypertension: a systematic review and meta-analysis. J Am
Heart Assoc. 2017;6 doi: 10.1161/JAHA.117.005526.
18. Panaitescu AM, Roberge S, Nicolaides KH. Chronic hypertension: effect of blood pressure control on
pregnancy outcome. J Matern Fetal Neonatal Med. 2017;1: pp. 1-7.

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Congenital Heart Defects in Down Syndrome

MITREA Geta1,2, PATRICIU Mihaela1,3, STEFANESCU Bogdan1,2


1 St. Andrew Emergency Dept. Hospital- Galati (ROMANIA)
2 Medical Faculty of the Lower Danube University Galati (ROMANIA)
3 Gr. T Popa University Iasi (ROMANIA)

Email: [email protected]

Abstract

Introduction
Complete atrioventricular septal defect, is a complex heart malformation, characterized by a
large, unrestrictive ventricular septal defect associated with an atrial septal defect ostium primum
like. Together these defects can give rise to a large communicating area in the inferior region of
the interatrial septum and a single atrio-ventricular valve, with different degrees of regurgitation
at the right or left valvular part. This type of defect is frequently associated with Trisomy 21
(Down Syndrome). This type of malformation represents 2-5% of all congenital heart defects.

Objective
Establishing the importance of early diagnosis of Down Syndrome and the possible
complications that can occur.

Results
Boy, postterm newborn, GA=43 weeks, BW=4300g, 4th pregnancy, 4th birth, born to a mother
without medical supervision during her pregnancy, presents at birth generalized cyanosis, trisomy
21 phenotype, postductal and preductal blood oxygen saturations 80-85% while receiving oxygen
under tent. Laboratory testing reveal severe trombocytopenia which was maintained over the
course of hospitalization , despite platelets micro-transfusions. On the 11th day of life Prednison is
introduced. On the 15th day of life he was transferred in the Pediatric Cardiology Ward of
Emergency Hospital “Sf.Maria” Iasi, where he received diuretics (Spironolactona,Furosemid),
conversion enzyme inhibitors (Ednyt). His evolution, from a cardiac stand point, was slow but
good. He was released after 15 days in good health, stable hemodynamically, pulmonary,
digestive, and satisfactory weight gain.

Conclusion
Fetal ultrasound is an important tool in detecting congenital defects. In regard to congenital
heart defects, they can appear in pregnancies without risk factors, which entails the necessity of
prenatal diagnosis and a multidisciplinary approach which should include pediatric cardiologists
and neonatologists for the manangement of the newborn with congenital heart defects. Screening
tests should be done before conception to identify if risk factors exist for certain diseases or if
there is a risk of passing on to the child the disease. These screenings combined with genetic
counseling could help in reducing the morbidity and mortality of genetically transmitted defects.
Keywords: Down Syndrome, congenital heart defect, trombocytopenia

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Introduction

Langdon-Down Syndrome (21 trisomy) is the most frequent genetic syndrome compatible
with survival. Trisomy 21 was described for the first time by J.E.D Esquirol in 1838 and by
Seguin Edouard in 1844. In 1959, the disease was identified as a trisomy of the 21st chromosome
by the French pediatrician and geneticist Jerome Lejeune and was recognized under the name
Down Syndrome or Trisomy 21.
The incidence of Down syndrome has been estimated at 1:733-800 births.
Down Syndrome represents a chromosomial mutation that results in the presence of an extra
copy of genetic material on the 21st chromosome, either completely or partially, as an effect of
translocation. Mother’s age influences the likelihood of conceiving a child with Down syndrome.
Congenital heart defects are found in 40% of newborns with Down syndrome. VSD
(ventricular septal defect) and persistence of atrio-ventricular canal are typical findings.

Objective

Establishing the importance of early diagnosis of Down Syndrome and the possible
complications that can occur.

Case presentation

Post-term male newborn, GA(gestational age) 43 weeks, BW(birth weight) 4300g, from an
unsupervised pregnancy, admitted in the Neonatology Ward of St. Andrew Emergency Hospital
Galati, diagnosed after birth with Down syndrome an atrioventricular canal.

Anamnestic data
Mother’s age 43 years old, 4th pregnancy, 4th birth, undergoing antipsychotic treatment, the
other children healthy. She did not have any medical supervision during this pregnancy. The
newborn was delivered vaginally from cranial presentation.

Clinical examination at birth


Mediocre appearance, generalized cyanosis, trisomy 21 phenotype, systolic murmur gr. I/VI
on the left parasternal border which led to his admittance in the NICU (Neonatal Intensive Care
Unit).
The following therapeutic measures were started: parenteral feeding, oxygen administration
under cephalic tent, diuretics (Furosemide i.v).
At approximately 4 hours after birth, the systolic murmur intensifies (gr. III/VI on the whole
cardiac area), preductal and postductal oxygen values between 80-85% while under oxygen,
peripheral arteries pulsatile, normal blood pressure.
Laboratory investigations revealed thrombocytopenia (17x103), C reactive protein and
procalcitonin were negative. During the hospitalization period he maintained low thrombocyte
values, bruises and bleeding at puncture sites. He received microtransfusions of platelet
concentrate AII positive (12 days) and one with packed red cells mass AII positive. Peripheral
cultures were negative.

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Fig. 1. Platelets value curve

Thoracic x-rays revealed normal lung aeration, cardiomegaly with a cardiothoracic index of
0.68. Cardiac ultrasound established the presence of an incomplete atrioventricular canal.

Fig. 2. Ultrasonography

On day 10 the newborn begins to exhibit short episodes of tachypnea with respiratory effort.
During the hospitalization the child did not present tachycardia, hepatomegaly or oedema.
At 15 days of life the newborn is transferred to the Pediatric Cardiology Ward at “Sf. Maria”
Emergency Hospital Iasi, where he received diuretic medication (Furesomide, Spironolactone)
and conversion enzyme inhibitors. (Ednyt)

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His cardiologic status slowly improved, being discharged after 15 days in a good general
health condition.

Outcome
The patient’s outcome will be linked to the complications that arise from the congenital heart
defect.

Special case considerations


We were faced with a newborn with Down syndrome and a congenital heart defect who
developed secondary thrombocytopenia unresponsive to treatment

Conclusions

Fetal ultrasonography and a prompt diagnosis have an important impact on the newborns
outcome.
Preconception screenings should be done to identify individuals at risk for specific pathologies
or for genetic disorders they can inherit, and, combined with genetic counseling could greatly
reduce morbidity and mortality cause by genetic disorders.

REFERENCES

1. Ferencz C, Rubin JD, McCarter RJ, Brenner JI, Neill CA, Perry LW, et al., Congenital heart disease:
prevalence at livebirth. The Baltimore-Washington Infant Study. Am J Epidemiol 1985; 121(1): pp. 31-6.
2. Eidem BW, Jones C, Cetta F. Unusual association of hypertrophic cardiomyopathy with complete
atrioventricular canal defect and Down syndrome. Tex Heart Inst J 2000; 27(3): pp. 289-91.
3. Garrod AE. On the association of cardiac malformations with other congenital defects. St Barth Hosp Rep
1894;30:53-61. Available from: http://hdl.handle.net/2027/nnc2.ark:/
13960/t9q24mm0h?urlappend=%3Bseq=89 [cited 2015 Aug 7].
4. Spicer RL. Cardiovascular disease in Down syndrome. Pediatr Clin North Am 1984; 31(6): pp. 1331-43.
5. Kurnit DM, Aldridge JF, Matsuoka R, Matthysse S. Increased adhesiveness of trisomy 21 cells and
atrioventricularcanal malformations in Down syndrome: a stochastic model. Am J Med Genet 1985; 20(2):
pp. 385-99.

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Hydranencephaly: Clinical and Paraclinical Considerations Based


on Two Presenting Cases

MITREA Geta1,2, PATRICIU Mihaela1,3, STEFANESCU Bogdan1,2


1 St. Andrew Emergency Dept. Hospital- Galati (ROMANIA)
2 Medical Faculty of the Lower Danube University Galati (ROMANIA)
3 Gr. T Popa University Iasi (ROMANIA)

Email: [email protected]

Abstract

Hydranencephaly is a congenital malformation of the central nervous system characterized by


abnormalities of the cerebral hemispheres and an accumulation of cerebrospinal fluid. Frequently,
this pathology appears in the early stages of development of the central nervous system. In most
cases, the cerebellum and brainstem develop normally, but in some rare instances cerebellar
atresia can occur.
In this paper we will be presenting two cases in a side by side method: the first case, of a male
newborn, GA=35 weeks, BW=2100g and the second of a term newborn, BW=3000g, both born
to mothers who did not undergo medical supervision during their pregnancies. The first newborn
developed medium respiratory distress syndrome and needed supplemental oxygen, parenteral
feeding and antibiotics. The second newborn had a satisfactory general state and mild hypotonia.
Both have undergone multiple cranial ultrasounds which were indicative of hydranencephaly.
At 13 days of life they were transferred to the Galati Pediatrics Hospital for further
investigations.
Keywords: premature, hydranencephaly, respiratory distress syndrome

Introduction

Hydranencephaly is a congenital malformation of the central nervous system which affects


cerebral hemispheres, with accumulation of cerebrospinal fluid. The frequency of this
malformation is of about 1:5000 newborns. It appears in the early stages of brain development.
The brain stem and cerebellum can be normally developed, and in rare cases cerebellum
agenesia can be present. The etiology is not completely clear, it affects both sexes in the same
degree.

Etiology

- Vascular implications : thrombosis, ischemia;


- Infectious vectors passed through the placenta, most frequently Toxoplasmosis, Epstein-
Barr, Herpes Simplex, Cytomegalovirus, enteric viruses, adenoviruses, parvoviruses,
syncytial respiratory virus;
- Congenital anomalies with obstruction of blood flow at the main carotid artery;

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- In monochorionic monoamniotic twin pregnancies with feto-fetal transfusion and


intrauterine death, in the second trimester, the surviving fetus has a high risk for
developing hydranencephaly.

Clinical features

- The pregnancy can progress without problems to full term;


- At birth, the newborn can have a normal cranium and face conformation or both can be
distorted;
- Archaic reflexes are diminished, high pitched cry, seizures, myoclonus, thermal
instability, respiratory distress.

Laboratory investigations

The diagnosis can be made in utero through fetal ultrasound. After birth, through
transfontanellar ultrasound, CT, IRM which make the positive diagnosis and differentiate
between other central nervous system malformations.

Differential diagnosis

1. Hydrocephaly – big head circumference, no structural anomalies, ventriculomegaly,


normal cortex, no dysmorphic face features;
2. Holoprosencephaly – normal cortex, normal ventricles, dysmorphic face features, normal
head circumference;
3. Porencephaly – cystic well defined cavity which is formed through focal brain matter
destruction, of vascular origin, followed by tissue resorption; normal cranium, normal
ventricles.

Treatment

Consists of cerebrospinal fluid drainage through multiple ventricle or lumbar punctures or by


placing a ventriculoperitoneal or ventriculoatrial shunt.

Prognosis

From a neurological standpoint, these newborns are in permanent vegetative state.

Case presetation

The following paper presents two newborns from pregnancies without medical supervision,
admitted to the Neonatology Ward of “Sf.Ap.Andrei” Emergency Hospital, Galati, diagnosed
after birth with hydranencephaly

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CASE 1 CASE 2

Male, medically unsupervised pregnancy, born Female, medically unassisted pregnancy, born in our
spontaneously in a public place, unassisted. hospital.

Mother 32 years of age, drug addict, multiple pregnancies. Mother 17 years of age, 3rd pregnancy, 2nd birth, green
amniotic fluid

BW=2500g, GA=35 weeks, L=46 cm, TP=29 cm, BW=3000g, GA=39 weeks, L=50 cm, TP=33.5, TC=34cm,
CP=29.5cm APGAR=8 at 1’

GENERAL HEALTH STATUS AT BIRTH/


ADDMITANCE IN HOSPITAL

General cyanosis, expiratory grunting, costal retractions, Good general appearance, acrocyanosis
nasal flaring.

Neurologic status: anterior fontanel 3/3 cm, open cranial Neurologic: wide anterior fontanel 4/4 cm, open cranial
sutures, mild hypotonia, uneven Moro reflex, archaic sutures, mild hypotonia, uneven Moro reflex.
reflexes diminished.

Admitted to the NICU. Admitted to Neonatal Ward.

EVOLUTION.TREATMENT

The respiratory distress syndrome accentuates and nasal During the hospitalization period, the newborn had a good
CPAP was introduced for 4 days, from day 5 he is put on general health condition, mild hypotonia, was breastfed but
oxygen under cephalic tent. he had a slow sucking rhythm., hypertensive anterior
fontanel and open sutures.

An umbilical catheter was placed and treatment with On day 5 he stops tolerating feedings, hypotonia
Vancomycin, Furosemide, Phenobarbital started. accentuates and is admitted to the NICU.

Enteral gavage feeding was initiated with formula for He receives i.v fluids and enteral gavage feeding is started
preterms but the newborn did not tolerate it. on day 7

On day 12 he presents abdominal distension with biliary On day 13 he is transferred to Sf.Ioan” Emergency Hospital
gastric residue and no stool emission. For these reasons he for Children,Galati.
was transferred to “Sf.Ioan” Emergency Hospital for
Children,Galati.

LABORATORY INVESTIGATIONS

-mild hypocalcemia correct through gluconic calcium i.v -high CK and LDH values
-inflammatory tests (C reactive protein, leukocytosis,
procalcitonin) were positive, but became negative under
antibiotherapy
-gastric colonization with E.coli
-negative blood cultures

OUTCOME IN THE PEDIATRIC WARD

The newborn deteriorates rapidly with multiple cardiac The newborn deteriorates rapidly with multiple cardiac
arrests. arrests.

Shallow breathing, bradichardia, oxygen dependent. After 4 days he develops irreversible cardiorespiratory
After 4 days he develops irreversible cardiorespiratory arrest.
arrest.

The newborn deteriorates, shallow breaths.


After 10 days develops irreversible cardiorespiratory arrest.

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Imaging studies
In both cases, transfontanelar ultrasound made the diagnosis. It showed the absence of
cerebral hemispeheres.

Fig. 1. Transfontanelar ultrasound for case 1 and 2

Fig. 2. CT imaging

Necropsy findings
1. Hydranencephaly
2. Pulmonary stasis and oedema
3. Dystrophic myocardial lesions
4. Splenic, renal, hepatic stasis

Conclusion

Hydranencephaly is a rare brain malformation, with a severe outcome. In utero diagnosis is


very important because this malformation is a medical indication for abortion. The medical
intervention after birth is palliative, these patients being in a permanent vegetative state. Surgical
treatment does not improve the neurologic status.

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REFERENCES

1. Kandel, Eric R. (2013). Principles of neural science (5. ed.). Appleton and Lange: McGraw Hill. p. 1020.
ISBN 978-0-07-139011-8.
2. Jump up. “Hydranencephaly: Definition, Information, Diagnosis & Prognosis”. Retrieved 24 February
2018.
3. Jump up to: a, b, c. National Organization for Rare Disorders. “Hydranencephaly”. Rare Diseases
Information.
4. Jump up to: a, b. National Institute of Neurological Conditions and Stroke, NINDS. “Hydranencephaly
Information Page”. Disorders.
5. Jump up. Ulmer S, Moeller F, Brockmann MA, Kuhtz-Buschbeck JP, Stephani U, Jansen O (2005).
“Living a normal life with the nondominant hemisphere: magnetic resonance imaging findings and clinical
outcome for a patient with left-hemispheric hydranencephaly”. Pediatrics. 116(1): pp. 242-5.
doi:10.1542/peds.2004-0425. PMID 15995064.
6. Jump up to: a, b, c, d, e. Kurtz & Johnson, Alfred & Pamela. “Case Number 7: Hydranencephaly”.
Radiology, 210, pp. 419-422.
7. Jump up. Dominguez, R; Aguirre Vila-Coro, A; Slopis, JM; Bohan, TP (June 1991). “Brain and ocular
abnormalities in infants with in utero exposure to cocaine and other street drugs”. American journal of
diseases of children (1960). 145(6): pp. 688-95. PMID 1709777.
8. Jump up to: a, b. Dubey, AK Lt Col. “Is it Hydranencephaly-A Variant?” (PDF). MJAFI 2002; 58: pp.
338-339. Archived from the original (PDF) on 2014-04-02. Retrieved 2011. Jump up “Everything Guide
to Children with Hydranencephaly” by Brayden Alexander Global Foundation for Hydranencephaly,
Incorporated.
9. Jump up McAbee GN, Chan A, Erde EL (2000). “Prolonged survival with hydranencephaly: report of two
patients and literature review”. Pediatr. Neurol. 23(1): p. 80-4. doi:10.1016/S0887-8994(00)00154-5. PMID
10963978.
10. Jump up Rare Disease Day: February 28. “What is a Rare Disease?” Rare Disease. Retrieved 2011.

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Opimization of the First Trimester Ultrasound Scan for Detection of


Fetal Structural Abnormalities

PĂTRU Ciprian Laurențiu1,2,3, TUDORACHE Ștefania2,3,


ȘOROP-FLOREA Maria1, DRAGUȘIN Roxana Cristina1,
ZORILĂ Lucian George1, STOICA Alin2, CRISTIAN Marinaș Marius1,2,3,
LAURA Cara Monica2, CERNEA Nicolae1,2,3, ILIESCU Dominic Gabriel1,2,3
1 ENDOGYN AM, Craiova, Department of Obstetrics and Gynecology, (ROMANIA)
2 University of Medicine and Pharmacy of Craiova, Department Mother and Child, Antenatal Diagnostic Unit, (ROMANIA)
3 Emergency County Hospital from Craiova, (ROMANIA)

Abstract

Objectives
To evaluate the effectiveness of fetal morphological scan in the first trimester, as well as the
causes of diagnostic errors.

Method
We studied the dynamics of optimized first-trimester ultrasound results in the ENDOGYN
center at 12-13 weeks of gestation. We included patients in the first trimester and with a known
outcome of pregnancy. As controls, we used: re-evaluations within the University of Medicine
and Pharmacy, autopsy and neonatal investigations. Time of evaluation, false-negative/positive
(RFP/RFN) results were recorded as an audit method for personal experience. The causes of
discordant diagnoses have been analyzed.

Results
77.77% of the major fetal structural abnormalities were identified in the first trimester. For
experienced examiners, the detection rate increased by 5% during the study period, and the false
positive rate decreased by 9%. There were no significant differences in the false negative rate
between examiners, regardless of experience, when the investigative protocol was complete.
However, completion of the protocol within 30 minutes was possible only in 63% of the cases
in the first year of training. The false positive rate was significantly higher in less experienced
examiners but decreased by 28%.

Conclusions
Ultrasound examination in the first trimester is feasible and effective in detecting major fetal
abnormalities, but leads to increased investigation time per patient. The rate of false results
decreases with the accumulation of experience and the ability to complete an extended
investigation protocol.
Keywords: fetal structural abnormalities, first trimester, ultrasound

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Introduction

The first trimester assessment of fetal anatomy is nowadays enabled by the improvement of
imaging due to high frequency and high resolution achieved through advances in signal
processing and image magnification [1].
At 12-13 weeks some fetal malformations can be are detected [2, 3, 4], some can never be and
others are potentially detectable depending on their association with increased nuchal
translucency, the phenotypic expression of the abnormality and the objectives set for such a scan
[5, 6]. The association between major structural abnormalities and chromosomal abnormalities is
well known [7].
According to the WHO-supplied data, the congenital defects represent an important cause to
death and birth rates (11% out of the neonatal deaths) [8].
The risk of significant morbidity and mortality of second trimester termination of pregnancy
increases with advancing gestation [9] and therefore, a first trimester diagnosis of fetal
abnormalities results in earlier and consequently safer termination of pregnancy [10].
Transvaginal examination is usually superior to transabdominal resolution in visualizing fetal
anatomy at 12 to 13 weeks of gestation but is regarded as a source of discomfort and sometimes
inadequate if the fetus is lying in an unfavorable position [11, 12].
We present the initial results of an ongoing study investigating ultrasonographic
morphological optimized screening for fetal structural abnormalities between 12+0 to 13+6
weeks of gestation using primary transabdominal scan and completed when needed with
transvaginal ultrasound in a low risk population.

Methods

In our study we included patients with gestational age between 12weeks +0 days to 13 weeks
+ 6 days with a known outcome of pregnancy. First trimester scans were performed by five
physicians and the scanning time for each examination was also noted. Information about the
study was given and verbal consent was obtained from each included patient.
The recruited patients initially underwent transabdominal fetal morphological survey using
Voluson GE Healthcare Systems by means of 2D and Color Doppler. The gestational age was
determined by the measurement of the fetal crown-rump length. If the fetal position did not
permit a complete morphological scan, transvaginal assessment was performed. In addition,
nuchal translucency measurements were also obtained and fetal karyotyping was offered if the
nuchal translucency was considered to be abnormal (over the >95th percentile).
The first trimester morphological protocol included visualization of the choroid plexuses,
skull, orbits, nose, lips, heart (four chamber and three-vessel view both in grey scale and color
Doppler and pulse Doppler of the ductus venosus -DV), abdominal wall, diaphragm, stomach,
umbilical cord insertion and vessels, kidneys, bladder, spine and fetal limbs (Figure 1).

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Fig. 1. First trimester fetal anatomy scan

As controls, we used re-evaluations within the University of Medicine and Pharmacy, autopsy
and neonatal investigations. False-negative/positive (RFP/RFN) results were recorded as an audit
method for personal experience. As a result of major structural abnormalities, pregnancies were
terminated by prostaglandin termination procedure.
The causes of discordant diagnoses have been analyzed. Patients and their obstetricians were
informed of major fetal structural abnormalities and an appropriate management was discussed
and initiated. If the first trimester anatomical survey was considered normal, the patients were
asked to re-attend for a routine 18-20 weeks anomaly scan.

Results

Fifthteen fetal structural abnormalities were diagnosed during the study period. Of these, 12
were diagnosed at the 12-13 weeks scan and three were diagnosed in the second trimester at 18-
20 weeks anomaly scan (one case of Tetralogy of Fallot, one case of bilateral club foot and one
case of multicystic kidney – table). Cranial abnormalities (hydrocephalus, anencephaly) were the
most common structural defects detected followed by cardiac abnomalities (atrio-ventricular
septal defect, hipoplastic heart), gastrointestinal and other structural abnormalities (cystic
hygroma, hydrops, omphalocele, spina bifida, limb abnormalities) (Figure 2, 3 and Table).

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Fig. 2. A, B, C-. Hydrocephalus; D, E, F, G- Cystic hygroma

Fig. 3. Spina bifida

As for false positive results, there were two fetuses, one with apparently prominent
omphalocele and one with hyperecogenic bowel; both fetuses were rescanned a week later and
considered as normal.
Pregnancies that were terminated as a result of major structural abnormalities followed an
antomopathological examination that confirmed the antenatal diagnosis.
Fetuses with chromosomal abnormalities were prenatally diagnosed by chorionic villous
sampling and amniocentesis. The intrauterine maneuvers were performed as a result of increased
nuchal translucency in the first trimester or for known association between major structural
abnormalities and chromosomal abnormalities. There were two cases of trisomy 21, one case of
trisomy 18 and one fetus with Turner syndrome. All of these cases associated major structural
abnormalities (Figure 4 and Table).

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Gestational
Abnormalities age at Scan mode used Outcome Comments
detection
Declined karyotype. Diagnosis confirmed post-
abortion. Other structural abnormalities
12w+2d TAUS PG/TOP
associated.
Holoprosencephaly
Karyotype- normal. Diagnosis confirmed post-
12w+5d TAUS/TVUS CVS. PG/TOP
abortion. Other structural abnormalities
associated.
Declined karyotype. Diagnosis confirmed post-
13w+1d TAUS PG/TOP abortion. Other structural abnormalities
associated.
Anencephaly
Declined karyotype. Diagnosis confirmed post-
12w+4d TAUS PG/TOP abortion. Other structural abnormalities
associated.
Karyotype: 45x0; diagnosis confirmed post-
12w+5d TAUS CVS.PG/TOP abortion. Other structural abnormalities
Cystic
associated.
hygroma/hydrops
13w+2d TAUS/TVUS CVS Normal karyotype; outcome-normal fetus. No
other structural abnormalities associated.
Karyotype - trisomy 18. Diagnosis confirmed
Atrio-ventricular
13s+2d TAUS/TVUS CVS. PG/TOP post-abortion. Other structural abnormalities
septal defect
associated.
Karyotype - trisomy 21. Diagnosis confirmed
CVS. PG/TOP post-abortion. Other structural abnormalities
13w+0d TAUS/TVUS
associated.
Tetralogy of Fallot Karyotype - trisomy 21. Diagnosis confirmed
Amniocentesis. post-abortion. Other structural abnormalities
19w+2d TAUS/TVUS
PG/TOP associated

Hypoplastic left Declined karyotype. Diagnosis confirmed post-


12w+3d TAUS PG/TOP
heart abortion.
CVS.
Omphalocele containing liver; normal
Omphalocele 12w+1d TAUS Intrauterine
karyotype.
fetal death
No meningocele; spinal deformity difficult to
Spina bifida 13w+4d TAUS/TVUS PG/TOP
see but cranial signs present.
CVS. Awaiting
Multicystic kidney 19w+2d TAUS neonatal Normal karyotype. Other kidney good function.
surgery
CVS. Ongoing Normal karyotype. Isolated abnormality.
13w+2d TAUS/TVUS pregnancy
Limb abnomalities Amniocentesis. Normal karyotype. Other structural
18w+4d TAUS/TVUS PG/TOP abnormalities associated. Diagnosis confirmed
post-abortion.
Table Major fetal structural abnormalities in the study population. TAUS = transabdominal ultrasound; TVUS =
transvaginal ultrasound; CVS = chorionic villous sampling; PG/TOP = prostaglandin termination of pregnancy.

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Fig. 4. Trisomy 18-A-Abnormal facial profile; B- Choroid plexus cysts; C- diaphragmatic hernia; D- Single
umbilical artery; E- Radial aplasia. Trisomy 21- F-Increased nuchal translucency; G- Tricuspid regurgitation; Turner
Syndrome- H, I-Hygroma.

For experienced examiners, the detection rate increased by 5% during the study period, and
the false positive rate decreased by 9%. There were no significant differences in the false
negative rate between examiners, regardless of experience, when the investigative protocol was
complete. However, completion of the protocol within 30 minutes was possible only in 63% of
the cases in the first year of training. The false positive rate was significantly increased in less
experienced examiners but decreased by 28%.

Discussions

This study demonstrates the potential of morphological ultrasound to screen for fetal
abnormalities in the first trimester at 12-13 weeks of gestation in low risk population. The
antenatal diagnosis was correlated with the anatomopathological results. This was also
demonstrated by literature [13, 14].
Cranial malformations were the most common structural fetal abnormalities detected in this
study; 90% of these were diagnosed by the first trimester morphological scan. As for
anencephaly, the diagnosis is feasible in the first trimester but the appearances are different
compared with the second trimester, as cerebral tissue is present and floats in amniotic fluid.
First trimester diagnosis of spina bifida is possible [15, 16, 17]. In our study there was no
missed diagnosis, but sometimes this can be difficult especially in the absence of a meningocele
or cranial signs. It was the recognition of cranial signs that improved the detection rate [18].
Therefore, in the absence of cranial signs in the first trimester, the sensitivity of detection of
spina bifida is unlikely to be as high as in second trimester scanning. However, Bernard, J.P. et.
al., demonstrated that a simple and reproducible BPD at 11-14 weeks of gestation could detect
half the cases of open fetal spina bifida by identifying 5% of pregnancies for expert scanning in
first- and second-trimester examinations of the fetal spine and cranium [19].
As for diagnosing omphaloceles in the first trimester, we had one false positive case, that was
considered normal after rescanning one week later, and one true positive case. According to
literature, visualization of omphaloceles is easy but care must be taken in the early diagnosis of
this condition since physiological mid-gut herniation is common, especially at less than 12 weeks
of gestation [20]. After 12 weeks of gestation, physiological mid-gut herniation is uncommon

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and only present in 0.1% of fetuses [20]. Our study results suggest that the abdominal wall can
be readily visualised at 12-13 weeks and this diagnosis should not be missed.
Renal abnormalities occurred in one fetus. This case was considered negative for
chromosomal markers and structural anomalies in the first trimester. The unilateral multicystic
kidney was diagnosed during the second trimester morphological scan. This demonstrates the
intrauterine dynamics of the fetal structure and the importance of the second trimester anomaly
scan.
Cystic hygroma is a structural abnormality easy to diagnose in the first trimester. But the
management of the diagnosed cases will include fetal karyotyping irrespective of the nature of
the lesion. In this study we detected two cases, one with normal fetal karyotype and no other
structural abnormalities and one that associated major structural defects and chromosomal
abnormalities (the fetal karyotype was 45 X0).
The feasibility of detecting fetal heart abnormalities using ultrasound from 12 weeks of
gestation in a high risk population has been demonstrated [21, 22]. The main problem with first
trimester echocardiography is the small size of the fetal heart, and also the later manifestation of
certain structural and functional abnormalities such as hypoplasia of one cardiac chamber and
myocardial hypertrophy. However, the association between increased nuchal translucency
measurement and cardiac defects raises the possibility of screening for heart defects by nuchal
translucency measurement in the first trimester [23].
Patience is required to satisfactorily visualise the skeletal system in the first trimester. The
study protocol demonstrates the ability to identify fetal limb bones and correct posture of hands
and feet by combined transabdominal and transvaginal ultrasound. However, we had one case of
bilateral club foot considered morphological normal after the first trimester scan and diagnosed
later at 18 weeks of gestation.
We conclude that an optimized ultrasound examination protocol in the first trimester is
feasible and effective in detecting major fetal abnormalities. The rate of false results decreases
with the accumulation of experience and the ability to complete an expanded investigation
protocol. However, the first trimester morphological scan cannot replace the second trimester
anomaly scan because of the intrauterine dynamics of the fetal structures and yet a number of
malformations cannot be detected so early in pregnancy. [24].

Acknowledgements
this paper was published under the frame of European Social Found, Competitivity
Operational Programme 2014-2020, POC-A.1-A.1.2.1-D-2015, Contract nr. 75/08.09.2016,
MYSMIS Code: 105076.

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5. Syngelaki A, Chelemen T, Dagklis T, et al., (2011) Challenges in the diagnosis of fetal non chromosomal
abnormalities at 11-13 weeks. Prenat Diagn; 31(1): pp. 90-102.
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Ethical and medico-legal aspects of the therapeutic abortion – our experience. Journal of Romanian Legal
Medecine 26(1), pp. 82-85.
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by transabdominal and transvaginal sonography. Br JObstet Gynaecol1996; 103: pp. 82-85.
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Case Report: Prematur Newborn 35 Weeks of Gestation with


Posterior Urethral Valve

PAUL Corina1, NODITI Georgeta2, PETRE Isabela3, ENATESCU Ileana3,


DIMA Mirabela3, VELEA Iulian Puiu1, IACOB Daniela4, RADU IACOB Emil5
1 Department of Pediatrics – University of Medicine and Pharamacy “V. Babes” Timisoara, (ROMANIA)
2 Neonatology Department – Emergency Clinical County Hospital Timisoara (ROMANIA)
3 Department of Obstetrics – Gynecology – University of Medicine and Pharmacy “V. Babes” Timisoara, (ROMANIA)
4 Department of Neonatology – University of Medicine and Pharamacy “V. Babes” Timisoara, (ROMANIA)
5 Department of Pediatric Surgery – University of Medicine and Pharamacy “V. Babes” Timisoara, (ROMANIA)

Email: [email protected]

Abstract

The posterior urethral valve represents a disorder of the urinary tract which is not evident in
the clinical examination. Clinical signs include: bilateral ureterohydronephrosis, bladder dilation,
posterior urethral dilation and increased bladder wall thickness. Posterior Urethral Valves (VUP)
morbidity is dependent on the degree of obstruction and is indirectly proportional with the age at
diagnosis; in the neonatal period, VUP might represent one of the causes of death, which is not
clinically evident, the diagnosis being established at necropsy. We present a prematurely
newborn, gestational age 35 weeks, diagnosed antenatally with posterior urethral valve and grade
III hydronephrosis and oligohydroamnios. According to literature data, in the premature
newborn, VUP is encountered with a frequency of 30-36%. Systematic use of ultrasound (US)
during pregnancy, allows the detection of the malformative uropathy in 1:500 fetus. Among
these malformations, VUP occurs in a proportion of ± 10%. Conclusion: the antenatal ultrasound
evaluation allows precocious surgery and avoids later complications.
Keywords: posterior urethral valves, premature newborn, oligohydramnios, antenatal diagnosis

Introduction

Posterior urethral valves in children is the most common anatomical obstacle of lower urinary
tract and affects exclusively males (1). The valves of the posterior urethra is an inapparent lower
urinary tract disorder, generally not evident on physical or local examination. The condition
characterize the small children.
Depending on the obstruction degree onset is at different ages, with different signs and
symptoms. Onset in infants is quoted at a rate of 30-36%; between 1 and 5 years, 50-55% and
over 5 years in other cases.
We report the case of premature infants (gestational age 34 weeks), extracted by cesarean
section in pelvic presentation, coming from monitored pregnancy. The diagnosis was bilateral
ureterohydronephrosis, bladder dilation, posterior urethral dilation, due to PUV. Preterm baby
was carried in Neonatal Intensive Care Unit (NICU) until he was transfered in a specialyzed
Clinics for surgical treatment.

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Case presentation

Premature male baby with birth weight of 1,450 g and Apgar score 4 – after 1 minute and 7-
after 5 minutes. In the delivery room infant showed poor general condition, generalized cyanosis,
absent vernix, hypotonia. It required respiratory resuscitation and tactile stimulation. After birth
the newborn baby presented mild respiratory distress, requiring special NICU care. Antenatal
renal ultrasonography showed: bilateral ureterohydronephrosis, renal dysmorphism (Figure 1).
Imaging investigations have revealed VUP obstacle consequences on the urinary tract.
Ultrasound highlighted: the development of an uretero-bilateral hydronephrosis (Fig. 2, 3, 4);
stretching and bladder dilatation, hypertrophy of the detrusor, with the formation of trabeculae,
Hutch diverticul at the uretero-vesicale junction (Fig. 5); posterior urethral dilatation and
elongation, without being present obstruction obstruction at the bladder neck, which is prominent
with detrusor initially thinned.
Cystography indicated a bilateral passive vesicoureteral reflux stressed during micturition
(Figure 6).

Fig. 1. Antenatal ultrasonography – multiple Fig. 2. Postnatal ultrasonography – right


images transonic to the kidney ureterohydronephrosis grd III

Fig. 3. Postnatal ultrasonography – left Fig. 4. Postnatal ultrasonography –marked dilatation


ureterohydronephrosis grd III of the ureter as sinuous aspect

In day 38 of life, clinical changes occured namely diffuse skin infiltrates, pale pink patch,
with a tendency to mottle, discreet subcostal circulation, oxigenodependency, slightly distended
abdomen volume, oliguria, tone and reactivity slightly reduced.

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Biologically, urea and creatinine increased, acidosis and hyperkalemia representing signs of
impaired kidney function. It was also denoted a positive C-reactive protein (increased values).
It was raised the suspicion of urinary tract infections, and adequate treatment was instituted.
Further, development was favorable in clinical and biological terms, being discharged from
NICU at 43 days old, weighing 2550g, good general condition, normal skin colour, balanced
cardiopulmonary, good digestion tolerance, present urinary diuresis, normal tone and reactivity.

Fig. 5. Postnatal ultrasonography – marked dilatation and


bladder elongation

Fig. 6. Cystography – important passive bilaterally vesicoureteral reflux after Foley


bladder catheterization and injection of contrast material

Management and outcome

At the delivery room, newborn required respiratory resuscitation: VPPO2 and tactile
stimulation. After intensive care maneuvers newborn presented spontaneous respiration,
intercostal space circulation, heart rate of 100 beats per minute, hypotension.

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It was placed in NICU in O2 servocontrol incubator, under cephalic tent and thermal comfort
with monitoring of vital functions (FC, SpO2, TA, stool, urine output), umbilical vein
catheterization (11 days).
Blood samples were collected for laboratory analysis (AGS, complete blood count, and RH
blood group. An urinary catheter was mounted.
Endovenous perfusion for acid-base fluid and electrolyte rebalancing, continuous infusion of
dopamine (to correct hypotension), broad spectrum empiric antibiotics have been administrated.
Oxygen saturation was maintained at 95-100%, with no respiratory effort, satisfactory general
state, balanced cardiovascular, digestive and nervous systems (in the normal range of
prematurity). In evolution, for urinary tract infection treatment was initiated with broad-spectrum
antibiotic and diuretic.

Discussions

Posterior urethral valves are the most common cause of congenital lower urinary tract outflow
obstruction in male infants (2). Incidenta valvelor de uretrã posterioarã se estimeazã a fi de
1:5000-8000 de nou-nãscuåi de sex masculin, şi constituie aproximativ 10% din hidronefrozele
diagnosticate prenatal (3). Incidence is estimated at 1:5,000-8,000 male infants, and are
responsible for 10% of prenatal hydronephrosis.
The anomaly is associated with considerable morbidity including urosepsis, urinary
incontinence (over-flow), chronic renal insufficiency, and even death [4-6].
Prenatal ultrasound screening of PUV has significantly increased early diagnosis and
management of this pathology in most developed societies. In fact, PUV are now commonly
diagnosed by the postnatal evaluation of infants who had prenatal hydronephrosis [7].
The gold standard for diagnosis of PUV is voiding cysto-urethrogram (VCUG) [8-12]. Studies
have documented different variables that may have predictive value or be responsible for the
long term development of end-stage renal disease after initial therapy. Prenatal detection of PUV
before 24 weeks of gestation, poor compliance and presentation before 1-year of age could
predict an unfavorable long-term renal function.
Others factors implicated include bilateral reflux, echogenic kidneys, loss of corticomedullary
differentiation, sub cortical cysts (indicative of renal dysplasia) and serum creatinine >70.4
µmol/L (0.8mg/dl) 1-month postvalve avulsion. Serum creatinine levels at 4-5 days of
continuous catheterization and glomerular filtration rate at a year old also strongly correlate with
final renal function [13-19].
The bladder dysfunction shows a changing pattern that is related to the age of the child.
Infants at 0-1 year has reduced functional bladder capacity that is associated with detrusor over
activity [20].
In our case, ultrasonography showed a large dilated bladder, thickening of the walls The
kidney pelvis was dilated with a thinning of the parenchyma of the kidney, on both sides. USG
does not give any idea of function only the dimensions and appearance of the organs being
looked at. In our case associated oligohydramnios, longer NICU admission, high initial serum
creatinine carry a poor prognosis for this low birth weight preterm.

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REFERENCES

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1983; 18(1): pp. 70-4.
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applications for by-pass grafts, Applied Mathematics and Computation, 272 part 3, pp. 604-613.
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development of end stage renal disease in posterior urethral valves. Indian J Pediatr. 2008; 75: pp. 695-7.
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urethral valves: Prognostic factors. BJU Int. 2003 ;91: pp. 687-90.
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gestational age at detection a predictor of outcome? J Urol. 1994;152w (2 Pt 2): pp. 698-701.
16. Petrica, Ligia; Gluhovschi, A; Gluhovschi, Cristina. Proximale tubule disfunction in renal diseases-
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2012 issue:2, pp. 97-107.
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dysfunction as a prognostic factor in patients with posterior urethral valves. BJU Int. 2002; 90: pp. 308-11.
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infancy to adolescence in boys with posterior urethral valves. BJU Int. 2000;85: pp. 1104-8.

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Morphological Heterogeneity of Hypoplastic Left Heart Syndrome –


Major Impact in the Therapeutic Strategy

LACATUSU Adrian1,2, GOLGOT Ioana2, PAUL Corina1,2, LASCU Ana3,


BRISAN Laura4
1 Clinic II Pediatrics, Emergency Clinical County Hospital “Pius Branzeu”, Timisoara, (ROMANIA)
2 Department of Pediatrics-University of Medicine and Pharmacy “Victor Babes”, Timisoara, (ROMANIA)
3 Department of Functional Sciences,University of Medicine and Pharmacy “Victor Babes”, Timisoara, (ROMANIA)
4 “Pius Brinzeu” Emergency Clinic County Hospital Timisoara, IInd Department of Obstetrics and Gynecology, Timisoara

(ROMANIA)
Emails: [email protected], [email protected]

Abstract

Background
Hypoplastic left heart syndrome (HLHS) is a syndrome outlining a group of lesions
characterized by underdevelopment of the left ventricle (LV), ascending aorta and
stenosis/atresia of mitral or/and aortic valve, which can be diagnosed antenatal since the 20th
weeks of gestation, by ultrasound by a competent obstetrician. HLHS is characterized by a large
diversity of forms and depending on this form, the long-term prognosis can be radically different.

Material and Methods


We present two cases, the first one, a three-month-old boy and the second, ten-day-old girl,
both diagnosed in utero with HLHS, on prenatal ultrasound examination. Both cases were re-
evaluated prenatal in a secondary cardiac surgery centre, where the diagnosis was confirmed and
due to the lesion complex, delivery and surgery have been decided in a tertiary cardiac surgery
centre. Only the first case had delivery in a specialised centre.

Results
The first patient didn’t receive prostaglandin because he had surgery a few hours after birth,
and biventricular correction was decided after the preoperative evaluation. The second case was
born in our centre and needed administration of prostaglandin E1, inotropes and diuretics. Also,
this patient has been sent to a specialised centre after the first week of life and underwent a
univentricular repair due to the extreme form of the syndrome.

Conclusions
1) HLHS is a group of complex lesions, severe and rare, which are diagnosed in most cases
prenatal. 2) Management of this lesion requires a multidisciplinary team consisting of
gynaecologist, neonatologist, paediatric cardiologist, cardiovascular surgeon and geneticist, in
some cases. 3) The variability of this syndrome determine the therapeutic strategy.
Keywords: hypoplastic left heart syndrome, prenatal diagnosis, fetal ultrasound, morphological heterogeneity

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Introduction

HLHS encompasses a spectrum of cardiac lesions defined by underdevelopment of the left


ventricle (LV) cavity, aortic and mitral valve. There is a great variability of this syndrome from
borderline forms, where the LV cavity is moderately hypoplastic and biventricular repair is
possible, to extreme forms where LV is just a slit in the ventricular mass. Basically, in this latter
situation the LV cavity doesn’t exist and functional it is a univentricular heart. In these cases, the
therapeutic option is a Fontan repair [2].
Moderate form of HLHS is characterized by aortic and mitral valve hypoplasia, but with a
moderately underdeveloped LV cavity. Thus, in this situations the anatomic repair is possible
and is superior to the unventricular repair [3].
The main factors determining the decision of the type of ventricular correction are the length
and the end-diastolic diameter of LV, the size and Z score of the aortic and mitral valve. The cut-
off value for Z score is -2 to +2, but with wide differences between centres [4].
The HLHS is unknown. Some hypothesizes affirm that there is a genetic predisposition that
cause underdevelopment of the aortic valve and secondary LV and ascending aorta hyploplasia.
[5, 6] Most theories are based on discoveries from post-mortem cases [7].
In recent years, the incidence of HLHS cases has increased in our country, possible due to the
comprehensive use of fetal ultrasound examination, used for screening of congenital
malformations. HLHS, is a major cause of neonatal death in our country, and is the main concern
of both obstetricians, who diagnosed it and neonatologists who are stabilised them. This is due to
the fact that, in Romania, the surgery of this kind of severe lesions is impossible. All cases that
survive early neonatal period are transferred to specialised centres abroad or the delivery is
performed directly in these places with the possibility of immediate surgical intervention. In both
situations, costs are very high.
The antenatal diagnosis of HLHS is established in the first 20th weeks of pregnancy by an
experienced obstetrician with an adequate ultrasound machine. In this way, the obstetricians can
diagnose prenatal, severe aortic stenosis, that if it left untreated, may evolve to the
underdevelopment of the left heart cavity [8]. In utero, aortic stenosis causes obstruction in the
LV outflow tract evolving towards myocardial dysfunction and ultimately to HLHS [8]. Thus,
the early diagnosis of this lesion in prenatal period, gives the obstetricians the opportunity to
send the salvageable left heart to a specialised centre for aortic valvotomy, with release of the
outflow tract of LV, that can develop normally after the procedure, preventing the evolution to
the HLHS [8].
On the other hand, prenatal diagnosis of this syndrome has a major psychological impact on
parents, and this allows the families to prepare for a child with a life-threatening congenital heart
disease that requires a multidisciplinary team to save their child. Moreover, the obstetrician can
discuss with the family what the most appropriate option for them is: pregnancy termination or
the best solution after the child is born [9-11].
At the fetal ultrasound examination, in the four-chamber incidence, during the first 20th weeks
of gestation, LV appears dilated, compared to right ventricle (RV), but hypocontractile, due to
restrictive fetal cardiomyopathy and endocardial fibrosis. However, during the later gestational
period, LV has normal development and becomes smaller than RV [12].
During the 18th to 21th weeks of gestational ultrasound examination, the complex LV-aorta
may have small dimensions, but it has the potential to grow and the situation can change

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dramatically until the end of the gestation. For this reason, the decision to stop the pregnancy at
this period implies a high risk of error. So, the dynamic following is extremely important.

Material and Methods

First case, the three-month-old male, coming from urban area, born from heathy parents, first
pregnancy, was diagnosed prenatal at eighteen weeks of gestation, with hypoplastic left heart
syndrome in our service, on screening ultrasound examination. Due to our organisational issues,
the mother was transferred in a specialised health services abroad where the delivery took place.
Second case, the fourteen-day-old girl, coming from rural areas, born from health parents, the
fifth child, was diagnosed prenatal at 17th week of gestation with HLHS, in our service. The
mother was transferred in a secondary centre in our country, where the diagnosis was confirmed
and because of the severity of the lesions it has been recommended that delivery and surgery be
succeed in a tertiary specialised centre.

Results

The first case was born by caesarean delivery, abroad, in a specialised centre, where
immediately after delivery, the antenatal diagnosis has been confirmed. He was evaluated by
echocardiography, and after assessing the major parameters and calculating the Z score, the
anatomic surgery was decided, which mean biventricular repair, with favourable evolution. The
surgical approach consists in reconstruction of the ascending aorta and aortic arch using a patch,
closure of the ductus arteriosus and atrial septal defect (ASD).
The second case was born also, by caesarean delivery in our service, at 37th weeks of
gestation, without incidents. Continuous infusion with prostaglandin E1 was started with
50mcg/kg/min and, then, 25mcg/kg/min after four days and milrinone according to the guideline.
The general condition of the baby has been relatively stable during the admission in our
hospital without any sign of cardiac arrest.

Fig. 1. Four chamber-view on postnatal echocardiography examination of the second case, that show severely
dilatation of right ventricle and rudimentary left ventricular cavity. This means a severe form of hypoplastic
left heart syndrome.

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Postnatal echocardiography performed by the paediatric cardiologist showed: situs solitus;


concordant venous and atrio-ventricular connections. Small size of left atrium. Right atrium
severely dilated. Large ASD 15 mm with non-restrictive shunt left to right. Intact Interventricular
septum. Present mitral valve, dysplastic, dysmorphic, retractable, apparently without flow.
Dysplastic aortic valve, 6 mm diameter, without flow. Hypoplastic ascending aorta 6 mm in
size, no anterograde flow, retrograde loaded through a large patent ductus arteriosus (PDA) 12
mm diameter. Dilated tricuspid ring with mild regurgitation. RV severely overloaded. Pulmonary
artery 14 mm with high flow. Conclusion: HLHA severe form – needs Norwood correction.
In the tenth postnatal day, the patient was transferred in a specialised centre, abroad, by plane.
After arriving in that centre she was reasserted by the medical team, and after calculated the Z
score, which is variable between centres, the stage I palliative operation – Norwood correction
was decided in order to create a non-obstructive flow between the LV and the neo-aorta which
result from the anastomosis of the main pulmonary artery with hypoplastic ascending aorta and a
patch on the aortic arch. Also, closure of PDA and ASD and creating of a systemic-to-pulmonary
artery shunt, followed by Fontan repair in the future. This mean a univenticular correction. Post-
operative evolution was favourable, with no major incidents [4].

Fig. 2. Apical five-chamber Color Doppler study of the second case, showing the hypoplastic ascending aorta,
with retrograde flow from arterial duct and very small left ventricle.

Discussion

Heterogeneity of HLHS is the factor that greatly influeces the surgical strategy decision-
making, from the borderline forms, where the biventricular correction is possible, to the extreme
forms, where the only solution remains the paleative multistadial univentricular type Noorwood
[13, 14].
In the last years, the diagnosis, the prenatal and postnatal management and the therapeutic
strategy have undergone profound changes. There are major differences beteeen the specialized
surgery centers, concerning the treatment option [15, 16]. Thus, in some centers, the clasic
surgical intervention is preferred, while in other centers, the hybrid technique, which combines
the interventional method with surgery, is the main option, being less invasive and having a low
mortality rate. In some other situations, the cardiac transplant is preferred, as the first therapeutic
option, in the neonatal period [17].

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HLHS is characterized by a marked morphologic polymorphism with a major impact on the


therapeutic strategy, so that, the short-term prognosis, but especially the long-term prognosis, is
completely different, from borderline forms, wiht anatomic correction that have a life expectancy
similar with that in the general population, to extremely severe forms, with multistadial
univentricular type corrections, in whom the prognosis is reserved and need cardiac transplant,
later, with all its consequences.
The prenatal diagnosis by fetal ecography has a decisive role in the evolution of this
syndrome, especially if a severe aortic stenosis has been identified. In these cases, the
obstetrician may recommend the pregnant woman to a specialized center, aiming for the
interventional dilating of the stenosis,followed by a normal development of the left heart parts,
so preventing the occurence of HLHS [17]. On the other hand, the cases with underdevelopment
of the left side of the heart, should be followed-up in dynamic, because it is possible that the left
ventricle would develop normally during pregnancy.

Conclusions

HLHS is a severe malformative complex, rarely encountered, with fatal prognosis immediatly
after birth if not diagnosed in utero. This is why, the antenatal diagnosis is essential for the later
management of the syndrome. FInally, the heterogeneity of this sindrome has a major impact in
choosing the optimal therapeutic strategy,while the fetal echography offers valuable details
which helps the cardiac surgeon to choose the right solution.
The management of these lesions requires a multidisciplinary team including the obstetrician,
neonatologist, pediatric cardiologist and, sometimes, a genetician.

REFERENCES

1. Christoph, H., et. al., (2015). Atresia of the Ascending Aorta in Hypoplastic Left Heart Syndrome-
Circulation, 131, pp. 925-926.
2. Hannah, R. Bellsham-Revell, et. al (2013). Serial Magnetic Resonance Imaging in Hypoplastic Left Heart
Syndrome Gives Valuable Insight Into Ventricular and Vascular Adaptation – Journal of the American
College of Cardiology 61(5), pp. 561-70.
3. Brosig, C., et. al., (2013). Neurodevelopmental Outcomes for Children With Hypoplastic Left Heart
Syndrome at the Age of 5 Years Pediatr Cardiol, Springer.
4. Martijn, H.T. den Dekker, et. al., (2013). Comparability of Z-Score Equations of Cardiac Structures in
Hypoplastic Left Heart Complex 26(11), pp. 1314-1321.
5. Filipoiu, et. al., (2013). Sudden death of a premature new-born with hypoplastic left heart syndrome.
Morfological study of the heart Rom J Leg Med 21, pp: 27-30.
6. Bernad, S.I., Bosioc, A.I., Bernad, E.S., Craina, M.L., (2015). Helical type coronary bypass graft
performance: Experimental investigations, Bio-Medical Materials and Engineering, 26(s1), pp. 477-486.
7. Anderson, et. al., 3rd ed. (2010) Paediatric Cardiology, pp. 625-645.
8. Tworetzky W., et. al., (2004). Balloon Dilation of Severe Aortic Stenosis in the Fetus Potential for
Prevention of Hypoplastic Left Heart Syndrome Candidate Selection, Technique, and Results of Successful
Intervention – Circulation 110, pp. 2125-2131.
9. Fruitman, D.S., (2000). Hypoplastic left heart syndrome: Prognosis and management options, Paediatr
Child Health 5(4), pp. 219-225.
10. Bernad, E.S., Bernad, S.I., Craina, M.L., (2014). Hemodynamic parameters measurements to assess
severity of serial lesions in patient specific right coronary artery, Bio-Medical Materials and Engineering,
24(1), pp. 323-334.
11. Bernad, S.I., Totorean, A.F., Vekas, L., (2016). Particles deposition induced by the magnetic field in the
coronary bypass graft model, Journal of Magnetism and Magnetic Materials, 401, pp. 269-286.

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12. Bellsham-Revell, H.R., et. al., (2013). Subjective Evaluation of Right Ventricular Systolic Function in
Hypoplastic Left Heart Syndrome: How Accurate Is It?, American Society of Echocardiography, 26, pp.
52-56.
13. Feinstein, J.A., et. al., (2012). Hypoplastic Left Heart Syndrome Current Considerations and Expectations,
56(1), pp. S1-S42.
14. Bernad, S.I., Totorean, A., Bosioc, A., Crainic, N., Hudrea, C., Bernad E.S. (2015). Fluid mechanics in
stented arterial model, International Conference of Computational Methods in Sciences and Engineering
2015 (ICCMSE 2015), AIP Conf. Proc., vol. 1702, 080008-1-080008-4.
15. Schlangen, J., et. al., (2013). Does left ventricular size impact on intrinsic right ventricular function in
hypoplastic left heart syndrome? International Journal of Cardiology, 167, pp. 1305-1310.
16. Totorean, A.F., Bernad, S.I., Susan-Resiga, R.F., (2016). Fluid dynamics in helical geometries with
applications for by-pass grafts, Applied Mathematics and Computation, 272 part 3, pp. 604-613.
17. Galantowicz, M., et. al., (2008). Hybrid Approach for Hypoplastic Left Heart Syndrome: Intermediate
Results After the Learning Curve, Ann Thorac Surg, 85, pp. 2063-2071.

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Succesful Outcome of Pregnancy in a Woman with Uncorrected


Tetralogy of Fallot

LASCU Ana1, PAUL Corina2,3, MITRACHE Dana4, LACATUSU Adrian2,3,


BRISAN Cosmin4, VRINCEANU Luminita5
1 Department of Functional Sciences,University of Medicine and Pharmacy “Victor Babes”, Timisoara, (ROMANIA)
2 Clinic II Pediatrics, Emergency Clinical County Hospital “Pius Branzeu”, Timisoara, (ROMANIA)
3 Department of Pediatrics-University of Medicine and Pharmacy “Victor Babes”, Timisoara, (ROMANIA)
4 “Pius Brinzeu” Emergency Clinic County Hospital Timisoara, II nd Department of Obstetrics and Gynecology, Timisoara

(ROMANIA)
5 Medlife Tirgu Jiu, (ROMANIA)

Emails: [email protected], [email protected]

Abstract

We report a case of pregnancy in a 20-years-old woman with uncorrected tetralogy of Fallot


(TOF). It is wellknown that there are many risks in patients with TOF without surgical
correction. Pregnancy was resolved successfully by caesarean section. Improvement of
fetomaternal outcome may be related to corrective procedures before conception to achieve
better functional heart capacity. Delicate multidisciplinary medical management is essential for
these limited cases to achieve optimal prognosis.
Keywords: hypoplastic left heart syndrome, prenatal diagnosis, fetal ultrasound, morphological heterogeneity

Introduction

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect and accounts
for 5% to 6% of congenital heart malformations [1]. Its hallmark, anterior and superior
infundibular septal displacement, gives rise to the tetrad of ventricular septal defect, aortic
override, infundibular obstruction, and right ventricular (RV) hypertrophy [2].

Methodology

The study is a case report of a 20-year-old primipara with uncorrected TOF. At 30 weeks of
gestation she presented in the Department of Obstetrics and Gynecology at the “Pius Brânzeu”
County Emergency Hospital in Timişoara, for continous fetal and gravida monitoring. The
ultrasound established the diagnosis of a gestational age of 30 weeks, with normal fetal
measurement and normal heart action.
The patient has been counseled regarding mode of delivery and accepted surgical
intervention. Patient had an uncomplicated caesarean section at 37 weeks.

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Results and discussions

A 20-year-old woman had been followed in Department of Pediatrics of the “Pius Brânzeu”
Emergency Clinical County Hospital Timisoara for several years because of Tetralogy of Fallot.
Although, she had been advised not to become pregnant, she presented herself at 7 weeks of
gestation. She decided not to intrerrupt pregnancy. In the first trimester of pregnancy she
presented nausea and vomiting. There was no maternal history of diabetes mellitus or
hypertensive disease. She had no febrile illness in the course of pregnancy. She did well until 30
weeks of gestation, when she was admitted to the hospital because of abdominal pain and for
continous fetal and mother monitoring.
Family history did not reveal similar ailment or any congenital deformity among her siblings.
There was no positive history of similar affections in maternal or paternal family members.
At the age of one year, a surgical correction of medium Tetralogy of Fallot was suggested.
Her parents decided not to follow the indication. The echography of the pregnant woman
before birth showed Situs solitus. Venous connections consistent. Dilated right atrium. Normal
left atrium. Mitral valve with morphology and normal flow. The tricuspid valve with minimum
regurgitation. Interventricular septum with ventricular septal defect (Fig. 1) approximate 19 mm.
The left ventricle of 44 mm with normal aspect.

Fig. 1. Septal membranous ventricular defect

The measurements of the right ventricle of 56 mm and the front wall with 16 mm revealed a
dilated concentric hypertrophy (Fig. 2). It was also revealed a dextroposition of the Aortic valve
with normal antegrade flow. The pulmonary valve with severe infundibular stenosis with
diameter of 18mm with a valvular and supravalvular stenosis. Without patent ductus arteriosus.
The diagnostic of this examinaton was a medium form of a Tetralogy of Fallot that required
surgical correction.
The evolution during hospitalization remained stable in both the fetus and the mother. Birth
by Caesarean section was performed at 37 weeks without obstetrical incident. The patient gave
birth to a healthy girl, weighting 2,800 grams with Apgar scores of 9 at 1 minute. Mother
remained stable during the Caesarean section and after, without major incidents.

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Fig. 2. Dilated concentric hypertrophy of the right ventricle

The echocardiography performed immediately after the baby was born showed: atrial situs
solitus. Consistent venous connection. Consistent atrioventricular and ventricular pressure
connections. Low tricuspid regurgitation. Normal aspect of mitral valve. The righ and the left
Ventricle were normal. The Aortic and the Pulmonar Valve were normal; without patent ductus
arteriosus. In conclusion, the baby’s cord had a normal structure, with no malformation.
During pregnancy the mother with congenital heart disease should be examined regularly for
complications such as anemia, hypertension, and infection. The fetus needs to be evaluated for
congenital heart disease and may be evaluated periodically for growth restriction. Vaginal
delivery is preferred [3, 4]. The index case was evaluated through pregnancy and there was
found no growth restriction or other cord malformation. Because our patient refused the surgical
correction of the heart, her delivery mode was caesarean section.
Unoperated pregnant patients or repaired patients with significant residual right ventricular
outflow tract (RVOT) obstruction, valve dysfunction, or ventricular dysfunction are at high risk
for right heart failure and arrhythmias due to the increased volume load of pregnancy [5, 6].
Even if our patient refused the surgical correction of the heart, she had a normal pregnancy
with a healthy baby and with no major problems during pregnancy. Classic ToF and its variants
have been observed as components of a number of heritable syndromes: most notably, the
branchial arch disorders associated with microdeletions at chromosome 22q11, including the
DiGeorge, velocardiofacial and conotruncal anomaly face syndromes [7, 8].
ToF is also among the variable cardiac defects occurring in Alagille syndrome (AGS), a rare
autosomal dominant condition characterized by biliary atresia, growth retardation, vertebral and
ocular anomalies, cognitive deficits, characteristic facies and right-sided heart defects,
predominantly peripheral pulmonic stenosis (PPS) [9, 10]. Mutations in the jagged1 gene (JAG1)
have been implicated in AGS [11]. Fortunately, in our case, the patient had no other associated
syndrom.

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Conclusions

Because of significant physiology adaptation and changes, pregnancy and delivery process are
troublesome for mostly unhealthy women, including those with uncorrected ToF. For ToF
patients, it remains an important cause of maternal morbidity, and even mortality and has
significant effects on fetal outcome.

REFERENCES

1. Hofman, J.I., (1995). Incidence of congenital heart disease: I. postnatal incidence. Pediatr Cardiol, 16, pp:
103.
2. Lillehei, C.W., Varco, R.L, Cohen, M., et al., (1986). The first open heart corrections of tetralogy of Fallot:
A 26 to 31year follow-up of 106 patients. Ann Surg, 204, pp: 490-502.
3. Khairy, P., et al., (2006). Pregnancy outcomes in women with congenital heart disease.Circulation, 113(4),
pp: 517-24.
4. Bernad, E., Pantea, S., Boglut, A., Duta, C., Bernad, S.I., Petre, I., (2016). Investigation of Chorionic
Artery Bifurcation Using Micro Vascular Casting Model, Revista de Chimie, 67(2), pp: 339-343.
5. Meijer, J.M., et al., (2005). Pregnancy, fertility, and recurrence risk in corrected tetralogy of Fallot. Heart,
91(6), pp: 801-5.
6. Bernad, S.I., Bernad, E.S., Barbat, T., Barbu, D., Albulescu, V., (2010). Assessment of the placental blood
flow in the developing and growth-restricted fetus, Proceedings of the 22th European Congress of Perinatal
Medicine, Granada, Spain, May 26-29, pp: 127-130.
7. Hou, J.W., Wang, J.K., Tsai, W.Y., Chou, C.C., Wang, T.R., (1997). CATCH 22: deletion of locus 22q11
in velocardiofacial syndrome, DiGeorge anomaly, and nonsyndromic conotruncal defects. J. Formos. Med.
Assoc., 96, pp: 419-423.
8. Totorean A.F., Bosioc A.I., Bernad, S.I., Susan-Resiga R., (2015). Critical flow regions in the coronary by-
pass graft anastomosis, Proceedings of the Romanian Academy, Series A, 16(2), pp: 201-208.
9. Alagille, D., Odievre, M., Gautier, M., Dommergues, J.P., (1975). Hepatic ductular hypoplasia associated
with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and
cardiac murmur. J. Pediatr., 86, pp: 63-71.
10. Bernad, S.I., Bosioc, A.I., Bernad, E.S., Craina, M.L., (2015). Helical type coronary bypass graft
performance: Experimental investigations, Bio-Medical Materials and Engineering, 26(s1), pp: 477-486.
11. Oda, T., Elkahloun, A.G., Pike, B.L., Okajima, K., Krantz, I.D., Genin, A., Piccoli, D.A., Meltzer, P.S.,
Spinner, N.B., Collins, F.S., Chandrasekharappa, S.C., (1997). Mutations in the human Jagged1 gene are
responsible for Alagille syndrome. Nature Genet., 16, pp: 235-242.

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Pregnancy with Occipital Encephalocel – Case Report

PAUL Corina1,2, LASCU Ana3, MITRACHE Dana4, MOZA Andreea3,4,


BRISAN Laura4, LACATUSU Adrian1,2
1 Clinic II Pediatrics, Emergency Clinical County Hospital “Pius Branzeu”, Timisoara, (ROMANIA)
2 Department of Pediatrics-University of Medicine and Pharmacy “Victor Babes”, Timisoara, (ROMANIA)
3 Department of Functional Sciences,University of Medicine and Pharmacy “Victor Babes”, Timisoara, (ROMANIA)
4 “Pius Brinzeu” Emergency Clinic County Hospital Timisoara, II nd Department of Obstetrics and Gynecology, Timisoara

(ROMANIA)
Emails: [email protected], [email protected], [email protected]

Abstract

The encephalocele is midline congenital malformation. Encephalocele is a form of neural tube


defect in which there is a congenital defect of the cranium through which occurs a protrusion of
brain matter or meninges. In the present study, we have a 30 years old primipara, whose
ultrasound revealed at 10 weeks of pregnancy the suspicion of encephalocele. The patient opted
for therapeutic abortion.
Keywords: anencephaly, neural tube defects, folic acid

Introduction

Embiologically speaking the neural tube defects appear due to absense of closing the anterior
and posterios pores in the neurilation process. Open neural tube defects suposes the exposure of
the neural tissue with cerebrospinal fluid leakeage. Cranial presentations of open neural tube
defects include: anencphaly, encepahlocele, craniorachischisis totalis and congenital dermal
sinus.

Case presentation

We present the case of a 30 years old primipara, with a 12 weeks pregnancy that came for a
routine check up. She had no significant family, or obstetrical past. She had two antenatal
consults: one at 5 gestational weeks when intrauterine pregnancy was confirmed, when 5mg of
folic acid/day was prescribed. The seconds follow up was at 10 gestational weeks when on
ultrasound raised the suspicion of encephalocele. She had no history of infection, exposure to
radiation or drug intake during pregnancy. So far she reported an uneventful pregnancy.
Ultrasound examination diagnosed a single intrauterine live fetus with discontinuity of the
fetal calvaria. Adjacent to the defect there was a cystic mass (Figure 1, 2). No other
morphological abnormalities were evidentiated. The diagnosis of encephalocele was confirmed.
The patient was informed about the possible evolution of the new-born with encephalocel,
about the complications and the prognosis. The patient decided to terminate the pregnancy.

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Fig. 1. Fig. 2.

Discussions

Several factors appear to lead to lower survival rates for infants with encephalocele, including
preterm (early) birth, low birthweight, having multiple birth defects [1].
In case of giant encephalocele, the head is smaller than the encephalocele. These giant
encephaloceles contain a large amount of brain tissue and pose considerable problems during
closure [2].
With ultrasonography (US) scanning, the diagnosis is based on the herniation of a spherical,
fluid-filled structure, more correctly diagnosed as a meningocele or brain parenchyma
(encephalocele) beyond the calvarial confines [3].
The location of the encephalocele greatly affects the prognosis. Those located in the front
have a 100 percent survival rate, while those located in the back have a 55 percent survival rate.
Approximately 13 to 44 percent of babies with encephaloceles have a chromosomal
abnormality, and approximately 75 percent of babies who survive will have some degree of
mental deficit.
Occipital encephaloceles are more common in females, with approximately 70% of them
occurring in girls. Anterior defects are more often in males and the frontobasal type shows no
sex predominance. Newborns with encephalocele have a high incidence of hydrocephalus in the
range of approximately 50% [4]. In our case, the foetus was female with an occipital
encephalocele.

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There are some risks during pregnancy as miscarriage or possible cesarean section. Fetuses
with an encephalocele are likely to die before birth. The cesarean section is a proper option if the
encephalocele is large because the baby’s head may be too big to fit through the birth canal [5].
In our study, the doctor informed the patient that her pregnancy is in high risk group and she
understood that her baby’s brain malformation is a congenital neurologic condition with an
extremely high morbidity and mortality in spite of the applied treatments. At 12 weeks of
gestation the patient choose the abortion on demand.
Most of the encephaloceles are diagnosed prenatally via fetal ultrasound through which the
structural defect is visualized. The diagnosis can be made as early as 13 weeks of gestation.
Imaging studies such as MRI or CT may be used after birth for more detailed assessment of
encephalocele before the surgical intervention [6]. In our case, the ultrasoud of 10 weeks raised
the suspicion of encephalocele. The estimated prevalence of this condition varies from in 12200
live briths (USA) to 3.3 in 10000 live births (Kenya), however the true prevalence is unknown
due to high rate of prengnancy termination [7, 8]. There is scarse knoweldge about mechanism
that determines this type of neural tube defect, however, reserch indicates that periconceptional
intake of folic acid and vitamin B complex reduces the incidence of neural tube defects by 50-
70% [9, 10].
The majority of the encephalocele are considered to be sporadic, however in a small percent
there can be a family predisposal. As far as risk factors are involved, maternal drugg intake like
cocaine have been sugested to be a cause of the cranial table defect due to a poor vascularization
of the embryo. Martin reports a 3% incidence of neural tube defect in infant of mothers that
consumed cocaine during pregnancy [10-14]. Ramírez reports a case with double encephalocele
(frontal and occipital) in a mother who reported consuming cocaine and smoking marihuana in
the first trimester [15, 16]. In our case, the gravida had no history of infection, exposure to
radiation or drug intake during pregnancy.

Conclusions

Compared with previous studies, 3D US can detect fetal encephalocele early and provide
additional vivid illustrations after various modes of reconstruction. In conclusion, 3D US may
contribute to early detection of fetal encephalocele and provide visual depiction, thus, assisting
substantially with prenatal diagnosis as well as genetic consultation.

REFERENCES

1. Parker SE, Mai CT, Canfield MA, Rickard R, Wang Y, Meyer RE, Anderson P, Mason CA, Collins JS,
Kirby RS, Correa A. Updated national birth prevalence estimates for selected birth defects in the United
States, 2004-2006. Birth Defects Res A Clin Mol Teratol. 2010 Dec 1;88(12): pp. 1008-16.
2. Mahapatra AK. Management of encephalocele. In: Ravi Ramamurthi., editor. Text book of operative
neurosurgery. Vol. 1. New Delhi: BI Publications Pvt. Ltd; 2005. pp. 279.90.
3. Boyd PA, Wellesley DG, De Walle HE. Evaluation of the prenatal diagnosis of neural tube defects by fetal
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Chromosome 5p Deletion in a Fetus with Dandy-Walker


Malformation

PETCA Aida1,2, ZVÂNCĂ Mona1,2, MĂRU Nicoleta1, PETCA Răzvan-Cosmin1,3*,


VEDUȚA Alina4, BOȚ Mihaela1,2
1 University of Medicine and Pharmacy Carol Davila, Bucharest, (ROMANIA)
2 Elias Emergency Hospital Bucharest, (ROMANIA)
3 Burghele Clinical Hospital, Bucharest, (ROMANIA)
4 Filantropia Clinical Hospital, Bucharest, (ROMANIA)

* Corresponding author, Burghele Clinical Hospital, Panduri Street no. 20, District 5, Bucharest, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected]

Abstract

Dandy-Walker malformation (DWM) is a rare condition characterized by cystic dilation of


the 4th ventricle and total or partial absence of the cerebellar vermis. We report such a case in a
21 weeks pregnancy in a 36 years primipara evaluated sonographically, which revealed
symmetrical intrauterine growth restriction and at the posterior fossa – the cerebellar vermis was
hypoplastic and direct communication between the fourth ventricle and the cisterna magna. The
diagnosis was completed with a fetal MRI (magnetic resonance imaging), which confirmed the
suspicion raised by the ultrasound. The amniocentesis performed at 22th week of gestation
revealed a chromosome 5p deletion – 46 XX, del (5p14), which is for the first time reported to be
related with DWM.
Keywords: Dandy-Walker malformation, chromosome 5p deletion, parental balanced translocation, fetal MRI

Introduction

Dandy-Walker malformation (DWM) comprises a group of posterior fossa malformations


characterized by hypoplasia and upward rotation of the cerebellar vermis, cystic dilation of the
4th ventricle [1], at the extent of almost completely filling the entire posterior fossa, elevation of
the tentorium, antero-lateral displacement of seemingly normal cerebellar hemispheres [2], while
hydrocephalus, and the enlargement of the posterior fossa are not part of the diagnostic criteria
[3].
We may consider the malformation as rare, with an incidence ranging from 1/25000 to
1/35000 births [2]. Affected individuals are diagnosed with apnea episodes, hypotonia,
developmental delay, seizures and cerebellar signs such as ataxia and nystagmus. The majority
of cases reported until now displayed moderate to severe intellectual disability, only few cases
have been reported with normal intelligence [4]. The etiology of DWM isn’t completely
understood, it seems to be multifactorial, with genetic aberrations diagnosed for the great
majority of cases. Reciprocal translocations are chromosomal structural rearrangements in
humans, reported in 1/673-1/1000 subjects [5]. Generally, carriers of balanced translocations
have a normal phenotype, but often their reproductive capacity is uncertain. They have the

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capacity to produce unbalanced gametes, and due to this fact, a high risk of recurrent abortion,
neonates with birth defects and infertility [6, 7]. In the last years, prenatal diagnosis became
efficient in detecting unbalanced chromosomal rearrangements resulting from a balanced
translocation in one of the genitors. When one of the parents has a balanced translocation, he is
capable of these four segregation patterns: one normal gamete, one gamete carrier of the
balanced translocation and two unbalanced gametes with segmental deletions of the
chromosomes involved in the rearrangement. The 50% chance of bad outcome makes genetic
counseling crucial and very challenging. Here we present the report of a foetus with Dandy
Walker malformation, with a deletion of 5 q, which proved to be inherrited from a maternal
reciprocal and balanced translocation between chromosome 5 and 14.

Case presentation

A 35 years old lady, G3P1, presented for the first trimester screening at 12 6/7 weeks gestation
according with Fetal Medicine Foundation guidelines. The corrected risk for trisomy 21 and
trisomy 13/18 were low at 1:6747 and <1:20000, respectively. The fetal crown-rump length was
slightly modified (57,1mm – 12 2/7 weeks gestation) and the nuchal translucency was normal
(1.8mm). The nasal bone was visualized. Her medical history contained two pregnancies
terminated at 6-7 weeks gestation as spontaneous abortions, and there was no history of
teratogenic exposure, she had protective levels of antibodies for both rubella and
cytomegalovirus. Prior to this pregnancy, she was married for the last 6 years with no h/o
consanguinity. Transabdominal ultrasound (US) examination performed at 21 2/7 weeks
gestation discovered overall decreased fetal growth parameters. The examination was carried out
using a Voluson E8 Expert ultrasound apparatus (GE Healthcare, Milwaukee, WI, USA) with a
multifrequency transabdominal RAB 4-8 D probe. Biparietal diameter (BPD) was 48.9 mm,
fronto-occipital diameter was 61.0 mm, cranial circumference was 172,6 mm and abdominal
circumference was 139,5 mm. Femur (FL) and humerus length (HL) measured 32.2 mm and
30,0mm, respectively. The estimated fetal weight was 309g; all the above indicating symmetrical
intrauterine growth restriction (IUGR). In the posterior fossa, the cerebellar vermis was
hypoplastic and rotated upword, with a wide cleft between the cerebellar hemispheres and direct
communication between the fourth ventricle and the cisterna magna (Fig. 1). The tentorium was
elevated. Besides these malformations, we observed only a two vessel umbilical cord (Fig. 2).
All these findings were consistent with DWM.

Fig. 1. Ultrasound images of the posterior fossa, the cerebellar vermis seems to be absent, with a wide cleft
between the cerebellar hemispheres and direct communication between the fourth ventricle and the cisterna
magna

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Fig. 2. Two vessels umbilical cord – observed during routine I trimester scan, and confirmed at second
trimester ultrasound

We have completed the diagnosis with a fetal MRI (magnetic resonance imaging), which
included sagittal views of the vermis. The MRI showed a small, hypoplastic, rotated and raised
cerebellar vermis, a large median posterior fossa cyst communicating widely with the fourth
ventricle – an enlarged posterior fossa, an upwardly displaced tentorium and antero-laterally
displaced but apparently normal cerebellar hemispheres, a normal brain stem (Fig. 3).

Fig. 3. MRI examination found a small, hypoplastic, rotated and raised cerebellar vermis (it proved that the
vermis existed), a large median posterior fossa cyst communicating widely with the fourth ventricle – an
enlarged posterior fossa, an upwardly displaced tentorium and antero-laterally displaced but apparently
normal cerebellar hemispheres, a normal brain stem (in axial and sagital view)

Taking in to consideration the fact that many of the cases with DWM were associated with
chromosomal aberrations [1], we appreciated as usefull to obtain the fetal karyotype. At 22
weeks gestation we performed an amniocentesis which revealed a chromosome 5 deletion – 46
XX, del (5p14) (Fig. 4).

Fig. 4. Fetal karyotype obtained at 22 weeks gestation – 46 XX, del (5p14)

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The couple underwent genetic counselling and chose to terminate the course of pregnancy,
which was accepted in according with romanian laws. The placenta was hypotrophic without
macroscopic or histologic lesions. The genetician found important to complete the case history
with bilateral parental karyotype. The maternal karyotype proved to be modified as follows – 46
XX, t (5; 14) (p14; q32) and the paternal karyotype was normal.

Discussions

DWM is a relatively common complex which can be diagnosed prenatal with transabdominal
ultrasound in the second trimester (not earlier than 18 weeks gestation, when it is generally
accepted to be the moment of complete cerebellar development) [8]. The complete diagnosis
relies strongly on fetal MRI from the 20th week of gestation onwards [9]. Since the etiology of
DWM is so scarcely understood, we believe it to be multifactorial, determined by chromosomal
anomalies or part of a defined syndrome [10], as well as linked with prenatal exposure to rubella,
cytomegalovirus. The genetic theory is sustained by other reports of Dandy-Walker cases
associated with chromosomal aberrations (Table 1).

Table 1
Dandy-Walker malformation associated with isolated chromosomal abnormalities
No. of cases with DWM Chromosomal abnormality Reference

27 Trisomy 18 Nyberg et al., (1991) (11)


Estroff et al., (1992) (12)
Ulm et al., (1997) (13)
Imataka et al., (2007) (14)
Lim FF et al., (2010) (15)
11 Duplication 3q Girnberg et al., (2004) (16)
deletion 3q25.1e25.33 Grinberg & Millen (2005)
(17)
Titomanlino et al., (2005)
(18)
Sudha et al., (2001) (19)
de Azevedo et al., (2005)
(20)
Ounap et al., (2005) (21)
11 Deletion 13q Patacchiola et al., (1999)
(22)
McCormack et al., (2003)
(23)
Alanay et al., (2005) (24)
Gul et al., (2005) (25)
9 Trisomy 13 Nyberg et al., (1991) (11)
Estroff et al., (1992) (12)
Ulm et al., (1997) (13)
4 Trisomy 9 Sepulveda et al., (2003) (26)
3 7p microdeletion/duplication C. Liao et al., (2012) (1)
2 69,XXX Ulm et al., (1997) (13)
1 5 p deletion Vialard et al., (2005) (27)
1 Trisomy 21 Estroff et al., (1992) (12)
1 Turner syndrome Nyberg et al., (1991) (11)
1 Duplication 11q Estroff et al., (1992) (12)
1 Duplication 1q Ulm et al., (1997) (13)

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To the best of our knowledge, to date, only one 5p deletion syndrome prenatally diagnosed
has been reported in the literature related to DWM, but that specific case associated agenesis of
the corpus callosum also [27]. In that report the 5p deletion appeared de novo in a male fetus,
involving p12 band. In our case, the 5p14 deletion appeared at a female fetus and it was
determined by an unbalanced chromosomal rearrangement resulting from the maternal balanced
translocation t (5; 14) (p14; q32) during meiotic seggregation. In our opinion, the decision to
complete the diagnosis with the fetal karyotype proved to be enlightening concerning the
patient’s reproductive future. This fetus karyotype explained the two past abortions and brought
to light the possibility of this couple to obtain: 2/4 affected offsprings, ¼ carriers of balanced
translocation and ¼ normal karyotype fetuses.
Tipically 5p deletion syndrome, also known as “cri du chat syndrome”, associates frequently
cardiac and cerebral malformations, while we found only a two vessels umbilical cord besides
the posterior fossa malformations consistent with DWM. The mechanical theories sustain that
secondary to the incomplete resorption of the membranous area of the primitive
rhombencephalic vesicle, appears a dilation of the fourth ventricle, though, recently it was
proved that gene FOXC1, strongly associated with DWM, is expressed by the leptomeninges,
carrying a great role in the posterior cerebral area developement [28, 29, 30].

Conclusion

The latest advances made in fetal ultrasound and the use of MRI in fetal medicine, along with
cytogenetic analysis allow the obstetricians to identify DWM syndrome earlier, when the couple
may choose to terminate the course of pregnancy. This peculiar case is the living proof that
accurate diagnoses obtained with molecular techniques are essential not only for management of
the current pregnancy, but especially for prenatal couple counseling in subsequent pregnancies.
Taking to consideration our patient’s history of consecutive abnormal pregnancies, we
strongly recommend parental karyotyping in case of recurrent pregnancy loss and prenatal
diagnosis for all individuals with balanced chromosome rearrangement.

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The Role of Ultrasound in Diagnosis and Management in Renal


Colic During Pregnancy

PETCA Răzvan-Cosmin1,2, POPESCU Răzvan-Ionuț2,*, MEHEDINȚU Claudia1,3,


BOȚ Mihaela1,4, VEDUȚA Alina5, PETCA Aida1,4
1 University of Medicine and Pharmacy Carol Davila, Bucharest, (ROMANIA)
2 Burghele Clinical Hospital, Bucharest, (ROMANIA)
3 Malaxa Hospital Bucharest, (ROMANIA)
4 Elias Emergency Hospital Bucharest, (ROMANIA)
5 Filantropia Clinical Hospital, Bucharest, (ROMANIA)
* Corresponding author, Burghele Clinical Hospital, Panduri Street no. 20, District 5, Bucharest, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected], [email protected]

Abstract

Objective
The aim of this study is to review the role of ultrasound in diagnosis and management of renal
colic in pregnancy when the conservative treatment fails.

Materials and methods


In this retrospective study performed in the Department of Urology of Burghele Clinical
Hospital we analyzed 45 cases of pregnant women. From the medical records we selected
patients history, signs and symptoms, diagnostic methods and treatment. All patients were
assessed with blood tests and urine analyses.

Results
The mean age was 30 years old with a mean gestation time of 24 weeks. The mean hospital
stay was 3 days. From the total of 45 patients’ 14 presented documented history of renal or
ureteral lithiasis. The most common presenting symptom was flank pain (4 patients complained
of bilateral lumbar pain). Nineteen cases had associated fever. Blood analysis revealed anemia in
most cases and increased number of leukocytes in 29 cases. The urine culture was positive for 17
patients. All patients were evaluated with transabdominal ultrasonography. Eighteen patients
presented stone associated disease. Nine cases received conservative treatment. There were
performed 20 double-J stent insertions and 16 cases received semirigid ureteroscopy followed by
double-j stent insertion guided by ultrasonography.

Conclusion
Ultrasonography is an effective imagistic method to safely evaluate renal colic in pregnancy.
When conservative approach fails, double-J stent insertion and ureteroscopy, both guided by
ultrasonography, for selected cases are considered to be the proper invasive treatment.
Keywords: renal colic, pregnancy, ultrasound, lithiasis, double j, ureteroscopy

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Introduction

Renal colic in pregnancy represents a challenging situation because of the few options of
imaging investigations and treatment. Usually, urolithiasis and physiological hydronephrosis
becomes symptomatic in the second and third trimester [1, 2]. The diagnostic during pregnancy
is difficult because of limitations on the use of X-rays [3]. Ultrasonography (US) is considered to
be the diagnostic choice for reasonable specificity and sensitivity without any impact on fetus
evolution [4]. When US becomes inefficient because its operator-dependent limitations,
magnetic resonance (MR) may be a safe solution in establishing a correct diagnostic. Some
authors suggest that low dose CT should be considered in the diagnostic algorithm [5]. The
initial management consists in conservative treatment that include analgesics, antispasmodics
and hydration. In most of cases conservative treatment is sufficient and the pregnant woman
reaches the term of birth without any complications.
Sometimes, renal colic can be associated with obstruction, upper urinary tract infection, sepsis
and perinephritic abscess [6]. In some cases the conservative treatment becomes inefficient and
pregnant womens requires hospitalization and a proper invasive treatment such as double J
insertion, percutaneous nephrostomy and ureteroscopic lithotripsy should be performed [7]. Both
double-J catether and percutaneous nephrostomy are safe techniques for urinary drainage and can
be achieved under US control.
Because of the urine modifications during pregnancy, the risk of catheter encrustation is
higher and it’s necessary stent replacement at 4-6 weeks [8]. In contrast to temporary urinary
drainage that has some disadvantages like pain or catheter associated infections and reduced
quality of life, ureteroscopic treatment can be a definitive treatment that can be carefully
performed. This procedure requires anesthesia in contrast to stent replacement that can be
performed under local anesthesia. There is also a higher risk of ureteral perforation.
Ureteroscopy can be used both as diagnostic and treatment method when necessary at
pregnant women with urolithiasis. For improved results in therapy of renal colic in pregnancy it
is necessary a simultaneous involvement of gynecologist and urologist.

Materials and methods

In this retrospective study, we carefully reviewed 45 pregnant women who were treated in the
Department of Urology of Burghele Clinical Hospital for renal colic during January 2016 to May
2018. From the medical records we included age, gestation trimester, presentation symptoms,
history for lithiasic disease, diagnostic method and type of surgical intervention. All patients
were assessed with complete blood analysis, urine analysis, urine culture, creatinine value. The
imagistic method of choice was ultrasonography in all cases because of cost effective reasons
and high specificity and sensitivity. The diagnostic was made on clinical examination, blood
tests, urine culture and was completed with ultrasonography for a correct evaluation of renal
calculi. No patient was exposed to ionizing radiations. We adapted our treatment based on first
clinical visit symptoms and blood analysis so we choose a conservative treatment such as
hydration, analgesia and antispasmodic as first line intention for patients without fever and
infectious signs. Where the conservative treatment failed we used surgical interventions as
double-J or semirigid ureteroscopy adapted to each case. Double-J insertion was made under
local anesthesia and cystoscopic direct visualization with postoperative ultrasonography.

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Semirigid ureteroscopic lithotripsy was chosen for selected cases. We used a 9.5 Fr semirigid
ureteroscope with a safety guide wire and an air pressure ballistic lithotriptor. Stone
fragmentation with complete extraction of the fragments followed by double-J stent insertion
was successfully achieved in all cases.

Results

In this study were included 45 women with a mean age of 30 years old (18- 42 years). The
mean gestation time at presentation was 24 weeks (range: 11- 33 weeks). The mean hospital stay
was 3 days (range: 2-7 days). From the total of 45 patients, 14 (31.1%) presented documented
history of renal or ureteral lithiasis in which 3 (6.6%) had urological surgery for lithiasis in our
clinic.
Symptoms and laboratory findings were structured in Table 1. The most common clinical
presentation symptom was flank pain in 44 cases (97.7%). Blood test revealed anemia for all
patients and leukocytosis in 29(64%). Urine analysis was positive for hematuria in 28(62.2%)
tested samples. Urine culture was sterile in most analyzed situation 28(63.64%). When urine
culture was positive, the most frequent bacteria involved in colonization the urinary tract was E.
Colli 9(20.45%).

Table 1. Symptoms and laboratory findings in study group


n %
Flank Pain 44 97.7
Hematuria 9 20
Fever 19 42.2
Urinanalysis Hematuria 28 62.2
Blood tests Leucocytosis 29 64.4
High Creatinine Level 2 4.4
Urine Culture Sterile 28 63.64
E.Coli 9 20.45
Enterococcus 3 6.82
Klebsiella 2 4.55
Proteus 1 2.27
Staphylococcus Aureus 1 2.27

When we tried to find a correlation between serum creatinine levels, number of leucocytes,
hemoglobin values and urinary tract infection, there were no significant intersections between
the analyzed parameters – Fig. 1.

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Fig. 1. Correlation between creatinine level, number of leucocytes, hemoglobin values and uroculture in study
group

All patients were evaluated with transabdominal ultrasound. Most cases were hydronephrosis
grade 1, followed by grade 2 – Table 2. US has correctly identified associated stone and their
location in 19 (42.2%) cases.

Table 2. Ultrasound diagnosis in study group


Hydronephrosis n (%)
Absent 4 (8.8%)
Grade 1 21 (46.6%)
Grade 2 19 (42.2%)
Grade 3 1 (2.2%)
Bilateral 3 (11.53% of physiological hydronephrosis)
Left 4 (15.38% of physiological hydronephrosis)
Right 19 (73.06% of physiological hydronephrosis)
Lithiasis
No 26 (57.7%)
Yes 19 (42.2%)
Left 9 (47.36% stone associated hydronephrosis)
Right 10 (52.63% stone associated hydronephrosis)

The graphic correlations between gestation time, hydronephrosis grade and associated stone
pathology showed that hydronephrosis grade 1 and 2 were more often diagnosed between the
20th and 30th week, with higher lithiasis prevalence after the 25th week – Fig. 2.

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Fig. 2. Correlations between gestation time, hydronephrosis grade and lithiasis

Conservative treatment was considered first line intention in all cases and it consisted in
hydration, analgesia and antispasmodic. When necessary, antibiotics were included. If
conservative treatment failed or there were signs of severe hydroneprosis, infection or sepsis,
uncontrolled fever or persistent pain, we proceeded with double-J stent insertion in 20 women
(44.4%) and semirigid ureteroscopy with ballistic lithotripsy followed by double-J stent insertion
in 16 cases (35.56%). Fragmentation with complete extraction was possible in 13 situations
while in 3 situations we preferred stone push back into the renal pelvis followed by JJ stent
insertion.
No percutaneous nephrostomy was needed.
The diagnosis of patients, established by US and endoscopic surgery guided only by US, is
presented in Table 3. Most frequent the diagnostic was physiological hydronephrosis. As we see
there were 18 cases of ureteral lithiasis. Ureteral stenosis was diagnosed in 2 patients who
recieved double-J stent after dilatation of ureter.

Table 3. Diagnosis of patients


Ureteral lithiasis n %
Lumbar 8 17.7
Pelvic 10 22.2
Physiological Hydronephrosis
Without infection 2 4.44
With infection 21 46.6
Infection 2 4.44
Ureteral stenosis 2 4.44

Discussions

Renal colic is an infrequent condition during pregnancy that can lead to serious problems
without a proper diagnosis and prompt treatment. During pregnancy, there are some physiologic
and mechanic changes that urinary tract undergoes beginning from the end of the first trimester.
Progesteron and gonadotropin are the main hormones which produces relaxation of the
smooth muscles and a secondary decrease in peristalsis. The mechanic action can be easily
explained by the growing fetus that compress the ureters with a higher prevalence on the right

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ureter. There are still some issues in how to differentiate lithiasis from physiological
hydronephrosis [9]. Radiographic investigations in various trimesters of pregnancy have been an
intense subject of debate because the teratogenic, mutagenic and carcinogenic effect that ionising
radiations have on the fetus. At this moment, the diagnostic investigation of choice for pregnant
women are renal and bladder ultrasonography and magnetic resonance urography. CT scan are
gold standard in diagnosis renal colic in adult but should not be performed in pregnancy. Low
dose CT exposes the fetus to a lower radiation degree and can be an option in diagnostic
algorithm. In our series ultrasonography performed by well trained staff determined with
accuracy the correct diagnostic. However, studies showed that false negative rate of detection is
high [10, 11].
Comparable to other studies, our study revealed predominance of physiological
hydronephrosis on the right side 73.06% [12] and an equal distribution for the incidence of
ureteral stones on both sides (Left-47.36%; Right-52.63%) [13]. It is accepted that physiological
appears at the end of the first trimester and it is caused by both hormonal changes and
mechanical effects. Renal colic due to stone passage it is accepted to have a small incidence.
In the absence of any complications, the conservative management with a multidisciplinary
approach (urologist, obstetrician, radiologist) should be tried first, as the studies revealed that
almost 50-70% of stones can pass spontaneously [14]. A proper conservative treatment provides
a good pain control and correct hydration. Pain control can be obtained with drugs such as
acetaminophen, hydrocodone or oxycodone and if necessary even morphine sulphate. If
vomiting is present some anti-emetics should be administered. To complete the treatment there
should be included antispasmodics and antibiotics if there are any signs of infection.
Some conditions such as: obstructed solitary kidney, presence of infection, persistent pain,
refractory to analgesia, fever requires intervention with temporary drainage through double-J
stent or percutaneous nephrostomy. There are no evidences that one is better than the other and
the decision should be made on case particularities. One major inconvenient of temporary
drainage is that urinary catheters should be changed every 3-4 weeks because of the
encrustations [15]. Double-J stent insertion is an effective method for achieving a proper renal
drainage that can be placed under US guidance without any use of radiation [16] but it can have
some serious disadvantages like stent associated infections, pain and hematuria.
In our study double J stents were successfully placed in 20 cases using a rigid cystoscope with
ultrasonography control during placement. There was no need of percutaneous nephrostomy.
Due to the muscle-relaxing effect of progesterone and gonadotropin, ureteroscopy can be well
performed as a diagnostic and therapeutic method, without major complications. One major
advantage of this procedure is that it can be used as a diagnostic and definitive treatment solution
with a direct visualization of the calculi. Ureteroscopy allowed to explore the ureter, from the
ureteral orifice to the renal pelvis without any radiations under epidural or spinal anesthesia.
Both semi rigid and flexible ureteroscopes can be used in management of urinary calculi. The
flexible ureteroscope has the advantage of an easily approach on a twisted ureter with a lower
risk of perforation [17].
In this study we used a 9.5 Fr semirigid ureteroscope with hydrophilic guide wire and
pneumatic lithotripter or stone baskets. In all cases fragments were succesfully extracted. Some
studies showed that electrohydraulic lipthotripsy is not indicated in the treatment of pregnant
women because it generates a high peak pressure and has narrow safety margins [18].
Ureteroscopy was shown to be safe and effective throughout the whole period of pregnancy
[4, 10, 19, 20].

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Conclusions

Renal colic in pregnant women remains a permanently challenge that requires a


multidisciplinary attention from both obstetrician and urologist. Ultrasonography remains the
imagistic tool of choice with high specificity and sensitivity and without any risks for both
mother and fetus. Conservative care represents the first option in treating pregnant patients
because most of them succeed in eliminating ureteral stones. Double-J stent insertion is an easy
solution for complicated cases. Ureteroscopy used both as diagnostic and treatment is a valid
solution when definite intervention is necessary.

REFERENCES

1. Semins, M.J., Matlaga, B.R. (2010). Management of stone disease in pregnancy. Curr Opin Urol 20(2), pp.
174-177.
2. Srirangam, S.J., Hickerton, B., Van Cleynenbreugel, B. (2008). Management of urinary calculi in
pregnancy: a review. J Endourol 22(5), pp. 867-876.
3. Juan, Y.S., Wu, W.J., Chuang, S.M., Wang, C.J., Shen, J.T. et al., (2007). Management of simptomatic
urolithiasis during pregnancy. Kaohsiung J Med Sci 23(5), pp. 241-246.
4. Fazl, P., Suleyman, Y., Mustafa, K., Hasan, B. (2011). Treatment outcomes of semirigid ureteroscopy and
intracorporeal lithotripsy in pregnant women with obstructive ureteral calculi. Urol Res 39, pp. 487-494.
5. White, W.M., Zite, N.B., Gash, J. et al., (2007). Low-dose computed tomography for the evaluation of
flank pain in the pregnant population. J Endourol 21(11), pp. 1255-60.
6. Pedro, R.N., Das, K., Buchholz, N. (2016). Urolithiasis in pregnancy. International Journal of surgery 36,
pp. 688-692.
7. Wang, Z., Xu, L., Su, Z., Yao, C., Chen, Z. (2014). Invasive management of proximal ureteral calculi
during pregnancy. Urology 83(4) pp. 745-749.
8. Semins, M.J,, Matlaga B.R. (2013). Management of urolithiasis in pregnancy. Int J Womens Health 5, pp.
599-604.
9. Andreoiu, M., MacMahon, R. (2009). Renal colic in pregnancy: Lithiasis or Physiological Hydronephrosis.
Urology 74(4), pp. 757-761.
10. Dumitrache, M., Merticariu, M., Rascu, S., Petca, R., Badescu, D., Jinga, V. (2013). Our clinic’s
experience with the management of renal colic in pregnancy. Eur Urol Suppl 12, e1247.
11. Butler, E.L., Cox, S.M., Eberts E.G., Cunningham, F.G. (2000). Simptomatic Nephrolithiasis complicating
pregnancy. Obstet Gynecol 96(5), pp. 753-756.
12. Swanson, S.K., Heilman R.L., Eversman W.G. (1995).Urinary tract stones in pregnancy. Surg Clin North,
75(1), pp. 123-142.
13. Parulkar, B.G., Hopkins, T.B., Wollin, M.R. et al., (1998). Renal colic during pregnancy: a case for
conservative treatment. J Urol 159(2), pp. 365-368.
14. Meher, S., Gibbons, N., DasGupta, R. (2014). Renal stones in pregnancy. Obstet Med 7(3), pp. 103-110.
15. Cormier, C.M., Canzoneri, B.J., Lewis, D.F., Briery, C., et al., (2006). Urolithiasis in pregnancy: current
diagnosis, treatment, and pregnancy complications. Obstetrical Gynecol Surv 61(11), pp. 733-741.
16. Jarrard, D.J., Gerber, G.S., Lyon, E.S. (1993).Management of acute ureteral obstruction in pregnancy
utilizing ultrasound guided placement of ureteral stents. Urology 42, pp. 263-268.
17. Lilienfeld, A.M. (1966). Epidemiological studies of the leukemogenic effects of radiation. Yale J Biol Med
39(3), pp. 143-164.
18. Blanco, L.T., Socarras, M.R., Montero, R.F., Diez, E.L., et al., (2017). Renal colic during pregnancy:
Diagnostic and therapeutic aspects. Literature review. Cent European J Urol, 70(1), pp. 93-100.
19. Semins, M.J., Trock, B.J., Matlaga, B.R. (2009). The safety of ureteroscopy during pregnancy: a systematic
review and meta-analysis. J Urol 181(1), pp. 139-43.
20. Hoscan, M.B., Ekinci, M., Tunckiran, A., et al., (2012) Management of symptomatic ureteral calculi
complicating pregnancy. Urology 80(5), pp. 1011-1014.

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Role of Transvaginal Ultrasound in the Assessment of Cervical


Cancer

PIRTEA Laurențiu1, BALINT Oana2, SECOȘAN Cristina2, SAS Ioan1,


GRIGORAȘ Dorin1
1University of Medicine and Pharmacy “Victor Babeș” Timișoara (ROMANIA)
2County Emergency Clinical Hospital Timişoara (ROMANIA)
Email: [email protected]

Abstract

Cervical cancer is the fourth most frequent cancer in women worldwide, with over 70% of
cases diagnosed in advanced stages. Although FIGO still recommends a clinical staging recently
has begun encouraging the use of different imaging methods for improving the pre-operative
local extent. MRI is currently considered the first line imaging technique in cervical cancer, but
it has a few limitation and disadvantages. In the last years, ultrasound has gained increased
attention. Current evidence suggests that ultrasound may be a useful technique for assessing local
extent of disease in cervical cancer, with high accuracy rates in detecting tumour presence,
assessing diameters, stromal involvement, and parametrial infiltration.

Introduction

Cervical cancer is the fourth most frequent cancer in women worldwide. (1) Despite its
screening method is efficient and largely available, and even newer methods like HPV
genotyping and immunohistochemical p16/Ki67 dual staining have become part of regular
clinical practice, cervical cancer still represents a major public health issue. (2-4) In developing
countries, over 70% of cases are diagnosed in advanced stages. (5)
Because cervical cancer tends to develop locally involving the cervix and the surrounding
structures, the International Federation of Gynecology and Obstetrics (FIGO) continues to
recommend a clinical staging system based on pelvic examination. However, this method of
staging has showed increased error rates, ranging from 26-66%. (6) Assessment of local
infiltration and parametrial invasion are essential for an individualized management. In the last
years, FIGO has begun encouraging the use of different imaging methods for improving the pre-
operative local extent, but without modifying the stadialization according to their findings, with
CT and MRI being the most recommended. (7)
Although transvaginal ultrasound examination represents the standard examination method
for diagnosing gynecological diseases, until recently, the use of ultrasound in the assessment of
cervical cancer was been considered less valuable. However, studies from the last years has
gathered enough evidence to draw increasing interest to this imaging method, less time
consuming, easier to perform and less expensive that the others.

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Grayscale ultrasound

The ultrasound detection rate of a cervical malignant tumors is 93%, both by transvaginal or
by transrectal method. (8, 9)
There have been described several steps for a thorough assessment of a cervical mass. (10)
First step is observing its presence, location (exocervix or endocervix) and its growth pattern
(exophytic or infiltrative). The second step is measuring the mass using three diameters. The
third step represents the distance from the tumor to the cervical internal os, of great importance if
a fertility-sparing procedure is considered. A distance of at least 10 mm being adequate for a
tumor-free margin an also providing enough length for a future pregnancy. The last step
evaluates the extent of the stromal invasion, as either partial (≤2/3 or >2/3) or full-thickness by
measuring the tumor-free stroma.
Morphological appearance of a cervical tumor is described as a solid lesion, usually
hypoechoic. In a study on 40 women, Epstein et al., analysed the ultrasound characteristics of
cervical tumors in relation to histology. A hypoechoic mass was associated in 73% of cases with
a squamous cell carcinoma while an isoechoic image was observed in 68% of cases with
adenocarcinoma. This finding is of great importance because of the frequency of undiagnosed
cases of adenocarcinoma at vaginal or cytological examination. Also, another finding was the
association between a mixed echogenicity and larger tumors probably related to the
inflammatory or necrotic changes within the tumor. (11)
An advantage that ultrasound has over MRI and CT is the dynamic examination technique
described by Testa et al. If a cervical malignant mass is present, it can be felt by moving the
ultrasound probe as a rigid, solid mass infiltrating the cervical stroma. Also, by moving the probe
against de cervix, the extent of the disease can be assessed by observing the mobility of the
cervix against the bladder and rectal walls. (12)
If the tumor infiltrates the entire stromal thickness, the extension in the parametrium is
mandatory. On ultrasound, parametrial infiltration appears as the extension of the hypoechoic
cervical mass into the pericervical tissues. Fischerova et al., suggests describing parametrial
invasion using 4 grades. In grade 1, the tumor infiltrates only the pericervical fascia. Grades 2-3
describes the continuous progression through the paracervical fascia into the parametrium or
non-continuously (“skip” metastases) for grade 4. (10)

2D Color Doppler assessment

Angiogenesis is recognized prognostic factor in many cancers, including cervical cancer. (13)
Therefore, assessment of the vascularization of a cervical tumor is important. Colour Doppler
allows easy identification of blood vessels within a tumor. Several studies analysed the
assessment of blood flow in cervical cancer and identified parameters that correlated with
prognostic factors.
Cheng et al., published two studies on a total of 139 (104 and 35) patients with cervical
cancer stage I to II. He observed the presence of color signals within 58% of the tumors and that
it was associated with large tumors, deeper stromal invasion, invasion of the parametrium and
lymph node metastases. Also, in his second study he associated significantly higher intratumoral
vascularity indexes with higher stage (II), >50% stromal invasion, presence of lymphovascular
tumoral emboli and lymph node metastases. (14, 15) Alcazar et al., reported an intratumoral
blood flow in all 49 women in his study group, explained by the use of more performant

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ultrasound machines. He observed abundant blood flow more frequently in squamous carcinoma,
moderately and poorly differentiated tumors, large tumors and advanced stages. He correlated
the same tumoral features with the exception of histologic type with a lower resistance index
(RI) and a higher peak systolic velocity (PSV). (16) In another study, Testa et al., showed similar
findings with Alcazar but a few discrepancies regarding RI. He also observed blood flow in all of
his patients included in the study. The prevalence of color score >2 was higher in tumors of over
4 cm, which also associated with lowest RI values (unlike Alcazar findings) and highest PSV
values. More, he correlated PSV values with serum levels of SCC antigen. (17) In a more recent
study, Jurado confirmed all previous results, concluding that tumors with abundant
vascularization were significantly associated with lymph nodes metastases, depth stromal
invasion >10mm, lymphovascular space invasion, tumoral dimensions >17.5mm and parametrial
involvement. (18)
Only one study evaluated blood flow in uterine arteries in relation with cervical cancer. Bolla
et al., presumed that the blood flow in the uterine arteries may be influenced by local expansion
of the cervical cancer, increased by angiogenesis. He analysed 25 patients and observed a
significant association between the maximum tumor diameter and FIGO stages with maximal
end diastolic velocity (EDV) and minimal peak systolic velocity. There were no associations
with PI or RI. (19)

3D and 3D Color Doppler Ultrasound

It is well known that three-dimensional ultrasound can estimate tumoral dimensions and
volumes more accurately than 2-D ultrasound, including cervical cancer. (20) However, there are
only a few studies assessing the role of 3D-US in cervical cancer and caution is advised since it
is not a standard technique and the results might not be reproducible in clinical settings.
In 2002, Suren et al., describes for the first time the vascularization of a cervical malignant
tumor as a chaotic network of tortuous vessels using 3D Color Power Angio™. (21) A few years
later, Testa et al., provides de quantitative characterisation of Suren’s findings, and observes that
three-dimensional vascular indices were significantly higher in advanced stages but without any
association with tumor size, tumor grade or histologic type. (17) Hsu et al., studied 141 patients
with cervical cancer using 3D Power Doppler US and observed an abundant intratumoral Power
Doppler signals with elevated vascularization index (VI), flow index (FI) and vascularization
flow index (VFI) in patients with cervical cancer compared with control group. He also
described four types of intratumoral vascularization patterns: localized, peripheral, scattered and
single-vessel. (22) In another study, Ghi et al., tries to assess the feasibility of 3D US in the local
staging of cervical carcinomas. Although the number of patients involved is small, he showed a
85% (12 of 14 patients) compatibility between the 3D US staging and pathology results. (23)
Partially similar results, regarding 3D Power Doppler evaluation, were obtained by Alcazar et
al., who also observed high vascularisation and PD indices related to advanced stages and poor
tumoral grading but not with tumoral volume, histologic type, lymphovascular space infiltration
or lymph node metastases. (24)

Ultrasound assessment of lymph-nodes involvement

Involvement of the lymph nodes is associated with poor clinical outcome. Also, it strongly
influences the management and treatment options. Differentiating a metastatic lymph node from

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a normal or reactive one is based on the association of several morphologic and vascular
characteristics. Metastatic nodes of cervical cancer are usually hypoechogenic or with
inhomogeneous echogenicity due to necrosis and calcification, round shaped, with a long: short
axis radio <2, an absent hilar sinus fat and increasing low attenuation of the cortex and a
peripheral vascular pattern. (10, 25)
In a recent meta-analysis, Gong et al., evaluated the diagnostic performance of different
imaging techniques for the detection of pelvic lymph nodes metastases. He included 8 studies
regarding ultrasound efficacy and obtained a sensitivity of 71% and a specificity of 99% (the
highest) for the ultrasound, compared with CT, MRI, DWI, PET and PET-CT. More, on an
analysis for different US techniques, the highest efficiency was shown for the laparoscopic US.
(26)

Value comparation of imaging methods

All imaging methods have been reported with overall good values for diagnostic accuracy.
Currently, there is no consensus as which is the best option in the assessment of the local
extent of cervical cancer. In the past, studies have suggested a limited role for ultrasound but
recent articles have reported similar or even superior results compared with MRI.
Testa et al., compared US and MRI in assessing the presence, size and extent of invasive
cervical cancer. He obtained similar high sensitivity and specificity with both methods for
detection of stromal invasion and low sensitivity and specificity with both methods for the
presence of parametrial infiltration. (8) Epstein et al., compared the value of US and MRI, using
pathology results as reference. The agreement between histology and US was significantly better
in assessing residual tumor and parametrial invasion than MRI. More, none of the methods were
significantly influenced by previous cone biopsy. (27) In a recent study, Arribas et al., evaluated
the agreement between clinical examination, 2D US, 3D US and MRI. He observed significant
correlations between clinical examination and MRI, MRI and 2D US; and MRI and 3D US for
tumor size estimation but as for the parametrial infiltration the best agreement was between MRI
and 3D US, and only moderate between MRI and 2D US. (28) Same agreement was evaluated by
Chiappa et al., but more detailed. Between 2D US and MRI the agreement in assessing
parametrial infiltration was 76%, better for the ventral parametrium (90%) and worse for the
dorsal parametrium (59%). As for the MRI and 3D US, the agreement was 79%, best for the
middle part of the cervix and poorest for the caudal part. (29)

Conclusions

Magnetic resonance imaging is currently considered the first line imaging technique for the
assessment of local extent in cervical cancer. But this method has its limitation and
disadvantages. Ultrasound has gained increased attention in the last years. Current evidence
suggests that ultrasound may be a useful technique for assessing local extent of disease in
cervical cancer, even with higher accuracy than MRI, especially for parametrial infiltration. It’s
role in assessing lymph nodes involvement remains limited. More, 2D and 3D Doppler
evaluation offer the advantage over MRI in assessment of several parameters of tumoral
vascularization associated with worse prognostic and response to treatment.

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17. Testa AC, Ferrandina G, Distefano M, Fruscella E, Mansueto D, Basso D, et al., Color Doppler
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21. Suren A, Osmers R, Kuhn W. 3D Color Power AngioTM imaging: a new method to assess intracervical
vascularization in benign and pathological conditions. Ultrasound Obstet Gynecol. 1998 Feb 1; 11(2): pp.
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22. Hsu K-F, Su J-M, Huang S-C, Cheng Y-M, Kang C-Y, Shen M-R, et al., Three-dimensional power
Doppler imaging of early-stage cervical cancer. Ultrasound Obstet Gynecol. 2004 Nov; 24(6): pp. 664-71.
23. Ghi T, Giunchi S, Kuleva M, Santini D, Savelli L, Formelli G, et al., Three-dimensional transvaginal
sonography in local staging of cervical carcinoma: description of a novel technique and preliminary results.
Ultrasound Obstet Gynecol. 2007 Sep 26; 30(5): pp. 778-82.
24. Alcázar JL, Jurado M, López-García G. Tumor Vascularization in Cervical Cancer by 3-Dimensional
Power Doppler Angiography. Int J Gynecol Cancer. 2010 Apr; 20(3): pp. 393-7.
25. Hall T., Barton DP., Trott P., Nasiri N, Shepherd J., Thomas J., et al., The Role of Ultrasound-guided
Cytology of Groin Lymph Nodes in the Management of Squamous Cell Carcinoma of the Vulva: 5-Year
Experience in 44 Patients. Clin Radiol. 2003 May; 58(5): pp. 367-71.
26. Gong Y, Wang Q, Dong L, Jia Y, Hua C, Mi F, et al., Different imaging techniques for the detection of
pelvic lymph nodes metastasis from gynecological malignancies: a systematic review and meta-analysis.
Oncotarget. 2017 Feb 21; 8(8).
27. Epstein E, Testa A, Gaurilcikas A, Di Legge A, Ameye L, Atstupenaite V, et al., Early-stage cervical
cancer: Tumor delineation by magnetic resonance imaging and ultrasound — A European multicenter trial.
Gynecol Oncol. 2013 Mar;128(3):449–53.
28. Arribas S, Alcázar JL, Arraiza M, Benito A, Minguez JA, Jurado M. Three-Dimensional Transvaginal
Sonography and Magnetic Resonance Imaging for Local Staging of Cervical Cancer. J Ultrasound Med.
2016 May; 35(5):pp. 867- 73.
29. Chiappa V, Di Legge A, Valentini AL, Gui B, Miccò M, Ludovisi M, et al., Agreement of two-dimensional
and three-dimensional transvaginal ultrasound with magnetic resonance imaging in assessment of
parametrial infiltration in cervical cancer. Ultrasound Obstet Gynecol. 2015 Apr; 45(4): pp. 459-69.

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The Importance of Ultrasound Assessment in Predicting Recurrence


after Transvaginal Sling Procedures

PIRTEA Laurentiu1, ILINA Razvan1, SECOSAN Cristina2, BALINT Oana2,


SAS Ioan1, GRIGORAS Dorin1
1University of Medicine and Pharmacy “Victor Babes” Timisoara (ROMANIA)
2County Emergency Clinical Hospital Timişoara (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected]

Abstract

Introduction

Ultrasound evaluation of the pelvic anatomy is an indispensable diagnostic procedure in


gynecology. Ultrasound imaging in the management of urinary incontinence and pelvic organ
prolapse has been proven to be very useful in decision making, is a widely available, cost-
effective and non invasive diagnostic procedure [1, 2].
Despite these advantages, contemporary guidelines attribute a limited utility to ultrasound
evaluation of patients with urinary incontinence. Recent International Federation of Gynecology
and Obstetrics (FIGO) Working Group guidelines recommend ultrasound only for measurement
of post-void residual volume, and the recommendations provided by the 5th International
Consultation on Incontinence do not recommend ultrasound in the primary evaluation of patient
with urinary incontinence [Level of evidence 3, Grade of recommendation C], and consider
ultrasound as on optional test in the evaluation of patients with complex or recurrent urinary
incontinence [Level of evidence 3, Grade of recommendation C] [2-4].
In case of suburethral slings, the ultrasound evaluation of tape placement is simple and precise
due to the highly echogenic polypropylene tape that can easily be identified posterior to the
urethra. Perineal, introital and andoanal ultrasound are the most recommended techniques [2, 5,
6].
Ultrasound imaging after sling procedures can be useful in the discovering the causes of
surgery failure or evaluation of postsurgical voiding dysfunctions [2].
The examination is usually performed in 2D, but certain benefits of using 3D or 4D imaging
have been described. 3D transperineal ultrasound can be useful in visualizing a number of
variations in tape placement such as twisting, division and asymmetry, which are difficult or
impossible to detect by 2D ultrasound [6].
Our purpose was to review the currently available literature in order to evaluate the
importance of postoperative ultrasound in the prognosis of recurrence of SUI after tension-free
mid-urethra sling procedures (transvaginal tape and transobturator tape).

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Tape position and tension

Tape position relative to the urethra is crucial for the success of the anti-incontinence
procedures. The ideal level for tape placement is considered the mid-urethra, between 50 and
75% of the urethral length, measured from the bladder neck to the external urethral meatus [2, 7-
13]. This section corresponds to the high pressure zone of the urethra [14].
Several authors have reported that the positioning of the suburethral sling at the level of the
bladder neck is associated with the highest stress urinary incontinence recurrence rate, with
procedure failure rates reported to exceed 50% [2, 10, 15] and even as high as 74% [9].
Regarding the tension of the tape, the optimal distance proposed is between 3 and 5 mm from
the tape to the urethral lumen. A distance <3 mm is associated with a greater risk of
complications such as voiding difficulties and de novo urgency [2, 7, 9, 10].
Lo et al., in a study on 90 women with SUI found a correlation between lifting of the mid-
urethra and voiding difficulties (10% of the patients with immediate postoperative voiding
difficulty having a pronounced mid-urethra angulation) [16].

Urethral and bladder neck mobility

Bladder neck mobility after transvaginal sling procedures can be easily evaluated by
sonography [12, 16-19], though other evaluation methods have been described (magnetic
resonance imaging, lateral cystourethrography, X‐ray imaging and the Q‐tip test).
The normal bladder neck mobility is estimated to be 15-20 mm [20]. Despite the fact that the
sling placement procedure should not affect the mobility of the area of the bladder neck [12, 16,
19] several authors have reported significant reductions in bladder neck mobility after TVT [17,
18, 21, 22].
Viereck et al., evaluated 191 patients who underwent the TVT procedure for SUI. Tape
position was checked sonographically immediately after surgery and at the 6‐month follow‐up.
He observed a significantly lower postoperative bladder neck mobility in patients with
recurrence of SUI or secondary cure. He noted that a bladder neck mobility of ≤10 mm had a
2.6-fold higher risk of therapeutic failure, and that mobility >15mm reduced the risk of
procedure failure [23].
Richter et al., reported a two-fold increase in sling failure associated with urethral
hypomobility (Q-tip at maximal straining angle <30°) [24], while Lo et al., report an increase of
unfavorable outcome of more than 4 times in patients with limited mobility of the urethra
detected by the Q-tip test or ultrasound [25].

Bladder neck angle

Transvaginal sling procedures decrease bladder neck angles at rest and valsalva, linear
movement on valsalva and elevate the bladder neck [12].
According to Pregazzi et al., the measurement of the bladder neck angle can identify SUI
better than urethrovesical mobility (sensitivity 96% vs 87%; specificity 92% vs 68%; positive
predictive value 85% vs 55%), and therefore can provide useful additional information to that
obtained by ultrasound evaluation of bladder neck mobility [26].

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Funneling of the bladder neck

In primary genuine stress incontinence, bladder neck funneling on ultrasound implies the
potential coexistence of poor anatomic support and an intrinsic sphincter defect [27].
After successful transvaginal sling procedures funneling at maximal Valsalva is decreased
[28].
Both preoperative and persistent postoperative bladder neck funneling are associated with an
increased probability of therapeutic failure or recurrence. Harms et al., reported a significantly
lower cure rate in patient with preoperative funneling (77.5%) in comparison to 96.6% in the
group without funneling [23, 29].
In a study on 56 women with SUI, Kuo et al., found a higher incidence of opening of the
bladder neck in patients with de novo urgency or urge incontinence (84.6% of patients), whereas
only 4.7% of patients who did not have postoperative urgency had opening of the neck [30].

Conclusions

We believe the ultrasound evaluation is safe and accessible in patients with SUI, can aid in
decision making, can be beneficial in the prediction of post-therapeutic failure in patients with
transvaginal slings and should be included as a routine investigation.

REFERENCES

1. Santoro GA, Wieczorek AP, Dietz HP, Mellgren A, Sultan AH, Shobeiri SA, Stankiewicz A, Bartram C.
State of the art: an integrated approach to pelvic floor ultrasonography. Ultrasound Obstet Gynecol. 2011
Apr; 37(4): pp. 381-96.
2. Bogusiewicz M. Ultrasound imaging in urogynecology – state of the art 2016. Przegla̜d Menopauzalny =
Menopause Review. 2016; 15(3): 123-132.
3. Medina CA, Costantini E, Petri E et al. Neurourol Urodyn. 2016. Evaluation and surgery for stress urinary
incontinence: A FIGO working group report.
4. Tubaro A, Vodušek BD, Amarenco G, et al. Imaging, neurophysiological testing and other tests. In:
Abrams P, Cardozo L, Khoury S, Wein A, editors. Continence. 5 th International Consultation on
Incontinence. Paris: 2012. Feb, pp. 507-621.
5. Tunn R, Schaer G, Peschers U et al. Updated recommendations on ultrasonography in urogynecology. Int
Urogynecol J (2005) 16: 236.
6. Dietz HP, Wilson PD. The ‘iris effect’: how two‐dimensional and three‐dimensional ultrasound can help us
understand anti‐incontinence procedures. Ultrasound Obstet Gynecol, 2014, 23: pp. 267-271.
7. Kociszewski J, Rautenberg O, Perucchini D, et al. Tape functionality: sonographic tape characteristics and
outcome after TVT incontinence surgery. Neurourol Urodyn. 2008; 27: pp.485-490.
8. Yang JM, Yang SH, Huang WC. Correlation of morphological alterations and functional impairment of the
tension-free vaginal tape obturator procedure. J Urol. 2009; 181: pp. 211-218.
9. Yang JM, Yang SH, Huang WC, Tzeng CR. Correlation of tape location and tension with surgical outcome
after transobturator suburethral tape procedures. Ultrasound Obstet Gynecol. 2012; 39: pp. 458-465.
10. Bogusiewicz M, Monist M, Gałczyński K, et al. Both the middle and distal sections of the urethra may be
regarded as optimal targets for ‘outside-in’ transobturator tape placement. World J Urol. 2014; 32: pp.
1605-1611.
11. Pirtea L, Sas I, Ilina R, Grigoraș D, Mazilu O. Transversal incision of the vagina favors the remaining of
the tape in the middle-third urethra compared to longitudinal incision during transobturator sling
procedures for stress urinary incontinence. BMC Surgery. 2015;15:84.
12. Atherton MJ, Stanton SL. A comparison of bladder neck movement and elevation after tension‐free vaginal
tape and colposuspension. BJOG 2000; 107: pp. 1366-1370.

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13. Ulmsten U, Hendriksson L, Johnson P, Varhos G. An ambulatory surgical procedure under local
anaesthesia for treatment of female urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 1996; 7:
pp. 81-86.
14. Westby M, Asmussen M, Ulmsten U. Location of maximum intraurethral pressure related to urogenital
diaphragm in the female subject as studied by simultaneous urethrocystometry and voiding
urethrocystography. Am J Obstet Gynecol. 1982; 144: pp. 408-412
15. Jiang YH, Wang CC, Chuang FC, Ke QS, Kuo HC. Positioning of a suburethral sling at the bladder neck is
associated with a higher recurrence rate of stress urinary incontinence. J Ultrasound Med. 2013 Feb; 32(2):
pp. 239-45.
16. Lo TS, Wang AC, Horng SG, Liang CC, Soong YK. Ultrasonographic and urodynamic evaluation after
tension free vaginal tape procedure (TVT). Acta Obstet Gynecol Scand 2001; 80: pp. 65-70.
17. Masata J, Martan A, Kasikova E, Halaska M, Voigt R, Drahoradova P. Ultrasound study of the effect of
TVT operation on the mobility of the whole urethra. Neurourol Urodyn 2002; 21: pp. 286-288.
18. Virtanen HS, Kiilholma P. Urogynecologic ultrasound is a useful aid in the assessment of female stress
urinary incontinence a prospective study with TVT procedure. Int Urogynecol J Pelvic Floor Dysfunct
2002; 13: pp. 218-223.
19. Sarlos D, Kuronen M, Schaer GN. How does tension‐free vaginal tape correct stress incontinence?
Investigation by perineal ultrasound. Int Urogynecol J Pelvic Floor Dysfunct 2003; 14: pp. 395-398.
20. Pizzoferrato AC, Fauconnier A, Bader G. Value of ultrasonographic measurement of bladder neck mobility
in the management of female stress urinary incontinence. Gynecol Obstet Fertil. 2011 Jan; 39(1): pp. 42-8.
21. Bakas P, Liapis A, Creatsas G. Q‐tip test and tension‐free vaginal tape in the management of female
patients with genuine stress incontinence. Gynecol Obstet Invest 2002; 53: 170–173.
22. Lukacz ES, Luber KM, Nager CW. The effects of the tension‐free vaginal tape on proximal urethra
position: a prospective, longitudinal evaluation. Int Urogynecol J Pelvic Floor Dysfunct 2003; 14: pp. 179-
184.
23. Viereck V, Nebel M, Bader W, Harms L, Lange R, Hilgers R, Emons G. Role of bladder neck mobility and
urethral closure pressure in predicting outcome of tension‐free vaginal tape (TVT) procedure. Ultrasound
Obstet Gynecol, 2006; 28: pp. 214-220.
24. Richter HE, Litman HJ, Lukacs ES, et al. Demographic and clinical predictors of treatment failure one year
after midurethral sling surgery. Urinary incontinence treatment network. Obstet Gynecol. 2011; 117: pp.
913-921.
25. Lo TS, Pue LB, Tan YL, Wu PY. Risk factors for failure of repeat midurethral sling surgery for recurrent
or persistent stress urinary incontinence. Int Urogynecol J. 2016; 27: pp. 923-931.
26. Pregazzi R, Sartore A, Bortoli P, Grimaldi E, Troiano L, Guaschino S. Perineal ultrasound evaluation of
urethral angle and bladder neck mobility in women with stress urinary incontinence. BJOG. 2002 Jul;
109(7): pp. 821-7.
27. Huang WC, Yang JM. Bladder neck funneling on ultrasound cystourethrography in primary stress urinary
incontinence: A sign associated with urethral hypermobility and intrinsic sphincter deficiency. Urology,
2003; 61. Pp. 936-41.
28. Masata J, Martan A, Svabik K, Drahoradova P, Pavlikova M. Ultrasound imaging of the lower urinary tract
after successful tension-free vaginal tape (TVT) procedure. Ultrasound Obstet Gynecol. 2006 Aug; 28(2):
pp. 221-8.
29. Harms L, Emons G, Bader W, Lange R, Hilgers R, Viereck V. Funneling before and after anti-incontinence
surgery a prognostic indicator? Part 2: tension-free vaginal tape. Int Urogynecol J Pelvic Floor Dysfunct.
2007 Mar; 18(3): pp. 289-94.
30. Kuo HC.Sonographic evaluation of anatomic results after the pubovaginal sling procedure for stress urinary
incontinence. J Ultrasound Med. 2001 Jul; 20(7): pp. 739-47.

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Ultrasound Assessment of Tape Position Following Suburethral


Sling Procedures

PIRTEA Laurențiu1, BALINT Oana2, SECOȘAN Cristina2, SAS Ioan1,


GRIGORAȘ Dorin1
1University of Medicine and Pharmacy “Victor Babeș” Timișoara (ROMANIA)
2County Emergency Clinical Hospital Timişoara (ROMANIA)
Email: [email protected]

Abstract

Suburethral slings are the most common primary surgical treatment for stress urinary
incontinence with high efficiency rates. Several techniques have been described with the most
used being the tension-free vaginal tape (TVT) or the transobturator tape (TOT). Post-
operatively outcomes of these procedures have been associated with different factors, tension of
the tape being the most recognized. In the last years, studies have suggested a possible role of the
position of the tape in relation with the urethral length. Given the echogenicity of the
polypropylene, ultrasound is considered the best imaging method in assessing anti-incontinence
surgery patients. However, due to the absence of a standardised evaluation, the importance of
sling location remains an unresolved issue, with conflicting results.

Introduction

Urinary incontinence is a frequent disorder, affecting up to 50% of women and it is associated


with an impressive impact on personal and social life. (1) Suburethral slings are the most
common primary surgical treatment for stress urinary incontinence (SUI) and reported efficiency
rates are over 90%, similar to those of colposuspension procedures. (2)
The principle behind this type of procedures, in accordance with the theories of De Lancey
and Petros is the reinforcement of the suburethral vaginal hammock by placement of a synthetic
non-absorbable polypropylene sling between the urethra and the anterior vaginal wall. (3, 4)
Depending on the anatomical path that the tape is taking, several techniques have been
described with the most used being the tension-free vaginal tape (TVT) or the transobturator tape
(TOT). Given their role, the middle section of the urethra was considered the ideal placement of
the slings, and several studies have confirmed. (5, 6) Besides, tape tension, universally
recognized as a factor with great influence over the anti-incontinence surgery outcomes, in the
last years, increasing evidence suggest that the position of the tape is one of the most important
factors determining their outcome.
Polypropylene slings are highly echogenic and can be easily identified using ultrasound.
Different ultrasound examination techniques are available for the assessment of lower urinary
tract disorders. Among them, the introital and translabial methods have gained the most interest
for the postoperative evaluation of anti-incontinence surgery patients. (7)

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However, due to the variable ultrasound techniques and parameters used in different studies,
several authors have reported contradicting results, transforming the role of tape position into a
debatable matter.

Role of tape position

According to Petros, the ideal placement of an anti-incontinence tape should be between the
point of maximum urethral closure at rest and the urethral knee, the so called high-pressure zone,
represented by the middle third of the urethra or more precisely between the 53 and 72% of the
urethral length. (4, 8) Positioning of the sling in other portions of the urethra has been associated
by several studies with persistence or recurrence of SUI. (9, 10)
Many attempts of improving the techniques of suburethral slings have been reported.
Kociszewski et al., proposed the one-third rule for the TVT placement describing the starting
point of the incision as the 1/3 of the distance of the distal end of the vaginal incision from the
external urethral orifice, with the extension of the incision 1 cm laterally in either sides. Using
this rule, he achieved tape positioning in the middle third of the urethra in 88.2% of patients. (11)
In the same manner, but for the TOT procedure, Viereck et al., proposed the rule of ½ of the
urethral length as the starting point of the incision. He obtain a correct placement of the tape in
98.4% of cases. (12) Also, a correct placement was obtained by paraurethral tape fixation
(95.12% versus 88.73% without fixation) or with the use of a transversal incision (88.23%). (13,
14)

TVT

Tension-free vaginal tape is one of the most popular anti-incontinence procedures. Its
placement comes as a substitute for the pubourethral ligament in supporting the suburethral
vagina. However, the exact mechanism of its anti-incontinence effect is not clearly defined.
Several studies have investigated the ultrasound characteristics of TVT placement in relation
with surgery outcomes. In one of the firsts reports, Dietz et al., observed a marked variation in
tape placement position ranging from 30 mm above to 12.7 mm below his chosen reference point
(symphysis pubis) with no consistent correlation with post-operative outcomes. (15) In the same
year Lo et al., performs TVT in 70 women. In 85.7% of cases the tape was placed in the mid-
urethral. In the remaining cases the tape was “misplaced” at the proximal urethra, yet continence
was achieved. Also, he observed that no shrinkage or significant descend (1.7 mm in a 3-years
follow-up) of the tape occurred. (16) In contradiction with those findings Kociszewski et al.,
demonstrated that the best surgery outcomes were obtained in patients with tape placement
between 40-70% of urethral length and a tape-urethral distance of 2-5 mm. A tape positioned
outside this area decreased significantly the likelihood of being cured. Moreover, he pointed out
the importance of tensioned tapes, observing the best outcomes in patient that had a stretched
position at rest and c-shape during straining. Persistence of c-shape during rest was associated
with a high rate of complication. He also, offers a possible explanation for his results as opposed
to previous studies suggesting the importance of using the urethra as a reference point and taking
into account the urethral length in placing the tape. (5)
A few mechanisms of anti-incontinence for the “misplaced” tapes can be presumed as a
conclusion of those studies. Higher tapes can achieve continence by urethral compression against
the symphysis and lower tapes by urethral kinking.

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TOT

Transobturator approach shows similar efficacy rates as TVT but with lower intraoperative
complication rates. Two techniques have been described, outside-to-in by Delorme and inside-to-
out by De Leval.
Because of the larger dissection plane needed for tape placement, TOT tape is, in theory at
least, more prone to slippage. Foulot et al., followed this theory and observed that post-
operatively in 95% of cases at least a portion of the tape (in this case Montarc tape, 11 mm wide)
was placed at the mid-urethra. Moreover, in six of eight unsatisfied patients, the tape position
was correct. (17) No significant role of TOT position is also reported by Chantarasorn et al.,
Instead, he confirms the role of the distance between symphysis pubis and sling, showing a
significant association between a wider distance (gap) and persistent or worsened urinary
incontinence following TOT. In the same time, a tighter gap was associated with symptoms of
voiding dysfunctions. (18)
Similar with the studies related to TVT, several authors report contradictory results about the
value of tape position and surgical outcomes. Yang et al., uses 4D ultrasound to assess the tape
position in relation with a successful TOT procedure. He evaluates 56 women analysing the tape
to symphysis distance (sTSD), tape-symphysis angle (sTSA) and tape position related to urethral
length expressed as tape percentile. His results showed a lower tape percentile in women who
reported SUI post-operatively, a shorter sTSD and a larger sTSA in women with post-operatively
overactive bladder symptoms and a larger sTSD and a lower sTSA in women with post-
operatively voiding dysfunctions. (6) In agreement with previous study, Bogusiewicz et al.,
analysed 141 patients with SUI treated by TOT and observed a strong association between tape
position and outcome of surgery. Placement of the tape proximally to the 40th percentile of the
urethral length was associated with a failure rate of 60% whereas a distally placement resulted in
a substantially higher cure rate. An interesting finding of this study was that the lowest failure
rate was observed with a tape placement at >70th percentile of the urethral length. (19)

Conclusions

The predictive role of tape position for the surgical outcomes is still a matter of scientific
debate. The related literature divides in two groups, authors suggesting that tape position has a
major influence on surgical outcome and authors that report that tape position has no significant
role. The difference can be at least partially explained by the lack of a standardised assessment,
with different ultrasound techniques and most important with different parameters and reference
points. At the same time, achieving continence following suburethral sling procedures seem to
have several underlying mechanisms.

REFERENCES

1. Norton P, Brubaker L. Urinary incontinence in women. Lancet. 2006 Jan;367(9504):57-67.


2. Practice Bulletin No. 155: Urinary Incontinence in Women. Obstet Gynecol. 2015;126(5).
3. DeLancey JOL. Structural support of the urethra as it relates to stress urinary incontinence: The hammock
hypothesis. Am J Obstet Gynecol. 1994 May;170(5):1713-23.
4. Petros PE, Ulmsten UI. An integral theory and its method for the diagnosis and management of female
urinary incontinence. Scand J Urol Nephrol Suppl. 1993;153:1-93.

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5. Kociszewski J, Rautenberg O, Perucchini D, Eberhard J, Geissbühler V, Hilgers R, et al. Tape


functionality: Sonographic tape characteristics and outcome after TVT incontinence surgery. Neurourol
Urodyn. 2008 Aug; 27(6):485-90.
6. Yang J-M, Yang S-H, Huang W-C, Tzeng C-R. Correlation of tape location and tension with surgical
outcome after transobturator suburethral tape procedures. Ultrasound Obstet Gynecol. 2012 Apr;39(4):458–
65.
7. Tunn R, Petri E. Introital and transvaginal ultrasound as the main tool in the assessment of urogenital and
pelvic floor dysfunction: an imaging panel and practical approach. Ultrasound Obstet Gynecol. 2003 Aug;
22(2):205-13.
8. Westby M, Asmussen M, Ulmsten U. Location of maximum intraurethral pressure related to urogenital
diaphragm in the female subject as studied by simultaneous urethrocystometry and voiding
urethrocystography. Am J Obstet Gynecol. 1982 Oct; 144(4):408-12.
9. Jiang Y-H, Wang C-C, Chuang F-C, Ke Q-S, Kuo H-C. Positioning of a Suburethral Sling at the Bladder
Neck Is Associated With a Higher Recurrence Rate of Stress Urinary Incontinence. J Ultrasound Med.
2013 Feb; 32(2):239-45.
10. Bogusiewicz M, Monist M, Stankiewicz A, Wozniak M, Wieczorek AP, Rechberger T. Most of the patients
with suburethral sling failure have tapes located outside the high-pressure zone of the urethra. Ginekol Pol.
2013 May; 84(5):334-8.
11. Kociszewski J, Rautenberg O, Kuszka A, Eberhard J, Hilgers R, Viereck V. Can we place tension-free
vaginal tape where it should be? The one-third rule. Ultrasound Obstet Gynecol. 2012 Feb; 39(2): 210-4.
12. Viereck V, Kuszka A, Rautenberg O, Wlaźlak E, Surkont G, Hilgers R, et al. Do different vaginal tapes
need different suburethral incisions? The one-half rule. Neurourol Urodyn. 2015 Nov; 34(8): 741-6.
13. Rechberger T, Futyma K, Jankiewicz K, Adamiak A, Bogusiewicz M, Bartuzi A, et al. Tape Fixation: An
Important Surgical Step to Improve Success Rate of Anti-Incontinence Surgery. J Urol. 2011 Jul;
186(1):180-4.
14. Pirtea L, Sas I, Ilina R, Grigoraș D, Mazilu O. Transversal incision of the vagina favors the remaining of
the tape in the middle-third urethra compared to longitudinal incision during transobturator sling
procedures for stress urinary incontinence. BMC Surg. 2015;15(1):84.
15. Dietz HP, Mouritsen L, Ellis G, Wilson PD. How important is TVT location? Acta Obstet Gynecol Scand.
2004 Oct; 83(10): 904-8.
16. Lo T-S, Horng S-G, Liang C-C, Lee S-J, Soong Y-K. Ultrasound assessment of mid-urethra tape at three-
year follow-up after tension-free vaginal tape procedure. Urology. 2004 Apr; 63(4):671-5.
17. Foulot H, Uzan I, Chopin N, Borghese B, Chapron C. Monarc transobturator sling system for the treatment
of female urinary stress incontinence: results of a post-operative transvaginal ultrasonography. Int
Urogynecol J. 2007 Jun 27; 18(8): 857-61.
18. Chantarasorn V, Shek KL, Dietz HP. Sonographic appearance of transobturator slings: implications for
function and dysfunction. Int Urogynecol J. 2011 Apr 22; 22(4): 493-8.
19. Bogusiewicz M, Monist M, Gałczyński K, Woźniak M, Wieczorek AP, Rechberger T. Both the middle and
distal sections of the urethra may be regarded as optimal targets for ‘outside-in’ transobturator tape
placement. World J Urol. 2014 Dec 17;32(6):1605-11.

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Unusual Outcome of Twin Pregnancies after IVF

PLES Liana1,2, SIMA Romina-Marina1,2, RAHIMIAN Hadi3,


VYTOULKAS Andreas4, STANESCU Anca Daniela1,2
1 “St. John” Hospital, “Bucur”, Maternity, Bucharest, (ROMANIA)
2 UMF “Carol Davila”, Bucharest, (ROMANIA)
3 Regina Maria Hospital Bucharest (ROMANIA)
4 Genesys Medsana Bucharest (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected]

Abstract

In humans incidence of multiple or twin pregnancies is rare in (1.5% twin of all births). MCT
pregnancies account for 30% twins and the literature is controversial concerning the increased
incidence of MCT following IVF some studies reporting a higher incidence especially when the
embryo is cultured till blastocyst stage. Multiple pregnancies and especially MCT are more
prone to complication (premature birth, miscarriage, IUGR, preeclampsia) and then singleton
and raise many issues concerning counseling and management.
Case series we present a series of 5 cases of IVF multiple pregnancies with unusual outcome.

Conclusions
The reported cases underline the importance and also the challenges that ultrasound
examination encounters in IVF following multiple pregnancies and the delicate issues raised by
counseling for anomalies in such cases.
Keywords: twin, IVF, unusual outcome

Introduction

In humans incidence of multiple or twin pregnancies is rare in (1.5% twin of all births). MCT
pregnancies account for 30% twins and the literature is controversial concerning the increased
incidence of MCT following IVF some studies reporting a higher incidence especially when the
embryo is cultured till blastocyst stage. Multiple pregnancies and especially MCT are more
prone to complication (premature birth, miscarriage, IUGR, preeclampsia) and then singleton
and raise many issues concerning counseling and management. Whenever the MCT are the result
of the ART counseling is even more sensitive considering the efforts made for obtaining the
pregnancy.
We report a series of 5 twin pregnancies after ART (IVF and ICSI) that had unusual outcome
and were a challenge for management and counseling.
Case 1: 34 years old primipara after 4 unsuccessful IVF presented with twin pregnancy (2
embryos transferred) at 12 weeks for first trimester anomaly scan. One fetus had increased NT
and no nasal bone. CVS was proposed but the couple was reluctant finally accepted genetic
diagnosis at 16 weeks. Amniocentesis was done and the caryotype of the affected fetus was T21.

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Selective feticide was performed at 18 weeks. At 25 weeks the patient was admitted in the
hospital for uterine contractility with amniotic fluid loss. Conservative treatment permitted
pregnancy evolution until 36 weeks when she delivered by CS a healthy 3100 female fetus.
Case 2: 42 years old primipara with a history of 12 years of infertility had a successful IFV
with 2 embryos transferred. At 12 weeks the ultrasound scan evidenced an MCT pregnancy that
was closely followed. At 22 weeks the umbilical cord displayed already signs of cord
entanglement. Selective feticide was proposed and denied. The patients returned at 30 weeks
when ultrasound identified a demised fetus and no signs of fetal damage at the remaining one.
Pregnancy’s evolution was close followed and was uneventful until 37 weeks when she
delivered by CS a healthy 2800g male fetus.
Case 3: 28 years secundipara known with mullerian anomaly (double uterus, double cervix
and a CS scar on the right uterus) had a IVF with 2 embryos implanted in each uterus. At the first
trimester anomaly scan the embryo in the right uterus had no cardiac activity and the left uterus
was inhabited by 2 embryos with discordance in length and liquid. At 16 weeks the MCT
pregnancy in the left uterus displayed signs suggestive for stage 1 TTS and was referred to a
specialist who recomended selective feticide considering the high risk of abortion or very
premature birth. The patient declined, laser coagulation of the anastomosis was performed and
the evolution was closely monitorised. She had several hospitalisation for uterine contraction and
abdominal pains. The pregnancy continued until the date of communication (31 weeks).

Fig. 1. Cord entanglement Fig. 2. Triple pregnancy – on trisomic fetus

Case 4: 30 years old primigravida with triple pregnancy after 2 implanted embryos was
referred for second opinion at 20 weeks considering the abnormal appearance of one fetus. The
scan showed that one fetus had encephalocel, cheiloschizis and holoprosencephaly. CAryotype
was performed and revealed T13.Selective feticide was performed at 22 weeks and the
pregnancy was carried on until 32 weeks when after PROM the patient delivered 2 female
fetuses of 1400 and respectively 1650g whom were discarded after 3 weeks of intensive care and
are doing well.
Case 5: 29 years old primigravida with tubal infertility presented with a triple pregnancy after
2 implanted embryos at 12 weeks. The ultrasound scan displayed a MCT pregnancy with one
dead fetus. The other implanted embryo was hydropic and also dead. The patient undergone
amniocentesis for the remained fetus with normal caryotype. The anomaly scan showed a normal
fetus and at 38 weeks the patient delivered a healthy 3200 baby.

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Fig. 3. Duble uterus –empty right cavity Fig. 4. Hydropic fetus in triple pregnancy

Twin pregnancy after normal conception is following the Hellin Law with an incidence of
1/89 a rate of 33% monozygotic twins (MZT) and 66% of dizygotic twins (DZT). Depending on
the time of embyo spliting the type of twin pregnancy can be: before 4 days -dichorionic,
diamniotic (DCDA) in 33%, between 4-9 days – monochorionic diamniotic (MCDA) 65% and
after 9 days in 2% – monochorionic monoamniotic (MCMA). In very rare situation of conjoint
twins the embryo splitted beyond the 12th day. In the situation of assisted reproduction (ART)
the studies are showing an increase of MZT of considerable amount of 2-12 times in SUA,
France and Netherland. [1, 2] It seems that there is no correlation between ovarian
hyperstimulation and the incidence of multiple pregnancies after ART. [3]
The mechanisms that are responsible for embryo division are not fully understood. The
frequency of division is almost constant – 3, 5 – 4/1000 pregnancies and is increased by ART
(from 2:1 to 3, 5:1 MC/DC). Micromanipulation techniques (ICSI, AH, PGD) can be related to
the increased rate of MST after ART. All those techniques manipulate the zona pellucida and
leave different size of defects in it. That could cause inner cell mass splitting and MZ twins. [4]
The main hypothesis involved in embryo division are: cellular “repulsion”, co-dominant
embryonic axes, low embryonic calcium level, blastomeric herniation. [5]
A recent metaanalysis identified the following risk factors associated with MZT after IVF:
young patients (<35 years) for the frozen cycles transfer and blastocyst transfer for fresh cycles.
[5] Manipulation techniques that damage the zona pellucida are controversial toward the
possibility of MZT. [6]
The main issues that a complicated twin pregnancy raises independent of the conception way
are;
A. To determine correctly the chorionicity. First trimester ultrasound scan is the
cornerstone of the chroonicity determination. In case of ART/IVF the number of the transffered
embryos do not coresponde always to the number of fetuses (some can vanish, others can split).
Moreover careful mapping of the fetuses and placentas is of tremendous importance since
invazive procedures or even selective feticide can be required and confusion can have desastrous
consequences. [7]
B. What are the risks of the pregnancy?
The incidence of complication although similar between DZT and DC MZT is considerable
higher for MCT and even bigger with MCMA twins. The main responsible risk factor are the
vascular anastomosis between the two placentas that can produce roughly speaking many types
of discordances: vascular and circulatory discordance resulting in twin-twin transfusion
syndrome (TTTS), selective growth discordance of the twins, Twin Reversead, Twin anaemia-

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polycythaemia sequence (TAPS -meaning antenatal or postnatal diagnosis of significant


haemoglobindifference between monochorionic twins, Twin reversed arterial perfusion sequence
(TRAP sequence is a monochorionic twin pregnancy where one twin, the‘pump’ twin, is
perfusing its co-twin, which has no cardiac activity and often is associated with major and lethal
fetal anomalies.
Monochorionic monoamniotic twin are a greater risk of complication and even death due to
cord entanglement [8].
Other risks that affects twins are 9 times more premature births (under 37 weeks of gestation),
7 times more exposed to neonatal mortality and higher risk of malformation especially is the
result of ART. [8]
Discordant structural anomalies can be observed among twins and especialy among MCT
with an incidence of 6.33% vs 3.43%. [9]
The risk of intrauterine death of a twin for the remaining one is different for DC and MC twin.
In case of DC there are no vascular anastomosis between circulation and the risk of
intrauterine death of the cotwin is 4% (IC 95%, 2%-7%), the risk of neurological damage of up
to 1% (IC 95%, 0%-7%) and the risk of preterm delivery of up to 57% (IC 95%, 34%-77%).
In case of MC the risks are higher mortality 10% to 26%(IC95%, 7%-18%) and of
neurological damage of 26% to 51% (IC 95% 11%-26%). [9]
C. How to counsel and manage in case of a severe anomaly of one fetus
Whenever there is a severe structural anomaly or chromosomal anomaly of one twin
counseling issues are extremely sensitive. The factors that should be taken into account are
related to chorionicity, risks/benefits ratio, social impact, ART pregnancy. [7]
Selective feticide or intrauterine therapy can be discussed with the couple and the impact that
the procedure can have on the cotwin is in the most cases determinant for the decision.
In terms of selective feticide chorionicity and gestational age are the main factors that can
influence the outcome.In that respect it is essential that at the time of procedure the pregnancy
mapping was carefully performed related to the position of the placenta, fetuses and is ideally to
be performed by the same operator who will perform the selective feticide. [9]
Chorionicity is determinant for the selective feticide: intra-cardiac injection of KCl or
lidocaine in DC pregnancies and umbilical cord occlusion in MC pregnancies. KCL intarcardiac
injection for MCT can lead to embolisation of the healthy fetus. Persistance of anastomosis can
determine cerebral haemorrhage in the remaining fetus with serious neurological injury. In the
case of MCT cord occlusion can be performed by radiofrequency ablation, bipolar cord
coagulation, laser cord coagulation or cord ligation. [10]
Fetal demise of the remaining twin remains a significant risk. In an extended study on 345 of
twin pregnancies that undergone selective feticide the outcome for the remaining fetus was
stratified according to the indication and method used. [11] They found that:
- the most frequent complication was premature rupture of membranes in 4 weeks time
after procedure in 22% or later but at lesser rate.
- fetal demise in 15% of cases within the 2 weeks after procedure (79%) than thereafter
(21%; P=004; odds ratio [OR], 6.12; 95% confidence interval [CI], 1.81-20.70)
without difference concerning the indication.
- improved rate of survival was after radiofrequency ablation (86%), 82% after cord
laser coagulation, 72% after laser coagulation and 70% after cord ligation.
Depending on the gestational age the feticide is reccomanded as early (11-15 weeks) in DC
pregnancies and delayed after 18 weeks in MC pregnancies.

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In the third Trimester the counseling should balance between the risk of miscarriage following
selective feticide and the risk of preterm delivery before selective feticide.
D. The time and mode of delivery. The answer depends again on the chorionicity and
pregnancy complication.
In case of the DA/DC twins and single fetus after selective feticide the pregnancy should
continue as close to term as it’s possible. delivery mode can be vaginally unless there are others
contraindications.
For the uncomplicated MC/DA pregnancies the guidelines recommend antenatal steroids and
elective delivery at 36 weeks by vaginal birth if there are no other specific clinic indications for
cesarean section. In case of MC/MA twins considering the risk of fetal death CS is imposed at
32-34 weeks. [10]

Conclusions

Twin pregnancies after ART raise peculiar problems in management and counseling. The
main determinants that must be considered are chorionicity, presence of major anomaly of the
fetuses, age of gestation at diagnosis. Fetal therapy is not always available and beneficial. In case
of selective feticide for MCT KCL infusion and intervals under 18 weeks and 24-30 weeks must
be avoided. Time and delivery mode are influenced also by the chorionicity and pregnancy
complication.

REFERENCES

1. Aston KI, Peterson CM, Carrell DT (2008) Monozygotic twinning associated with assisted reproductive
technologies: a review. Reproduction. Oct; 136(4), pp 377-86.
2. Hoekstra C, Willemsen G, van Beijsterveldt TC, Montgomery GW, Boomsma DI(). Familial twinning and
fertility in Dutch mothers of twins. Am J Med Genet A. 146A, pp 3147-3156.
3. Pacu I, Ionescu CA, Vladareanu S, Banacu M, Neacsu A, Calin A M. Predictive Value of the AMH Level
and Serum Estradiol for Ovarian Hyperstimulation Syndrome in the Assisted Human Reproduction
http://www.revistadechimie.ro.
4. Sobek A, Prochazka M, Klaskova E, Lubusky M, Pilka R. (2016). High incidence of monozygotic twinning
in infertility treatment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 160(3): 358±62.https
5. 5 Bing Song, Zhao-Lian Wei, Xiao-Feng Xu, Xue Wang, Xiao-Jin He, Huan Wu, Ping Zhou, Yun-Xia Cao
(2017). Prevalence and risk factors of monochorionic diamniotic twinning after assisted reproduction: A
six-year experience base on a large cohort of pregnanciesPLOS One November 6.
6. Yi-Fan Gu, Qin-Wei Zhou, Shuo-Ping Zhang, Chang-Fu Lu, Fei Gong, YueQiu Tan, Guang-Xiu Lu, Ge
Lin (2018).Inner cell mass incarceration in 8-shaped blastocysts does not increase monozygotic twinning in
preimplantation genetic diagnosis and screening patients PLoS One. 2018; 13(1): e0190776.Published
online 2018 Jan 9. doi:10.1371/journal.pone.0190776.
7. National Institute for Health and Clinical Excellence. Multiple pregnancy. The management of twin and
triplet pregnancies in the antenatal period. NICE clinical guideline 129. Manchester: NICE; 2011.
8. M.L. Ognean, R. Chicea, R. Dumitra, O. Boantă, M. Codru (2017). IN VITRO FERTILIZATION –
NEONATAL OUTCOME, 2nd jENS, https://www.mcascientificevents.eu/jens-2017/
9. Lewi L, Jani J, Blickstein I, Huber A, Gucciardo L, Van Mieghem T, et al., (2008).The outcome of
monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study.
AmJ Obstet Gynecol;199:514.e1.
10. Kilby MD, Bricker L (2016). On behalf of the Royal College of Obstetricians and Gynaecologists.
Management of monochorionic twin pregnancy. BJOG 124: e1-e45.
11. Cristina Rossi, Vincenzo D’Addario (2008). Umbilical cord occlusion for selective feticide in complicated
monochorionic twins: a systematic review of literature DOI:https://doi.org/10.1016/j.ajog.2008.08.039

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Fetal Legal Statute in Romanian Law

PLES Liana1,2, SIMA Romina-Marina1,2, POENARU Mircea Octavian1,2,


OLARU Octavian-Gabriel1,2
1“St. John” Hospital, “Bucur”, Maternity, Bucharest, (ROMANIA)
2UMF “Carol Davila”, Bucharest, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

The fetal rights and legal status is a concept that raises lately many debates on national and
international level. In Romania, after the new provisions of the Penal Code concerning the fetus,
its legal status changed since the fetus can be now passive object of the criminal deeds that
provoke its death or damage.

Material and methods


We analyzed the main fetal statute according to the Civil and Penal Codes and we compared
the provisions with the legal norms in other legislations.

Discussion
The embryo and the fetus are not juridical persons according to our legislation. A fetus
becomes a person only after birth if he is viable and he can inherit according to the Civil Code.
Although the debate if the fetus is a “thing” or a “person” is not solved from the Penal points
a view, the law prohibits embryos from experiments and traffic and there are new provisions that
protect the fetal rights by punishing pregnancy interruption outside the legal frame, fetal damage
during pregnancy or at birth. Another issues concerning the embryo legal statute is raised by the
medical pregnancy interruption when there is a fetal anomaly or the fate of the embryos left
behind IVF.

Conclusion
Fetal rights in recent Romanian law are a new concept but further legal frame is required
because the progress of medical science and technology raise new problems.
Keywords: fetus, patient, law

Introduction

Fetus as a patient is a notion that needs to be integrated in our way of thinking and in our
laws. Nowadays in Romania we are in the condition when science and technology is ahead of
laws protocols and medical regulations. We diagnose, treat, and consider the fetus a patient
according to our individual beliefs and ethic concepts solving issues and overcoming conflicts
without other guidance than the common sense. As professionals we are not aware of the legal
statute of the fetus and this paper intends to highlight some legal aspects concerning the fetus.

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We can focus on four main directions concerning fetus statute: international and European
regulation, civil regulation, criminal regulation and specific norms (related to special situation as
ART) [1].
The Fetus and embryo legal statute and rights are still incertain no only in the Romanian Law
System. Steady devlopment in prenatal medicine and human assisted reproduction matched with
the expansion of fetal rights and raised lately many debates especially in the Anglo-American
countries [1].
There are many international documents that protect and speak about the right to life but they
also leave to the states that signs the Convention the liberty to define when the life starts, at the
conception moment, during intrauterine life or at birth. Art 4 of the American Convention of
Human Rights states that the right to life should be protect “usually starting with conception
moment” [2].
The Oviedo Convention on Human Rights and Biomedicine is eluding the definition of
“person” leaving the member States to define it [3].
European Convention on Human rights treats the matter in the same way as it provides the
right to life of each person, terms that are the core of the whole Convention but fails to define
what life and person means (Art. 2) [4]. There is no general accepted definition for the
“beginning of life” among different states jurisdiction and in juridic doctrine. In present CEDO
avoid to qualify the unborn child as a person according to art 2 of the Convention (CEDO) and
the logic consequence is that the fetus is not a “person” in the art 2 sense and it’s right to life
exists but in implicitly limited by the mother’s rights and interests [5, 6].
In that respect although the fetus and the embryo are not persons in the legal strict way the
Law does not deny their existence. Our time is framed by tremendous scientific and
technological aquisitions that aloud to prove fetal and embryo life, to explore and asses in many
aspects their evolution and health and even to intervene in many ways in producing life or
treating disease in the fetal period of life. In such circumstances the law fails to keep the same
pace with the science evolution but at least recognize and protects the life and some rights of the
fetus. That means that the fetus cannot be reduced to a “thing” and harming or losing the fetus
although not comparable to lose a life it cannot be reduced to lose or harm an “object”.
Also the Romanian Constitution in art 22 refers to the right to life but the juridical doctrine
has two ways to speak of life in a restraint physical way and in a more broad meaning as an
universe of phenomena, deeds, demands and whishes that complete and aloud the physical
existence [7]. The fetus is in that view integrated in the complex frame of the conception,
pregnancy and birth phenomena and its right to live derives from that undeniable reality.
In the respect of the constitutional provisions the fetus detains the right to health protection
that is part of the constitutional general protected values. The protection is insured through the
pregnancy protection: prenatal medical assistance, pregnant women measures of protection a
social and medical insurance protection. There are also some fundamental rights that the fetus
can access indirectly through its parents private life and family life protection but they are
limited by the mother’s autonomy and rights.
Romanian legislation mention the fetus and embryo in a couple of legal provisions but their
statute is unclear since they are not juridical persons but still have some rights implicitly
recognized and protected by law as: the right to be born, the right to be unharmed and healthy,
the right to receive treatment. The main provisions are penal and refer to abortion and fetal
aggressions. According to the Law the fetus cannot be but a person or a thing since the Law
recognize only those two categories. How is the Law defining the Fetus is also not clear but it we

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can guide according to the project of the Reproductive Health which says that “the fetus is an
organism in the intrauterine period of life following the embryonic period until birth”. Obviously
the Fetus and embryo are a form of life, a particular one that cannot stand by itself apart from the
mother until a certain stage of development or need. That makes the mother and the fetus a
unique juridical person with two uneven components.
The issues that can be raised:
- the fetus/embryo is a person or a thing;
- what are the fetus’s rights;
- how are the interest conflicts solved.
From the Legal point of view the fetus is not a person, he can become a person only at birth:
Romanian Civil Code defines the person in the civil right subject’s section as “art. 25 The
physical person is the individual human being as civil rights and obligation holder” [8].
Civil Code recognize the Fetus as a person only after birth following the Latin quote «Infans
conceptus pro nato habetur quoties de commodo ejus agitur» [8]. The legal text is comprised in
art 36 “The child rights are recognised since conception but only if he is born alive. Art 412
provisiona reffering at the legal time of conception are incident” [8]. This is ithe retroactive
personality of the fetus theory which implies that the fetus is a persona whenever it’s interest is
concerned but the right operates only retroactive after birth. For instance the fetus can inherit his
father who dies before his birth but only if he or she will be born alive.
It is obvious that the juridical personality of the fetus is acquired at birth which is recognized
by an administrative act – birth declaration and birth certificate. Even if the baby decease before
he is declared officially but was born alive he has the rights of a person. In that case two
certificates will be issued one of birth and one of demise.
When the child is born alive and viable all rights that were potential since conception become
effective. The maternal or paternal filiations can be established, the child can receive a donation,
inherit or benefit from a life insurance in his name. He becomes owner of all patrimonial rights
that were constituted in his name before birth. The parents are his curators and preserve his
rights. In this respect the mother cannot dispose his baby before pregnancy by a contract
according to the present regulation the contract would be null (against public order). The
surrogate mother is not aloud so far in our legislation and the future reproductive Law will have
to regulate this notion.
Even before birth, although the fetus is not a patient he benefits from some universal rights
protection: the right to life, the right to health, according to art 3 of the Human Rights Universal
Declaration: “Article 3 Everyone has the right to life, liberty and security of person. Article 5:
No one shall be subjected to torture or to cruel, inhuman or degrading treatment or punishment”
[1].
Other questions that can be raised and the legal frame but fails to clarify are: when and where
starts the life, who is deciding for the juridical binominal person and what are the rights and the
obligations of the fetal-maternal binom.
In that respect the Romanian Penal Code doesn’t recognize the same rights to life for the fetus
as for the born child who has full rights recognition. Even so the New Penal Code protects the
fetus by including new provisions that incriminate aggressions against the fetus. Also in the
penal doctrine there is no agreement between authors in terms of when the right to life starts:
when the birth begins or after delivery when the baby starts its extra uterine life, moment that in
medico-legal terms is equivalent with the first breath. [9].

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The Law doesn’t consider the fetus as a person in order to protect the right of the mother to
abortion but limits that right according to the Criminal Code:
The present Penal Code (adopted by Law nr. 286/2009) introduce a new incrimination in the
chapter titled “Aggressions against the fetus”. The provisions are inspired by the Spanish Code
and are similar to others provisions (Italian and Turkish Penal Codes). There are two new penal
deeds that are incriminated by the art 201 (pregnancy termination) and 202 (Fetal harm) [10].
Art 201 refers to illegal abortion and aims to protect the pregnant woman life, integrity and
health but also fetal life beyond 14 weeks and implicitly the right of the fetus to life and to be
born in good health and without anomalies. The legal provision lacks clarity and is prone to
much interpretation. One of the confusion is the fact that the termination of pregnancy can be
performed beyond 14 weeks until 24 and even later based on “therapeutically” reason both for
the mother and fetal benefit. Obviously in that case the mother’s interest prevails and there is no
fetal benefit to interrupt the pregnancy when the viability limit is not reached. It is a question of
maternal-fetal conflict and who can decide. The mother as a person with civil capacity has the
right to decide for both of them. She is allowed to choose abortion until 14 weeks but unlike
other possible active subjects is not punishable if she interrupts by herself the pregnancy. It
seems that the fetus’s rights are protected against everybody but not against his mother. If the
fetal life is terminated at a time when he could live by himself (24 weeks theoretically) the
mother can chose to interrupt the pregnancy on a therapeutically background so the fetal rights
protection limit is the mother’s interest. More explicit terms for therapeutically reason would
benefit for all involved parts and the French legal provisions although very concise are also
extremely helpful: medical pregnancy termination is permitted in case of serious danger for the
mother’s health or if there a fort probability that the fetus is attaint by a particularly severe
disease recognized as incurable at the diagnosis time [10].
In art 202 the Penal Code aims to extend the protection of the fetus it’s right to life and health
by incriminating any deed that could harm him. The legal text speaks of two periods of time:
during the birth process or during pregnancy. The law maker intention is obvious directed to
protect the fetus against any harm not only medical that could intervene (for instance fetal harm
following a car accident or mother’s physical assault that could lead to fetal damage or even
death). There are also two forms of guilty provided by intent or fault, the later being related more
to a medical intervention or omission [10, 11].
It is a novelty in the Romanian penal doctrine that the fetus is a passive subject of an
infraction directed against his integrity or his existence but recognizing the fetus as a detainer of
rights that must be protected is again limited by the mother’s rights since if the mother is the
active subject of the infraction she is not punish. Beyond the fact that the mother can harm the
baby directly or by accident (i.e. performing risky activities) she is in no way bound to care
about the baby. In fact the mother has no legal obligation to care (i.e. to avoid risks as smoking,
drug consuming, to undergone prenatal investigation or treatments in order to avoid fetal
damage) and she cannot be compelled to care about the unborn baby.
We could think that the Law is asymmetric or even unfair towards the fetus: it is punished the
fetal harming by everyone else but the mother. But the fetus is part of the mother-fetus binom
and its status is dependent on the mother’s decision to comply or no to recommendation for the
fetus benefit. The mother can smoke, take illicit drugs, not taking medicine for harmful
condition, refusing fetal therapy and even provoking pregnancy termination without being
punished or obliged to refrain.

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The issues of the conflictual situations in the mother fetus binom are mainly raised by the
pregnancy termination. This is legal according to the 201 art of Criminal Code (see above). The
mother is the only one who can decide for a voluntary TOP until 14 weeks of gestation without
any reason and after based on therapeutically ground. But also the mother has the right to refuse
TOP even in cases of severe fetal handicap. In this case the fetal fundamental rights to life health
and dignity are restraint by the mother autonomy [12].
There are also special situation when the fetal legal status should be clarified such as the
status of the embryos and fetuses obtained by human reproductive techniques. There is no clear
regulation about the preserved embryos and their fate. They are not persons but they are neither
object. If they can be donated the rules are those that governs donation of “Things” in the Civil
Law. What about the “abandoned embryos” that couples forgot about what to do with them?
They cannot be destroyed without the “owner’s” consent. Sometimes they even cannot be
kept any longer and could become a subject of trade. Since the embryo cannot be used for
research purpose in order to assure protection of its fundamental rights the future regulation are
due to define the frame of embryo creation in vitro as a “parental project” and nor in other
purposes.

Conclusions

As in many other Law systems the fetus statute is still unclear and subject to many debates on
legal and ethical ground.
The fetus is not a person according to the Law but he has rights that are protected by specific
norms.
As a part of fetus-mother binome the fetal rights are limited by the mother’s rights who have
the whole autonomy and can freely dispose of the pregnancy.

REFERENCES

1. A. Nanu, D. Bulgaru-Iliescu, T. Rotaru, L. Oprea (2015) The Gap between Bioethics Principlism and
Judicial Responsibility: How Social Sciences Can Help Romanian Law – Revista de cercetare si interventie
sociala, (49), pp 216-228.
2. American Convention on Human Rights Adopted at the Inter-American Specialized Conference on Human
Rights, San José, Costa Rica, 22 November 1969.
3. Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the
Application of Biology and Medicine: Convention on Human Rights and Biomedicine * Oviedo,
4.IV.1997.
4. Convention for the Protection of Human Rights and Fundamental Freedoms Rome, 4.XI.1950 European
Court of Human Rights Council of Europe.
5. CEDO, 8 iulie 2004, cauza Vo c. Franţa. Jean-François Renucci.
6. CEDO, 7 martie 2006, Evans c. Regatul Unit, nr. 6339/05, Jean-François Renucci, op. cit., pag 104.
7. Antonie Iorgovan, Elena Simina Tănăsescu. Constituţia României revizuită. Comentarii şi explicaţii, C.H.
Beck, 2004, Bucureşti, pag. 36.
8. Noul Cod Civil (Legea 287/2009), actualizat 2018, republicat în Monitorul Oficial nr. 505/2011.
9. Boroi A-Aspecte juridice în legătură cu momentul naşterii şi mom entul morţii, Revista Dreptul nr.
12/1998, pag 131-132.
10. CODUL PENAL din 17 iulie 2009 (LEGEA nr. 286) M.Of. nr. 510 din 24 iulie 2009.
11. Pițuru S, Vlădăreanu S, Păun S, Nanu A. Malpractice and professional liability of medical perssonel. Rev.
Farmacia, 2015, Vol. 63, 2 ISSN: 0014-8237.
12. Valerian Cioclei – Drept Penal. Parte special. Infracţiuni contra persoanei, C.H. Beck, 2009, Bucureşti, pag
176.

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Ultrasound Evaluation of Endometrum in Fibroids Treated with


Ulipristal Acetat

PLEȘ Liana1,2, SIMA Romina-Marina1,2, SGARBURĂ Zorela Adriana3,


BĂLĂLĂU Denisa-Oana1,2, CARP Delia1, RÎCU Anca1
1 “St. John” Hospital, “Bucur”, Maternity, Bucharest, (ROMANIA)
2 UMF “Carol Davila”, Bucharest, (ROMANIA)
3 “Egometax”, Clinic, Bucharest, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected], [email protected]

Abstract

Introduction
Uterine fibroids are the most commune genital benign tumour in reproductive age women that
can produce abnormal uterine bleeding and affect fertility. Conservative treatment for uterine
fibroids is a must whenever the main objective is fertility preservation and menstrual bleeding
control. Selective Progesteron Receptors Modulators (SPRM) are a class of drugs that includes
mifepristone, asoprisnil ulipristal acetate (UPA) and the new vilaprisan who exhibits both
agonist and antagonist effects on uterine progesteron receptors and can be used as conservative
treatment of uterine fibroids.

Material and methods


We performed an observational study on women with symptomatic uterine fibroids. The main
symptoms were represented by abnormal uterine bleeding. The patients received UPA in doses
of 5 mg po daily starting with the first or second menstrual day for 12-13 weeks. At the
beginning of the study the patients undergone a clinical check, blood count and endometrial
biopsy. Endometrial thickness and fibroids dimensions were recorded before and after treatment.

Results
51 women were enrolled in the study included, but we registered 7 drops off. Mean age was
42.5 years (ranges 54 and 32 years) for the 44 patients included in the study. 35 patients had one
fibroid with diameters between 2cm and 8 cm and 9 patients had multiple fibroids. We observed
that mean fibroid dimensions was 5.6 cm for cases with multiple fibroids. At admission the mean
endometrial thickness evaluated by ultrasound was 12.6 mm. It was correlated with uterine
fibroids dimensions and patients body mass index. All patients underwent uterine curretage with
endometrial biopsy, followed by treatment with UPA 5 mg daily for 3 months. All patients had
improvement of metrorrhagia. After treatment the patients were evaluated by ultrasound and it
was observed that mean diameters of fibroids was about 4.8 cm and the endometrial thickness
decreased to 11.8 mm. We had one case with intracavitary fibroid that descended through the
cervix after UPA treatment and needed vaginal myomectomy.

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Conclusions
In our study the endometrial thickness decreased after UPA treatment, being correlated with
fibroid dimension reduction. It was discordant with literature review and our expectations of
increased endometrial thickness.
Keywords: UPA, fibroids, endometrium, ultrasound

Introduction

Uterine fibroids are the most common benign tumors in women and frequently the cause of
chronic pelvic pain, pelvic pressure, excessive uterine bleeding, dyspareunia [1]. Conservative
treatment for uterine fibroids is a must whenever the main objective is fertility preservation and
menstrual bleeding control. Selective Progesteron Receptors Modulators (SPRM) are a class of
drugs that includes mifepristone, asoprisnil ulipristal acetate (UPA) and the new vilaprisan who
exhibits both agonist and antagonist effects on uterine progesteron receptors and can be used as
conservative treatment of uterine fibroids [2]. Ultrasound is the gold standard technique to
evaluate fibroids and endometrium. The aim of our study was to evaluate the endometrium
thickness before and after UPA treatment for fibroids.

Material and methods

We performed an observational study on women with symptomatic uterine fibroids. The main
symptoms were represented by abnormal uterine bleeding. The patients received UPA in doses
of 5 mg po daily starting with the first or second menstrual day for 12-13 weeks. At the
beginning of the study the patients undergone a clinical check, blood count and endometrial
biopsy. Endometrial thickness and fibroids dimensions were recorded before and after treatment.

Results

51 women were enrolled in the study included, but we registered 7 drops off. Mean age was
42.5 years (ranges 54 and 32 years) for the 44 patients included in the study. 35 patients had one
fibroid with diameters between 2cm and 8cm and 9 patients had multiple fibroids. We observed
that mean fibroid dimensions was 5.6cm for cases with multiple fibroids.
At admission the mean endometrial thickness evaluated by ultrasound was 12.6 mm. It was
correlated with uterine fibroids dimensions and patients body mass index. All patients underwent
uterine curretage with endometrial biopsy, followed by treatment with UPA 5 mg daily for 3
months. All patients had improvement of metrorrhagia. We had no case of malignant cases in
pathological results.

Fig 1. and 2. Ultrasound evaluation of the endometrium after UPA treatment

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After treatment the patients were evaluated by ultrasound (Fig. 1 and 2) and it was observed
that mean diameters of fibroids was about 4.8 cm and the mean endometrial thickness was to
11.8 mm. (Fig. 3) The peculiarity of the study group is that we had a patient with intracavitary
fibroid. The initial ultrasound evaluation revealed that it had a diameter of 6 cm. The patient
received UPA for three months and the fibroid descended through the cervix. The curative
surgical intervention was vaginal myomectomy.

Fig. 3. Endometrial thickness related to UPA treatment

Discussions

Progesterone is a regulator of female reproduction and it has an important role in endometrial


differentiation by decreasing its levels during a non-pregnant cycle with accelerated endometrial
shedding during menstruation [3]. Progesterone responses are mediated through a ligand-
activated transcription factor. It has been demonstrated that within endometrium there are present
two main isoforms of the receptor (PR-A and PR-B) [4]. Due to their expression and their great
number within endometrial tissue, the uterine function is kept within normal range.
Activation of P-responsive genes is connected with reduced apoptosis and increased
proliferation of fibroid cells. The effect of SPRMs is tissue-dependent and varies depending on
bioavailabilty of different PR isoforms and concentrations of different co-repressor and co-
activator proteins in different cell types [5].
Synthetic progestins are currently used as medical therapy in heavy menstrual bleeding,
though, they often fail to diminish symptoms or they are associated with unacceptable side
effects. Gonadal hormones are responsible for fibroid growth, therefore, SPRM have been
evaluated as therapeutic agents [6, 7]. Administration of the SPRMs, such as, Mifepristone and
Asoprisnil reduce fibroid volume and menstrual blood loss. Currently, Ulipristal Acetate (UPA)
is the only member of SPRM licensed in Europe for short-term treatment of fibroids prior to
hysterectomy and intermittent treatment of moderate to severe symptoms of leyomatata. Clinical
studies showed that repeated doses of UPA decreased the median fibroid volume by 45% and
almost 90% of patients reported a significant reduction in menstrual bleeding [8]. CDB-2914, is
a relatively pure progesterone antagonist, binding only PR. Although it’s structure is similar to
Mifepristone, UPA has less antiglucocorticoid activity, allowing long-term use [9, 10].
Treatment with PRMs causes changes in endometrium, described under the name of PRM
Associated Endometrial Changes (PAEC). According to Williams et al., the key features

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distinguishing PAEC from proliferative endometrium or hyperplasia are: low mitotic activity,
abortive subnuclear vacuoles, apoptosis and absence of stromal breakdown and glandular
crowding. The histological appearance of PAEC reveals inactive and proliferating epithelium,
asymmetry of stromal and epithelial growth with prominent cystically dilated glands. This kind
of pattern has been observed in almost 60% of patients treated with UPA for 3 months. These
changes disappear after treatment is stopped and menstruation occurs and they should not be
confused with unopposed estrogen effect or endometrial hyperplasia [11].
There were two phase III clinical trials that determined the efficacy and safety of UPA in the
treatment of uterine fibroids. The architecture of the glands varied within the endometrium of
individuals with many subjects showing scattered cystic glands intermixed with small tubular to
more dilated, tortuous or irregular folded glands and a few subjects showing mostly diffusely
cystic glands (and rarely a cystic gland is present with a circumferential cellular stromal collar
invariably lined by secretory or ciliated metaplastic epithelium). Gland crowding was limited to
microscopic foci, typically in areas of variable gland architecture. Glandular epithelium appears
inactive with low cuboidal, non-stratified epithelial cells showing infrequent mitoses. Ciliated
metaplasia can be sometimes observed, particularly affecting the epithelium lining of cystic
dilated glands. Abnormal vasculature was commonly seen, usually taking the form of aggregates
of arteriolar vessels with thickened walls containing smooth muscle cells; “chicken wire
capillaries” and ectatic thin-walled vessels were occasionally present [12]. The majority of
studies have evaluated the fibroids dimensions and endometrial pathological changes.
There were few studies concerned on ultrasound evaluation of the endometrium and it’s
thickness [13]. In our study it was observed that endometrial thickness decreased after UPA
treatment. It is extremely important to evaluate the impact of different substances on cell
differentiation because it is benefic to prevent cancer than to treat it [14]. There are substances
such as polyphenols that recently have proven their impact on cancer prevention [15]. The UPA
effects should be very well evaluated clinically, imagistic and by pathological exam because if
the good results are superior to side effect SPRM treatment should be used safety for
preoperative preparation of fibroids.

Conclusions

In our study the endometrial thickness decreased after UPA treatment, being correlated with
fibroid dimension reduction. It was discordant with literature review and our expectations of
increased endometrial thickness.

REFERENCES

1. Cramer SF, Patel A. The frequency of uterine leiomyomas (1990). Am J Clin Pathol. 94,pp. 435-438.
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2. Elger W, Bartley J, Schneider B, Kaufmann G, Schubert G and Chwalisz K (2000) Endocrine
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3. Chegini N, Ma C, Tang XM, Williams RS (2002). Effects of GnRH analogues, ‘add-back’ steroid therapy,
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growth factor-beta expression. Mol Hum Reprod. 8, pp. 1071-1078.
4. Chabbert-Buffet N, Meduri G, Bouchard Ph, Spitz I M (2005). Selective progesterone receptor modulators
andprogesterone antagonists: mechanisms of action and clinical applications Human Reproduction Update,
11(3), pp. 293-307.

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5. Donnez, J, Tatarchuk, T.F., Bouchard, P, Puscasiu, L, Zakharenko, N.F, Ivanova, T et al., (2012). Ulipristal
acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 366, pp. 409-420.
6. Tang XM, Williams RS (2002). Mol Hum Reprod. Effects of GnRH analogues, ‘add-back’ steroid therapy,
antiestrogen and antiprogestins on leiomyoma and myometrial smooth muscle cell growth and transforming
growth factor-beta expression. Dec; 8(12), pp. 1071-8.
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10. Passaro MD, Piquion J, Mullen N, Sutherland D, Zhai S, Figg WD, et al., (2003). Luteal phase dose-
response relationships of the antiprogestin CDB-2914 in normally cycling women. Hum Reprod. 18, pp.
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11. Williams AR, Critchley HO, Osei J, Ingamells S, Cameron IT, Han C, Chwalisz K. (2007).The effects of
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12. J. Simon, W. H. Catherino, J. Segars, R. Blakesley, A. Chan, V. Sniukiene, A. Al-Hendy. (2016). First us-
based phase 3 study of ulipristal acetate (upa) for symptomatic uterine fibroids (uf): results of venus-i.
Fertility and Sterility sept, Issue 3, Supplement, pp. e376.
13. Fauser BC,Donnez J, Bouchard P, Barlow DH, Vázquez F, Arriagada P, Skouby SO, Palacios S,
Tomaszewski J, Lemieszczuk B, William AR (2017). Safety after extended repeated use of ulipristal
acetate for uterine fibroids. PLoS One. Mar 7; 12(3):e0173523.
14. Petca A, Vladareanu S, Radu DC, Bot M, Berceanu C, Mastalier Manolescu SM, Medar C, Petca RC.
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polyphenols in the prevention and treatment of cervical cancer-an overview. Molecules. Aug 17; 21(8).
pii: E1055.

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Prognosis of Non Syndromic Fetal Diaphragmatic Hernia

POENARU Mircea Octavian1,2, BRAICU Flavia1, VALCEA Ionut1,


STERIE Ionut Emil1, STANESCU Anca Daniela1,2
1 “St. John” Hospital, “Bucur”, Maternity, Bucharest, (ROMANIA)
2 UMF “Carol Davila”, Bucharest, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

Introduction
The incidence of congenital diaphragmatic hernia (CDH) is approximately one in 2000-4000
newborns and represents 8% of all major congenital anomalies.

Material and method


We realized a literature review based on CDH. We evaluated studies related to diagnosis,
management and outcome of CDH.

Results
The majority of CDH are detected with ultrasound between 18 and 20 weeks of gestation.
However, there are numerous cases where detection is late, at the beginning of the 3rd
trimester when abdominal organs protrusion through the thorax becomes evident. The best
parameter for evaluating the severity of CDH and for predicting survival chances is the
lung/head ration (LHR) associated with the presence or absence of hepatic intrathoracic
protrusion. The optimal intervention period is considered to be in the prenatal period. The
objective of Fetoscopic Endotracheal Occlusion (FETO) is not the reconstruction of the
diaphragm but for improving pulmonary development. The FETO technique, which assures a
survival rate up to 78% depending on the LHR ratio, remains an efficient therapeutic solution in
severe cases, although it imputes a series of abnormal histopathological results, which includes
oligomaacroalveolar development and a decrease in the number of type 2 alveolar cells.

Conclusion
The therapeutic future regarding CDH is heading towards researching pharmacological and
cellular strategies, these being less invasive in comparison to surgical interventions.
Keywords: congenital diaphragmatic hernia, FETO

Introduction

The incidence of CDH is approximately 1 in 2000-4000 newborns and represents 8% of of all


major congenital anomalies. More than 60% of CDHs are solitary [1, 2] and in other cases can be
associated with a series of anomalies like congenital cardiac malformations (atrial/ventricular

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septal defects, atrioventricular canal defect, ventricular hypoplasia, coarctation of aorta), CNS
anomalies, intestinal atrasia and aneuploidies [3].

Aetiology of CDH
The aetiology of CDH seems to be multifactorial. Genetic factors, nutritional deficiencies and
medium are considered possible causes for CDH [4]. Several studies performed on rodents have
shown evidence of a deficiency in Vitamin A metabolism [5, 6]. It was demonstrated that
administration of Nitrofen in a group of gestating rodents, had as a result the appearance of CDH
in the majority of descendents [7, 8].

Diagnosis of CDH
The rate of prenatal detection with ultrasound is around 60% [6]. The majority of CDH are
detected with ultrasound between 18 and 20 weeks of gestation, considering that detection is
possible still during screening time of 1st trimester [6]. A main ultrasound feature that suggests
CDH is represented by an abnormal position of fetal heart, being deviated to the opposite side of
the diaphragmatic defect [9]. Identification of a horizontal stomach in the abdomen represents an
ultrasound diagnostic marker for liver herniation in right CDH [10]. 25% of left CDH can be
associated with hepatic herniation. This can be identified with ultrasound through the presence of
intrathoracic hepatic vessels or through left deviation of umbilical vein [11]. Right CDH is more
difficult to diagnose because the fetal heart is well positioned and the herniated liver can be
easily mistaken for the lung [12]. Eventual restriction of intrauterine growth is caused by a
smaller abdominal circumference due to intrathoracic mobilization of the abdominal content
[13].

Ultrasound evaluation of CDH


Ultrasound index LHR- lung to head ratio was found to have a correlation with fetal survival
rate. An LHR larger than 1.4 has been associated with better neonatal prognosis. It has been
demonstrated that LHR is dependent on gestational age [12], increasing as pregnancy progresses.
This is the reason why it was proposed to use o/e LHR- observed/expected lung to head ratio
for the correction of the gestational age effect. Decreased values of o/e LHR and intrathoracic
hepatic herniation are factors associated with a poor prognosis [14].

Prenatal Management of CDH


Prenatal therapy’s main objective is the limitation of pulmonary hypoplasia and reduction of
pulmonary hypertension, not reparation of the diaphragmatic defect [15]. This can be achieved
by Fetoscopic Endotracheal Occlusion (FETO). Through iatrogenic occlusion of fetal trachea,
evacuation of the surfactant produced by respiratory tract epithelium is prevented, which
determines distension of pulmonary tissue, pulmonary maturation and vascular histology
modification [16, 17]. Although FETO insures an increase in pulmonary mass, it also is
accompanied by abnormal histopathologic results, including oligomacroalveolar development
and a decrease in the number of type II alveolar cells [18]. Moreover, repositioning of the liver in
the fetal abdominal cavity can be accompanied by the inversion of flux in the venous duct and
obstruction of blood flux in the umbilical vein [16].
Prenatal therapeutic strategy in CDH consists in the realisation of fetal tracheal occlusion
between 26 to28 weeks in severe cases and between 30 to 32 weeks in moderate cases. Mild or
moderate CDH is not an indication of intrauterine surgery [18]. LHR evaluation can be

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significantly improved if combined with the evaluation of pulmonary circulation. Determining


the pulse index (PI) and the debit of Endothelium-derived relaxing factor (EDRF), both
measured at the level of the proximal branches of the intrapulmonary artery between 20 to 24
weeks of gestation, can be useful in the selection of foetuses that can benefit from fetal therapy
[19].
Evaluating the efficiency of FETO is verified through the relative increase in LHR values
combined with increase in blood perfusion of pulmonary tissue. One week after FETO, if the o/e
LHR value is higher than 50% and pulmonary tissue perfusion is over 30% then the prognosis is
excellent (100% survival rate) [19]. Fetoscopic removal of the balloon is ideal if realised at the
gestational age of 34 weeks [18].
Premature birth frequently occurs due to premature rupture of membranes. It has been
demonstrated that one third of premature births happen before 34 weeks. In these cases removal
of balloon must be performed immediately, which may also produce tracheal lesions leading to
fetal death [20]. Balloon removal before birth increases survival rates and decreases morbidity.
The actual technique is less invasive and is done under local anaesthesia. Side effects of the
balloon on the trachea include tracheomegaly but it does not have a significant clinical impact
[21].

Postnatal management in CDH


Postnatal management is primarily based on adequate oxygenation and CO2 clearance [22].
For more favourable results regarding newborns with CDH, early medical stabilization is
necessary as well as delaying surgical repair of defect. Immediate measures include pulmonary
ventilation through endotracheal intubation with minimum sedation and insertion of nasogastric
tube for gastric and intestinal decompression. Pulmonary vasodilators such as inhaled nitric
oxide or sildenafil, can be used in cases of CDH with pulmonary hypertension. In case
conventional ventilation fails, we can use Extracorporeal Membrane Oxygenation (ECMO), to
prevent or ameliorate right cardiac insufficiency [23]. Only after obtaining clinical stability is
when surgical intervention is sought to repair the diaphragmatic defect with reduction of
herniated content. It is estimated that 30% of cases will need lifelong oxygen therapy,
bronchodilators, antireflux treatment and in some cases parenteral nutrition. Long-term
morbidity include respiratory, cardiovascular, gastrointestinal, musculoskeletal and neurological
[24].
Gastroesophageal reflux disease (GERD) may persist in 40% of cases [25]. 25% of survivors
will have abnormal pulmonary function and a reduced effort capacity during childhood and
adolescence [26]. Despite all that, there is no legal recommendation of interrupting pregnancy
even in severe cases of CDH [27].

Prognosis of CDH
According to the Extracorporeal Life Support Organization Registry, it is estimated that
survival rate of children with CDH is approximately 60% [28], considering limitations of
pulmonary hypoplasia, persistent fetal circulation (PFC) and associated anomalies [29]. The best
predictor to define the severity of CDH and for anticipation of neonatal survival and morbidity is
represented by LHR [29]. LHR evaluation requires a high level of experience on the specialists
part, therefore suspicious cases of CDH should be redirected towards centers of fetal medicine
with pre and post-therapeutic experience in treating CDH [30].

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Fetal cardiac ultrasound can provide useful information in predicting the results of isolated
left CDH [9]. It has been demonstrated that the tricuspid/mitral valve ratio (TV/MV ratio) can be
a reliable indicator of isolated left CDH. A TV/MV ration higher than 1.72, indicates
unfavourable prognosis with a good sensitivity and specificity [31]. LRH less than 1,
intrathoracic hepatic herniation, and abnormal positioning of the stomach can be used to identify
fetuses with higher risk of persistent pulmonary hypertension [32]. Intrathoracic hepatic
herniation represents a negative prognostic factor [14, 22].

Therapeutic perspectives in CDH


It looks like the therapeutic future of CDH is heading towards pharmacological and cellular
strategies, which are far less invasive. In rodents with induced CDH through nitrofen
administration, it has been established that CDH can be treated by transplacental administration
of retinoic acid. However, its teratogenic effect makes it inapplicable in humans [33]. Another
interest in treating CDH is heading towards prenatal administration of sildenafil to the mother,
this having had encouraging results in rodents [34]. Researchers are giving a lot of attention to
stem cells in treating CDH. The majority are concentrated on using exogenous cell, including
mesenchymal stem cells (amniotic fluid, bone marrow or blood from the umbilical cord). Stem
cells can be also used in tissue engineering through creating a protective biologic pad for a more
functional surgical reconstruction, as suggested initially by Fauza [35].

Conclusions

CDH represents a severe anomaly with high neonatal mortality and morbidity. Ultrasound
examination is considered the gold standard in diagnosing CDH. The most reliable prediction
factor of neaonatal survival and morbidity is LHR. LRH less than 1, intrathoracic hepatic
herniation, and abnormal positioning of the stomach can be used to identify fetuses with higher
risk of persistent pulmonary hypertension. Future therapy of CDH is heading towards
researching pharmacological and cellular strategies.

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hernia: Long-term risk of gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr 2010.
26. Muratore CS, Kharasch V, Lund DP, Sheils C, Friedman S, Brown C, Utter S, Jaksic T, Wilson JM (2001)
Pulmonary morbidity in 100 survivors of congenital diaphragmatic hernia monitored in a multidisciplinary
clinic. J Pediatr Surg, 36: pp. 133-140.
27. Olaru OG, Ionescu CA, Lesnic A, Filipescu G A, Ples L (2018). Ethical and medico-legal aspects of the
therapeutic abortion – our experience. Rom J Leg Med 26, pp. 82-85.
28. Kotecha, S., Barbato, A., Bush, A., Claus, F., Davenport, M., Delacourt, C., Deprest, J., Eber, E.,
Frenckner, B., Greenough, A., Nicholson, A.G., Antón-Pacheco, J.L. and Midulla, F. (2012) Congenital
Diaphragmatic Hernia. European Respiratory Journal, 39, pp. 820-829.

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29. Jani JC, Benachi A, Nicolaides KH, Allegaert K, Gratacos E, Mazkereth R, Matis J, Tibboel D, Van Heijst
A, Storme L, Rousseau V, Greenough A, Deprest JA (2008). Prenatal prediction of neonatal morbidity in
survivors with congenital diaphragmatic hernia: A multicenter study. Ultrasound Obstet Gynecol.
30. Cruz-Martinez R, Figueras F, Moreno-Alvarez O, Martinez JM, Gomez O, Hernandez-Andrade E,
Gratacos E (2010). Learning curve for lung area to head circumference ratio measurement in fetuses with
congenital diaphragmatic hernia. Ultrasound Obstet Gynecol 36, pp 32-36.
31. Yamoto M, Tanaka Y, Fukumoto K, Miyake H, Nakajima H, Koyama M, et al., (2015). Cardiac fetal
ultrasonographic parameters for predicting outcomes of isolated left-sided congenital diaphragmatic hernia.
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32. Lusk LA, Wai KC, Moon-Grady AJ, Basta AM, Filly R, Keller RL (2015) Fetal ultrasound markers of
severity predict resolution of pulmonary hypertension in congenital diaphragmatic hernia. Am J Obstet
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33. Tzimas G, Nau H. (2001) The role of metabolism and toxicokinetics in retinoid teratogenesis. Curr Pharm
Des 7:803e31.
34. Luong C, Rey-Perra J, Vadivel A, et al., (2011)Antenatal sildenafil treatment attenuates pulmonary
hypertension in experimental congenital diaphragmatic hernia. Circulation 123:2120e31.
35. Fauza DO, Marler JJ, Koka R, Forse RA, Mayer JE, Vacanti J P(2001). Fetal tissue engineering:
diaphragmatic replacement. J Pediatr Surg 36:146e51.

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Ultrasound Diagnosis of Aortic Arch Anomalies – Literature Review


and Case Report

POENARU Mircea Octavian1,2, BRAICU Flavia1, STERIE Ionut1, VALCEA Ionut1,


PLES Liana1,2
1“St. John” Hospital, “Bucur”, Maternity, Bucharest, (ROMANIA)
2UMF “Carol Davila”, Bucharest, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

Introduction
Vascular rings are congenital anomalies of the aortic arch that result in compression of the
trachea and/or esophagus, leading to respiratory and gastrointestinal symptoms after birth and
even in intrauterine live. Ultrasound detection rate at second trimester screening seems to be
0,092%. Incorporation of 3VT section into cardiac ultrasound screening protocols increases
prenatal diagnosis of arch abnormalities, including DAA.

Material and method


We report the case of a fetus diagnosed during pregnacy with aortic arch anomalies.

Results
We present the case of D.M., 25 years old, secundiparous, who performed the screening of
fetal abnormalities in the first trimester that did not reveal severe embryonic abnormalities and
the combined test risks were low for aneuploidies, preeclampsia, intrauterine grouth restriction
and prenatal birth.
At 21weeks + 4 days, the second trimester screening was performed, where were obtained
images strongly suggesting the existence of a double aortic arc with right dominance, and with
normal left arterial duct. No other anomaly has been identified by the exhaustive examination of
the fetus. No minor or severe marker for aneuploidy has been identified.The patient gave birth by
caesarean section to a 3660g fetus, apgar 9. Echocardiography performed after birth did not
identify any aortic arch abnormality.
The child, clinically healthy, was examined after 3 months when was detected the right aortic
arch. The computerized angio-tomography of the torax, performed after 5 months, confirmed the
presence of the vascular ring. At the age of 15 months, the left aortic arch is resected with
favorable post-operative outcome. Further development of the child is a favorable one, and he
will be reevaluated after one year.

Conclusions
The particularity of the case is the late diagnosis of more than one year of life, although
presence of double aortic arch has been demonstrated since the second trimester of pregnancy.

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The echocardiographic examinations performed by the pediatric echocardiography specialist


have only identified the image of the right aortic arch. Only angio MRI has established the
diagnosis when the abnormality has become symptomatic.
Keywords: congenital heart defects, ultrasound, arch aortic, angio MRI

Introduction

Vascular rings are congenital anomalies of the aortic arch that result in compression of the
trachea and/or esophagus, leading to respiratory and gastrointestinal symptoms after birth and
even in intrauterine live. They can be classified as complete, when both the trachea and
esophagus are fully encircled by a vascular anomaly. Irving described for the first time in 1939
this kind of pathology, but Edwards explained, in 1953, his embryological theory. [1, 2] In
double aortic arch aorta divides anteriorly to the trachea and esophagus, with one arch coursing
to the left of the trachea and esophagus and the other to the right . The arches rejoin into a single
descending aorta posterior to the trachea and esophagus. The failure of the dorsal right root to
regress creates the vascular ring witch completely encircling the two structures.

Case report

We present the case of D.M., 25 years old, secundiparous, who performed the screening of fetal
abnormalities in the first trimester, correctly and completely. These investigations did not reveal
severe embryonic abnormalities and the combined test risks were low for aneuploidies,
preeclampsia, intrauterine grouth restriction and prenatal birth. [3] At 21 weeks + 4 days, the
second trimester screening was performed, where were obtained images strongly suggesting the
existence of a double aortic arc with right dominance, and with normal left arterial duct (Fig. 1,
Fig. 2). No other anomaly has been identified by the exhaustive examination of the fetus. No
minor or severe marker for aneuploidy has been identified.

Fig. 1. Double aortic arc with righ dominance, Fig. 2. Double aortic arc with right dominance,
with normal left arterial duct with normal left arterial duct
The patient gave birth by caesarean section to a 3660g fetus, apgar 9. Echocardiography
performed after birth did not identify any aortic arch abnormality. The child, clinically healthy,
was examined after 3 months when was detected the right aortic arch. The computerized angio-

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tomography of the torax, performed after 5 months, confirmed the presence of the vascular ring,
as it had been described in fetal life (Fig. 3). It also revealed the presence of moderate tracheal
compression which explained the clinical manifestations (persistent cough without infectious
etiology, at the moment of tomography). (Fig. 4) Genetic studies have not found any aneuploidy
or 22q11 deletion.

Fig. 3. Computerized angio-tomography Fig. 4. Images that argue the presence of


of the torax confirm the presence of the moderate tracheal compression
vascular ring

At the age of 15 months, the left aortic arch is resected with favorable post-operative
evolution, however marked by a persistent coughing. The computerized angiotomography of the
torax performed 2 months postoperative did not reveal the presence of an extrinsic compression,
only a small narrowing of the tracheal lumen at the level of the ascending aorta bifurcation, in
remission from the preoperative examination (Fig. 5, Fig. 6). Further development of the child is
a favorable one, and he will be reevaluated after one year.

Discussions

Aortic arch anomalies are rare malformations accounting for approximately 1 to 3 percent of
congenital heart disease. [4] The true incidence in the general population remains unknown, and
the diagnosis is sometimes only made as an incidental finding during cross-sectional imaging
undertaken for other clinical indications. [5, 6] Males have a 1.4 to 2 times greater risk of having
a vascular ring than females. [7] There have been no evidence of exposure to teratogenic agents.
[3]
The left and right aortic arches form a vascular ring around the esophagus and trachea. In 70%
of double-aortic-arch cases, the right arch is dominant. [8]. Only 11% have left arch dominance.
[9] In many cases, the left subclavian artery and ductus arteriosus arise from the diverticulum of
Kommerell, a vascular structure which may contribute to the posterior compression of the
esophagus and trachea, and may produce symptoms even after surgical division of the vascular
ring, if it is not resected at the time of surgery. [10]

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Symptomatology is given by varying degrees of airway compression, in the form stridor,


severe respiratory compromise or symptoms of chronic airway compression. Dysphagia may also
occur due to compression of the esophagus and can be associated with symptoms of recurrent
aspiration and recurrent respiratory infections. [5] Naidu recognized the intrauterine airway
obstruction by lung brightness, flattened diaphragm and polyhydramnios (amniotic fluid index
>95th centile). However 88% of fetuses do not develop any tracheal and/or esophageal
obstruction at presentation or on serial ultrasound examination. [9]
Associated anomalies are common in children with vascular rings, with a reported prevalence
of up to 50 percent although other authors have found that more than 78% of cases had isolated
DAA. [9, 11] The majority of these anomalies could be a second cardiac lesion such as
ventricular septal defect, tetralogy of Fallot, coarctation of the aorta, or a patent ductus
arteriosus. [10] Associated cardiac anomalies are present in only 23% of DAA cases. [12]
Noncardiac anomalies including tracheoesophageal fistula, cleft lip-palate, subglottic stenosis,
and genetic or malformative syndromes (e.g., DiGeorge syndrome, Down syndrome, or
CHARGE syndrome) was found in 19% of cases of DAA. [12, 13] Association with
chromosomal abnormalities, 22q.11 deletion in particular, has been reported to be as high as
24%. [14] As we have already shown, no other structural or genetic abnormalities have been
identified in the presented case.
Ultrasound detection rate at second trimester screening seems to be 0,092%. [15] This may
explain the fact that this case is the first detected in our maternal fetal department over the past
10 years, since the ecocardiographic examination protocol, which includes the main standard
sections, was introduced as mandatory. These standard sections includes three vessels and
trachea view (3VT) whitch come into notice on the possibility of the existence of an aortic arch
anomaly. U-sign is the main image who argues the presence of an right aortic arch. If a right
aortic arch is identified prenatally, further evaluation should be undertaken to exclude a double
aortic arch. [5] Fetal echocardiography have to be performed to identify arch dominance and the
origin of the head and neck vessels. 4D ultrasound with B-flow imaging and spatio-temporal
image correlation (STIC) are techniques which apparently facilitates visualisation and detailed
examination of the anatomical features of the DAA. [16]
Antenatal diagnosis requires confirmation after delivery with further imaging. Computerised
angio-tomography ( CT) or magnetic resonance angiography (MRA) provides three-dimensional
visualization of the vascular anatomy, which accurately makes the diagnosis of a vascular ring
and gives detailed anatomic information needed to plan the operative procedure. [17]
For patients with symptomatic vascular rings, is recommended surgical correction. Early
surgical repair of a double aortic arch has a favorable long-term prognosis, therefore prompt
detection and intervention are required to prevent long-term morbidity. [18] In our case the
patient olso underwent the surgical correction of the vascular ring at 15 months after birth, when
the presence of the anomaly became symptomatic, with a good evolution and prognosis.
For asymptomatic patients who are incidentally diagnosed with vascular rings, surgical
correction is not recommended. [13]

Conclusions

This case highlight the clinical importance of the 3VT view. Incorporation of 3VT into
screening programs increases prenatal diagnosis of arch abnormalities, including DAA. Even if
the incidence of the disease is very low and the prognosis for early detected cases is favorable,

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special attention should be paid to the counseling of the affected fetus parents as the DAA
prognosis varies depending on the associated anomalies and the degree of tracheal stenosis. At
the same time, medicolegal aspects should not be neglected. [19]
Only patients with symptomatic aortic vascular rings suffer surgical correction. For
asymptomatic patients who are incidentally diagnosed with this anomaly, surgical correction is
not recommended.
The particularity of the case is the late diagnosis of more than one year of life, although
presence of double aortic arch has been demonstrated since the second trimester. The
echocardiographic examinations performed by the pediatric echocardiography specialist have
only identified the image of the right aortic arch. Only angio MRI has established the diagnosis
when the abnormality has become symptomatic.

REFERENCES

1. Irving JW. Syndrome of constricting double aortic arch in infancy (1939). Report of a case. J Pediatr 14, pp.
527-533.
2. Edwards J. (1948) Anomalies of the derivatives of the aortic arch system. Med Clin North,Am 32,pp 925–
949.
3. Moga, M.; Ples, L.; Bigiu, N.; Manitiu, I. (2011). An Overview Of The Risk Of Adverse Reproductive And
Developmental Disorders Due To Exposure To Pesticides Journal Of Environmental Protection And
Ecology 12(3A), pp. 1311-1319.
4. Licari A, Manca E, Rispoli GA, et al., (2015). Congenital vascular rings: a clinical challenge for the
pediatrician.Pediatr Pulmonol; 50, pp. 511.
5. L. Hunter, N. Callaghan, K. Patel, L. Rinaldi, H. Bellsham-Revell, G. Sharland, (2015). Prenatal
echocardiographic diagnosis of double aortic arch. Ultrasound Obstet Gynecol; 45,pp. 483-485.
6. Ples, L; Sima, RM; Stanescu, AD; Olaru O-G. (2017). The Importance of a National Congenital Anomalies
Registry – the Role of the Prenatal Diagnosis. Proceeding paper for the 5TH ROMANIAN CONGRESS OF
THE ROMANIAN SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY, pp. 505-510.
7. Woods RK, Sharp RJ, Holcomb GW 3rd, et al., (2001). Vascular anomalies and tracheoesophageal
compression: a single institution’s 25-year experience. Ann Thorac Surg; 72, p. 434.
8. Alsenaidi K, Gurofsky R, Karamlou T, Williams WG, McCrindle BW. (2006). Management and outcomes
of double aortic arch in 81 patients. Pediatrics 118: e, pp. 336-1341.
9. D. P. Naidu, C. Wohlmuth, H. M. Gardiner, (2017). Prenatal diagnosis of double aortic arch: can we predict
airway obstruction (pseudo-CHAOS) and need for airway EXIT? Ultrasound Obstet Gynecol 49, pp. 660-
661.
10. Backer CL, Hillman N, Mavroudis C, Holinger LD. (2002). Resection of Kommerell’s diverticulum and left
subclavian artery transfer for recurrent symptoms after vascular ring division. Eur J Cardiothorac Surg 22:64
11. Humphrey C, Duncan K, Fletcher S. (2006). Decade of experience with vascular rings at a single institution.
Pediatrics 117:e903.
12. V. De Robertis1, G. Tuo2, G. Rembouskos, T. Fanelli1, M. Marasini, P. Volpe (2016) Fetal double aortic
arch: 2D and 4D echocardiography, associations and outcome. Ultrasound in Obstetrics & Gynecology; 48
(Suppl. 1), pp. 167-269.
13. Amy L Juraszek, David R Fulton, (2018) Vascular rings and slings. Official reprint from UpToDate,
www.uptodate.com © UpToDate, Inc. and/or its affiliates. All Rights Reserved, Nov 04, 2016.
14. McElhinney D, Clark B, Weinberg P, Kenton M, McDonald-McGinn D, Driscoll D, Zackai E, Goldmuntz E
(2001) Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and
branching. J Am Coll Cardiol; 37, pp. 2114-2119.
15. K. Tsujimura, R. Izumi, H. Ishimoto, S. Izumi, M. Tokuyama, M. Kawataki(2009) Three cases of double
aortic arch diagnosed in fetal period. Ultrasound in Obstetrics & Gynecology; 34 (Suppl. 1), pp. 177-284.
16. Ionescu, Cringu (2010) Fetal Echocardiography in the Second Trimester of Pregnancy. GINECO RO, ,
Volume: 6, Issue: 3, pp. 142-146.
17. Smith BM, Lu JC, Dorfman AL, et al., (2015) Rings and slings revisited. Magn Reson Imaging Clin N Am
23:127.

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18. Ullmann N, Menchini L, Salerno T, Tom’a P, Cutrera R. (2014) Late diagnosis of double aortic arch:
consequences on long-term follow-up. Pediatr Pulmonol; 49, pp. 75-77.
19. Olaru OG, Ionescu CA, Lesnic A, Filipescu G A, Ples L (2018). Ethical and medico-legal aspects of the
therapeutic abortion – our experience. Rom J Leg Med (26), pp. 82-85.

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A Severe Case of Immunisation to the Rhesus D Antigen in the


XXIst Century

POPESCU Ina1, GHEORGHIU Diana1, BANACU Mihail1, ROBOTIN Carmen1,


MATEI Alexandra1, IONESCU Andra1, DAN Adelina1, POPESCU Mihail2,
PACU Irina3, SOCEA Bogdan3
1 Dpt. of Ob-Gyn, “Saint Pantelimon” Emergency Hospital, Bucharest (ROMANIA)
2 Dpt. of Ob-Gyn, Ramnicu Sarat Municipal Hospital, Ramnicu Sarat (ROMANIA)
3 Carol Davila University of Medicine and Pharmacy, Bucharest (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected]

Abstract

Introduction
After the discovery in 1966 of the anti-D immunoglobulin use in Rh D negative mothers the
rate of fetal haemolytic disease dropped majorly. More so, severe cases of alloimunisation are
becoming rarer, a fact that makes their management difficult.

Case presentation
We report the case of a 23 years old O negative patient, V gesta, IV para, with 3 prior C-
sections, who during her pregnancy developed fetal hydrops. The particularity of the case is the
nonreassuring fetal status which posed a challenge for both obstetrical and neonatal team.

Conclusions
We hereby try to draw the attention of the medical community to the fact that the lack of basic
care during pregnancy may lead to devastating results.
Keywords: alloimunization, hydrops fetais, fetal anemia, Rh negative

Introduction

After the discovery in 1966 of the anti-D immunoglobulin use in Rh D negative mothers the
rate of fetal haemolytic disease dropped majorly. More so, severe cases of alloimunization are
rare, at list in developed countries, a fact that makes their management difficult. Even though, in
Romania, there are programmes for the prophylaxis of alloimunization, either antenatal or
postnatal, we still encounter cases of severe haemolytic disease of the fetus and newborn
(HDFN), mostly in the uneducated population [1].
The pathogenesis of the allomunization process is due to the presence of the anti-D IgG
antibodies in the maternal circulation, developed after the mother has been exposed to RhD
positive red blood cells (RBCs) that cross the placenta and opsonize fetal RBCs [2]. The
opsonized fetal RBCs are afterwards phagocytized, thus leading to fetal anemia. In case of severe
anemia (meaning a deficit of at least 7g/dL) the fetus develops what is known as hydrops fetalis

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[3], a condition that consists of two or more of the following signs – skin edema, ascites, pleural
effusion and/or pericardial effusion [2].

Case Report

We present the case of a 23 years old woman, V gesta, IV para, 32 weeks of gestation with 3
previous C-sections, which was admitted to our ward due to contractions. She had no medical
documents from the previous pregnancies or from the ongoing pregnancy. Her personal history
shows that she had 3 C-sections in 2010, 2012 and 2016 which resulted in healthy newborns and
1 abortion. She also mentioned the fact that during the ongoing pregnancy she received no
medical care. She could not provide any other personal data.
Fetal ultrasound finds a fetus in breech presentation, with a normal biometry except the
abdominal circumference (corresponding to 35 weeks and 4 days), a normal fetal heart rate but,
easily visualised, severe ascites, skin edema and pericardial effusions – thus establishing the
diagnosis of hydrops fetalis. The Doppler parameters were as following – pulsatility index (PI)
on umbilical artery (UA)-0.97, resistance index (RI) on UA-0.63, the systolic/diastolic ratio
(S/D) on UA-2.74 while on the middle cerebral artery (MCA) the PI-1.68, the R-0.84 and the
S/D-6.14 while the peak systolic velocity (PSV)-78,65cm/s. Using the calculator:
http://perinatology.com/calculators/MCA.htm we determined that the PSV on MCA was
corresponding to 1.79 MoM determining the diagnosis of severe fetal anemia.
The team’s first suspicion for the cause of the fetal anemia and the hydrops fetalis was
alloimunization. While the determination of the blood group and the Rh factor was done
immediately and the results showed that the woman was OI with negative Rh, the determination
of the antibodies took several days. Meanwhile, we asked for a consult from the department of
the maternal fetal medicine from Filantropia Maternity which confirmed the preliminary
diagnosis and raised the same suspicion.
Four days after she was first admitted the results of the antibody screen were ready showing a
titre of RhD antibodies of 1/2048-1/4096 and no alloimunization for other types of RBCs
antigens. She was immediately transferred to the Filantropia Maternity for intrauterine fetal
transfusion.
At 33 weeks of gestation the patient undergoes the first intrauterine fetal transfusion followed
by a second one at 34 weeks of gestation with the fetal haemoglobin rising from 3.9g/dl to
12.3g/dl. During this period of time, corticotherapy is administered for fetal pulmonary
maturation.
At 35 weeks of gestation the patient (who’s antibodies titre was now 1/4096-1/8192) is
transferred back to our clinic due to regular uterine contractions and undergoes immediate C-
section. The newborn is apneic, bradycardic, and cyanotic, with generalized hypotonia, receives
an Apgar score of 4 at 1 minute after birth and is transferred to the neonatal intensive care unit
(NICU). Oro-tracheal intubation is needed due to his severe state.
The abdominal ultrasound confirms hepatosplenomegaly and massive ascites due to which the
newborn undergoes peritoneocentesis. – 200ml of yellow ascites fluid is extracted with massive
reduction in abdominal volume. The cardiac ultrasound confirms the diagnosis of pericarditis. At
5 hours after birth, exchange transfusion is performed with OI negative blood, 250 ml of fetal
blood being replaced. The fetal antibodies titre decreases from 1/2048 to 1/128-1/256 after the
exchange transfusion. During his stay in the NICU he needed 4 transfusions. After 14 days of
mechanical ventilation, 1 day of continuous positive airway pressure nasal ventilation and 5

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more days with no respiratory support the newborn is discharged from the neonatal ward. At
discharge all the parameters were within normal limits.

Discussions

When encountering a fetus with hydrops fetalis, of major importance is the differential
diagnosis of the causes that might have led to this condition. Therefore the first step requires
establishing the type of hydrops-immune-related hydrops fetalis (IHF) or nonimmune-related
hydrops fetalis (NIHF). While IHF is caused by alloimunization, the NIHF can be caused by a
great number of conditions, mainly fetal cardiac anomalies or chromosomal anomalies. Using
tools at our disposal in the XXIst century, such as antibody titration, cell free DNA testing [4]
and modern ultrasound scanning technics [5] the type of hydrops should be easily established. Of
great importance for practitioners when confronted with a patient who’s fetus is hydropic, is not
to forget the fact that other anomalies, not tied to the obvious problem, can occur [6] – these have
to be diagnosed, differentiated from the panel of symptoms characterising the hydrops and, if
treatable, treated separately.
After the IHF diagnosis has been set, the management of the case becomes of major concern.
Assessing the degree of anemia is done using Doppler velocimetry of the MCA [7]. There are
studies that show that the sensitivity of MCA-PSV is 100% [8] – therefor MCA-PSV based
management is indicated after 20 weeks of gestation [9, 10]. Studies show a good correlation
between MoM MCA-PSA and MoM haemoglobin [11] – and using a threshold of a 1.5 MoM
PSV confers a good enough sensitivity and specificity when diagnosing moderate to severe
anemia. As long as MCA-PSV remains below 1.5 MoM the pregnancy is continued with
frequent check-up and the delivery is scheduled at 37-38 weeks of gestation [10]. When and if
the level of MCA-PSV raises above 1.5 MoM intrauterine transfusion is indicated after the
determination of the level of haemoglobin (as there are false positive cases even in cases of high
MCA-PSV) [12]. If MCA-PSV raises above 1.5 MoM at ≥35 weeks of gestation, intravascular
intrauterine transfusion is considered too risky, therefore the guides suggest delivery and
postnatal treatment of anemia [13].
In cases of women who developed antibodies during the pregnancy, our counsel is usually
contraception [14] in order to avoid other pregnancies, because of the high risk of developing a
more severe or earlier onset of the haemolytic disease [10]. Even though the prevention of the
disease in future pregnancies is possible using assisted human reproduction techniques
(implantation of Rh-D negative embryos), this is rarely done due to high costs of the procedure
[10, 15]. The use of combined screening test in the first trimester can be influence by the BMI of
the pregnant woman, although the presence of Rh negative does not influence the value of the
screening test [16]. First trimester anomaly scan can give false positive results in immune related
hydrops fetalis [17]. In cases of stillbirth after intrauterine transfusion the postmortem exam
could be useful for counseling of the patient [18, 19, 20]. Association between a pregnancy with
alloimunization and severe medical disease like myeloproloferative disorder, diabetets mellitus,
cardiac disease, or hepatic disease, is not always associated with a negative prognosis for the
fetus. [21]
In any case, the doctors’ obligations include counseling the pregnant women about the
situation with the possible risks, possible outcome and her choices along the way. [22]

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Conclusions

Our aim is to draw your attention towards the necessity of proper prenatal care in low income
communities as the lack of basic care during pregnancy may lead to devastating results. More so,
we consider of great importance for the medical community to keep up to date with the
protocols.

REFERENCES

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Gonzalez R, Gomez R, Oz U, Detti L, Copel JA, Bahado-Singh R, Berry S, Martinez-Poyer J, Blackwell
SC. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell
alloimmunization. Collaborative Group for Doppler Assessment of the Blood Velocity in Anemic Fetuses.
N Engl J Med. 2000; 342(1): p. 9.
9. S.D.Neamtu, M.B.Novac, M.Fortofoiu, M.C.Fortofoiu, M.Siminel. Maternal fetal incompatibility
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10. https://www.uptodate.com/contents/management-of-pregnancy-complicated-by-rhesus-d-
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on 28.03.2018.
11. Cristian ANDREI, Radu VLADAREANU. The Value of Reference Ranges for Middle Cerebral Artery
Peak Systolic Velocity in the Management of Rhesus Alloimmunized Pregnancies. Maedica (Buchar) 2012
Jan; 7(1): pp. 14-19.
12. Zimmerman R, Carpenter RJ Jr, Durig P, Mari G. Longitudinal measurement of peak systolic velocity in
the fetal middle cerebral artery for monitoring pregnancies complicated by red cell alloimmunisation: a
prospective multicentre trial with intention-to-treat. BJOG. 2002; 109(7): p. 746.
13. Klumper FJ, van Kamp IL, Vandenbussche FP, Meerman RH, Oepkes D, Scherjon SA, Eilers PH, Kanhai
HH. Benefits and risks of fetal red-cell transfusion after 32 weeks gestation. Eur J Obstet Gynecol Reprod
Biol. 2000; 92(1): p. 91.

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14. Ionescu, CA (Ionescu, Cringu Antoniu); Navolan, D (Navolan, Dan); Calin, A (Calin, Alina); Matei, A
(Matei, Alexandra); Bohiltea, R (Bohiltea,Roxana); Dimitriu, M (Dimitriu, Mihai); Ilinca, C (Ilinca,
Corina); Ples, L (Ples, Liana). Hormonal Contraception in Postpartum Patients with Gestational Diabetes
Mellitus. Source: REVISTA DE CHIMIE Volume: 69 Issue: 2 Pages: 478-483 Published: FEB 2018.
15. Pacu, I (Pacu, Irina); Ionescu, C (Ionescu, Cringu); Vladareanu, S (Vladareanu, Simona); Banacu, M
(Banacu, Mihai); Neacsu, A (Neacsu, Adrian); Calin, A (Calin, Alina). Predictive Value of the AMH Level
and Serum Estradiol for Ovarian Hyperstimulation Syndrome in the Assisted Human Reproduction.
REVISTA DE CHIMIE Volume: 68 Issue: 5 Pages: 1118-1121 Published: MAY 2017.
16. Navolan, D (Navolan, Dan); Ionescu, CA (Ionescu, Cringu Antoniu); Carabineanu, A (Carabineanu,
Adrian); Birsasteanu, F (Birsasteanu, Florin); Cretu, O (Cretu, Octavian); Szasz, F (Szasz, Florin);
Vladareanu, S (Vladareanu, Simona); Ciohat, I (Ciohat, Ioana); Gidea, R (Gidea, Ramona); Nemescu, D
(Nemescu, Dragos); Farcas, S (Farcas, Simona); Andreescu, N (Andreescu, Nicoleta); Simu, S (Simu,
Sebastian); Stoian, D (Stoian, Dana) .Influence of Weight of Pregnant Women on First Trimester
Biochemical Markers Values REVISTA DE CHIMIE Volume: 68 Issue: 12 Pages: 2836-2838, DEC 2017.
17. Tudorache Ş, Iliescu DG, Turcu A, Florea M, Dragusin R, Novac L, Cernea N, First Trimester Anomaly
Scan-The Last Redoubt Won: Open Spina Bifida, Donald School J Ultrasound Obstet Gynecol 2015; 9(1):
pp. 80-90.
18. Florea M, Iliescu DG, Tudorache S, Simionescu C, Cernea N, Novac LV, Tanase F, Cotarcea S,
Comanescu A, Dragusin R, Patru C, Carbunaru O, Zorila L, Cernea D. The importance of perinatal
autopsy. Review of the literature and series of cases. Rom J Morphol Embryol. 2017; 58(2): pp. 323-337.
19. Şorop-Florea M, Ciurea RN, Ioana M, Stepan AE, Stoica GA, Tănase F, Comănescu MC, Novac MB,
Drăgan I, Pătru CL, Drăguşin RC, Zorilă GL, Cărbunaru OM, Oprescu ND, Ceauşu I, Vlădăreanu S,
Tudorache Ş, Iliescu DG. The importance of perinatal autopsy. Review of the literature and series of cases.
Rom J Morphol Embryol. 2017; 58(2): pp. 323-337.
20. Ionescu Antoniu Cringu; Popescu Ina; Banacu M; Matei Alexandra; Bohiltea, Roxana; Dimitriu, Mihai. Is
it Possible to Predict Stillbirth in the Third Trimester? 5 TH ROMANIAN CONGRESS OF THE
ROMANIAN SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY Edited by:
Vladareanu, S; Marginean, C; Vladareanu, R Pages: 194-198 Published: 2017.
21. Bohiltea, RE (Bohiltea, Roxana Elena); Cirstoiu, MM (Cirstoiu, Monica Mihaela); Ionescu, CA (Ionescu,
Cringu Antoniu); Niculescu-Mizil, E (Niculescu-Mizil, Emilia); Vldareanu, AM (Vldareanu, Ana Maria);
Voican, I (Voican, Irina); Dimitriu, M (Dimitriu, Mihai); Turcan, N (Turcan, Natalia). Primary
myelofibrosis and pregnancy outcomes after low molecular-weight heparin administration A case report
and literature review. MEDICINE Volume: 96 Issue: 46 Number: e8735 DOI:
10.1097/MD.0000000000008735 Published: NOV 2017.
22. Olaru Gabriel Octavian, Cringu Ionescu, Anca Lesnic, George Alexandru Filipescu, Liana Ples. Ethical and
medico-legal aspects of the therapeutic abortion – our experience. Rom J Leg Med 2018, (26), pp. 82-85.

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Fetal Left Femoral Hypoplasia Associated with Left Fibular


Agenesis – A Rare Case

POSTOLACHE Iulia1, SURDU Monica2, NICULESCU Costin1,


IZVORANU Silvia1, STERIU Liliana1, MOCANU Diana1, TICA Vlad Iustin1

1 Obstetrics-Gynecology Clinic I, Saint Andrew Clinical Emergency Hospital Constanta


2 Neonatology Clinic I, Saint Andrew Clinical Emergency Hospital Constanta
E-mails: [email protected]

Abstract

Introduction/Objective
Unilateral femoral hypoplasia and ipsilateral fibular agenesis are a rare association, and the
incidence and detection rates are not clearly known. Femoral hypoplasia and fibular agenesis can
be diagnosed by prenatal ultrasound, which is important for enabling parents to be counseled in
order to make informed decisions.

Methods/Methodology
We present a case of a 32-year-old woman whose fetus was diagnosed with femoral digenesis
at 14 gestational weeks by ultrasound. The length of the fetal left femur was below the 10 th
percentile and the left fibula could not be visualized. No other ultrasound abnormalities were
detected.

Results
Counseling was offered to the mother and she decided to continue the pregnancy. After
delivery at 38 gestational weeks, the diagnosis was confirmed by x-ray, showing left fibular
agenesis and left femoral hypoplasia. The facies was normal and no other abnormalities were
detected.

Conclusion/Discussions
The importance of fetal prenatal ultrasound, differential diagnosis and management of this
rare pathology are presented.
Keywords: femoral hypoplasia, fibular agenesis

Introduction

With the advance of ultrasound technology, skeletal malformations are more frequently
diagnosed ante-partum, at an early gestational age, allowing the parents to make informed
decisions regarding the course of the pregnancy.
Limb buds are visible via high frequency ultrasonography by the end of the 7th gestational
week [1]. Biometry of the long bones is possible from the 11th week of gestation [2].

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Grande et al., found that limb reduction detection rates in the first trimester were
approximately 57% [3]. Patient weight, the ultrasound machine, and the experience of the doctor
are important factors, which influence the detection rate of abnormalities [4].
Congenital fibular deficiency is the most common long-bone deficiency. Its incidence is
estimated at 1-2/100,000 live births [5]. It is often sporadic and of unknown etiology,
predominantly unilateral, but it can also be part of a syndrome or a multisystem entity [6].
There are several classifications of congenital fibular deficiency. One of the most used,
Achterman and Kalamchi’s classification, is based on morphology: type IA: fibular hypoplasia,
type IB: absence of the proximal fibula and type II: complete fibular absence [7].
The incidence of congenital femoral deficiency ranges from 1 in 50,000 to 200,000 live births.
Femoral deficiency is often associated with a fibula defect, in approximately 50-80% of the
cases [8]. Congenital femoral deficiency is often unilateral and sporadic, but it, also, may be part
of a syndrome.
Therefore, if a femoral or fibular abnormality is found, a detailed analysis of the fetal anatomy
is necessary and genetic counseling should be offered [9].

Case report

We present a case of a 39 year old patient, gravida 1, para 1. The patient’s medical history
revealed no consanguinity with husband, no family history of genetic or congenital
abnormalities, no history of exposure to toxins, teratogen drugs or viral infections in the first
trimester of pregnancy. She was not a smoker.
The physical examination revealed no significant findings. The patient’s 14 weeks ultrasound
revealed a shortened left femur, below the 5th percentile [10] (Fig. 1), with a left femoral length
(FL) of 0.61 cm, and a right FL of 1.45 cm
The biparietal diameter (BPD), head circumference (HC) and abdominal circumference (AC)
were corresponding to the gestational age. No other abnormalities were observed.

Fig. 1. 14 week ultrasound

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The mother was counseled and she decided to continue her pregnancy, no matter what the
implications were. She had follow-up ultrasound examinations (Fig. 2), which found that the
head and abdomen biometry continued to be compatible with the gestational age, left femoral
hypoplasia, left fibular aplasia.

Fig. 2. 16 week ultrasound

A cesarean-section was performed at 38 gestational weeks, for premature rupture of


membranes, breech presentation, the patient having a previous birth through caesarian section.
A 2600 g female with an Apgar score of 9 was delivered. The face appeared normal and no
other abnormalities were found.
The diagnosis was confirmed post-partum by fetal X-ray (Fig. 3).

Fig. 3. Fetal X-ray

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Discussions

We present a very rare case of femur-fibula-ulna syndrome, with very few cases reported in
the literature.
The differential diagnosis in this case is particularly important, in order to be able to counsel
the parents regarding the prognosis and the risk of associated abnormalities, so that they can
make an informed decision regarding the course of the pregnancy. It is sometimes difficult to
diagnose a specific skeletal dysplasia by ultrasound alone.
Femoral digenesis appears in several conditions, such as proximal focal femoral deficiency,
femur-fibula-ulna syndrome, femoral hypoplasia/unusual facial syndrome, or femoral
hypoplasia-unusual facial syndrome.
There were several arguments for the femur-fibula-ulna complex: asymmetric defects of the
femur, fibula, with a normal axial skeleton, no internal organ malformations, with a normal facial
profile. There were cases of FFU syndrome described with normal arms [11].
Prognosis mainly depends on the severity of the limb malformations and the possibility of
orthopedic surgery, and the treatment plan is sometimes difficult to choose [12].
This case underlines the importance of measuring both left and right long bones of the arms
and legs. The American Institute of Ultrasound in Medicine recommends assessing evaluating
both legs and arms in the second trimester scan [13].
The early detection of skeletal abnormalities allows for early parental education, genetic
counseling, planning for postnatal care with a multidisciplinary team – pediatric surgeon,
pediatric orthopedic surgeon.

REFERENCES

1. Callen’s Ultrasonography in Obstetrics and Gynecology, 6 th Edition – Norton, Scoutt, Feldstein.


2. IE Timor-Tritsch – Sonoembryology, J Clin Ultrasound, 1990.
3. Grande M, First trimester detection of structural abnormalities and the role of aneuploidy markers,
Ultrasound Obst Gynecol 2012.
4. Emanuel PG, Garcia GI, Angtuaco TL. Prenatal detection of anterior abdominal wall defects with US.
Radiographics. 1995.
5. Aouni S, Bigot J, Petit S, et al., Apport du scanner spiralé au diagnostic prénatal d’une forme sévère
d’hémimélie fibulaire. J Radiol 2011; 92: p. 431.
6. Ismat Ghan. Epidemiology, etiology, and genetic aspects of reduction deficiencies of the lower limb, em, J
Child Orthop. 2008
7. Achterman C, Kalamchi A. Congenital deficiency of the fibula. J Bone Joint Surg Br. 1979 May;61-B(2):
pp. 133-7.
8. Marthese Ellul. Proximal femoral focal deficiency – a case report, Malta Medical Journal, 2008.
9. AT Papageorghiu et al., Outcome of fetuses with antenatally diagnosed short femur, Ultrasound Obstet
Gynecol. 2008.
10. Pam Loughna, Lyn Chitty, Tony Evans & Trish Chudleigh – Fetal Size and Dating: Charts Recommended
for Clinical Obstetric Practice, Ultrasound, 2009.
11. W. Lenz, U. Feldmann. Unilateral and asymmetric limb defects in man: delineation of the femur-fibula-
ulna complex. Birth Defects Orig Artic Ser, 13 (1) (1977), pp. 269-285.
12. De Lewis B. Holmes. Common Malformations. p. 178.
13. AIUM practice guideline for the performance of obstetric ultrasound examinations. J Ultrasound Med
2010.

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Late Diagnosis of Hydrocephalic Fetus. A Case Report and Ethical


Dilemmas

POSTOLACHE Iulia1, SURDU Monica2, NICULESCU Costin1,


IZVORANU Silvia1, STERIU Liliana1, MOCANU Diana1
1Obstetrics-Gynaecology Clinic I, Saint Andrew Clinical Emergency Hospital Constanta (ROMANIA)
2Neonatology Clinic, Saint Andrew Clinical Emergency Hospital Constanta (ROMANIA)
Email: [email protected]

Abstract

Introduction/Objective
Congenital hydrocephalus is a heterogeneous pathology with a variety of causes and clinical
presentations.

Methods/Methodology
We present the case of a 39 year old patient, 39 weeks pregnant, gravida 6, para 6, diagnosed
at admission with fetus hydrocephalus. The fetus was delivered by cesarean section and the
diagnosis was confirmed after birth.

Results
The management of congenital hydrocephalus diagnosed in the third trimester, prior to
delivery, poses medical, psychological and ethical challenges. Do we avoid the risks for the
mother of delivering by cesarean section, and advise for a cephalocentesis in order to facilitate
vaginal delivery? Do we recommend a cesarean delivery in the interest of the fetus? Lacking
clear medical guidelines, clinicians face questions that may prove difficult to answer.

Conclusion/Discussions
The access of pregnant women to prenatal care is key for the early diagnosis of fetal
abnormalities, which will enable the clinicians to offer early counseling in choosing a
management strategy.
Keywords: hydrocephalus, Dandy Walker malformation, ethical dilemmas

Introduction

Congenital central nervous system abnormalities are some of the most frequent fetal
malformations, therefore understanding and diagnosing them is an important part of the prenatal
ultrasound [1].
Congenital hydrocephalus is the dilatation of the fetal brain’s ventricular system. The
prevalence of hydrocephalus in Europe was found to be: 4.65/10,000 births [2].
Dandy Walker Malformation (DWM) has an incidence of 1/30,000 births [3]. DWM is
associated with 4-12% of congenital hydrocephalus [1]. The prognosis of this pathology is

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variable. There are studies reporting that up to 50% of surviving infants have normal
intelligence, the rest having variable degrees of disability [4].
The DWM has been classified as follows [5]: classical DWM (with a dilated 4th ventricle,
vermian agenesis, hydrocephaly and an elevated tentorium); Dandy Walker variant (with
variable vermian hypoplasia); mega-cisterna magna (which has no cerebellar dysgenesis).

Case report

A 31-year-old patient, gravida 6, para 6, presented to the Emergency Department of our


hospital at 38 gestational weeks. The patient had no antenatal visits to the obstetrician, nor did
she have a prenatal visit to a family physician. She had poor socio-economic status and could not
read or write.
Her medical history showed nothing significant, without any ovarian pathologies/ectopic
pregnancies or clinical genetic syndromes [6], [7]. She and her husband were unrelated, they had
no family history of genetic or congenital abnormalities, as far as they could tell. She was not a
smoker, and she was not exposed to any toxins or drugs during the pregnancy – with possible
teratogenic effect [8], no HIV infection [9]. There was no history of viral infection during the
pregnancy, no assisted reproduction techniques – and possible side effects or endocrinological
changes [10], [11].
The patient’s laboratory tests at admission showed a Blood group O(I), RhD positive, with
increased liver function tests (alanine aminotransferase = 455 U/L, aspartate aminotransferase =
247 U/L, direct bilirubin = 0.33 mg/dL, lactate dehydrogenase = 305 U/L). Her uric acid was 5.9
mg/dL, but with no pregnancy-associated biliary or tumoral pathology [12], [13]. The 24-hour
proteinuria was 1383.2 mg/24h, with no sign of pregnancy-induced hypertension [14] – the
blood pressure of the patient had normal values throughout the admission period.
The obstetrical ultrasound revealed a live fetus, with a BPD = 11.30 cm and a HC = 41.58 cm
– above the 95th percentile [16]. Severe hydrocephalus was detected, with the dangling chroroid
sign, and the cerebral hemispheres pushed to the periphery (Fig. 1). The posterior fossa also
showed abnormalities: a mega cisterna magna, with a diameter of over 1 cm and vermian
dysgenesis.
The rest of the biometry was normal. The echocardiography appeared normal.

Fig. 1. Obstetrical ultrasound

The patient was counseled regarding the risk for delivery by caesarian section for the mother,
and regarding the risk for the fetus being delivered through vaginal birth. This process was

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difficult, as the mother had a low intellectual level and it was the first time she heard the fetus
had a malformation.
A 4100 g male with Apgar score 9 was delivered by caesarian section.
The diagnosis was confirmed postpartum. Forty minutes after birth, a transfontanelar
ultrasound was performed, shown below in Fig. 2. On a sagital section, the presence of the
corpus callosum was confirmed, as well as important dilatation of the IIIrd, IVth and lateral
ventricles. There was significant hydrocephalus, with the cerebral substance being pushed to the
periphery. The HC was 42.5, above the 97th percentile. On a coronal section, the presence of
important dilatation of the cysterna magna was found, along with a hypoplasic cerebellar vermis.
The ultrasound signs support the suspicion of Dandy Walker Malformation.

Fig. 2. Transfontanellar ultrasound

A native cranio-encephalic CT scan was performed, revealing: enlarged retrocerebellar fluid


space, with the cerebellar hemispheres pushed antero-laterally, and a vermian hypoplasia. The
IIIrd and IVth ventricles were enlarged, and midline structures were in normal position (Fig. 3).

Fig. 3. Fetal cranio-encephalic CT scan

The fetal head perimeter of the new-born was measured weekly, and in increased from 42,5
cm to 46,5 cm over the course of 4 weeks (Fig. 4).

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Fig. 4. Fenton preterm growth chart – boys

In this case, surgical intervention was recommended

Discussions

Several ethical dilemmas arise in the management of this case. There are only a few studies
and case series studying the best mode of delivery for fetuses with hydrocephalus. The Expert
Advisory Group on Caesarean Section in Scotland recommends caesarian section in the case of
hydrocephalus, for fetal reasons (Evidence level III) [16].
Some authors suggest that vaginal birth provides better outcomes for fetuses with
hydrocephalus, but they are based on a limited number of cases [17]. Other authors report an
increased caesarian section rate, mainly due to prolonged labor [17], [18], no matter what kind of
partogram used and not clearly related to ADP/Ca2+ system in the myometrium [19], [20]. Of
course, in case of a better prenatal care, amniocentesis copuld have been discussed [21].
The lack of clear guidelines and the fact that the prognosis of DWM is variable, make
counseling the parents difficult.

Conclusion

Prenatal visits are important for detecting fetal anomalies such as hydrocephalus and DWM.
This allows the parents and the obstetrician to monitor the fetus, choose the time and way of
delivery and establish a plan with a multidisciplinary team (Obstetrician, Neonatologist,
Geneticist, Pediatric Neurosurgeon).

REFERENCES

1. F. Gary Cunningham, Kenneth Leveno, Steven Bloom, Catherine Spong, Jodi Dashe, Barbara Hoffman,
Brian Casey, Jeanne Sheffield, Radu Vlădăreanu. Williams Obstetrică. 2017.
2. Garne E1, Loane M, Addor MC, Boyd PA, Barisic I, Dolk H. Eur J Paediatr Neurol. 2010 Mar; 14(2): pp.
150-5.

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3. Osenbach RK, Menezes AH. Diagnosis and management of the Dandy-Walker malformation: 30 years of
experience. Pediatr Neurosurg. 1992; 18(4):179.
4. Gandolfi Colleoni G1, Contro E, Carletti A, Ghi T, Campobasso G, Rembouskos G, Volpe G, Pilu G,
Volpe P. Prenatal diagnosis and outcome of fetal posterior fossa fluid collections. Ultrasound Obstet
Gynecol. 2012 Jun; 39(6): pp. 625-31.
5. Jurcă MC1, Kozma K, Petcheşi CD, Bembea M, Pop OL, MuŢiu G, Coroi MC, Jurcă AD, Dobjanschi L.
Anatomic variants in Dandy-Walker complex. Rom J Morphol Embryol. 2017; 58(3): pp. 1051-1055.
6. Tica V. Primary ovarian pregnancies. Gineco.ro 2011; 7(26): pp. 179-180.
7. Tica I, Tica OS, Nicoară AD, Tica VI, Tica A-A. Ovarian teratomas in a patient with Biedl Bardet
syndrome, a rare association. Rom J Morphol Embryol 2016, 57(4): pp. 1403-1408.
8. Tica OS, Tica AA, Brǎiloiu CG, Cernea N, Tica VI. Sirenomielia after Phenobarbital and carbamazepine
therapy in pregnancy. Birh Defects Reasearch (Part A): Clinical and Molecular Teratology 2013; 97(6): pp.
425-428.
9. Cocu M, Thorne C, Matusa R, Tica V, Florea C, Asandi S, Giaquinto C. Mother-to-child transmission of
HIV infection in Romania: results from an education and prevention programme. AIDS Care.
2005;17(1):76.
10. Tica V, Hedon B, Eid J, Audibert F, Benos P, Boulot P, Laffargue F, Viala JL. Determination of adverse
reactions to the stimulation of ovulation in vitro fertilization. [Effets secondaires de la stimulation
ovarienne dans le cadre de la fécondation in vitro.] Contraception Fertilité Sexualité. 1991; 19(7-8): pp.
580-582.
11. Tica V. Laparoscopic ovarian drilling. Gineco.ro 2011;l7(25): pp. 119-120.
12. Tica I, Tica VI, Teren O. Pregnancy, parity and maternal age – predictive factors for occurrence of billiary
pathology (gallstones and sludge)? Gineco.ro 2010, 6(22):218-222.
13. Tica AA, Tica OS, Saftoiu A, Camen D, Tica VI. Large Pancreatic Mucinous Cystic Neoplasm during
Pregnancy: What Should Be Done? Gynecol Obstet Invest. 2013;75(2): pp. 132-138.
14. Tica V. Preeclampsia - an unsolved prophylaxis chapter. Gineco.ro 2012;8(27): pp. 3-4.
15. Pam Loughna, Lyn Chitty, Tony Evans, Trish Chudleigh. Fetal size and dating: charts recommended for
clinical obstetric practice Ultrasound, 2009.
16. Expert Advisory Group on Caesarean Section in Scotland. Report and Recommendations to the Chief
Medical Officer of the Scottish Executive Health Department. 2001.
17. Moritake K; Nagai H; Nagasako N; Yamasaki M; Oi S; Hata T. Diagnosis of congenital hydrocephalus and
delivery of its patients in Japan. Brain & Development. 30(6): pp. 381-6, 2008 Jun.
18. Rosslein R; Kummer M. [Congenital hydrocephalus an analysis of the course of pregnancy, prenatal
studies and labor]. [German] Zeitschrift fur Kinderchirurgie. 43(3): pp. 201-4, 1988 Jun.
19. Galazios G, Tica V, Vrachnis N, Vlachos G, Zervoudis S, Ceausu I, Trypsianis G, Zographou C, Tsikouras
P. Assessment of labor using a new type partogram compared to the classical Fisher partogram. J Matern
Fetal Neonatal Med. 2015;28(1): pp. 82-7.
20. V. I. Tica, V Cojocaru, Oana Sorina Tica, Sabina Berceanu, A. A. Tica. Cyclic-ADP-ribose/Ca 2+ system
in uterine smooth muscle cells. Gineco.ro 2011, 7(26): pp. 193-194.
21. Tica V. One small step/one giant leap in the rate of fetal loss after amniocentesis. Gineco.ro 2011, 7(24).

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Prenatal Diagnosis of Isolated Lissencephaly: Case Studies and


Literature Review

PUIU Serghei1, TAMBALA Carolina2


1State University of Medicine and Pharmacy “Nicolae Testemitanu” (REPUBLIC OF MOLDOVA)
2“Ana Maria” Medical Center (REPUBLIC OF MOLDOVA)
Emails: [email protected], [email protected]

Abstract

We report two cases of isolated fetal lissencephaly. We sought to assess the sonographic
features leading to the aforementioned diagnosis. Besides microcephaly and wide pericerebral
space, we identified an abnormal simplified gyral pattern and an abnormal cerebral lamination
pattern for the expected gestational age. The findings conducted to the diagnosis of
lissencephaly. Both newborns died short after birth. The diagnosis was confirmed by postnatal
autopsy. Despite probable early suspicion, a definite diagnosis of lissencephaly based on
sonographic criteria can be established mostly by late second-trimester of gestation; even more
cases remain undetected until close to delivery.
Keywords: lissencephaly, cerebral sulci, cerebral lamination, cortical development

Introduction

Lissencephaly is a rare cortical dysplasia caused by impaired neuronal migration, resulting in


abnormal formation of cerebral gyri. The discrepancy between anatomic development and
sonographic findings make prenatal diagnosis challenging. Familiarity with the normal
sonographic patterns of fetal cortical development can lead to the diagnosis of lissencephaly.

Case Series

We report two cases of fetal lissencephaly referred to our fetal medicine unit for a second
opinion. Both fetuses had an unremarkable second trimester scan, until a Head Circumference
(HC) less than the mean values for gestational age was detected. There was no history of cerebral
defects in both cases. Brain morphology was assessed according to the existing guidelines [1-3]
on Voluson expert scanner. If one or more main sulci appeared abnormal for the expected
gestational age or an abnormal fetal cerebral lamination pattern was present, cortical
development was considered delayed. No other brain malformations were detected.

Case 1
A 26-year-old woman (gravida 2, para 1) was referred to our medical unit for second opinion
due to microcephaly at 28 weeks and 1 day of gestation. Fetal head biometry revealed HC
corresponding to 2,3 percentile for the gestational age (Fig. 1a). Also we noticed wide
pericerebral space (Fig. 1b), mild ventriculomegaly and Sylvian fissure of abnormal shape (Fig.
1e). The central (Fig. 1b), cinguli (Fig. 1c) and calcarine (Fig. 1d) fissures were absent, causing

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smooth appearance of the cortex. Sonographic findings were deemed suspicious of


lissencephaly. Ultrasound follow-up showed progressive decrease of HC and extremely shallow
sulci. The pregnancy has been continued and the child was delivered at 37 weeks of gestation.
After birth, the baby had difficulty breast-feeding and died shortly after birth. Lissencephaly
was confirmed postnatally at autopsy.

Fig. 1. (a) Microcephaly; HC – 2,3 percentile for the gestational age. (b) Wide subarachnoidal space (short arrows),
absent central fissure (long arrow). (c-d) Absent cingular and calcarine fissures. (e) Delayed Sylvian fissure
operculization, corresponding to 24th week.

Case 2
A 24-year-old woman (gravida 1) at 35 weeks and 4 days of gestation was referred to our
medical unit for a second opinion for small for gestational age fetus. The fetus corresponded to
30 gestational weeks and weighted 1569 grams. We found severe microcephaly, where HC was
8.6 SD below the mean value for the gestational age (Fig. 2a). Shallow Sylvian fissure was
barely visible (Fig. 2b). Parieto-occipital, cingular and central fissures were absent (Fig. 2c-d).
Mild ventriculomegaly and large pericerebral space were detected (Fig. 2c, e). Also we found
an abnormal cerebral laminar pattern, unusual for the 36th week of gestation (Fig. 2f).
Sonographic findings suggested lissencephaly. The fetus weighted 1800 grams when born at
37 gestational weeks. The baby had difficulty breastfeeding, had an abnormal muscles tone and
died a week after birth. Lissencephaly was confirmed postnatally at autopsy.

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Fig. 2. (a) Severe microcephaly in a retarded fetus. (b) Shallow Sylvian fissure. (c-d) Large pericerebral space (long
arrows) and absent parieto-occipitalis, central and cinguli fissures (short arrows). (e) Thin cerebral mantle (short
arrow) and ventriculomegaly (long arrow). (f) Abnormal cerebral laminar pattern for the 36 th week of gestation.

Discussion

Cerebral cortical development is a complex process characterized by gestational age-specific


changes, comprising three consecutive stages: proliferation and differentiation of neuronal
precursors and glial cells, migration of neurons from the periventricular germinal zone to cortical
plate and cortical maturation [4-10]. Disruption of any stages in cerebral development can result
in a spectrum of cortical malformations, which are common causes of neurodevelopmental delay
[11]. In 1996 the term of Malformation of Cortical Development (MCD) and classification were
introduced [12] and permanently updated [13]. The migration mainly takes place up to the 22nd
week of gestation and ends when germinal matrix disappears, usually by the 28th week [14].
Waves of neuronal migration form a transient laminar pattern [6] determined by synchronized
migration of neurons generated at the same time [15, 16]. Lamination disappears in a variable
manner between 28-34 weeks [17].
Lissencephaly is a rare congenital disorder due to abnormal transmantle migration (radial and
non-radial), including either absence (agyria) or reduction (pachygyria) of cerebral gyri and
subcortical band heterotopia, as all part of the lissencephaly spectrum [13, 14]. Aberrations of
LIS1, DCX, ARX, TUBA1A, RELN and XLIS genes have been reported [18-21]. The
phenotypes caused by lissencephaly are associated with neurodevelopmental delay and poor

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prognosis [4, 11, 13]. There are three groups of lissencephaly. Group A (previous type I), the
most common form, characterized by a thick cortex with four, rather than six layers of neurons.
It may be isolated [22] or associated with phenotypes such as Miller-Dieker syndrome
(17p13.3 monosomy) or the Norman-Roberts syndrome [23]. Group B (previous type II,
cobblestone lissencephaly) characterized by a disorganized, unlayered, uneven cortex and
associated with the Walker–Warburg syndrome [24]. Group C (previous type III), characterized
by fatal akinesia and associated with Neu-Laxova syndrome [25].
Migration defects have diverse sonographic appearances. Lissencephaly may be suspected by
ultrasound when microcephaly, delayed sulcation, wide subarachnoid space and abnormal
cortical lamination are seen. Any decrease in cephalic biometry below 5th percentile raises
suspicion of underlying microcephaly, but “true” microcephaly refers to HC below 3th percentile
or 3 SD below the expected mean for the gestational age, associated in most cases with brain
abnormalities, including lissencephaly [26-29]. Assessment of subarachnoid space, usually
enlarged, is useful for the diagnosis and severity of some brain abnormalities [25, 29].
Anatomical studies have shown that cortical development follows a predictable timetable
throughout gestation [9, 30, 31]. The studies of Malinger et al., [1] and Toi et al., [32]
demonstrate that lissencephaly can be suspected in utero by ultrasound as early as 23 weeks of
gestation, based on the knowledge of deviations from the normal patterns of sulcal development.
As the Sylvian fissure represents the main landmark for gyration and brain maturational
processes, knowledge regarding its shape and depth, according to gestational age, is requiered
[33].
Quarello et al., proposed a semi-quantitative assessment of Sylvian fissure operculization
[34].
Abnormal shape, as well as existing sonographic reference ranges of the depth of brain sulci
in normal fetuses [7] may be helpful in the detection of delayed cortical development. Also,
abnormal fetal cerebral lamination patterns may be visible on sonography. The hipoechoic
subplate and more echogenic intermediate zones are normal transient sonographic laminar
patterns of cerebral development between 17 and 28 weeks and are consistent with histological
studies [6, 35]. Between 28 and 34 weeks cerebral lamination disappears and after 34 weeks is
not visible, since subplate and intermediate zone gradually transforms into white matter and
become isoechoic. Persistence of laminar patterns on ultrasound can be suggestive of migration
disorders [35]. However, they are better seen on fetal MR [36]. Also, fetal MR provides clear
differentiation between lissencephaly and microcephaly with simplified gyral pattern or diffuse
polymicrogyria based on analysis of cortical thickness (cortical ribbon) that cannot be achieved
by ultrasound [37].

Conclusion

Despite the advances in postnatal diagnosis of cerebral migration disorders, many fetuses are
not prenatally diagnosed. Major cortical developmental events occur during the second half of
gestation. Therefore, a routine scan at 18-21 weeks may fail to detect pathological conditions
associated with later events. Prenatal detection of lissencephaly remains challenging and is
possible by ultrasound mostly in the late second trimester or even the third trimester of
pregnancy. Familiarity with normal ultrasound patterns of sulcal development and normal
cerebral lamination patterns according to the gestational age can lead to correct diagnosis. Since
there is a wide spectrum of cerebral involvement in lissencephaly, mostly severe forms can be

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detected on prenatal ultrasound. MR, which is the method of choice for the detection of MCD, is
not always available, has limited use and cannot be a primary method of investigation, even for
fetuses at risk, being useful for abnormal or borderline findings. If lissencephaly suspected,
further investigations should include dedicated fetal neurosonography, MR and appropriate
cytogenetic testing. These second-line assessments will improve management and counseling.

REFERENCES

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diagnosis of malformations of cortical development by dedicated neurosonography. Ultrasound Obstet Gynecol
29, pp. 178-191.
2. Paladini D, Malinger G, Monteagudo A, Pilu G, Timor-Tritsch I, Toi A. (2007). Sonographic examination of
the fetal central nervous system: Guidelines for performing the “basic examination” and the “fetal
neurosonogram.” Ultrasound Obstet Gynecol 29(1), pp. 109-116.
3. B. Cohen-Sacher, T. Lerman-Sagie, D. Lev and G. Malinger. (2006) Sonographic developmental milestones of
the fetal cerebral cortex: a longitudinal study. Ultrasound Obstet Gynecol 27, pp. 494-502.
4. Volpe, JJ. (1995). Neuronal proliferation, migration, organization and myelination. In Neurology of the
newborn, Volpe JJ (ed.). W. B. Saunders: Philadelphia, PA, pp. 43-90.
5. Gray’s Anatomy. (2016). The Anatomical Basis of Clinical Practice, Elsevier. 41 th edition, pp. 261-264.
6. Kostovic I, Judas M, Rados M, Hrabac P. (2002). Laminar organization of the human fetal cerebrum revealed
by histochemical markers and magnetic resonance imaging. Cereb Cortex 12, pp. 536-544.
7. I. Alonso, M. Borenstein, G. Grant, I. Narbons and G. Azumedi. (2010). Depth of brain fissures in normal
fetuses by prenatal ultrasound between 19 and 30 weeks of gestation. Ultrasound Obstet Gynecol 36, pp. 693-
699.
8. Afif A, Bouvier R, Buenerd A, Trouillas J. (2007). Development of the human fetal cortex: study of the
gyration from 13 to 28 weeks. Brain Struct Funct 212, pp. 335-346.
9. Bendersky M, Musolino P, Rugilo C, Shuster G, Sica R. (2006). Normal anatomy of the developing fetal brain.
Ex vivo anatomical-magnetic resonance imaging correlation. J Neurol Sci 250, pp. 20-26.
10. Garel C. (2004). MRI of Fetal Brain. Normal Development and Cerebral Pathologies. Springer-Verlag:
Heidelberg.
11. Norman MG, McGillivray BC, Kalousek DK, Hill A, Poskitt KJ. (1995). Congenital Malformations of the
Brain: Pathological, Embryological, Clinical, Radiological and Genetic Aspects. Oxford University Press: New
York, NY, pp. 223-277.
12. Barkovich AJ, Kuzniecky RI, Dobyns WB, Jackson GD, Becker LE, Evrard P. (1996). A classification scheme
for malformations of cortical development. Neuropediatrics 27, pp. 59-63
13. A. James Barkovich, Renzo Guerrini, Ruben I. Kuzniecky, Graeme D. Jackson and William B. Dobyns. (2012).
A developmental and genetic classification for malformations of cortical development: update 2012. Brain 135,
pp. 1348-1369.
14. Wu Q, Liu J, Fang A et al., (2014). The dynamics of neuronal migration. Adv Exp Med Biol 800, pp. 25-36.
15. Merot Y, Retaux S, Heng JI-T. (2009). Molecular mechanisms of projection neuron production and maturation
in the developing cerebral cortex. Semin Cell Dev Biol 20, pp. 726-34.
16. Lui JH, Hansen DV, Kriegstein AR. (2011). Development and evolution of the human neocortex. Cell 146, pp.
18-36.
17. Rados M, Judas M, Kostovic I. (2006). In vitro MRI of brain development. Eur J Radiol 57, pp. 187-198.
18. Morris-Rosendahl DJ, Najm J, Lachmeijer AM, Sztriha L, Martins M, Kuechler A, et al., (2008). Refining the
phenotype of alpha-1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly. Clin Genet 74, pp.
425-33.
19. Kumar RA, Pilz DT, Babatz TD, Cushion TD, Harvey K, Topf M, et al., (2010). TUBA1A mutations cause
wide spectrum lissencephaly (smooth brain) and suggest that multiple neuronal migration pathways converge
on alpha tubulins. Hum Mol Genet 19, pp. 2817-27.
20. Guerrini R, Parrini E. (2010). Neuronal migration disorders. Neurobiol Dis 38(2), pp. 154-66.
21. Verloes A, Elmaleh M, Gonzales M, Laquerriere A, Gressens P. (2007). Genetic and clinical aspects of
lissencephaly. Rev Neurol (Paris) 163, pp. 533-547.
22. Dobyns WB, et al., (1992). Causal heterogeneity in isolated lissencephaly. Neurol 42, pp. 1375-1388.

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23. Dobyns WB et al., (1984). Syndromes with lissencephaly I: Miller Dieker and Norman Roberts syndrome and
isolated lissencephaly. Am J Med Genet 18, pp. 509-526.
24. Dobyns WB et al., (1985). Syndromes with lissencephaly II: Walker Warburg and cerebro-oculomuscular
syndromes and a new type I lissencephaly. Am J Med Genet 22, pp. 157-195.
25. Allias F, Buenerd A, Bouvier R, Attia-Sobol J, Dijoud F, Clemenson A, Encha-Razavi. (2004). The spectrum of
type III lissencephaly: a clinicopathological update. Fetal Pediatr Pathol 23, pp. 305-317.
26. den Hollander NS, Wessels MW, Los FJ, Ursem NT, Niermeijer MF, Wladimiroff JW. (2000). Congenital
microcephaly detected by prenatal ultrasound: genetic aspects and clinical significance. Ultrasound Obstet
Gynecol 15, pp. 282-287.
27. Pilu G, Malinger G. Microcephaly. Visual Encyclopedia of Ultrasound in Obstetrics and Gynecology.
www.isuog.org [Accessed 15 February 2018].
28. L. Guibaud and A. Lacalm. (2016). Diagnostic imaging tools to elucidate decreased cephalic biometry and fetal
microcephaly: a systematic analysis of the central nervous system. Ultrasound Obstet Gynecol 48, pp. 16-25
29. Guibaud L, Lacalm A. (2015). Etiological diagnostic tools to elucidate ‘isolated’ ventriculomegaly. Ultrasound
Obstet Gynecol 46, pp. 1-11.
30. Chi JG, Dooling EC, Gilles FH. (1977). Gyral development of the human brain. Ann Neurol 1, pp. 86-93.
31. Dorovini-Zis K, Dolman CL. (1977). Gestational development of brain. Arch Pathol Lab Med 101, pp. 192-195.
32. Toi A, Lister WS, Fong KW. (2004). How early are fetal cerebral sulci visible at prenatal ultrasound and what
is the normal pattern of early fetal sulcal development? Ultrasound Obstet Gynecol 24, pp. 706-715.
33. Guibaud L, Selleret L, Larroche JC, Buenerd A, Alias F, Gaucherand P, Des Portes V, Pracros JP. (2008).
Abnormal Sylvian fissure on prenatal cerebral imaging: significance and correlation with neuropathological and
postnatal data. Ultrasound Obstet Gynecol 32, pp. 50-60.
34. Quarello E, Stirnemann J, Ville Y, Guibaud L. (2008). Assessment of fetal Sylvian fissure operculization
between 22 and 32 weeks: a subjective approach. Ultrasound Obstet Gynecol 32, pp. 44-49.
35. D. Pugash, G. Hendson, C. P. Dunham, K. Dewar, D. M. Money and D. Prayer. (2012). Sonographic
assessment of normal and abnormal patterns of fetal cerebral lamination. Ultrasound Obstet Gynecol 40, pp.
642-651
36. Kostovic I, Jovanov-Milosevic N, Rados M et al., (2012). Perinatal and early postnatal reorganization of the
subplate and related cellular compartments in the human cerebral wall as revealed by histological and MRI
approaches. Brain Struct Funct 219, pp. 231-53.
37. Guibaud L. (2009). Contribution of fetal cerebral MRI for diagnosis of structural anomalies. Prenat Diagn29,
pp. 420-433.

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The Effectiveness of Passive Cooling Methods in Neonates with


Severe Perinatal Asphyxia in Maternities with Limited Resources

RADULESCU Luiza1, NASTASE Leonard1,2, MOHORA Ramona1,2,


STOICESCU Silvia1,2
1University Of Medicine And Pharmacy “Carol Davila” (ROMANIA)
2National Institute Of Mother And Child Health (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Neuroprotection with therapeutic hypothermia (TH) is standard of care for perinatal hypoxic-
ischemic encephalopathy (HIE) and it decreases death and neurodevelopmental disability, but in
order to obtain a maximum benefit it must be initiated within the first 3-6 hours of life before the
onset of secondary energy deficiency [2]. For multiple reasons, the transfer of these newborn
cases from lower-level maternities with limited infrastructure and resources is delayed for more
than 6 hours of life. Thus, therapeutic passive hypothermia may be extremely useful in these
cases, or during neonatal transport or while waiting for active hypothermia. We present the case
of a newborn who had suffered asphyxia at birth and who benefited from passive and post-active
therapeutic hypothermia.
Keywords: newborn, hypoxic-ischemic encephalopathy, therapeutic hypothermia, passive cooling

Introduction

Among term infants, an important cause of neurodevelopmental deficit in childhood is


hypoxic-ischemic encephalopathy due to acute perinatal asphyxia. Infants who present moderate
encephalopathy have a death risk of 10 percent, and the survivers have a 60 percent risk of
disabilities. [4]
Therapeutic hypothermia is now the standard of care for newborns with moderate to severe
hypoxic ischemic encephalopathy (HIE), being recognized as an effective intervention in
ameliorating the neurological evolution of this category of newborns. [1]
But in order to obtain a maximum benefit for newborns with HIE, hypothermia should be
initiated before the secondary energetic insufficiency that contributes significantly to the
progression of brain injury, in the first 3-6 hours of life. [3]
Maternities with limited infrastructure and resources may not be able to carry newborns in a
specialized center where therapy may be initiated within 6 hours, which could lead to the
exclusion of newborns who could benefit from this therapy.[2] In order to initiate hypothermia
therapy earlier, some centers have implemented passive cooling (removing newborn external
sources of heat) before initiating active cooling, especially because many hospitals and transport
teams cannot perform active and controlled hypothermia during transport.
We present the case of a newborn who had suffered asphyxia at birth and who benefited from
passive and post-active therapeutic hypothermia.

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Newborn G.R.A-M, female, GA: 40 w, BW:2670 g, p=10-25%, Length:49 cm, p=50%,


PI:2.2, p<10%, vaginal birth, crown presentation.
Maternal history: 37 yo, GII, PII, B-negative blood type, low adequacy prenatal care.
At birth the newborn presented with nuchal cord, meconium stained amniotic fluid, Apgar
Score of 2 at 10 and at 15 minutes of life, partially colored skin, labored breathing and moderate
hypotonia for which it received airway suction, PPV with bag and mask (FiO2=100%), chest
compressions, metabolic corrections (sodium bicarbonate 4.2%).
Afterwards the newborn was transferred in our clinic at 6 hours of life.
On admission the newborn presented with a core temperature of 33 degrees C, cold pale-
cyanotic extremities, meconium impregnated nailbeds, heart rate = 70-110 bpm, O2Sat = 44% at
FiO2:100%. Fig. 1

Fig. 1. Aspect of the newborn on admision

The initial blood tests revealed mixt severe acidosis with a pH of 6.5, undetectable blood
pressure, as well as negative central and peripheral cultures. Fig. 2, 3.

Fig. 2. Arteriolar blood gas measurements: oxygen pressure (pO2), carbon dioxide pressure (pCO2)

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Fig. 3. Arteriolar blood gas measurements:


bicarbonate (HCO3), base excess (BE), anion gap (An Gap), lactat and pH

Imaging studies showed

Transfontanelar ultrasound at 22h of life-severe cerebral edema which evolved and at 2 weeks
of life the newborn presented subependymal hemorrhage, left hypoxic-ischemic periventricular
left frontal region. Fig. 3

Fig. 3. Transfontanelar ultrasound showing severe cerebral edema, with normal right and left lateral ventricles in the
form of slots, and normal falx cerebri

The pulmonary radiography showed a pulmonary hypertransparency suggesting persistent


pulmonary hypertension, which was confirmed by cardiac ultrasound.
The cardiac ultrasound revealed situs solitus with levocardia, consistent vetriculoarterial and
atrioventricular conexions and systemic and pulmonary veins with normal drainage. Also, an
atrial septum defect (ADS) of approximately 5-7 mm. Initially the shunt in the ADS was right-
left and during ultrasound after about 30 minutes it shifted from left-right. During the initial
assessment O2 saturation on the monitor was 37-42% at an FiO2 of 100%. The interventricular
septum was intact. The ductus arteriosus was about 4mm wide, with a left to right initial flow,

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the flow reaching the aorta, the aortic arch, and after about 30 minutes the shunt becomes
bidirectional, predominantly left to right in systole and left to tight in diastole. The valves had
normal morphology. The global kinetics was good. The right cavities were initially dilated, and
subsequently balanced. The aortic arch was normal, and the pericardium was free. Fig. 4, 5

Fig. 4, 5. Cardiac ultrasound: Severe pulmonary hypertension crisis, moderate to severe pulmonary hypertension
(shunt: R->L and during US it shifted from L->R), a small to moderate atrial septal defect and a large PCA

On admission in our NICU it was decided, considering the severe asphyxia to continue with
therapeutic hypothermia, by maintaining the core temperature at 33.5-34 C for up to 12 h of life.
On a respiratory basis, considering meconium aspiration syndrome, HFOV-MV was elected.
Fig. 6

HFOV IPPV SIMV O2tent

Fig. 6. The evolution of the modes of ventilation and oxygen administration

After the catheterization of umbilical vein, iv fluids were administered for hydroelectrolitic
equilibration.
Due to bradycardia and severe unresponsive hypotension inotropes were gradually added to
the treatment, respectively Dobutamine, Dopamine, Adrenaline and Noradrenaline. The blood
pressure was corrected and maintained above 40 mmHg.
For the persistent pulmonary hypertension, Milrinone, Sildenafil and Alprostadil were added
to the treatment. Sedation and curarization were necessary in order to ensure an optimum
ventilation with minimal ventilatory parameters and so, Atracurium and Midazolam were used.
Antibiotherapy was administrated prophilacticaly according to guidelines.
The newborn received three fresh frozen plasma infusions and one platelet transfusion for the
prophylaxis and amelioration of the bleeding syndrome and for thrombocytopenia. (Fig. 7)

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Fig. 7. Changes in neonatal haematological profile

Total parenteral nutrition was initiated from the 1rd day of life. In the 5th day of life trophic
enteral feeding with good gastrointestinal tolerance.

Evolution and development

Under treatment the newborns progress was slowly favorable. Pulmonary hypertension
remitted under treatment with Sildenafil.
On a neurologically basis the newborn presented a normal aEEG (Amplitude-integrated
electroencephalography) in the third day of life (Fig. 8) with moderate axial hypotonia and left
laterocollis. At seven months the infant had a normal neurological exam.

Fig. 8. Two channel (four-electrode) aEEG display. Normal or Continuous Normal Voltage (CNV):
upper margin >10 μV and a lower margin >5 μV. Normal or Continuous Normal Voltage (CNV): upper margin >10
μV and a lower margin >5 μV.

Fig. 9. The newborn at 10 days of life Fig. 10. The newborn at 15 days of life

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Conclusions

Hypothermia has become a standard of care for newborns with GA ≥36wks presenting with
perinatal hypoxic-ischemic encephalopathy (HIE) but its effectiveness depends on speed of
induction. [4]
In order to benefit from this modern therapy the transfer of these newborns must be done in
the first 6 hours of life. From a practical point of view, in case o transport we suggest
noninvasive hypothermic therapy which includes, no heating device during resuscitation,
removing the newborn’s external heat sources, possibly adding them- 1-2 refrigerated gel pads
placed on the thorax or sternum.
Thus, therapeutic passive hypothermia may be extremely useful in these cases, or during
neonatal transport or while waiting to initiate active therapeutic hypothermia.

REFERENCES

1. Gunn AJ, Battin M, Gluckman PD, Gunn TR, Bennet L J. Therapeutic hypothermia: from lab to NICU.
Perinat Med. 2005; 33(4):340-6.
2. Fuentes-Ruiz JA1, Lagares-Franco C, Rodríguez-Molina Ó, Cordero-Cañas E, Benavente-Fernández I.
Assessment of therapeutic passive hypothermia in newborns with hypoxic-ischemic encephalopathy that
need interhospital transport. Rev Neurol. 2015 Apr 1;60(7):303-8.
3. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic
ischaemic encephalopathy. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD003311.
4. Long M, Brandon DH. Induced hypothermia for neonates with hypoxic-ischemic encephalopathy. J Obstet
Gynecol Neonatal Nurs. 2007 May-Jun; 36(3):293-8.

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The Moment for Extracting Intrauterine Growth Restricted


Preterms, a Beneficial Materno-Fetal Factor

STOICESCU Silvia1,2, NASTASE Leonard1,2, MOHORA Ramona1,2,


RADULESCU Luiza1
1University Of Medicine And Pharmacy “Carol Davila” (ROMANIA)
2National Institute Of Mother And Child Health (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Introduction/Background
Prematurity and intrauterine growth restriction are important risk factors for neonatal
mortality and morbidity and they involve a difficult management due to the increase of
complications of prematurity by the effect of a suboptimal growth. [1] Despite recent advances
in fetal investigation and although fetal growth monitoring has improved, [2] due to inconsistent
classification and characterization, lack of treatment and an antenatal surveillance dependent
management, the moment of extraction is still controversial.

Objectives
The evaluation of the relationship between pathological changes detected by ultrasound in the
umbilical artery and middle cerebral artery, associated maternal pathology and perinatal
evolution in intrauterine growth restricted preterm neonates within a third-level maternity.

Methods/Methodology
We retrospectively reviewed data of mother-newborn couples from 2016-2017. The exclusion
criteria for the sample were: newborn malformations, congenital infections, fetal death,
gestational age above 34 weeks.

Results
In the studied group the vast majority of cases of prematurity with intrauterine growth
restriction were caused by maternal hypertension and preeclampsia. These were also the
determining maternal indication in the decision to extract the fetus.

Conclusions/Discussion
By anticipating increased risks for specific neonatal complications and by changing neonatal
management based on information obtained from antenatal assessment we can avoid severe
neonatal complications.
Keywords: intrauterine growth restriction, modified diastolic flow, caesarean section, preterm

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Introduction

Prematurity (gestational age (GA) < 37 weeks) and intrauterine growth restriction (birth
weight < the 10th percentile for GA) are, individually but even more when associated, important
risk factors for neonatal mortality and morbidity. [3]
The management of these newborns is difficult due to the increase of complications of
prematurity by the effect of a suboptimal growth. [1]
Despite recent advances in fetal investigation, particularly in ultrasound and Doppler and
although fetal growth monitoring has significantly improved, due to inconsistent classification
and characterization, lack of treatment and an antenatal surveillance dependent management, the
moment of extraction is still controversial. [2]

Objectives

The evaluation of the relationship between pathological changes detected by Doppler


ultrasound in the umbilical artery, middle cerebral artery and uterine arteries, associated maternal
pathology and perinatal evolution in intrauterine growth restricted preterm neonates within a
third-level maternity.

Methodology

We retrospectively reviewed data of all births in the period 01.01.2016-31.12.2017 in the


National Institute for Mother and Child Health-Polizu Maternity. We selected mother-newborn
couples and obtained maternal and neonatal data from medical sheets. Maternal information was
collected on the possible etiopathogenicity of concomitant prematurity with intrauterine growth
restriction and neonatal information regarding anthropometric growth and adaptation to
extrauterine life. The exclusion criteria for the sample were: newborn malformations, congenital
infections, fetal death, gestational age above 34 weeks.

Results

Between 1 January 2016 and 31 December 2017, 6130 newborns were born, out of which
18.4% (1136 newborns) had a gestation age (GA) at birth <37 weeks and 19% had a birth weight
(BW) of less than 2500g. Among preterm neonates, 53.1% (607 newborns) had a gestation age
between 34-36 weeks, 37.3% (409 newborns) had a gestation age between 29-33 weeks and
10,6% (114 newborns) were below 28 weeks.
The studied sample included 36 mother-newborn couples with 36 preterm newborns with
intrauterine growth restriction (IUGR) born through caesarean section. Fig. 1

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The mean gestational age was 31 weeks, the mean birth weight was 1050.6 g, situated on the
10 percentile, the mean length of the newborn was 38 cm, situated between the 10th-25th
th

percentile, the mean head circumference of the newborn was 27 cm, situated between the 10th-
25th percentile and the mean ponderal index was 1.9 and it was situated below the 10th percentile.
Table 1.
Table 1. Features of IUGR preterm neonates
Gestational age, mean, SD (weeks) 31±1.68 (28-33w)
Birth weight, mean, SD (g) 1050.6±161.9
Length, mean, SD (cm) 38±2.39
Head circumference, mean, SD (cm) 27±1.66
PI, mean, SD 1.9±0.2
Apgar Score at 1 min, mean, SD 5±1.66
Apgar Score at 5 min, mean, SD 6±2.48
Weight at release, mean, SD 2470±326.24

Although the mean Apgar scores were 5 at 1 min and 6 at 5 min showing hypoxia, evaluation
of blood gases in the first hour of life after initiation of resuscitation were relatively normal, thus
indicating an efficient resuscitation. Table 2.

Table 2. Biochemical features of the IUGR preterm neonates


pH, mean, SD 7.2±0.132
Hemoglobin, mean, SD (g/dL) 14.5±2.08
Hematocrit, mean, SD (%) 42.6±6.07
PCO2, mean, SD (mmHg) 49.8±37.9
PO2, mean, SD (mmHg) 95.0±35.61
HCO3, mean, SD (mmol/L) 12.8±8.4
BE, mean, SD (mmol/L) 6.5±5.33
Glucose, mean, SD (g/dL) 42.0±12
Lactate, mean, SD (mmol/L) 4.9±2.75

Doppler ultrasound evaluation indicated that the majority of the fetuses presented anomalies
on the middle cerebral artery, followed by the umbilical artery and the uterine arteries. Table 3

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Table 3. Frequency of Doppler ultrasound abnormal indices in the studied studied group
Blood vessels Abnormal Doppler indices
Umbilical artery 19.4 % (7/36)
Middle Cerebral artery 22.2 % (8/36)
Uterine arteries 8.33 % (3/36)

The treatment was complex and it included positive pressure ventilation, intubation, surfactant
administration and mechanical ventilation. Table 4

Table 4. Resuscitation at birth of the IUGR preterm neonate


Intubation+Surfactant 8.3% (3/36)
PPV (bag and mask) 11.1% (4/36)
T-piece resuscitator 44.4% (16/36)
Free flow O2 5.55% (2/36)
Warmth, stimulation, airway suctioning 33.3% (11/36)

The predominant associated maternal pathology were hypertension disorders, infections and
preterm premature rupture of membranes.
The vast majority of cases of prematurity with intrauterine growth restriction were caused by
maternal hypertension and preeclampsia. These were also the determining maternal indication in
the decision to extract the fetus. Fig. 2.

Fig. 2. Frequency of associated maternal complications in the studied studied group

Conclusions

The moment of extraction was determined based on Doppler ultrasound flow modifications of
middle cerebral artery and umbilical artery, a decision which was supported by the normal mean
head circumference.
Relationships between perinatal outcome, arterial and Doppler status and gestational age
require ongoing observational research effort.

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By anticipating increased risks for specific neonatal complications and by changing neonatal
management based on information obtained from antenatal assessment we can avoid severe
neonatal complications.

REFERENCES

1. Sharma D, Shastri S, Sharma P. Intrauterine Growth Restriction: Antenatal and Postnatal Aspects. Clinical
Medicine Insights Pediatrics. 2016;10:67-83.
2. Alberry M, Soothill P. Management of fetal growth restriction. Archives of Disease in Childhood Fetal and
Neonatal Edition. 2007;92(1):F62-F67.
3. Battaglia FC, Lubchenco LO. A practical classification of newborn infants by weight and gestational age. J
Pediatr. 1967;71(2):159.

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Late Detection of Fetal Congenital Heart Defects – Counseling and


Management Issues – Case Report

RÎCU Anca1, VÂLCEA Ionuţ1, POENARU Mircea-Octavian1,2, CARP Delia1,


SIMA Romina Marina1,2
1
“St. John” Hospital, “Bucur”, Maternity, Bucharest, (ROMANIA)
2
UMF “Carol Davila”, Bucharest, Romania, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

Introduction
Complete atrioventricular septal (AVSD) defect is a common cardiac defect found in 4-5% of
fetuses with a cardiac defect, approximately 0.1% of live births. AVSD can be associate with
other cardiac (such as heterotaxy) or genetic anomalies (such as Down syndrome, which is often
associated with balanced AVSD in up to 45% cases). Surgical intervention before 6 months of
age is a relatively low risk procedure and has recently been reported to significantly improve
morbidity and mortality. Whenever an AVSD is prenatally diagnosed the counselling and
pregnancy management highly depend on the associated anomalies that will impact the
prognosis.

Case report
We present you a case of prenatally diagnosed AVSD in the fetus of a 22-year-old
noninvestigated primigravida woman, who had her first pregnancy ultrasound scan at 30 weeks
of pregnancy. Sonographic findings included AVSD, right isomerism, unilateral renal agenesis
and single umbilical artery. Considering the association of multiple anomalies, genetic diagnosis
was recommended, but the couple denied it. Prenatal evaluation was performed by a team that
included a perinatologist, fetal and pediatric cardiologists, a genetic counselor, a neonatologist
and a pediatric cardiac surgeon. Fetal well-being was followed closely by fetal ultrasound and
nonstress tests. The baby was born at 38 weeks by cesarean delivery, in a relatively good state.
The pediatric cardiology assessment confirmed the diagnosis of AVSD, TAPVR, right
isomerism. The baby was referred to a multidisciplinary center for surgery.

Conclusion
Early diagnosis of AVSD (ideally at 11w-13w6d Scan) is important in order to institute
appropriate medical and supportive treatment and to plan timely surgical intervention.
Keywords: congenital heart desease, outcomes, prenatal diagnosis

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Introduction

The term ‘atrioventricular septal defect’ (AVSD) includes a spectrum of congenital heart
malformations characterized by a common atrioventricular junction associated with deficient
atrioventricular septation. The partial form is characterized by separate atrioventricular valvular
orifices and a common junction, associated with deficiency of the atrial septum primum [1].
Complete atrioventricular septal defect (AVSD) is a common cardiac defect found in 4-5% of
fetuses with a cardiac defect, approximately 0.1% of live births. Complete AVSD is a
combination of an atrial septum primum defect and an inlet ventricular septal defect with a
common atrioventricular valve abnormally arranged with five leaflets.[2], [3]
Prenatal detection of AVSD is very important because it is usually associated with
chromosomal abnormalities such as Trisomy 21, which occurs in at least 50% of all cases [4]. It
is often associated with other cardiac and extracardiac anomalies [5], [6].
This case report aims to emphasise the significance of ensuring positive patient outcomes
through thorough high quality investigation of the fetal heart, during ultrasound screening for
fetal anomaly and was undertaken to examine the impact that prenatal diagnosis and early
management has on birth and early neonatal outcomes.

Case report

A 22-year-old woman presented for a routine ultrasound scan for first time in pregnancy at
that time, at 30 weeks of pregnancy. The patient was a gravida 0, para 0, non-smoker, body mass
index of 21.4, take no medications and there was no relevant familial history. The pregnancy was
a spontaneous conception.
On transabdominal imaging with well visibility, the four-chamber heart view was abnormal
demonstrating an atrioventricular septal defect. Other fetal abnormality included right isomerism,
unilateral renal agenesis and single umbilical artery. (Fig. 1)

a b c
Fig. 1:
(a) Apical four-chamber view showing a complete atrioventricular septal defect
(b) Color Doppler ultrasound of the umbilical cord in which only the right umbilical artery in seen
(c) Unilateral renal agenesis

The 2D real-time ultrasonographic examination revealed biometric measurements appropriate


for 30 weeks of pregnancy. Situs ambiguus and right isomerism was confirmed. The aortic arch
was on left sided. During diastole, the four-chamber heart view acquired, captured the
atrioventricular valve in an open phase and disclosed an open defect in the centre of the heart, at
the cardiac crux. An AVSD was confirmed with equal ventricular volumes and outflow tracts.

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Aortic and pulmonary valves were observed to be of similar diameter. The atrioventricular
valves were, abnormally offset, with chordal attachment at the ventricular crest, and there was no
inflow obstruction or regurgitation. The outflow was unobstructed. Aortic arches were
unobstructed, and the fetal heart rate was normal and register at 165 beats per minute.
Considering the association of multiple anomalies, genetic counselling were discussed with
the patient but she denied it. Prenatal evaluation was performed by a team that included a
perinatologist, a pediatric fetal cardiologist, a genetic counselor, a neonatologist and a pediatric
cardiac surgeon. The immediate fetal and neonatal risks were presented: increased work of
breathing, tachypnoea, poor feeding and weight gain or failure to thrive. Fetal well-being was
followed closely by fetal ultrasound and nonstress tests. The baby was born at 38 weeks by
cesarean delivery, in a relatively good state. The pediatric cardiology assessment confirmed the
diagnosis of AVSD, TAPVR, right isomerism. The baby was referred to a multidisciplinary
center for surgery.

Discussions

Congenital malformations are single or multiple defects identifiable at birth or during the
intrauterine life. Their global birth prevalence is about 2-3%. Both genetic and environmental
factors, as well pesticide exporeas may induce developmental defects [7], [8].
There is no National Registry of congenital malformation or prenatally diagnosed anomalies
in Romania, lacking the reporting obligation. Moreover, the practice of the prenatal diagnosis is
not regulated by therapeutic protocols or agreements, being random and inconsistent, which
mirrors directly on the couple management and counseling in such cases [9].
Congenital heart defects are the most common form of birth defects and have a prevalence
that has been estimated at 7-9 per 1000 births [10].
Major developments in diagnosis and management over the last decade have led to
considerable improvements in survival. Early diagnosis and timely appropriate management of
critical CHDs is indispensable to improve outcome. An antenatal diagnosis permits the clinician
to counsel parents regarding the diagnosis, prognosis and management of CHD. If necessary, a
referral can be made to identify any co-existing chromosomal or extra-cardiac abnormalities.
Parents may use this information to decide whether or not to terminate the pregnancy, and if
they choose to continue the pregnancy [11]. Abortion on demand becoming illegal after 14
weeks of amenorrhoea, in Romania, in the second trimester the medical discontinuation of the
pregnancy is possible only for therapeutic reasons [12].
An AVSD known as atrioventricular canal defect, endocardial cushion defect or AV canal
malformation is subdivided into two types: partial and complete. Partial AVSD includes a
primum atrial septal defect and a split within the left AV valve [13]. 97% of fetal atrioventricular
septal defects identified are of the complete type [14]. Complete AVSD is associated with
chromosomal abnormality, primarily Trisomy 21 (Down syndrome) and Trisomy 18 (Edwards
syndrome) [15].
Differential diagnosis can include: isolated inlet ventricular septal defect, a dilated coronary
sinus associated with a persistent left-sided superior vena cava, isolated linear off set of the AV
valves without a septal defect as seen with Down syndrome, a large unbalanced AVSD
misdiagnosed for a single ventricle heart, persistent left superior vena cava with or without
unroofed coronary sinus, accessory or double orifice left atrioventricular valve, single papillary
muscle in the left ventricle and additional muscular ventricular septal defects [16].

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Atrioventricular septal defect is an significant congenital cardiac abnormality, which can be


diagnosed prenatally with appreciable accuracy. Fetuses with this diagnosis do not form a
homogeneous group but differ in their associations with additional congenital cardiac defects,
visceral heterotaxy and chromosomal disorders [17].
Antenatal diagnosis of complete atrioventricular septal defects is not always easy. When the
atrial and septal defects are large, the four-chamber view shows an obvious deficiency of the
central core structures of the heart. Color Doppler associated with 4D Spatio-Temporal Image
Corelation (STIC) can improve the identification of cardiac structures up to a percentage of 90%
[18], [19]. Color Doppler ultrasound can be useful in that it facilitates the visualization of the
central opening of the single atrioventricular valve [20].
Lateral fetal position during heart assessment can have a negative impact on detection rates of
a small AVSD. Perseverance and techniques to change fetal position must be employed to assure
the highest possible image quality. Prenatal diagnosis of isolated AVSD is associated with an
overall increase of survival rate in the order of 32%. First trimester screening using nuchal
translucency measurements has facilitated early diagnosis of major chromosome abnormality and
has also been shown to be an effective means of screening for heart defects in the absence of
chromosomal abnormality [21].
The prognosis of the congenital heart defects depends upon the association of chromosomal
anomalies, integration in a syndrome or IUGR. The chromosomal anomalies and syndromes
cannot be treated or prevented and the outcome is poor. As for the IUGR there are some studies
that are showing outcome improvement whit Aspirin treatment until 36 weeks [22].
Prenatal diagnosis of isolated atrioventricular septal defect is associated with an increase of
survival rate in the order of 32%. When associated with other cardiac or extra cardiac
abnormalities, the survival rates, however, are very low.The associated risk of Trisomy 21 is
significant at 50-60% [23].
In complete AVSD, symptoms of congestive heart failure and growth restriction appear
shortly post-partum, usually within the first few weeks of life. [11]
Presurgical management of the neonate is mainly performed by cardiologists and general
paediatricians, where symptoms of congestive heart failure and other associated features of
chromosomal anomalies, like Trisomy 21, are monitored and managed in the short term. This
may include the use of diuretics and oral vasodilators such as angiotensin-converting enzyme
inhibitors. [10]
The objective of surgical repair of an AVSD is the removal of the left to right cardiac shunt,
via closure of the atrial and ventricular septal defects using a patch or patches of tissue taken
from the pericardium. Alternatively, a prosthetic patch technique is possible. [11] Reconstruction
of two AV valves is carried out using the abnormal singular AV valve, and the left-sided AV
valve cleft is repaired. [10]
Surgical repair of AVSDs has been successfully performed for the past 50 years. Careful
patient selection criteria, early surgical intervention and advanced post-surgical care have
reduced morbidity and mortality substantially [24].
Post-operatively survival rates are now approximate 91% with mortality during surgery as
low as 2% [2]

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Conclusion

Fetal anomaly screening is an excellent tool to identify significant congenital heart defects
prenatally. Antenatal diagnosis helps in clinical decision making and planning of delivery,
preparing parents for anticipated problems an improves outcome for infants.
Sonographers play a decisive role in the early detection of AVSD. A thorough evaluation of
the four-chamber heart view in both systole and diastole should be a focal point of the routine
second-trimester fetal anomaly scan. Consolidation of high quality training in fetal anomaly
screening and robust clinical governance to monitor detection of congenital heart defects are
crucial in continually improving the detection rate.
Early detection of AVSD allows patient to be offered amniocentesis and adequate genetic
counselling. Parents options will be at a maximum as will prenatal and postnatal management
strategies if an early diagnosis.

REFERENCES

1. Anderson RH, Ho SY, Falcao S, Daliento L, Rigby ML. (1998) The diagnostic features of atrioventricular
septal defect with common atrioventricular junction. Cardiol Young 8, pp 33-49.
2. Abuhamad A, Chaoui R. (2010) A Practical Guide to Fetal Echocardiography, 2 nd edn. Philidelphia:
Lippincott Williams and Wilkins.
3. RobinsonSW, Morris CD, Goldmuntz E, Reller MD, Jones MA, Steiner RD, et al., (2003) Missense
mutations in CRELD1 are associated with cardiac atrioventricular septal defects. Am J Hum Genet 72(4),
pp 1047-52.
4. L. D. Allan, G. K. Sharland, S. K. Chita, S. Lockhart, and D. J. Maxwell, (1991) “Chromosomal anomalies
in fetal congenital heart disease,” Ultrasound in Obstetrics and Gynecology, vol. 1, no. 1, pp. 8-11.
5. B. Craig, (2006) “Atrioventricular septal defect: from fetus to adult,” Heart, 92(12), pp. 1879-1885.
6. L. D. Allan, D. C. Crawford, R. H. Aanderson, and M. Tynan, (1985) “Spectrum of congenital heart
disease detected echocardiographically in prenatal life,” British Heart Journal, 54( 5) pp. 523-526.
7. Giovanni Corsello, Mario Giuffre, Congenital malformations, (2012) The Journal and Maternal-Fetal &
Neonatal Medicine 25, pp 25-29.
8. Moga, M.; Ples, L.; Bigiu, N.; Manitiu, I. (2011). An Overview Of The Risk Of Adverse Reproductive And
Developmental Disorders Due To Exposure To Pesticides Journal Of Environmental Protection And
Ecology 12(3A), pp. 1311-1319.
9. Ples, L; Sima, R M; Stanescu, A D; Olaru OG. The Importance of a National Congenital Anomalies
Registry – the Role of the Prenatal Diagnosis. (2017) Proceeding paper for the 5TH ROMANIAN
CONGRESS OF THE ROMANIAN SOCIETY OF ULTRASOUND IN OBSTETRICS AND
GYNECOLOGY, pp. 505-510.
10. RobinsonSW, Morris CD, Goldmuntz E, Reller MD, Jones MA, Steiner RD, et al., (2003) Missense
mutations in CRELD1 are associated with cardiac atrioventricular septal defects. Am J Hum Genet; 72(4) ,
pp. 1047-52.
11. Yogen Singh, Luke McGeoch, (2016) Fetal Anomaly Screening for Detection of Congenital Heart Defects,
Singh and Geoch, J Neonatal Biol 2016, 5:2
12. Olaru OG, Ionescu CA, Lesnic A, Filipescu G A, Ples L. (2018) Ethical and medico-legal aspects of the
therapeutic abortion – our experience. Rom J Leg Med (26) , pp. 82-85.
13. Henningsen C (2004). Clinical Guide to Sonography. St Louis Missouri: Mosby.
14. Rumack C, Wilson S, Charbonaeu W, Levine D. (2010)Diagnostic Ultra-sound, 4th edn. Philadelphia:
Elsevier/Mosby.
15. Kaufman J, Goldberg S, Ibrahim J, Ivy D, Wise-Faberowski L, Buckvold S, et al., (2010) Complete
atrioventricular septal defects. In: Munoz R, Morell V, Cruz E, Vetterly C, eds. Critical Care of Children
with Heart Disease. London: Springer; pp. 177-89.
16. Corno A (2003). Atrioventricular septal defect. Congenital Heart Defects: Steinkopff; pp. 25-32

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17. Ian C. Huggon, Andrew C. Cook, Nigel C. Smeeton, C Alan G. Magee,Gurleen K. Sharland, (2000),
“Atrioventricular Septal Defects Diagnosed in Fetal Life: Associated Cardiac and Extra-Cardiac
Abnormalities and Outcome”, Journal of the American College of Cardiology, 36(2) 2000.
18. Lima AI, Araujo Júnior E, Martins WP, Nardozza LM, Moron AF, Pares DB. (2013) Assessment of the
fetal heart at 12-14 weeks of pregnancy using B-mode, color Doppler, and spatiotemporal image
correlation via abdominal and vaginal ultrasonography. Pediatr Cardiol 34, pp. 1577-1582.
19. Ionescu, C; Gheorghiu, D; Davitoiu, B; Pacu, I; Vladescu, T (2009). Visualization of the atrioventricular
valve plane in fetuses with atrioventricular defect using STIC technique. GINECO RO 5(4), pp. 210-215.
20. L. D. Allan, G. K. Sharland, S. K. Chita, S. Lockhart, and D. J. Maxwell (1991), “Chromosomal anomalies
in fetal congenital heart disease,” Ultrasound in Obstetrics and Gynecology, 1(1) pp. 8-11.
21. Nicolaides KH, Brizot ML, Snijders RJM. (1994) Fetal nuchal translucency thickness: ultrasound screening
for fetal trisomy in the first trimester of pregnancy. Br J Obstet Gynaecol 1994(101) pp. 782-6.
22. Stanescu AD, Banica R, Sima RM, Ples L. (2018) Low dose aspirin for preventing fetal growth restriction:
a randomised trial. J Perinat Med. 2018 Jan 30. pii: /j/jpme.ahead-of-print/jpm-2017-0184/jpm-2017-
0184.xml. doi: 10.1515/jpm-2017-0184.
23. Dahnert W. (2007) Radiology Review Manual, 6 th edn. Philidelphia: Lippincott Williams and Wilkins.
24. Penny DJ, Vick III GW. Ventricular septal defect. Lancet 377 (9771): 1103.

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Congenital High Airways Obstruction Syndrome – Diagnosis


Principles

RUICAN Dan1, STOICA Alin2,3, SÂRBU Mirela2,4, NOVAC Marius2,5,


ŞOROP-FLOREA Maria2,6, DRĂGUŞIN Roxana-Cristina2,6,
ZORILĂ Lucian-George2,6, CĂPITĂNESCU Răzvan-Grigoraş1,2,
PĂTRU Ciprian-Laurenţiu1,2,6, CERNEA Nicolae1,2, TUDORACHE Ştefania1,2,
ILIESCU Dominic-Gabriel1,2,6
1 University Emergency County Hospital Craiova, Department of Obstetrics and Gynecology (ROMANIA)
2 University of Medicine and Pharmacy Craiova, Department Mother and Child (ROMANIA)
3 University Emergency County Hospital Craiova, Department of Pediatric Surgery (ROMANIA)
4 University Emergency County Hospital Craiova, Department of Neonatology (ROMANIA)
5 University Emergency County Hospital Craiova, Department of Intensive Care (ROMANIA)
6 SC ENDOGYN AM, Craiova, Department of Obstetrics and Gynecology (ROMANIA)

Abstract

Introduction

Congenital high airways obstruction syndrome (CHAOS) refers to a rare condition associated
with poor prognosis in which the trachea or the larynx are blocked due to multiple factors like
laryngeal or tracheal atresia, subglottic stenosis, laryngeal cyst or web-like membranes present at
this level. Prenatal ultrasound findings are characteristic and typically the lungs are bilateraly
enlarged and hyperechogenic, the airways are dilated and the diaphragm is flattened or inversed.
We report here a case diagnosed antenatally and describe the ultrasound and pathology
findings in a fetus congenital high airway obstruction syndrome (CHAOS).

Case report

A 32-year-old woman (gravida 3, para 1) presented in the ER for pelvic and abdominal pain
which appeared 6 hours before admission and had a progressive character. The gestational age
was 24 weeks 2 days and she had 2 abortions-on-demand. Her past medical history and surgical
history was negative. She denied any known drug allergies and she had not taken any
prescription drugs. Her social history was negative for tobacco, alcohol or illicit drug use.
On the ultrasound examination, the fetus had enlarged hyperechogenic lungs with dilated
primary bronchi and trachea and the diaphragm was flattened (Fig. 1). Above the trachea, we
noticed the presence of an obstruction. (Fig. 2)
To determine the fetal management we used an extended fetal morphologic protocol. The
heart was small and centrally situated. Using color Doppler a heart disease was excluded. At the
cephalic extremity examination, the cavum septi pellucidi was increased and the corpus callosum
was hypoplastic. Both the nuchal fold and the prenasal thickness were increased. These findings
were also seen using volumetric ultrasound which, in addition, revealed low set ears. The
abdominal scan revealed ecogenic kidneys and the adrenal glands were not seen. The placeta was

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anteriorly situated and the ombilical cord had a unique umbilical artery. The lack of umbilical
coiling was also noted. The fetus also presented clenched hands.
The patient was counseled about the prognosis of CHAOS and the meaning of the associated
findings. She decided to terminate the pregnancy. Postmortem examination confirmed the
ultrasound findings. The enlarged lungs compressed the heart, and due to their size, the rib marks
were present on the pulmonary surface (Fig. 3). The upper airways obstruction was a laryngeal
obstruction (Fig. 4). In addition, imperforated anus and paraventricular cysts were discovered.
The cysts etiopathology is unknown. The ELISA for patient’s TORCH infection revealed no
recent infection.

Fig. 1. Antenatal ultrasound: (a) large hyperechoic Fig. 2. Sagital view – obstruction above the
lungs; (b) dilated trachea; (c) flattened diaphragm trachea

Fig. 3. Enlarged lungs with rib Fig. 4. Laryngeal obstruction


marks on the surface. Heart
compressed by the lungs

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Discussions

Chaos is a rare malformation, usually associated with poor prognostic and high lethality if it is
not recognised before delivery. The most common cause is laryngeal atresia but other etiologies
include laryngeal or tracheal webs, laryngeal cysts, tracheal atresia, subglottic stenosis or atresia,
and laryngeal or tracheal agenesis.
Physiologically, the liquid produced by the fetal lungs leaves via the trachea. In an obstructed
airway, the intratracheal pressure is increased and the clearance of the fluid is reduced resulting
in enlarged lungs due to the accumulation of fluid. Due to the lung compression, the heart
displaces centrally becomes small with its functions altred and the venous return is decreased
leading to hydrops. [1], [2] Severe subcutaneous edema of scalp, face, neck, and trunk and
markedly distended abdomen are present in fetal hydrops. Facial features like eyes, ears, nose,
and lips can be compressed due to severe edema. [3] When a partial obstruction or a
tracheoesophageal fistula are present, the pathophysiollogy changes. The fluid clearance is not
impaired therefore the lungs to not expand. [4]
This series of modifications is responsible for the ultrasonographic findings. The trachea can
be dilated,the lungs appear enlarged and hyperchogenic and the diafragm can be flattened or
inversed. The fetal heart is centrally displaced and small. Decreased venous return and
dysfunctional cardiovascular system may cause ascites and hydrops. Usually, amniotic fluid
index is normal. However, compression of the esophagus by the dilated trachea may result in
polyhydramnios. Oligohydramnios may be present in some cases, such as Fraser syndrome, or
when there is impaired swallowing or altered renal function. [5], [6]
CHAOS can be associated with other structural abnormalities. The fetus can present
micrognathia and abonormalities of the toes. [7] There are some genetic syndromes associated
with CHAOS such as Short-rib polydactyl syndrome, Shprintzen-Goldberg Omphalocele
syndrome. Furthermore, some chromosomal abnormalities (deletions of 22q11.2, deletion of
chromosome 5p, 47, XXX, partial trisomy 9 and partial trisomy 16q) have been reported in
association with CHAOS. [8], [9] Moreover, CHAOS may be a part of an association, which has
been given the acronym TACRD (Tracheal Agenesis, complex Cardiac anomalies, Radial ray
defects, and Duodenal atresia). [10]
Regarding treatment, there are intrauterine and intrapartum options to manage this condition.
Fetoscopic and ultrasound-guided decompression of the fetal trachea was succesfully used in
a laryngeal atresia asociated with Fraser syndrome. [11] Despite the poor prognosis, neonatal
survival is possible following an ex-utero intrapartum treatment (EXIT). [12], [13]
Unfortunately, the outcome of our case was unfavourable, due to the gestational age at the
first presentation for detailed morphological assessment. Fetal autopsy represents an important
component of ethical and medico-legal aspects of the therapeutic abortion [14-16].

Conclusions

CHAOS is a severe abnormality, where the gestational age and the extent of the ultrasound
anatomical survey at diagnosis are very important for the fetus management if any interventions
are considered. Postnatal therapeutic conduit in new-borns with CHAOS is difficult and usually
the prognosis is poor. Without treatment, the mortality of CHAOS is 100%.

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REFERENCES

1. E. Ekmekci, S. Gencdal, and N. Kiziltug, “Prenatal ultrasonography findings of fetus with congenital high
airway obstruction (chaos): A case report and review of literature,” Clinical Obstetrics, Gynecology and
Reproductive Medicine, vol. 3, no. 5, 2017.
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obstruction syndrome-antenatal diagnosis of a rare case of airway obstruction using multimodality
imaging,” Med J Armed Forces India, vol. 68, no. 1, pp. 78-80, Jan. 2012.
11. T. Kohl et al., “Fetoscopic and ultrasound-guided decompression of the fetal trachea in a human fetus with
Fraser syndrome and congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia,”
Ultrasound Obstet Gynecol, vol. 27, no. 1, pp. 84-88; discussion 88, Jan. 2006.
12. H. Bui et al., “Successful EXIT (Ex Utero Intrapartum Treatment) Procedure in a Fetus Diagnosed
Prenatally with Congenital High-Airway Obstruction Syndrome Due to Laryngeal Atresia,” European
journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] =
Zeitschrift für Kinderchirurgie, vol. 10, pp. 328-33, Nov. 2000.
13. S. Lehmann et al., The EXIT procedure HNO, vol. 61, no. 8, pp. 683-688.
14. Olaru GO, Crangu Ionescu A, Lesnic A, Filipescu GA, Ples L. “Ethical and medico-legal aspects of the
therapeutic abortion – our experience.” Journal of Romanian Legal Medecine 26(1), 82-85
15. Șorop-Florea M, Capitanescu R, Drăgușin RC, Pătru CL, Zorilă LG, Ciurea R, Marinaș C, Tudorache S,
Novac M, Dragoescu A, Stoica A, Gheonea M, Coleta E, Stepan A, Simionescu C, Cara M, Cernea N,
Iliescu DG. “Correlations of the Fetal Anomaly Scan with Fetal Autopsy Results.” Conference Proceedings,
5th Congress of The Romanian Society of Ultrasound in Obstetrics and Gynecology, Targu Mures,
Romania, 20-22 April 2017, First Ed Published June 2017, p. 242-247, ISBN 978-88-95922-88-1.
16. Florea M, Iliescu DG, Tudorache S, Simionescu C, Cernea N, Novac LV, Tanase F, Cotarcea S,
Comanescu A, Dragusin R, Patru C, Carbunaru O, Zorila L, Cernea D. “The importance of perinatal
autopsy. Review of the literature and series of cases” Rom J Morphol Embryol. 2017; 58(2): pp. 323-337.

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Prevalence and Antimicrobial Resistance Pattern of Escherichia


Coli Isolates from Postpartum-Urinary Tract Infections

RUS Maria1, CIRLEA Natalia1, KRASTA Anca1, TAMAS Alina1,


IONESCU Constantin1, DIACONU Mircea1, NITU Razvan1, DRAGOMIR Tiberiu1,
HORHAT Delia1
1University of Medicine and Pharmacy “Victor Babeș” Timișoara (ROMANIA)
Email: [email protected]

Abstract

Aims
The aim of our study was to determine the prevalence of Escherichia coli strains, isolated
from urine cultures of breastfeeding women hospitalized in the Obstetrics and Gynecology
department of a Western Romanian hospital, and their resistance patterns, in particular to beta-
lactam antibiotics.

Methods
Identification of germs and extensive antimicrobial tests (by dilution antimicrobial
susceptibility tests) were done with the help of the automatic Vitek 2C (bio-Mérieux) analyzer.

Results
We isolated 167 microbial strains with hospital acquired potential of 309 urines samples, from
which 128 (76.65%) were Escherichia coli. These strains have been most commonly resistant at
aminopenicillines and I-II generation cephalosporins. All these strains associated other resistance
phenotypes as well.

Conclusions
The high prevalence of Escherichia coli strains resistant to antimicrobial agents isolated in
our study, enforces a proper surveillance of medical staff and a rational necessity to improve our
antibiotic policy.
Keywords: urine cultures, Escherichia coli, resistance phenotype, breastfeeding women

Introduction

Urinary tract infection (UTI) is the most frequent hospital acquired (HA) infection, especially
at hospitalized women who have undergone urological manipulation (frequently catheterization)
[1, 2].
Catheter-related UTIs can be acquired from the patient’s fecal flora, or by transfer of bacteria
from patient to patient through the hands of medical staff.

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The incidence of catheter-associated UTIs depends on the duration and method of


catheterization. Most of the patients undergoing long-term catheterization will develop finally
bacteriuria [3].
HA-UTIs could be produced by resistant organisms and the choice of therapy is dependent on
the antimicrobial sensitivity tests [3, 4].
While breastfeeding, the therapy of UTIs requires more consideration, because of the ability
of certain medications to penetrate the breast milk and it is also affected by the antimicrobial
resistance pattern [5].
Acquired antimicrobial resistance is an increasing-problem worldwide, caused among others,
by the recognized decline of microbial susceptibility, especially to the third and fourth-
generation cephalosporins and the fluoroquinolones [6, 7].
The emergence of new classes of antibiotics becomes a necessity due to the extension of the
multi drug resistance (MDR) phenomenon, characterized by the loss of sensitivity to 3 or more
than 3 categories of antimicrobial agents. At the moment, new different substances have been
tested by numerous researchers but their results can not yet be put into practice [8, 9, 10, 11, 12].

Material and methods

During one year (2016), we collected 309 urine samples from breastfeeding women
hospitalized in the Obstetrics Department’s of the Timişoara Emergency Clinical County
Hospital. From 167 positive urine cultures we isolated 128 Escherichia coli strains.
Urine specimen were cultured by inoculating on culture media (Mac Conkey agar and
Columbia agar supplemented with 5% sheep blood) using a measured quantity of urine with the
help of calibrated loops, designed to provide a known volume. Identification was based on
biochemical characteristics and colonial appearance. Comprehensive antimicrobial sensitivity
tests (dilution method) were done with the help of the automatic with Vitek 2C (bio-Mérieux)
analyzer. For susceptibility tests we used the folowing antimicrobial agents: ampicillin,
amoxicillin/clavulanic acid, piperacillin, piperacillin/tazobactam, cefazolin, cefoxitin,
cefotaxime, ceftazidime, cefepime, imipenem, amikacin, gentamicin, ciprofloxacin, norfloxacin,
tetracycline, nitrofurantoin, trimethoprim/sulfamethoxazole.

Results

We isolated 167 strains with HA potential, of 309 urines samples, from which 128 were
Escherichia coli strains (76.65%).
Emphasis has been placed on beta-lactam resistance, antibiotics preferentially administered to
breastfeeding women.

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Table 1. Resistance of Escherichia coli isolates to ß-lactam antibiotics


ß-lactam antibiotic Susceptible Intermediate Resistant

No. % No. % No. %


Ampicillin 33 25.78% - - 95 74.22%

Amoxicillin/ 81 63.28% 5 3.91% 42 32.81%


clavulanic acid

Piperacillin 33 25.78% - - 95 74.22%


Piperacillin/tazobactam 81 63.28% 11 8.59% 36 28.13%

Cefazolin 33 25.78% 47 36.72% 48 37.50%

Cefoxitin 128 100% - - - -

Cefotaxime 118 92.19% - - 10 7.81%

Ceftazidime 118 92.19% - - 10 7.81%

Cefepime 118 92.19% - - 10 7.81%


Imipenem 128 100% - - - -

Table 2. Resistance of Escherichia coli isolates to other antimicrobials


Antibiotic Susceptible Intermediate Resistant

No. % No. % No. %


Amikacin 123 96.09% - - 5 3.91%

Gentamicin 99 77.34% - - 29 22.66%

Ciprofloxacin 102 79.69% - - 26 20.31%

Norfloxacin 103 79.23% - - 26 20.31%

Tetracycline 122 95.31% - - 6 4.69%


Nitrofurantoin 104 81.25% - - 24 18.75%

Trimethoprim/sulfa 110 85.94% - - 18 14.06%


methoxazole

Discussions

E. coli strains are considered to be important HA and also community acquired pathogens
involved in the aetiology of UTI. Unfortunately, over the last four years (2012-2015), resistance
of the E. coli to third-generation cephalosporins increased significantly, being also associated
with fluoroquinolone and aminoglycoside resistance. Also, in recent times more countries
reported over than 50% resistance to aminopenicillins. Therefore these agents cannot be used for
too long period of time as therapeutically options for the empirical treatment of these infections
[13].
In our study, 10 strains (7.81%), of 128 E. coli strains, were extended spectrum beta-
lactamases (ESBL) producers. This means that bacteria are resistant to aminopenicillins, first,

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second, third and fourth generation cephalosporins, and aztreonam (but not to carbapenems or
cephamycins). Antibiotics recommended to be safe for breastfeeding women are amoxicillin,
cephalosporins, trimethoprim/sulfamethoxazole, nitrofurantoins and ciprofloxacin.
The most frequent cause of ESBL phenotypes is represented by point mutations in the blaTEM,
blaSHV, or blaCTX genes resulting in alterations of the primary amino acid sequence of the enzyme
[14].
Since these genes are generally found on plasmids, many of the organisms that harbor ESBLs
are also resistant to other classes of antibiotics, such as aminoglycosides, fluoroquinolones,
tetracyclines, chloramphenicol, and sulfonamides [15]. Many of these strains are MDR, being
sensitive only to imipenem [16].
In this study, third and fourth-generation cephalosporin resistance have been associated with
resistance to aminoglycosides and fluoroquinolones. We have not isolated any resistant strain to
imipenem or cefoxitin.
There is a considerable geographical difference in the occurrence of ESBLs in the European
countries. In a SENTRY worldwide surveillance program report, ESBL phenotypes were
detected in 1-8% of E. coli strains [17].
E. coli strains from our study have also been resistant to: aminoglycosides (22.66%),
quinolones (20,31%), tetracyclines (4.69%), trimethoprim/sulfamethoxazole (14.06%) and
nitrofurantoin (18.75%).
Minimal invasive procedures that require shorter hospitalisation are to be encouraged in order
to lower the risk for infection. [18]

Conclusions

In our study, 7.81%, of E. coli isolated strains, were (ESBL) producers and no carbapenemase
producing strains have been reported.
Detection of the ß-lactam resistance phenotypes of the E. coli clinical isolates is very
important because of the therapeutic issues related to the fact that these antibiotics are
preferentially administered to breastfeeding women.
In this regard, a proper surveillance of medical staff and a rational necessity to improve our
antibiotic policy are needed.

Informed consent of Patients and Study Participants


This study was approved by the local Ethics Comittee. The breastfeeding women were
included in our study only after obtaining their informed consent and based on the norms of
ethics generally applicable regarding the human individual protection according to the
stipulations of Law no. 206/2004. The 98/44/EC and 2001/20/EC Norms of the European
Parliament and the Council of European Union regarding the protection of personal data and the
deployment of good clinical practice have been respected.

REFERENCES

1. Licker,M., Moldovan, R., Hogea, E., Muntean, D., Horhat, F., Baditoiu, L., et al., (2017). Microbial biofilm
in human health-an updated theoretical and practical insight. Romanian Journal of Laboratory Medicine
25(1), pp. 9-26.

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2. Pirtea, L., Raica, M., Cimpean, A. (2012). Endothelial cell activation and proliferation in ovarian tumors:
Two distinct steps as potential markers for antiangiogenic therapy response. Molecular medicine reports
5(5), pp. 1181-1184.
3. Chiţă, T., Timar, B., Muntean, D., Bădiţoiu, L. Horhat, F. Hogea, E. Moldovan, R. Timar, R. Licker, M.
(2017). Urinary tract infections in Romanian patients with diabetes: prevalence, etiology, and risk factors.
Therapeutics and clinical risk management 13, pp.1-7.
4. Horhat, F G., Gundogdu, F., David, V., et al., (2017). Early Evaluation and Monitoring of Critical Patients
with Acute Respiratory Distress Syndrome (ARDS) Using Specific Genetic Polymorphisms. Biochemical
Genetics 55(3) pp. 204-211.
5. 5. Sarau, C., Lighezan, D., Doros, I., et al., (2015). The involvement of upper airway in Wegener’s
granulomatosis – about four cases. Romanian journal of morphology and embryology 56(2) pp. 613-618.
6. David, V., Ercisli, M,. Rogobete, A,. et al., (2017) Early Prediction of Sepsis Incidence in Critically Il
Patients Using Specific Genetic Polymorphisms. Biochemical Genetics 55(3), pp. 193-203.
7. Licker, M., Anghel, A., Moldovan, R., Hogea, E., Muntean, D., Horhat, F., et al., (2015). Genotype-
phenotype correlation in multiresistant Escherichia coli and Klebsiella pneumoniae strains isolated in
Western Romania. European review for medical and pharmacological sciences 19(10), pp. 1888-1894.
8. Ledeţi, I., Bercean, V., Alexa, A., Şoica, C., Şuta, LM., Dehelean, C., et al., (2015). Preparation and
antibacterial properties of substituted 1, 2, 4-triazoles. Journal of Chemistry 2015, ID 879343,
doi:10.1155/2015/879343.
9. Pavel, IZ., Danciu, C., Oprean, C., Dehelean, C., Muntean, D., Csuk, R., et al., (2016). In vitro evaluation of
the antimicrobial ability and cytotoxicity on two melanoma cell lines of a benzylamide derivative of
maslinic acid. Analytical Cellular Pathology 2016, ID 27876232016.
10. Danciu, C., Borcan, F., Soica, C., Zupko, I., Csanyi, E., Ambrus, R., Muntean, D., et al., (2015).
Polyurethane Microstructures-a Good or Bad in vitro Partner for the Isoflavone Genistein?. Natural product
communications 10(6), pp. 951-954.
11. Oprean, C., Zambori, C., Borcan, F., Soica, C., Zupko, I., Minorics, R., Bojin, F., et al., (2016). Anti-
proliferative and antibacterial in vitro evaluation of the polyurethane nanostructures incorporating
pentacyclic triterpenes. Pharmaceutical biology 54(11), pp. 2714-2722.
12. Horhat, F., Rogobete, A., Papurica, M., et al., (2016). The Use of Lipid Peroxidation Expression as a
Biomarker for the Molecular Damage in the Critically Ill Polytrauma Patient. Clinical Laboratory 62(9), pp.
1601-1607.
13. Lorian, V. (2005). Antibiotics in laboratory medicine. Lippincott Williams &Wilkins.
14. Annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). (2015).
Antimicrobial resistance surveillance in Europe. Stockholm 2017. ISBN 978-92-9498-029-8; doi
10.2900/6928.
15. Winokur, PL., Canton, R., Casellas, JM., et al., (2001). Variations in the prevalence of strains expressing an
extended-spectrum-beta-lactamase phenotype and characterization of isolates from Europe, the Americas,
and the Western Pacific region. Clin Infect Dis 32(Suppl 2), S94-S103.
16. Nathisuwan, S., Burgess, DS., Lewis, JS. (2001). Extended-spectrum beta-lactamases: epidemiology,
detection, and treatment. Pharmacotherapy 21, pp. 920-928.
17. Bush, K. (2001). New ß-lactamases in Gram-negative bacteria: diversity and impact on the selection of
antimicrobial therapy. Clin Infect Dis 32, pp. 1085-1089.
18. Pirtea L, Sas I, Ilina R, Grigoras D: Transversal incision of the vagina favors the remaining of the tape in the
middle-thkd uretlra compared to longitudinal incisio.n during transobturator sling procedures for stress
urinary incontinence; BMC Surg. 2015 Jul l7;15:84.

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Omega-3 Supplementation During Pregnancy to Prevent Different


Obstetrical Complication: Systematic Review of Literature

SANDULESCU Maria Sidonia*,1, VICOL Mircea Ramona*,2,


MANOLEA Magdalena1, PATRASCU Anca1, VELISCU Andreea3
1 Universitatea De Medicina Si Farmacie, Spitalul Municipal Filantropia, Craiova (ROMANIA)
2 Universitatea De Medicina Si Farmacie, Carol Davila, Bucuresti, Insmc Alessandrescu-Rusescu, Bucurest (ROMANIA)
3 Universitatea De Medicina Si Farmacie, Carol Davila, Bucuresti, Spitalul Clinic De Obstetrica-Ginecologie Prof Panait

Sarbu, Bucuresti (ROMANIA)


* First two authors contributed equally to the manuscript

Email: [email protected]

Abstract

Intrauterine growth restriction (IUGR) is a complication of pregnancy that can be associated


with increased risk of neonatal mortality and morbidity. Women who have a prior pregnancies
complicated by IUGR is the highest risk group and a lot of studies show that those patients have
an increased risk of approximately 20% for recurrence of IUGR in a subsequent pregnancy.
Along with IUGR, premature birth, spontaneous abortion, preeclampsia are just some of the
major complications of a pregnancy that can lead to increased neonatal morbidity and mortality.
One of the most important risk-reducing factors is represented by the change in the patient’s
lifestyle. About the diet, all pregnant women should eat a well-balanced diet incorporating a
variety of food, including fish. It has been suggested that during pregnancy, supplementing with
fish oil – or increasing the amount of fish in the diet – prevents pregnancy-induced hypertension,
prolongs gestation, increases the baby’s birth weight.
The aim of this study is to evaluate the efficacy of omega-3 supplementation during
pregnancy in reducing the incidence of IUGR, premature birth, preeclampsia, postnatal
depression, etc by studying the papers published so far.
Keywords: birth weight, omega 3, intrauterine growth restriction, premature birth, depresia

Introduction

Omega-3 Long Chain Polyunsaturated Fatty Acid (LCPUFA) it is characterized by a double


bond at the third carbon atom from the methyl end of the carbon chain. (1) Some of this fatty are
essential for humans, in particular alpha-linoleic acid (ALA), eicosopentaenoic acid (EPA) and
docosohexaenoic acid (DHA). (2) Major dietary sources of omega-3 LCPUFA are fish and
seafood so, their levels vary worldwide, depending on local dietary customs and habits. (3, 4)
The studies published so far have demonstred that LCPUFA are present in all human tissues
and they may also play a proprietary structural role, which have many functional implications.
(5)
Omega-6 derivatives promote inflammation, while omega-3 derived agents (such as resolvins
and protectins) exert opposing effect. (6) For this reason, a balance of LCPUFA is important for
a normal inflammatory response. (7, 8) Onother important role of omega 3 is that is involved in

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maintenance of the balance between generation of reactive oxygen and nitrogen species and
antioxidant defense. (1-10) Excessive inflammatory and/or oxidative stress may disrupt the
process that can potentially leading to pregnancy disorders. (5)
The first moment when the organism need for PUFA – “polyunsaturated fatty acids” (both
Omega-6 and Omega-3) related to pregnancy occurs during the last 3 months before birth (25th
and 35th week of pregnancy). (10-12) This critical period in terms of cell division requires ARA
(polyunsaturated fatty arachidonic acid) and DHA to facilitate development because DHA is
important for the optimal development of the nervous system and during the last trimester of
pregnancy. (12-14) A feeding of the mother rich in DHA will increase the concentration of DHA
in the blood of the newborn baby. (13-17)
It has been suggested that during pregnancy, supplementing with fish oil – or increasing the
amount of fish in the diet – prevents pregnancy-induced hypertension, prolongs gestation,
increases the baby’s birth weight and reduces the possibility of premature birth. (1-15) Recent
data suggest that during pregnancy the amount of DHA that should be consumed is at least 0.1-
0.4 g/day. (2-10)

Methods

We made a systematic literature search on the PubMed database of English literature (search
terms was omega 3, premature birth, IUGR, preeclampsia, postpartum depresion) from 2010 to
2017 and cross referencing. We gave priority to meta‐analyses, randomized controlled trials
reviews and cohort studies. We analyzed the benefits of omega 3 suplimentation during
pregnancy.

Results

1. IMPLICATION OF OMEGA 3 IN PRETHERM BIRTH PREVENTION


Preterm birth accounts for more than 85% of all perinatal complications and deaths and the
most premature birth occur spontaneously, without identifiable risk factors. (12-18) A lot of
studies are focused on finding a broadly applicable and effective strategy for primary preventions
for this complication. (13-14) Many authors showed that maternal supplementation until delivery
with omega-3 long chain polyunsaturated fatty acid (LCPUFA), predominantly as DHA, resulted
in a 50% reduction in the incidence of EPTB and an increase in the incidence of post-term
induction or post-term prelabour caesarean section due to extended gestation. (17-19) These
conclusions are based on the fact that the balance between the metabolites of 3 and 6 fatty acids
plays an important role in the maintenance of normal gestation length and is a critical element in
cervical ripening and the initiation of labour. (1-5) It has been shown that if local production of 6
derived prostaglandins within the fetoplacental unit is too high, or local accumulation of 3
LCPUFA is too low, the cervix may prematurely ripen and uterine contractions increase, which
may in turn lead to preterm birth. Because of this reason, WHO recommends an intake of 300
mg/day of 3 LCPUFA for pregnant women. (20-25)
The strongest evidence to support the efficacy of 3 LCPUFA supplementation to reduce
EPTB comes from our docosahexaenoic acid (DHA) to Optimise Mother Infant Outcome
(DOMInO) trial, the largest trial to date of 3 LCPUFA supplementation in pregnancy. DOMInO
was designed to assess the effect of 3 LCPUFA supplementation during the last half of
pregnancy on the prevalence of postnatal depression in women and on early childhood

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neurodevelopmental outcomes. (10-15) In this study, they have shown that women delivering
prematurely had markedly decreased n-3 DHA and elevated n-6 arachidonic acid (ARA) and n-6
linoleic acid (LA) pools in both RBC membranes and plasma phospholipids and increased RBC
membrane n-6 docosapentaenoic acid (DPA), a biomarker for n-3 fatty acid insufficiency. (20-
27) This report demonstrated that supplementation with 300-600mg/day DHA from the 20th
week of pregnancy resulted in a 2.9-day increase in gestational length accompanied by increased
birth weight, length, and head circumference and reduction in preterm birth at <34 weeks.
However, results from randomized controlled trials remain inconclusive. (25-27)

2. OMEGA 3 SUPPLEMENTATION FOR PREVENT INTRAUTERINE GROWTH


RESTRICTION
Many meta-analyses have evaluated the efficacy of omega-3 supplementation during
pregnancy. (3-8) The use of omega-3 supplementation during pregnancy has been studied as a
possible strategy to prevent several conditions, e.g. PTB, pre-eclampsia and IUGR, as well as to
increase birth weight. (1) The theories behind the studies were based on observations of longer
gestation in communities with a high consumption of fish oil but the biological plausibility is not
completely clear. (15) Long chain polyunsaturated fatty acids may delay initiation of cervical
ripening by inhibition of the production of prostaglandins. (16) They decrease the synthesis of
PGE2, by switching the PGs synthetic pathway from PGE2 to PGE3, which has anti-
inflammatory effects. Moreover, omega-3 fatty acids increase placental labyrinthine antioxidant
capacity. (1-6) It has been hypothesized that omega-3 increases fetal growth rate by improving
placental blood flow due to a lowered thromboxane/prostacyclin ratio and blood viscosity by
correcting the imbalance in vasoactive PG. (10-14)
Based on these studies, omega-3 supplementation during pregnancy can be recommended
currently for prevention of IUGR in women with singleton pregnancies and a history of
pregnancy complicated by IUGR. (28-29) Since the year 1986, Olsen et al., suggested that intake
of omega-3 during pregnancy may increase fetal and birth weights. (9-12, 30-32)

3. OMEGA 3 SUPPLEMENTATION FOR PREVENT PREECLAMPSIA


During pregnancy, the number of blood lipids and triglycerides, but also cholesterol levels or
blood pressure may increase. (10,33 )The risk of suffering pre-eclampsia and the possibility of a
premature birth increases if these otherwise normal increases exceed certain levels. Due to the
significant hypoglycemic (triglyceride) and hypotensive effects of Omega-3 fatty acids, together
with other nutrients may prove useful in preventing pre-eclampsia. (34-36)
There are numerous health benefits associated with n-3 LCPUFA (2-7). The vast majority of
health benefits attributed to n-3 LCPUFA is in cardiovascular disease. The GISSI prevenzione
trial showed that supplementation of 0.85g of EPA and DHA per day in men who had a previous
myocardial infarction resulted in 20% reduction in total death, 30% reduction in cardiovascular
death and 45% reduction in sudden death (5).
Fatty acids in general, and LCPUFA in particular, play numerous roles at this stage of the
pregnancy. During implantation, they are required as structural components and functional
regulators for normal a growth process. (25) AA and its prostaglandin derivatives are important
as mediators of vascular permeability and cytotrophoblast invasion. However, excessive action
of prostaglandins may result in implantation failure. Therefore, abnormal omega-3/omega-6 ratio
may support excessive inflammatory and oxidative events, that hamper or disrupt embryo

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development and placentation. Later on, during the first trimester, LCPUFA stimulate the
expression of various factors, that help trophoblasts in their angiogenic mission. (26-32)
Oxidative stress in placenta occurs naturally, when invading cytotrophoblasts encounter a
steep positive oxygen tension gradient. This gradient might regulate cytotrophoblast proliferation
and differentiation. (1-5, 30-37) LCPUFA play dual role in this process. Omega-3 fatty acids and
particularly DHA reduce placental oxidative stress and increase the levels of resolvins and
protectins that also help to keep oxidation at bay. (30-35)
Increasing the amount of Omega-3 fatty acids during pregnancy is a prudent recommendation
that will act beneficial to the heart and circulation of the mother, and DHA will definitely
contribute to brain development of the fetus' nervous system. (10)

4. OMEGA 3 FOR PREVENT DEPRESION IN PREGNANCY


Safe strategies for managing depression in pregnancy are needed, and the possible efficacy of
omega-3 polyunsaturated fatty acids (PUFA) for depression, especially eicosapentaenoic acid
(EPA), has been suggested. (23-30) Generally, fish consumption is higher and the prevalence of
depression is lower in East Asian countries, such as Japan and Taiwan, compared to Western
countries, but there are considerable differences among East Asian countries. (22-30) It is
difficult to exclude the possibility that improvement of depression is due to a placebo effect,
spontaneous remission or improvement. (35-37)

Conclusions

Based on this data, omega 3 supplementation during pregnancy can be recommended because
it is very useful in preventing many complications. The study of effectiveness of LCPUFA on
pregnancy is just beginning and much more research is needed to prove its benefit.

REFERENCES

1. American College of Obstetricians and Gynecologists. ACOG Practice bulletin no.134: fetal growth
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9. Kaviani M, et al., The effect of Omega-3 fatty acid supplementation on maternal depression during
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20. Bohiltea, R (Bohiltea, Roxana); et al., The Incidence of Prematurity and Associated Short-Term
Complications in a Multidisciplinary Emergency Hospital from Romania Edited by: Vladareanu S;
Marginean C; Vladareanu R Source: 5TH ROMANIAN CONGRESS OF THE ROMANIAN SOCIETY OF
ULTRASOUND IN OBSTETRICS AND GYNECOLOGY Pages: 105-112 Published: 2017.
21. Decsi T, et al., Effect of n-3 polyunsaturated fatty acid supplementation in pregnancy: the Nuheal trial. Adv
Exp Med Biol 2005; 569: pp. 109-113.
22. Tofail F, et al., Supplementation of fish-oil and soy-oil during pregnancy and psychomotor development of
infants. J Health Popul Nutr 2006; 24: pp. 48-56.
23. Makrides M, et al., Effect of DHA supplementation during pregnancy on maternal depression and
neurodevelopment of young children: a randomized controlled trial. JAMA 2010; 304: pp. 1675-1683.
24. Ionescu, C et al., Fetal-maternal toxicology: fetal somatic consequences of noxious habits in pregnant
women. ROMANIAN JOURNAL OF LEGAL MEDICINE Volume: 25 Issue: 1 Pages: 82-88 DOI:
10.4323/rjlm.2017.82 Published: APR 2017.
25. Colombo J, et al., Maternal DHA and the development of attention in infancy and toddlerhood. Child Dev
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27. Borod E, et al., Effects of third trimester consumption of eggs high in docosahexaenoic acid on
docosahexaenoic acid status and pregnancy. Lipids 1999; 34: (Suppl) 231.
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30. Smuts CM, et al., A randomized trial of docosahexaenoic acid supplementation during the third trimester of
pregnancy. Obstet Gynecol 2003; 101: pp. 469-479.

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31. D’Almeida A, et al., Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil
(eicosapentaenoic+docosahexaenoic acid) versus magnesium, and versus placebo in preventing
preeclampsia. Women Health 1992; 19: pp. 117-131.
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controlled trial. Obstet Gynecol 1998; 91: pp. 585-590.
33. D. Iliescu et al., Feasbility of neurosonogram adjusted with recently described markers at the 11-13 +6
week scan, Conference Proceedings Advance in Perinatal Medicine, XXII European Congress of Perinatal
Medicine, Granada, Spain, May 26-29, 2010, pp. 143-148, Publisher: MONDUZZI EDITORI, ISBN 978-
88-6521-027-7.
34. Manolea, Maria Magdalena; et al., Yolk Sac and Embryonic Heart Rate as Predictors for Early Pregnancy
LossEdited by: Vladareanu, S; Marginean, C; Vladareanu, R Conference: 5 th Romanian Congress of the
Romanian-Society-of-Ultrasoundin- Obstetrics-and-Gynecology Location: Targu Mures, ROMANIA Date:
APR 20-22, 2017 Sponsor(s): Romanian Soc Ultrasound Obstetr & Gynecol pp. 318-323.
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fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci U S A 2003; 100: pp. 1751-1756.

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An Interesting Case of Placental Abruption


SERBANESCU Lucian1, COSTEA Daniel Ovidiu2
1Department of Obstetrics & Gynecology, Faculty of Medicine, Ovidius University from Constanta, (ROMANIA)
2Department of General Surgery, Faculty of Medicine, Ovidius University from Constanta, (ROMANIA)
Email: [email protected]

Abstract

We present an interesting case of placental abruption in a 16-years-old pregnant woman at 24


weeks of gestation, who gave birth by caesarean section.
The specificity of the case consisted in the fact that, although the pregnancy was only 24
weeks and the placenta was detached in over two-thirds of the surface, the fetus survived. The
uterus, although present in the bloodstream, responded to the ergometrine maleate with a positive
Reeb test, and remained in place. The primary etiological factor considered to be involved in this
case was pregnancy-induced high blood pressure and smoking as a secondary factor (the patient
smoked about 20 cigarettes per day).
Cesarean emergency surgery has proven to be vital to both the mother and the fetus.
Keywords: placental abruption, aetiological factors, high blood pressure, smoking

Introduction

Placental abruption (PA) or premature detachment of a normal insertion of placenta represent


a complication of pregnancy occurring usually in the third trimester, leading to a better
monitoring of both mother and fetus. Between many risk factors involved, the alterations of
morphological and functional functions together with hypertension are also seen to occur. The
breakdown of maternal blood vessels showed to be the main mechanism approach [1].
In these report, we present a patient with PA in which the evolution has been favorable for
both the patient and the fetus, considering the presence of the etiological factors involved.

Case Report

Patient I.S. aged 16, pregnant in 24-25 weeks, was hospitalized by emergency service of “Sf.
Apostol Andrei” Emergency Hospital Clinic from Constanta, Romania for lumbar and moderate
vaginal bleeding. The informed consent of the patient was taken.
The clinical examination reveals the pale, agitated, scared patient. Upon palpation of the
uterus, there was a hypercontractile uterus, characteristic of the “wooden uterus”.
Fetal active movements (FAM) were difficult to perceived.
From the examination with the valves, there was a null, non-inferior cage, in which the blood
appears in a moderate amount. At the vaginal touch it was observed that the cervix was short,
admited the medius, the intact membranes, with an the mobilizable presentation.
Blood pressure was 180/100 mmHg, with ventricular aura of 100 bpm, present fetal heart beat
of 90 bpm. There was a suspicion of a premature detachment of a normally inserted placenta

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(placental abruption). At the echographic examination: a retroplacentar, a hypoecogenic


formation was seen to take off approximately 2/3 of the placental surface, being a hematoma of
approximately 600-700 ml. The placenta touches the inner cervix of the uterus with the lower
pole.
Emergency hemoleogram shows: leukocytes 24.91 thousands/μl [normal range=3.500-
10.500/µl], hemoglobin 7.8g/dl [normal range=12.1-15.1g/dl], hematocrit 22.7% [normal
range=36.1-44.3%], platelets 104.000/μl[normal range=160 000-450 000/mm3].
It was established as a diagnosis: primigravida, primipara, pregnancy 24-25 weeks, intact
membranes, single fetus alive, suspicion of placental abruption.
Emergency intervention occurs and caesarean section was performed in about 15-20 minutes
and a live fetus, weighing 550g was extracted, with Apgar score 1.
Under the placental surface a hematoma of approximately 600-700 ml was shown.
The uterus was contracted at the ergometin maleate (Positive Reeb Test). Moreover, it was
showed to have numerous blood subfunds extending to the uterus and both bilaterally to
salpinge.
The evolution of the case was favorable. Postoperativ hemoleogram: 17.52 thousands/ul
leukocytes, 7.2g/dl hemoglobin, 21.1% hematocrit and 107.000/µl platelets.
The uterus contracts, and vaginal bleeding was physiological. The patient was re-equilibrated
with 2 IU of izogrup izoRh blood. Miraculously the fetus survived, and its evolution was
favorable over time.
Evolution of the patient was favorable under uterotonic, antialgic and antihypertensive
therapy (Dopegyt 1 cpr/8h).

Discussions

Placental abruption remains one of the most obstetric emergencies, and its appearance “as a
stroke on a clear sky” can have dramatic effects on both the fetus and the patient. Although, in
our case, evolution has been favorable for both the patient and the fetus, this is a relatively rare
condition [1, 2, 3].
The retroplacental hemorrhages seen in our case could be due to the evolution of two factors,
arterial and venous [2, 3]. Although arterial pressure exceeds venous pressure; it was showed to
be maximal in the central 2/3 of the placental. That’s way the placental abruption is most seen in
the central part, which could result in fast delivery and fetal hypoxia [2, 3, 4]. The arterial
hemorrhage appears mostly in cases with preeclampsia [2, 3, 4, 5, 6], ischemia-reperfusion injury
[7] or stress due to traumatic injuries [2, 8]. In contrast, venous hemorrhage showed to develop at
peripheral part, being less supported comparing with central veins being also a consequence of
oxidative stress and are largely correlated with age [5].
The retroplacental hematom volumes are in correlation with the gravity of the clinical form
[1, 9].
In our case, the fact that the patient presented himself urgently at the hospital and the
diagnosis and surgery were carried out quickly, led to a favorable resolution.
Placental low insertion led to the lower placental pole detachment and vaginal bleeding
exteriors, was quickly noticed by the patient, who had an emergency on the hospital.
Although, the association of placental abruption is often a case of sever gravity [1, 9], the
amount of vaginal bleeding is summed up with the accumulated in the hematoma, basically the
effect is amplified (vaginal bleeding + blood hematoma + coagulapathy) [1, 7, 9].

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Pregnancy height blood pressure and smoking were the main etiologic factors suspected of
being involved in the production of placental abruption in this case, the patient being also a
smoker (over 20 cigarettes a day).
Pregnancy height blood pressure and smoking are the major etiological factors involved in the
production of placental abruption [1, 2, 9, 10, 11, 12].
In this case, we cannot exclude drugs abuse. One of the important etiological factors of
placental abruption is drugs abuse [1, 9, 13].
Although, the uterus had numerous blood subfusions, the Reeb Test was positive witch let to
the maintenance of the uterus.
This was probably due to the fact that the diagnosis was made in a timely manner and that
cesarean surgery was performed urgently before necrotic uterine hypoxia was established when
the process would become virtually irreversible.
If uterine necrosis was installed and Reeb’s trial was negative, hysterectomy of necessity
would have been inevitable.
Hysterectomy of necessity in such cases may be accompanied by bilateral anexectomy if the
necrosis process also includes the annexes [1, 9, 14].

Conclusions

Placental abruption remains one of the greatest obstetric emergencies.


Furthermore, pregnancy induced hypertension and smoking remain the major etiological
factors involved in the development of these condition.
Diagnosing and treating the patients in the shortest possible time are paramount in the
development of the case.

REFERENCES

1. Tica, V.I., Şerbănescu, L., Tica, Irina. (2006). Etiologic, clinical and prognostic correlations in abruptio
placentae. Rev Med Chir Soc Med Nat Iaşi. 110 (3), pp. 633-8.
2. Tica VI, Şerbănescu L, Zaher M. (2006). Dezlipirea prematură de placentă normal inserată – istoric,
frecvenţă, etiologie, recurenţă. Gineco.ro. II(6), pp. 16-18.
3. 3.Okamoto, PP., Cesar, NAS., Silva, RF. (2016). 146 Early placental abruption – Case report in a teriary
service in Western Amazon: Perinatal outcomes. Pregnancy Hypertension: An International Journal of
Women’s Cardiovascular Health 6(3), p. 252.
4. Harris, BAJr., Gore, H., Flowers, CEJr (1985). Peripheral placental separation: a possible relationship to
preamature labor. Obstet Gynecol 66, pp. 774-778.
5. Matijevic, R., Meekins, JW., Walkinshaw, SA. et al. (1995). Spiral artery blood flow in the central and
peripheral areas of the placental bed in the second trimester. Obstet Gynecol 86, pp. 289-292.
6. Brosens, IA., Robertson, WB., Dixon, HG. (1972). The role of the spiral arteries in the pathogenesis of pre-
eclampsia. In: Wynn R, ed. Obstetrics and Gynecology Annua. New York, NY: Appleton Century Crofts,
pp. 177-191.
7. Thiéba, B., Lankoandé, J., Akotionga, M., Koné, B., Ouédraogo, A., Kyelem, C. (2003). The Placental
Abruption in the Gynecology and Obstetrics Department of the National Hospital Center Yalgado
Ouédraogo of Ouagadougou: Epidemiological, Clinical and Prognostic Aspects. Gynécologie Obstétrique &
Fertilité 31, pp. 429-433.
8. Nothenberger, D. Blunt maternal trauma: a review of 103 cases. (1978). J Trauma 18, pp. 183-189.
9. Șerbănescu, L. (2008). Aspecte anatomice, clinice, morfopatologice și terapeutice în cadrul dezlipirii
premature de placentă normal inserate. Teză Doctorat.

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10. Witlin, AG., Saade, GR., Mattar, F. et al. (1999). Risk factors for abruptio placentae and eclampsia: analysis
of 445 consecutively managed women with severe preeclampsia and eclampsie. Am J Obstet Gynecol 180,
pp. 1332-1329.
11. Sibai, BM. (2005). Preeclampsia. Lancet 365, pp. 785-789.
12. Ananth, C.V., Smulian, J.C., Vintzileos, A.M. (1999). Incidence of placental abruption in realation to
cigarette smoking and hypertensive disorders during pregnancy: a metaanalysis of observational studies.
Obstet Gynecol 93(4), pp. 622-8.
13. Hoskins, I.A., Friedman, D.M., Frieden, F.S. (1991). Relationship between antepartum cocaine abuse,
abnormal umbilical artery Dopler velocimetry and placental apruption. Obstet Gynecol 78(2), pp. 279-82.
14. Şerbănescu, L., Tica V. (2002). Apoplexia utero-placentara: aspecte etiologice, morfopatologice,
psihologice şi terapeutice. Revista Spitalul. VIII(1), p. 36.

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A Brief Review of the Aetiological Factors Involved in Placental


Abruption

SERBANESCU Lucian1, COSTEA Daniel Ovidiu2


1Department of Obstetrics&Gynecology, Faculty of Medicine, Ovidius University from Constanta, (ROMANIA)
2Department of General Surgery, Faculty of Medicine, Ovidius University from Constanta, (ROMANIA)
Email: [email protected]

Abstract

The study was conducted at the 2nd Clinic of Obstetrics and Gynecology from “Sf. Apostol
Andrei” Emergency Hospital Clinic from Constanta on a group of 110 pregnant patients who had
placental abruption. Sheets of paper and surgical protocols were used as working material. The
main etiological factors involved in the production of the disorders were analyzed.
In conclusion, the main etiological factors involved in the production of disorders remain the
higher blood pressure induce by pregnancy, followed by smoking, extreme maternal ages and
presented fibromatous uterus.
Keywords: pregnancy, placental abruption, aetiological factors, higher blood pressure

Introduction

The main risk factors of placental abruption can be divided into three sections: the history of
the patients, including behaviors, and past obstetrical events, current pregnancy, or trauma.
These include smoking, different drugs consumed during pregnancy like cocaine, maternal
ages under 17 year or over 35 years, hypertension or placental abruption in prior pregnancies [1,
2, 3, 4].
Although the exact etiology of placental abruption is unknown, in the present study we analyzed
the main contributing factors involved in placental abruption.

Methods

The study was performed on 110 patients from the “Sf. Apostol Andrei” Emergency Hospital
Clinic from Constanta, Romania who had placental abruption and gives birth by cesarean
section, between January 2016 and December 2017. The informed consent of the patients was
taken.
The age, socio-economic and educational level, the appearance of fibroma, smoking, the
alcohol consumption, and blood pressure were analysed.

Results

From the total of 110 patients, 15% of patients where under 17 years old and 15% over 35
years old, 30% had low socio-economic and educational levels. Furthermore about 20% of the
patients had fibroma uterus and aproximately 40% of patients smoked over 10 cigarettes a day

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during pregnancy. From the total patients analysed, 10% consumed over 200 ml of alcohol per
day and 20% had a higher blood pressure (at 70 patients was induced by pregnancy, and at 30
patients aggravated by pregnancy).

Discussions

Placental abruption usually occurs when the vascular structure which supports the placenta is
compromise. More precisely, it occurs when the vascular matrix which connects the maternal
side is torn. The importance of these structures are resides from the fact that are delivered the
oxygen and nutrients to the fetus [5, 6]. One of the disrupting causes could be considered to be
the hypertension or some substances which cause stretching of the uterus [7] or the contact with
different nosocomial rotaviral gastroenteritis or Clostrium difficile [8], or even the implication of
smoking in pregnancy related disorders [2, 3, 9].
The diagnosis of placental abruption is not supported by any laboratory tests or diagnostic
procedures, although an ultrasound examination could be useful in helping the leading through
correct diagnosis and eliminating by differential diagnosis, like the placenta previa. In the acute
phase of placental abruption it was showed that hemorrhage was isoechoic or similar with the
sounding tissue. Anyway, the visualization of both the hemorrhage from placental abruption and
the hemorrhage from the surrounding tissue is difficult [10].
One study showed that the frequency of placental abruption to be 3.49% in comparison with
1.27% into placenta praevia [11]. Another authors showed that from the total number of cases
which was propose for labour, about 1.87% has placental abruption before birth [12].
In the same context, other study showed that patients younger than 20 years or older than 35
years presented a great risk of developing placental abruption, being in agreement with our study
[1-3, 13-15].
However, it was seen a 2-5% increase risk of placental abruption development in pregnant
women with previous cesarean section [16, 17].
However, in our study, the main etiological factors inherited in placental abruption showed to
be higher blood pressure (pregnancy-induced or pregnancy-worsened), smoking, extreme
maternal ages and fibromatous uterus.
Furthermore, there is a much higher incidence of uterine fibroid (20% versus 5% for new lots
in our previous reports from 2000-2008) and also a worrying rise in cases with low socio-
economic and education level (about 1/3 of cases).

Conclusions

Placental abruption represents an obstetrical emergency, being a serious medical condition. In


this respect, physicians must be aware that patients who have higher blood pressure, are
smoking, had extreme maternal ages and presented fibromatous uterus are at increased risk of
placental abruption. Early diagnosis, cesarean section and prenatal follow-up could improve the
maternal and fetal prognosis.

REFERENCES

1. Tica, V.I., Şerbănescu, L., Tica, Irina. (2006). Etiologic, clinical and prognostic correlations in abruptio
placentae. Rev Med Chir Soc Med Nat Iaşi. 110 (3), pp. 633-8.

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2. Tica VI, Şerbănescu L, Zaher M. (2006). Dezlipirea prematură de placentă normal inserată – istoric,
frecvenţă, etiologie, recurenţă. Gineco.ro. II(6), pp. 16-18.
3. Șerbănescu, L. (2008). Aspecte anatomice, clinice, morfopatologice și terapeutice în cadrul dezlipirii
premature de placentă normal inserate. Teză Doctorat.
4. 4.Qin, J., Liu, X., Sheng, X., Wang, H., Gao, S. (2016). Assisted reproductive technology and the risk of
pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-
analysis of cohort studies. Fertil Steril 105(1), 73-85, pp. e1-6.
5. Diaconu, C., Bălăceanu, A., Vlădăreanu, S. (2015). Treatment of arterial hypertension in pregnant women.
Gineco.eu 11, 40(2), pp. 92-94. DOI:10.18643/gieu.2015.92.
6. Bohîlțea, R., Turcan, N., Munteanu, O., Baros, A., Bodean, O., Voicu, D., Vasilescu, S., Cîrstoiu, M.
(2016). Manifestations of chronic venous disease of the pelvis in pregnancy. Gineco.eu 12, 45(3), pp. 151-
154. DOI:10.18643/gieu.2016.151
7. Macheku, GS., Philemon, RN., Oneko, O., Mlay, PS., Masenga, G., Obure, J., Mahande, MJ. (2015).
Frequency, risk factors and feto-maternal outcomes of abruptio placentae in Northern Tanzania: a registry-
based retrospective cohort study. BMC Pregnancy Childbirth15, p. 242.
8. Halichidis, S., Stoicescu, RM., Carp, DS., Cambrea, CS. (2015). Clostrium difficile enterocolitis: current
public health problem. JEPE 16(1), pp. 352-355. WOS: 000353528800043.
9. Navolan, D., Birsasteanu, F., Carabineanu, A., Cretu, O., Badiu, LD., Ionescu, CA., Mehedintu, C.,
Vladareanu, S., Craina, M., Boia, M., Ciohat, I., Craciunescu, M., Simu, S., Nemescu, D. (2017). Does
active smoking influence the second trimester biochemical markers concentrations? Revista de Chimie
68(10), pp. 2234-2236. WOS: 000416750000007.
10. Kwiatkowski, S., Kwiatkowska, E., Rzepka, R., Torbe, A., Dolegowska, B. (2016). Ischemic placental
syndrome-prediction and new disease monitoring. J Matern Fetal Neonatal Med 29(12), pp. 2033-2039.
11. Pitaphrom, A., Sukcharoen, N. (2006). Pregnancy outcomes in placental abruption. J Med Assoc Thai 89,
pp. 1572-1578.
12. Abbasi, RM., Rizwan, N., Mumtaz, F., Farooq, S. (2008). Maternal outcome among abruption placentae
cases at a University Hospital of Sindh. JLUMHS 7, pp. 106-109.
13. Ananth, CV., Smulian, JC., Demissie, K., Vintzileos, AM., Knuppel, RA. (2001). Placental abruption
among single to and twin births in the United States: Risk factor profiles. Am J Epidemiol 153, pp. 771-
778.
14. McDonald, SD., Vermeulen, MJ., Ray, JG. (2007). Risk of fetal death associated with maternal drug
dependence and placental abruption: A population-based study. J Obstet Gynaecol Can 29, pp. 556-559.
15. Tikkanen, M., Nuutila, M., Hiilesmaa, V., Paavonen, J., Ylikorkala, O. (2006). Clinical presentation and
risk factors of placental abruption. Acta Obstet Gynecol Scand 85, pp. 700-705.
16. Daltveit, AK., Tollånes, MC., Pihlstrøm, H., Irgens LM. (2008). Cesarean delivery and subsequent
pregnancies. Obstet Gynecol 111, pp. 1327-1334.
17. Odibo, AO., Cahill, AG., Stamilio, DM., Stevens, EJ., Peipert, JF., Macones, GA. (2007). Predicting
placental abruption and previa in women with a previous cesarean delivery. Am J Perinatol 24, pp. 299-
305.

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Hemorrhage in the Placenta Previa – Risk Factors and Prognosis

SOCOLOV Razvan1,2, HALICIU Ana1,3, POPOVICI Diana1,2, AKAD Mona1,


ADAM Ana2, SOCOLOV Demetra2
1 Spitalul de Obstetrică Ginecologie Elena Doamna-Iaşi (ROMANIA)
2 Departamentul Medicina Mamei şi a Copilului-Universitatea de Medicină şi Farmacie Gr. T. Popa-Iaşi (ROMANIA)
3 Departamentul Stiinţe Morfofuncţionale I-Universitatea de Medicină şi Farmacie Gr. T. Popa-Iaşi (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected], [email protected]

Abstract

Placenta previa increases the risk of maternal and neonatal mortality and morbidity due to
massive hemorrhage. Prenatal assessment of factors associated with a high risk of excessive
blood loss during pregnancy, and around the Cesarean section, would improve the preparation
and management of surgery, including the necessity for admission to hospital, preservation of
autologous blood, and the timing of the Cesarean section.

Material and methods


We have done a retrospective study that included placental complications of previa with
haemorrhage resolved by caesarean surgery during 2017. Using our selection criteria of
hemorrhagic placenta previa we found 42 cases from which active hemorrhage was found in 16
patients.

Results
The age of these patients was between 35 and 41 years with a median of 38; according to the
ultrasound, there were 2 placents of central type and 14 marginal type; 3 were scarred uterus; the
birth weight was between 2300 and 4000gr (median 3300gr). The placenta previa confirmed
represented 2.6% of caesarean section in our group, and the central variety 12.5% of them.

Discussion
We believe that symptomatic women less than 34 weeks of gestation who are
hemodynamically stable or quickly stabilized and have a normal fetal heart rate pattern are
candidates for expectant management. The goal is to prolong pregnancy to enable further fetal
growth and maturation, without placing the mother at excessive risk from persistent or recurrent
bleeding. Management of placenta previa after acute bleeding is based upon findings from
observational studies and clinical experience. Diagnosis of previa placenta remains an obstetrical
emergency and the extension of our study over a longer period, and possibly multicenter studies,
can better clarify risk and prognostic factors.
Keywords placenta praevia, hemorrage, cesarean section

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Introduction

The placenta begins to develop after blastocyst implantation into the endometrium. In some
cases, the placenta is implanted in the lower uterine segment close to or even covering the
internal cervix os, or invades through the endometrium and myometrium, which causes placenta
previa and placenta accreta, respectively, which may lead to hemorrhage when vaginal delivery
is attempted [1]. Placenta previa increases the risk of maternal and neonatal mortality and
morbidity due to massive hemorrhage. Problems of massive bleeding associated with placenta
previa occur not only during pregnancy, but also at and shortly after the Cesarean operation. The
morbidities associated with placenta previa include hysterectomy [relative risk (RR)=33.26, 95%
confidence interval (CI)=18.19-60.89], antepartum bleeding (RR=9.81, 95% CI=8.92-10.79),
intrapartum (RR=2.48, 95% CI=1.55-3.98), and postpartum (RR=1.86, 95% CI=1.46-2.36)
hemorrhages, as well as the need for blood transfusion (RR=10.05, 95% CI=7.45-13.55) [2, 3].
Prenatal assessment of factors associated with a high risk of excessive blood loss during
pregnancy, and around the Cesarean section, would improve the preparation and management of
surgery, including the necessity for admission to hospital, preservation of autologous blood, and
the timing of the Cesarean section.
The mechanisms of hemorrhage resulting from placenta previa during pregnancy are not
clearly known. However, when the placenta is present in a low uterine segment, it can be easily
detached from the decidua basalis, even when only slight uterine contraction and effacement
occur. Abnormal placentation and a poor blood supply from the uterine wall at the lower
segment of the uterus, may lead to active hemorrhage during pregnancy [4, 5].
Contractions, cervical effacement, and dilatation during the third trimester, may cause the
separation of the placenta, leading to unavoidable abnormal antenatal bleeding in cases with
placenta previa [6]. It is common practice to measure the cervical length using transvaginal
ultrasound to predict preterm delivery.
Though some ultrasonographic findings, such as a short uterine cervix and marginal sinus, are
associated with antenatal bleeding from placenta previa, these findings were evaluated in the
third trimester. Therefore, the obstetrician should be aware that sudden bleeding during
pregnancy may occur in patients with placenta previa, even if no such ultrasonographic findings
are detected during the second trimester [7].
Placenta previa is more common among women who:
- have had a baby
- have scars on the uterus, such as from previous surgery, including cesarean deliveries,
uterine fibroid removal, and dilation and curettage
- had placenta previa with a previous pregnancy
- are carrying more than one fetus
- are age 35 or older
- are of a race other than white
- smoke
- use cocaine [8].

Material and methods

We have done a retrospective study that included placental complications of previa with
haemorrhage resolved by caesarean surgery during 2017.

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Inclusion criteria were represented by ultrasound-proven previa diagnosis, complicated with


haemorrhage, resolved by caesarean section. Exclusion criteria were represented by cases where
the initial diagnosis suspicion was not confirmed by ultrasound, geminal pregnancies, gestational
pregnancies under 24 weeks, placenta previa without haemorrhage. We have done a analysis to
determine possible risk factors, such as: high maternal age, previous cesarean, previous placental
location, association of placental adherence abnormalities. We also studied the postoperative
evolution of the patient and the fetus.

Fig. 1. Algorithm for our cases

Results

Of the total of 602 cesareans performed in our service in 2017, 71 had an indication that
included the placenta previa (11.8%).
Of these, using the selection criteria mentioned, there were 42 who were retained in the study.
Of these, only 16 had haemorrhage and found the description of the ultrasound examination
during admission.
The age of these patients was between 35 and 41 years with a median of 38.
According to the ultrasound, there were 2 placents of central type and 14 marginal type.
3 were scarred uterus. Such an image is described in Figure 2.

Fig. 2. Ultrasound image of placenta previa

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The birth weight was between 2300 and 4000 gr (median 3300gr).
All cases were with a cranial presentation and had a favorable postoperative progression.
Under no circumstances was abnormal placental adherence noted.
The placenta previa confirmed represented 2.6% of caesarean section in our group, and the
central variety 12.5% of them.
The small number of cases in which suspicion of placenta previa has been confirmed by
ultrasound shows the importance of ultrasound excerpts practiced as close as possible to the
term, and the exact type of recording according to the ultrasound classification.
Advanced age as a risk factor is also verified in our study.
The scarring uterus, although considered to be a risk of complications and complications of
placenta previa, was mentioned in only 18% of the analyzed cases, which may explain why other
complications (accretion, haemorrhage requiring post-glaucoma hysterectomy) have not been
encountered.

Discussions

In a recent statement The Society of Maternal Fetal Medicine [9] recommended the following
approaches:
Stable patient with no other obstetric complications: planned to be born between 36w0d –
37w6d (Grad1B).
Early bleeding accompanied by one or more haemorrhagic episodes <34 weeks, birth
planning is considered: risk of recurrent haemorrhage.
Bleeding slightly between 34-35 weeks until consultation: management is questionable.
Do not routinely measure the length of the cervical canal to determine the risk of future
bleeding in patients with >34 weeks of pregnancy (Grade 2C).
Ultrasound evaluation is indicated to identify placental localization before practicing the
vaginal examination. In previa placenta: use the transvaginal probe.
For the stabilizing the patient for birth is necessary two venous lines, the results of the
laboratory tests (blood group), blood reserves O-neg 2-4 compatible blood units. It is obligatory
to use the protocols in the event of bleeding in Units in which they are available. It is obligatory
to have a monitor fetal heart beats.
In the case of active bleeding is not indicated for antenatal corticosteroid administration
(Grade 1B).
No antenatal corticosteroid administration >34 weeks if birth is indicated (Grade 1B).
Antenatal corticotherapy is administered if (Grade 1A) birth is planned within the next 7 days,
gestational age 34w0d – 36w6d, corneal corticosteroid therapy has not been administered before.
A small number of bleeding >34 weeks bleeding, which stopped spontaneously before the
patient can reach a doctor, can be treated as expected if both mother and fetus are stable, absence
of active contractions and bleeding, the patient lives near a specialized clinic.
In our opinion, we believe that symptomatic women less than 34 weeks of gestation who are
hemodynamically stable or quickly stabilized and have a normal fetal heart rate pattern are
candidates for expectant management. The goal is to prolong pregnancy to enable further fetal
growth and maturation, without placing the mother at excessive risk from persistent or recurrent
bleeding.

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The diagnostic of placenta previa is based very much on the awareness of the obstetrician of
the typical images and risk factors, and it should also be used for searching other asoscieted fetal
or uterine pathologies [10, 11]
Management of placenta previa after acute bleeding is based upon findings from
observational studies and clinical experience. A systematic review that attempted to assess the
impact of clinical interventions in these pregnancies concluded there were insufficient data upon
which to make evidence-based recommendations for clinical practice; only three randomized
trials involving a total of 114 women were identified [12, 13].
Diagnosis of previa placenta remains an obstetrical emergency and the extension of our study
over a longer period, and possibly multicenter studies, can better clarify risk and prognostic
factors.

REFERENCES

1. ACOG committee opinion (2002). Placenta accreta. Number 266, January 2002. Int J Obstet Gynecol, 77,
pp. 77-78.
2. Crane JM, Van den Hof MC, Dodds L, Armson BA, Liston R. (2000). Maternal complications with placenta
previa Am J Perinatol, 17, pp. 101-105.
3. Hasegawa J, Matsuoka R, Ichizuka K, Mimura T, Sekizawa A, Farina A, et al., (2009). Predisposing factors
for massive hemorrhage during Cesarean section in patients with placenta previa. Ultrasound Obstet
Gynecol, 34, pp. 80-84.
4. Oyelese Y, Smulian JC (2006). Placenta previa, placenta accreta, and vasa previa. Obstet gynecol, 107, pp.
927-941.
5. Hasegawa J, Higashi M, Takahashi S, Mimura T, Nakamura M, Matsuoka R, et al., (2011). Can
ultrasonography of the placenta previa predict antenatal bleeding? J Clin Ultrasound, 39, pp. 458-462.
6. Ghi T, Contro E, Martina T, Piva M, Morandi R, Orsini LF, et al., (2009). Cervical length and risk of
antepartum bleeding in women with complete placenta previa. Ultrasound Obstet Gynecol, 33, pp. 209-212.
7. Hasegawa J, Matsuoka R, Ichizuka K, Mimura T, Sekizawa A, Farina A, et al., (2009). Predisposing factors
for massive hemorrhage during Cesarean section in patients with placenta previa. Ultrasound Obstet
Gynecol, 34, pp. 80-84.
8. Miller DA, Chollet JA, Goodwin TM. (1997). Clinical risk factors for placenta previa-placenta accreta. Am
J Obstet Gynecol, 177, pp. 210-214.
9. Society for Maternal-Fetal Medicine (SMFM), Gyamfi-Bannerman C. Society for Maternal-Fetal Medicine
(SMFM) Consult Series #44 (2018). Management of bleeding in the late preterm period. Am J Obstet
Gynecol, 218(1), pp. B2-B8.
10. Bohiltea R, Cirstoiu M, Ionescu C, Niculescu Mizil E, Vladareanu AM, Voican I, Dimitriu M, Turcan N.
(2017). Primary myelofibrosis and pregnancy outcomes after low molecular weight heparin administration
A case report and literature review. Medicine, 96 (46), pp. 8735-8738.
11. Herghelegiu D, Ionescu C, Pacu I, Bohiltea R, Herghelegiu C, Vladareanu S.(2017) Antenatal diagnosis and
prognostic factors of aneurysmal malformation of the vein of Galen – A case report and literature review.
Medicine, 96, e7483-7490.
12. Y. Oyelese, W.E. Scorza, R. Mastrolia, J.C. Smulian. (2007) Postpartum hemorrhage. Obstet Gynecol Clin
North Am, 34, pp. 421-441.
13. Neilson JP. (2003) Interventions for suspected placenta praevia. Cochrane Database Syst Rev 2003 (2).

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Detection of Conotruncal Anomalies in the First Trimester, Using


an Optimized Morphological Protocol

ȘOROP-FLOREA Maria1,2, DRAGUȘIN Roxana Cristina1,2,


PATRU Ciprian-Laurențiu1,2,3, ȘOROP Virgiliu Bogdan4,
ZORILĂ George Lucian1,2, MARINAȘ Cristian1,5, DINU marina3,
NOVAC Marius6, CARA Monica1,TUDORACHE Ștefania1,3, CERNEA Nicolae1,3,
ILIESCU Dominic-Gabriel1,2,3
1 University of Medicine and Pharmacy of Craiova (ROMANIA)
2 ENDOGYN AM, Department of Imaging in Obstetrics and Gynecology, Craiova (ROMANIA)
3 Department of Obstetrics and Gynecology, Prenatal Diagnostic Unit, University Emergency Hospital, Craiova (ROMANIA)
4 Department of Obstetrics and Gynecology, University of Medicine and Pharmacy “Victor Babeș” Timișoara (ROMANIA)
5 Department of Anatomy, University of Medicine and Pharmacy Craiova (ROMANIA)
6 Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy Craiova (ROMANIA)

Email: [email protected]

Abstract

Introduction/Objectives
To evaluate effectiveness of the late first trimester (FT) detection of conotruncal anomalies
(CTA) on fetal echocardiography, using an optimized morphological protocol.

Methods/Methodology
Our prospective study consecutively enrolled pregnancies referred for early anomaly scan. A
morphologically optimized protocol was used to evaluate. We used re-examination by a team of
specialists, subsequent re-examination (second trimester and postpartum) and pathological
examination, as the reference standard methods.

Results
The group of 500 pregnant women was examined between January 2015 and January 2018
and a detailed late first trimester early anomaly screening was performed. Of these, 14 fetuses
(2.8%) were diagnosed to have CTA, representing 20% of the total anomalies diagnosed during
the study period. Conotruncal defects were as follows: tetralogy of Fallot (TOF); transposition of
the great arteries (GAT); double aortic arch (DAA); right aortic arch – left ductus (RAA-LD);
right aortic arch (RAA).

Conclusions
Conotruncal anomalies can be diagnosed by early prenatal echocardiography with a high
degree of accuracy. The most indicative sign of conotruncal anomalies is the abnormal V-sign.
Isolated CTA are more common and most of these may have a favorable outcome.
Keywords: conotruncal anomalies, fetal echocardiography, first trimester

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Introduction/Objective

Conotruncal anomalies are a broad category of congenital heart disease (CHD) that includes a
variety of conditions like Tetralogy of Fallot (TOF) and its variants absent pulmonary valve
(TOF-APV) and pulmonary atresia (TOF-PA), double outlet right ventricle and its variants
(DORV), Transposition of great arteries (TGA) and persistent truncus arteriosus (TA). These are
relatively common anomalies in the post-natal series comprising about 10-12% of all congenital
heart defects (CHD) diagnosed after birth [1, 2].
However, prenatal diagnosis of these anomalies is more challenging since most of these
anomalies have a normal four-chamber view during routine fetal heart screening [3-7]. The
prevalence in reported fetal series varies from 2.5-21% with a diagnostic accuracy of 75-90% for
achieving a complete diagnosis [8-13]. Accurate echocardiographic diagnosis in utero permits
counseling of the parents with regard to prognosis and treatment options. It is of paramount
importance when termination of pregnancy is being considered for the more severe cases.
Therefore, the aim of this study was to define the accuracy of fetal echocardiography for the
prenatal diagnosis of conotruncal anomalies and to examine the prognosis of those fetuses
identified.

Materials and methods

Prospective study of 500 consecutive pregnant women examined at 12 to 13 + 6 gestational


weeks (GW), using an optimized morpho-genetic ultrasound protocol. Parental consent was
obtained for all investigations. Our aim was to evaluate effectiveness of the late first trimester
(FT) detection of conotruncal anomalies (CTA) on fetal echocardiography, using an optimized
morphological protocol (Table 1). Definition of fetal conotruncal anomalies was attempted from
multiple scan planes including four-chamber, long- and short-axis as well as aortic arch and
ductal arch views. Doppler color flow mapping and pulsed Doppler interrogation were used to
facilitate identification of great vessel relationship, location and severity of ventricular outflow
obstruction.

Table 1. Standard planes and targets in cardiac evaluation


Standard planes Targets of evaluation
• Abdominal situs with the stomach in the left abdominal side
and aorta to the left of the spine;
• The four chambers of the heart with the heart lying on the left
side angled at 45◦ from the midline, occupying one quarter of the
chest; atrioventricular valve offsetting;
• The aorta arising centrally in the heart from the left placed
Transversal sweep gray-scale ventricle and crossing to the fetal left side over the ascending
aorta;
• Interventricular septum; when possible – septo-aortic continuity
in the left outflow view;
• The anteriorly positioned ductal arch, converging with the
transverse aortic arch on the left side of the fetal spine, with
approximative similar size.

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• Equal filling of both ventricles in the four chambers view


• Emergence of aorta with deduction of septo-aortic continuity
based on the entire aortic flow arising from the visualized left
Color-flow Doppler investigation ventricle;
(in order to increase the accuracy and to • Arterial duct outflow: visualization with power Doppler. ‘X’
shorten the examination time) sign (the crossing of the main pulmonary artery with the aorta);
• The transversal course of the two arches: ‘b’ sign (the straight
line of the pulmonary artery surrounded by aortic arch; ‘V’ sign
(the connection of the aorta and ductus arteriosus).
• Tricuspid valve flow assessment, to search for significant
Pulsed Doppler – investigation regurgitation.
(assessment of functional parameters) •Ductus venosus flow assessment, to search for reversed “a”-
wave.

Ultrasound morphological assessments were performed in the Prenatal Diagnostic Unit of the
University Emergency County Hospital Craiova by sonographers with extensive experience in
first trimester genetic anomaly scan. The acquisition of images were realized transabdominally
and transvaginally, using probes from GE Voluson medical Systems. Transabdominal approach
was preferred in most cases and transvaginal sonography was carried out only in few selected
cases in order to obtain good visualization of the fetal heart. Only the patients with extended first
trimester anomaly scan and complete follow-up were considered. We used as controls the serial
scans, follow-up scans, the secondary experienced team evaluation, pediatric cardiologist
examination, pathologic and neonatal evaluations. Post-natal echocardiography was also
performed as soon as feasible after birth using a standard protocol for pediatric
echocardiography.

Results

The group of 500 pregnant women was examined between January 2015 and January 2018
and a detailed late first trimester early anomaly screening was performed. All pregnant women
fulfilled the study requirements, with a median maternal age of 28 years (26 vs. 28 years). Of
these, 14 fetuses (2.8%) were diagnosed to have CTA, representing 20% of the total anomalies
diagnosed during the study period. Conotruncal defects were as follows: tetralogy of Fallot
(TOF-n=3 ) (Figure 1); transposition of the great arteries (GAT-n=5); double aortic arch (DAA-
n=1); right aortic arch – left ductus (RAA-LD-n=3); right aortic arch (RAA-n=2). The most
common anomaly diagnosed was GAT (35,71%) (Figure 2 ). We noted all different normal and
abnormal aspects of these cases. The visualization rate reached 98% with some supplementary
investigation time in some cases with unfavourable fetal position or maternal high body mass
index.

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B
.

Fig. 1. A. First trimester: tetralogy of Fallot (TOF) and right aortic arch (RAA-prenatal ultrasound and conventional
autopsy correlations; B. Microarray CGH has detected multiple microdeletions and microdunctions; C. abnormal
profile and discordance between great arteries.

Fig. 2. Types of conotruncal anomalies diagnosed (N=14)

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According to statistical analysis, our study found an accuracy of 99,16% of detection of CAT
malformations after examining the proposed parameters. The sensitivity of the examination
protocol was 93,33% and the specificity of 99,59% (Figure 3).

0,00% 20,00% 40,00% 60,00% 80,00% 100,00%

93,33%
Se (DR)

99,59%
Sp

0,41%
FPR

7%
FNR

12,50%
FDR

87,50%
PPV
99,79%
NPV
Fig. 3. Statistical results of the study

Discussions

This study shows that conotruncal anomalies can be diagnosed in fetal life by
echocardiography with a high degree of accuracy [14-17]. Difficulties in defining the spatial
relationship of the great arteries are a limiting factor in diagnosing conotruncal anomalies in
some instances. Despite this, the accuracy of prenatal diagnosis of conotruncal anomalies
including the great vessel orientation was 90% in this study [18]. As mentioned previously,
transvaginal sonography improved considerably the detection conditions, especially in cases of
maternal high body mass index [19, 20]. The main advantages of a FT anomaly scan using an
extended protocol is the early reassurance regarding fetal anatomy, and that the option of earlier
and safer termination of pregnancy is offered for the majority of MA, with less parental
psychological morbidity [21, 22, 23]. Furthermore, couples prefer earlier screening, when
possible [24, 25].

Conclusion

Conotruncal anomalies can be diagnosed by early prenatal echocardiography with a high


degree of accuracy. The most indicative sign of conotruncal anomalies is the abnormal V-sign.
The prognosis of the fetuses with chromosomal abnormalities or extracardiac anomalies was
worse than that of the fetuses without. Focus in developing countries should shift towards earlier
referral, improving awareness about treatment options and a comprehensive evaluation for
associated anomalies.

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Acknowledgements
This paper was published under the frame of European Social Found, Competitivity
Operational Programme 2014-2020, POC-A.1-A.1.2.1-D-2015, Contract nr. 75/08.09.2016,
MYSMIS Code: 105076.

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3. Gardiner HM. Fetal echocardiography:20 years of progress. Heart. 2001; 86 (Suppl II):12-22.
4. Bull C. Current and potential impact of fetal diagnosis on prevalence and spectrum of serious congenital
heart disease at term in the UK. Lancet. 1999; 354: pp. 1242-7.
5. Iliescu DG, Cara ML, Tudorache S, Antsaklis P, Novac LV, Antsaklis A, Cernea N. Agenesis of ductus
venosus in sequential first and second trimester screening. Prenat Diagn. 2014 Nov; 34(11): pp. 1099-105.
doi: 10.1002/pd.4434.
6. Iliescu DG, Tudorache S, Cernea N. Agenesis of ductus venosus with complex intra- and extrahepatic
umbilical drainage. J Obstet Gynaecol Res. 2014 Apr; 40(4): pp. 1163-4. doi: 10.1111/jog.12339.
7. Iliescu DG, Comanescu AC, Tudorache S, Cernea N. Right aortic arch with patent right ductus arteriosus
and normal heart. Ultrasound Obstet Gynecol. 2012 Jul; 40(1): pp. 115-6. doi: 10.1002/uog.10076.
8. Tometzki AJ, Suda K, Khol T, Kovalchin JP, Silverman NH. Accuracy of prenatal echocardiographic
diagnosis and prognosis of fetuses with conotruncal anomalies. J Am Coll Cardiol. 1999; 33: pp. 1696-701.
9. Galindo A, Mendoza A, Arbues J, Graneras A, Escribano D, Nieto O. Conotruncal anomalies in fetal life.
Accuracy of diagnosis, associated defects and outcome. Eur J Obstet Gynecol Reprod Biol. 2009; 146: pp.
55-60.
10. Paladini D, Rustico M, Todros T, Palmieri S, Gaglioti P, Benettoni A, et al. Conotruncal anomalies in
prenatal life. Ultrasound Obstet Gynecol. 1996;8:241–6.
11. Sivanandam S, Glickstein JS, Printz BF, Allan LD, Altmann K, Solowiejczyk DE, et al. Prenatal diagnosis
of conotruncal malformations: Diagnostic accuracy, outcome, chromosomal abnormalities and extra cardiac
anomalies. Am J Perinatol. 2006; 23: pp. 241-5.
12. Allan LD, Sharland GK, Milburn A, Lockhart SM, Groves AM, Anderson RH, et al. Prospective diagnosis
of 1006 consecutive cases of congenital heart disease in the fetus. J Am Coll Cardiol. 1994; 23: pp. 1452-8.
13. Khoshnood B, Vigan CD, Vodovar V, Goujard J, Lhomme A, Bonnet D, et al. Trends in prenatal diagnosis,
pregnancy termination and perinatal mortality of newborns with congenital heart disease in France 1983-
2000: A population based evaluation. Pediatrics. 2005; 115: pp. 95-101.
14. Davis GK, Farquhar CM, Allan LD, et al. Structural cardiac abnormalities in the fetus: reliability of prenatal
diagnosis and outcome. Br J Obstet Gynaecol 1990; 97: pp. 27-31.
15. Pătru CL, Iliescu DG, Tănase F, Drăgușin RC, Șorop-Florea M, Căpitănescu R, Comănescu A, Pană RC,
Zorilă LG, Marinaș MC, Novac M, Stoica A, Sîrbu M, Cernea N, Tudorache S. Fetal Heart in the First
Trimester. The Added Value of the Outflow Tracts Evaluation. Conference Proceedings, 5th Congress of The
Romanian Society of Ultrasound in Obstetrics and Gynecology, Targu Mures, Romania, 20-22 April 2017,
First Ed Published June 2017, p. 471-475, ISBN 978-88-95922-88-1.
16. Șorop-Florea M, Capitanescu R, Drăgușin RC, Pătru CL, Zorilă LG, Ciurea R, Marinaș C, Tudorache S,
Novac M, Dragoescu A, Stoica A, Gheonea M, Coleta E, Stepan A, Simionescu C, Cara M, Cernea N,
Iliescu DG. Correlations of the Fetal Anomaly Scan with Fetal Autopsy Results. Conference Proceedings,
5th Congress of The Romanian Society of Ultrasound in Obstetrics and Gynecology, Targu Mures, Romania,
20-22 April 2017, First Ed Published June 2017, p. 242-247, ISBN 978-88-95922-88-1.
17. Iliescu D.G., Cara M., Tudorache Ştefania, Antsaklis P., Ceausu I., Paulescu D., Novac L., Cernea N.,
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D. G. Iliescu. First trimester diagnostic accuracy of a twodimensional simplified ultrasound technique in
congenital heart diseases and great arteries anomalies. Obstetrica i Ginecologia LXIV (2016) pp. 165-176.

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19. S Tudorache, Iliescu Dominic Gabriel, A. Comanescu and N. Cernea Early fetal anatomic surveillance.
Transabdominal and transvaginal first trimester scan. How good are we?. Ultrasound in Obstetrics &
Gynecology, Volume 38, Issue S1, 2011, pp. 188-189.
20. Tudorache, S., Iliescu, D.G., Cara, M., Burada, F., Ioana, M., Simionescu, C., Novac, L., Cernea, N. and
Cernea, D. (2014), OC02.01: First trimester 2D cardiac assessment for congenital heart diseases. Ultrasound
Obstet Gynecol, 44: 3. doi:10.1002/uog.13469.
21. Sorop-Florea M, Iliescu DG, Tudorache S, Simionescu C, Cernea N, Novac LV, Tanase F, Cotarcea S,
Comanescu A, Dragusin R, Patru C, Carbunaru O, Zorila L, Cernea D. The importance of perinatal autopsy.
Review of the literature and series of cases. Rom J Morphol Embryol. 2017; 58(2): pp. 323-337.
22. Mărginean C, Gozar L, Mărginean C O, Suciu H, Togănel R, Muntean I, Mureșan M C, Prenatal diagnosis
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24. Mărginean C, Suciu H, Brînzaniuc K, Mărginean O Ethical considerations in screening and ultrasound
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Echographic Significance of Retroplacental Hematoma Detection

STĀNICA Cātālina Diana1, BOBEI Tina2


1 Department of Obstetrics and Gynecology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, (ROMANIA)
2 St. John Emergency Hospital, Bucur Maternity, Department of Obstetrics and Gynecology, Bucharest (ROMANIA)

Abstract

Ante and intrapartum obstetrical haemorrhage has as the most common sub-layer the placenta
praevia and the retroplacental hematoma. The retroplacental hematoma is the consequence of
breakage of spiral arterioles at the decidua boundary – the placental basal plate. The higher the
number of broken arterioles, the more bleeding is more severe. In this regard, we face the
retroplacental hematoma in the minor, intermediate or severe form, known in practice as abruptio
placentae.
The objective of the study is the clinical and sonographic correlation in order to establish the
therapeutic conduct for a good maternal-fetal prognosis.
Ultrasound represents rapid and non-invasive exploration in case of a retroplacental
hematoma. It is important to know that the evolution of the hematoma is irreversible from minor
to severe form. The ultrasound is important for the visualization of the intercalated hematoma
between the placental basal plate and the decidua, as an anechoic area, located centrally or
peripherally at the insertion of the placenta. In minor and intermediate forms, this anechoic area
is small in size, while in severe forms it is large, exceeding an average of 150 ml of blood. In
minor and intermediate forms, the fetus is alive but in distress. In severe forms, the fetus is
usually dead.
In minor and intermediate forms of retroplacental hematoma, the vital fetal and maternal
prognosis is good when decision and practice of surgery are rapid. In severe forms of abruption
placentae, total hysterectomy may be necessary to prevent secondary fibrinolysis and save the
mother’s life.
Keywords: haemorrhage in parturition, retroplacental hematoma, ultrasound, fetal viability

Introduction

Ante and intrapartum obstetrical haemorrhage has as the most common sub-layer the placenta
praevia and the retroplacental hematoma. The retroplacental hematoma is the consequence of
breakage of spiral arterioles at the decidua boundary – the placental basal plate. The higher the
number of broken arterioles, the more bleeding is more severe. In this regard, we face the
retroplacental hematoma in the minor, intermediate or severe form, known in practice as abruptio
placentae.
The phenomenon of diminished trophoblastic invasion, followed by sclerosis, has been
described in some cases of preeclampsia and ascent of the normally inserted placenta [1, 2].
Inflammation or infection can be a contributory factor, and it is more common in premature
ascent of the placenta [3, 4, 5, 6].

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The incidence of retroplacental hematoma is on average between 0.5-1% to 200 births [7, 8, 9,
10]. Regarding the extended placental ascent resulting in fetal death, the incidence was 0.24% in
1967 [11]. The decreasing number of multiparous pregnant women that give birth and the
increase in the accessibility to prenatal care and emergency transport have led to a decrease in
placental ascent frequency to 0.12% in 1989 and a further decrease to 0.048% in 2012.
The objective of the study is the clinical and sonographic correlation in order to establish the
therapeutic conduct for a good maternal-fetal prognosis.

Material and Method

We studied 12 pregnant women who were diagnosed with retroplacental hematoma, aged 32
to 44, in the third trimester of gestation. From their personal obstetric history we have noted that
they had between 2 and 4 births and between 2 and 5 abortions. Of the 12 pregnant women, 3
patients were in emergency with retroplacental hematoma in a severe form, without having
undergone analyses and investigations during pregnancy. The other 9 cases performed specific
analyses and investigations during pregnancy and showed numerous admissions during
pregnancy for additional investigations, so 4 patients were diagnosed with preeclampsia, 3 cases
had thrombophilia and 2 pregnant women had pregnancy-associated fibromatosis.

Results and Discussions

The ultrasound is important for the visualization of the hematoma intercalated between the
placental basal plate and the decidua, as an anechoic area located centrally or peripherally at the
insertion of the placenta. In minor and intermediate forms, this anechoic area is small in size,
while in severe forms it is large, exceeding an average of 150 ml of blood.
In minor and intermediate forms, the fetus is alive but in distress [12, 13]. In severe forms, the
fetus is usually dead [14].
The amount of blood lost vaginally, the alteration of the maternal general condition, the
ultrasound revealing the retroplacental hematoma leads to an active obstetrical conduct –
caesarean section extraction to save the life of the fetus and mother [15, 16, 17].
In the case of the 3 patients who presented in emergency with retroplacental hematoma in a
severe form, the fetus was dead; surgery was carried out urgently in order to save the mother’s
life.
Therapeutic conduct in cases with retroplacental hematoma depends on the clinical condition,
the gestational age and the volume of associated haemorrhage [18]. In the case of a live fetus (9
cases) and in the absence of a vaginal delivery trigger, emergency birth by caesarean section is
mandatory for saving the mother’s and the fetus’s lives. For the assessment of the fetal status,
ultrasound confirmation of foetal cardiac activity is required. If the fetus is dead or insufficiently
developed and matured to survive in the extrauterine environment, and the maternal general
condition is good, vaginal delivery is preferred.
Hydroelectrolytic and haematological rebalancing with crystalline solutions and blood are
mandatory for filling the vascular bed and replacing the lost blood due to retroplacental
haemorrhage, aiming to save the mother’s life and, if possible, the fetus’s life.
A major danger is consumption coagulopathy, the more severe as the ascent is more extensive
and the fetus is dead. Preoperative preparation includes assessment of the coagulation status and
hemodynamic and cardiovascular rebalancing.

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There are situations where the obstetrical history suspects such events, requiring an active
monitoring of the foetal status. The realization in Romania of a national registry of congenital
malformations or fetal anomalies diagnosed prenatally would reduce neonatal morbidity and
mortality [19]. In case of outpatient surveillance, there are attempts to monitor foetal heart
function with sensors integrated into textile material [20, 21]. In the future, including in our
country, the development of intelligent textile systems for the monitoring of vital functions is
foreseen [22].

Conclusions

Ultrasound represents a rapid and non-invasive exploration of the retroplacental haematoma.


It is important to know that the evolution of the haematoma is irreversible from minor to
severe form. In minor and intermediate forms of retroplacental haematoma, the vital foetal and
maternal prognosis is good when decision and practice of surgery are rapid. In severe forms of
abruption placentae, total hysterectomy may be necessary to prevent secondary fibrinolysis and
save the mother’s life.

Conflict of Interests: The authors declare they have no conflict of interests.

REFERENCES

1. Brosens I, Pijnenborg R, Vercruyase L. (2011). The great obstetrical syndromes are associated with
disorders of deep placentation. Am J Obstet Gynecol 122(2). p. 193.
2. Brăila AD, Forțofoiu C, Zamfir EM, Velea R, Brăila M .(2017). Eclampsia And Epilepsy. Differential
Diagnosis. Associated Diagnosis, Filodiritto International Proceedings, Congress of the Romanian-German
Society of Obstetrics-Gynecology, pp. 84-87.
3. Nath CA, Ananth CV, Smulian JC. (2007). Histologic evidence of inflammation and risk of placental
abruption. Am J Obstet Gynecol 197: 319e1.
4. Schenone MH, Schlabritz-Loutsevitch N, Zhang J. (2012). Abruptio placentae in the baboon (papio spp).
Placenta 33 (4): p. 278.
5. Schlabritz-Loutsevitch N, Hubbard G, Zhang J. (2013). Recurrent abruption placentae in a synomolgus
monkey (Macaca fascicularis). Placenta 34(4): p. 388.
6. Schlabritz-Loutsevitch N, Schenone A, Schenone M. (2013). Abruptio placentae in cinomolgus macaque
(Macaca fascicularis). Male bias. J Med Primatol 42(4): p. 204.
7. Salihu MH, Bekan B, Aliyu MH. (2005). Perinatal mortality associated with abruption placenta in
singletons and multiples. Am J Obstet Gynecol 193: p. 198.
8. Ananth CV, Oyelese Y, Yeo L. (2005). Placental abruption in the United States, 1979 through 2001:
temporal trends and potential determinants. Am J Obstet Gynecol 192(1): p. 191.
9. Roberts JM, Myatt L, Spong CY. (2010). Vitamins C and E to prevent complications of pregnancy-
associated hypertension. N Engl J Med 362(14): p. 1282.
10. Roberts JM, Muller PR, Allan R. (2012). Precise mid-trimester placenta localisation: does it predict adverse
outcomes? Aust N Z J Obstet Gynecol 52(2): p. 156.
11. Pritchard JA, Brekken AL. (1967). Clinical and laboratory studies on severe abruption placentae. Am J
Obstet Gynecol 97: p. 681.
12. Brăila AD, Brăila M, Velea R, Neacșu A. (2017). Delivery Management: Past, Present And Perspective,
Filodiritto International Proceedings, Congress of the Romanian-German Society of Obstetrics-
Gynecology, p. 77-80.
13. Brăila A, Gogănău A, Brăila M, Neacşu A. (2017). Caudal analgezia continues in controled birth. 5 year
clinical study, Proceedings of the 14th National Congress of Urogynecology and the National Conference of
the Romanian Association for the Study of Pain, Filodiritto Editore – Proceedings, p. 323-324.

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14. Braila AD, Marinov Krastev B, Mihai-Zamfir E, Caraveteanu DC, Nawaf Al Krayem, Braila M, Velea R,
Neacsu A. (2017). Uteroplacental apoplexy associated with invasive cervical neoplasm. Romanian Journal
of Morphology and Embryology, 58(4), pp. 1465-1470.
15. Brăila AD, Gluhovschi A, Neacșu A, Lungulescu C, Brăila M, Cotoi BV, Goganau A. (2018). Placental
abruption. etiopathogenic aspects, diagnostic and therapeutic implications. Romanian Journal of
Morphology and Embryology 59(1).
16. Braila AD, Brăila M, Nawaf Alkrayem, Gogănău A. (2017). Uterine Haemostasis In Puerperality By
Radical And Conservative Surgical Procedures, Filodiritto International Proceedings, Congress of the
Romanian-German Society of Obstetrics-Gynecology, pp. 81-83.
17. Brăila M, Neacșu A, Velea R, Brăila A. (2017). Caesarian Section And The Forceps Use -5 Year Study In
Craiova Scju Maternity Section ,Filodiritto International Proceedings, Congress of the Romanian-German
Society of Obstetrics-Gynecology, pp. 91-94.
18. Poalelungi C V, Ples L, Hudita D, Ceausu I. (2018). Risk factors and clinical follow-up of patients with
preterm births in a tertiary referral maternity unit in Bucharest, Romania. Journal of the Pakistan Medical
Association 68(4), pp. 559-564.
19. Ples L, Sima R M, Stanescu A D, Olaru O G.(2017).The Importance of a National Congenital Anomalies
Registry – the Role of the Prenatal Diagnosis.Proceeding paper for the 5TH ROMANIAN CONGRESS OF
THE ROMANIAN SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY, pp. 505-
510.
20. Bougia P, Kairvounis E, Fotiadis D I. (2007). Chapter 10 – Smart medical textiles for monitoring
pregnancy. In: Van Langenhove L (eds). Smart textiles for medicine and healthcare: Materials, systems and
applications, Woodhead Publishing Limited, Cambridge, England, 2007, pp. 183-204.
21. Chen W, Hu J, Bouwstra S, Oetomo S B. (2011). Sensor integration for perinatology research. International
Journal of Sensors Networks 9 (1), pp. 38-49.
22. Onose G, Chendreanu C, Neacsu A, Grigorean V, Stambu V, Toader C, Spanu A, Andone I, Anghelescu A,
Onose L, Haras M, Sinescu C J, Artino M, Ciornei C, Mirea A. (2009). Smart textiles for noninvasive
monitoring of physiological signals. Industria Textila 60 (3), pp. 124-133.

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Antepartum Haemorrhage in Placental Pathology in Third


Trimester of Pregnancy

STĀNICA Cātālina Diana1, BOBEI Tina2


1 Department of Obstetrics and Gynecology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, (ROMANIA)
2 St. John Emergency Hospital, Bucur Maternity, Department of Obstetrics and Gynecology, Bucharest (ROMANIA)

Abstract

Third-trimester placental pathology comprises two major entities in obstetrics, both in terms
of haemorrhagic emergency and maternal-foetal management. Antepartum haemorrhage is
present in premature ascent of the placenta and in placenta praevia.
Premature ascent of the placenta is a brutal accident characterized by partial or total placenta
separation from its normal insertion site at any time before delivery. When antepartum bleeding
comes from placental marginal ascent, symptoms are slight and bleeding stops without maternal
or foetal consequences.
The placenta praevia is also a brutal accident in which bleeding occurs without premonitory
signs and is painless. Both in the case of partial and total placenta praevia, a certain degree of
spontaneous placental ascent is an inevitable consequence of lower uterine segment remodelling
and cervical dilation.
Ultrasound visualization of the placenta helps putting a diagnostic differential to other
pathologies that are manifested by haemorrhage, hypertonia or hyperkinesia.
The objective of the study is to determine by early ultrasound the two haemorrhage
emergencies, the premature ascent of placenta and the placenta praevia, the reduction in the risk
of suffering and foetal death inside the uterus, complications and maternal death.
Keywords: placenta praevia, premature placental ascent, maternal-foetal management

Introduction

Third-trimester placental pathology comprises two major entities in obstetrics, both in terms
of haemorrhagic emergency and maternal-foetal management [1, 2]. Antepartum haemorrhage is
present in premature ascent of the placenta and in placenta praevia.
The uterine haemorrhage source is not always identified, as the antepartum bleeding may
come from the placental marginal ascent, so that the symptoms are slight and the bleeding stops
without maternal or foetal consequences. Premature ascent of the placenta is a brutal accident
characterized by partial or total placenta separation from its normal insertion site at any time
before delivery. There are several predisposing factors that increase the risk of placental ascent:
pregnant woman aged above 40, hypertension and preeclampsia [3], premature rupture of
membranes, lupus anticoagulant and thrombophilia, uterine leiomyomas, multi-fetal pregnancy.
The placenta praevia is also a brutal accident in which bleeding occurs without premonitory
signs and is painless. Both in the case of partial and total placenta praevia, a certain degree of
spontaneous placental ascent is an inevitable consequence of lower uterine segment remodelling

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and cervical dilation. Placenta praevia has on average an incidence of 0.3% [4]. Factors that
increase the risk for placenta praevia are: multi-fetal pregnancy [5, 6], maternal age [7], multi-
parity [8], abnormally implanted placenta [9], uterine scarring [10, 11, 12, 13], abnormally high
maternal serum alpha-fetus-protein levels.
The objective of the study is to determine by early ultrasound the two haemorrhage
emergencies, the premature ascent of placenta and the placenta praevia, the reduction in the risk
of suffering and foetal death inside the uterus, complications and maternal death.

Material and Method

The study was conducted on a sample of 26 pregnant women, 12 of whom were diagnosed
with premature ascent of normally inserted placenta and 14 patients were diagnosed with
placenta praevia. All pregnant women had between 2 to 5 prior deliveries and between 2 to 7
abortions in their personal history. Pregnant women were in the third trimester of pregnancy and
were aged between 30 and 45 years. Pregnant women have undergone haematological and
urinary investigations, have been monitored by ultrasound and in some cases have performed
additional investigations to establish the pathology associated with pregnancy.
Of the 12 cases of premature placental ascent, 3 cases presented in the emergency room, with
dead foetus and massive haemorrhage and requiring emergency surgery, the other 9 cases had
good foetal-maternal prognosis. The 12 cases of placenta praevia were admitted for low or
medium bleeding and 2 cases for abundant bleeding; they had good maternal-foetal prognosis.

Results and Discussions

In placenta praevia, ultrasound has established placenta localization on the lower segment and
in relation to the internal cervical opening: placenta praevia, when the internal cervix was
partially or completely covered by the placenta (5 cases); the low inserted placenta was the
placenta implanted in the lower uterine segment, so that the placental edges did not reach the
internal cervical opening and remained outside a 2 cm perimeter around it (9 cases).
When bleeding was slight or moderate in the premature ascent of the placenta,
ultrasonography revealed the accumulation of blood between the uterine wall and the placenta as
a homogeneous area of echogenicity, clots having an echogenicity different from that of the
placenta (9 cases). Most blood accumulated at the level of a retroplacental hematoma in the event
of an ascent is of maternal origin. This is due to separation in the maternal decidua, while
placental villi initially remain intact [14].
The management of pregnant women with placenta praevia depends on the foetal age, the
presence of labour and the severity of bleeding. When the foetus was premature and there was no
active, persistent bleeding, maternal and foetal monitoring was preferred (4 cases). In the case of
near-term and non-bleeding pregnancies, foetal extraction by caesarean section is planned after
foetal maturation and reduction to minimum of the antepartum haemorrhage (8 cases). It has
been suggested that women with placenta praevia are best managed by elective delivery at 36-37
gestational weeks [15]. In the case of suspicions of placenta accreta syndromes, delivery was
recommended at 34-35 gestational weeks or according to other obstetrics schools, it is preferred
to be expected to reach 37-38 gestational weeks.
The treatment conduct in pregnant women with premature ascent of normally inserted
placenta has been established according to: bleeding amount, mother’s general condition,

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gestational age, and viability of the foetus [16, 17, 18]. In cases of live foetus and non-triggered
labour, emergency caesarean section with good foetal-maternal prognosis (9 cases) was urgently
performed. Dead foetus cases with massive bleeding were resolved by caesarean section to save
the mother’s life (3 cases).

Conclusions

Ultrasound visualization of the placenta helps putting a diagnostic differential to other


pathologies that are manifested by haemorrhage, hypertonia or hyperkinesia.
The early ultrasound determination of the two haemorrhage emergencies, the premature
ascent of placenta and the placenta praevia, decrease the risk of suffering and foetal death inside
the uterus, complications and maternal death.

Conflict of Interests: The authors declare they have no conflict of interests.

REFERENCES

1. Brăila AD, Brăila M, Velea R, Neacșu A. (2017). Delivery Management: Past, Present And Perspective,
Filodiritto International Proceedings, Congress of the Romanian-German Society of Obstetrics-
Gynecology, pp. 77-80.
2. BrăilaM, Neacșu A, VeleaR, Brăila A. (2017). Caesarian Section And The Forceps Use -5 Year Study In
Craiova Scju Maternity Section ,Filodiritto International Proceedings, Congress of the Romanian-German
Society of Obstetrics-Gynecology, pp. 91-94.
3. Brăila AD, Forțofoiu C, Zamfir EM, Velea R, Brăila M. (2017). Eclampsia And Epilepsy. Differential
Diagnosis. Associated Diagnosis, Filodiritto International Proceedings, Congress of the Romanian-German
Society of Obstetrics-Gynecology, pp. 84-87.
4. Martin JA, Hamilton BE, Sutton PD. (2005). Births: final data for 2003. Natl Vital Stat Rep 54(2): p. 1.
5. Ananth CV, Demissie K, Smulian JC. (2003). Placeta previa in singleton and twin births in the United
States, 1989 through 1998: a comparison of risk factor profiles and associated conditions Am J Obstet
Gynecol 188: p. 275.
6. Weis MA, Harper LM, Rochl KA. (2012). Natural history of placenta previa in twins. Obstet Gynecol
120(4), p. 753.
7. Biro MA, Davey MA, Carolan M. (2012). Advanced maternal age and obstetric morbidity for women
giving birth in Victoria, Australia: a population-based study. Aust NZ J Obstet Gynaecol 52(3), p. 229.
8. Babinszki A, Kerenyi T, Torok O. (1999). Perinatal outcome in grand and greatgrand multiparity. Effects
of parity on obstetric risk factors. Am J Obstet Gynecol 181, pp. 669.
9. Pleș L, Sima R M, Moisei C, Moga M A, Dracea L A. (2017). Abnormal Ultrasound Appearance of the
Amniotic Membranes-diagnostic and significance:a pictorial essay. Medical Ultrasonography 19(2), pp.
211-215.
10. Silver R M, Landon M B, Rouse D J. (2006). Material morbidity associared with multiple repear cesarean
deliveries. Obstet Gynecol 107, p. 1226.
11. Gurol-Urganci I, Cromwell D A, Edozien L C. (2011). Risk of placenta previa in second birth after first
birth cesarean section. BMC Pregnancy child birth 11, p. 95.
12. Gesteland K, Oshiro B, Henry E. (2004). Rates of placenta previa and placental abruption in women
delivered only vaginally or only by cesarean section. Abstract No. 403. J Soc Gynecol Investig 11, 208A.
13. Gilliam M, Rosenberg D, Davis F. (2002). The likelyhood of placenta previa with greater number of
cesarean deliveries and higher parity. Obstet Gynecol 99, p. 976.
14. Braila A D, Marinov Krastev B, Mihai-Zamfir E, Caraveteanu D C, Al Krayem N, Braila M, Velea R,
Neacsu A. (2017). Uteroplacental apoplexy associated with invasive cervical neoplasm. Romanian Journal
of Morphology and Embryology 58(4), pp. 1465-1470.
15. Spong C Y, Mercer B M, Dalton M. (2011). Timing of indicated late-preterm and early-term birth. Obstet
Gynecol 118(2Pt 1), p. 323.

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16. Brăila A D, Gluhovschi A, Neacșu A, Lungulescu C, Brăila M, Cotoi B V, Goganau A. (2018). Placental
abruption. etiopathogenic aspects, diagnostic and therapeutic implications. Romanian Journal of
Morphology and Embryology 59(1).
17. Brăila A, Gogănău A., Brăila M, Neacşu A. (2017). Caudal analgezia continues in controled birth. 5 year
clinical study, Proceedings of the 14th National Congress of Urogynecology and the National Conference of
the Romanian Association for the Study of Pain, Filodiritto Editore – Proceedings, pp. 323-324.
18. Braila A D, Brăila M, Al Krayem N, Gogănău A. (2017). Uterine Haemostasis In Puerperality By Radical
And Conservative Surgical Procedures, Filodiritto International Proceedings, Congress of the Romanian-
German Society of Obstetrics-Gynecology, pp. 81-83.

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Transvaginal Ultrasound. Significance in the Diagnosis of


Endometrial Bleeding

STĀNICA Cātālina Diana1, BOBEI Tina2


1 Department of Obstetrics and Gynecology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, (ROMANIA)
2 St. John Emergency Hospital, Bucur Maternity, Department of Obstetrics and Gynecology, Bucharest (ROMANIA)

Abstract

Uterine endometrial bleeding is more common in women over 40 years of age. Their substrate
is most frequently represented by hormonal disorders that can lead to different variants of
endometrial hyperplasia (simple or complex hyperplasia without atypia, hyperplasia with simple
or complex atypia). Uterine bleeding in menopausal women has endometrial adenocarcinoma
substrate. Submucosal leiomyofibroma produces endometrium denudation with its elimination,
occurrence of uterine bleeding.
The objective of the study consists in correlating uterine, endometrial and myometrial
ultrasound imaging, biopsy curettage and histopathological examination of hyperplasia and
adenocarcinoma. Transvaginal ultrasound highlighted the structure, size and shape of the uterus,
myometrium, endometrium thickness, cervix and ovarian condition. The ultrasound findings
compared with the endometrium obtained by biopsy curettage and histopathological examination
accounted for over 90% of cases with histopathological positive diagnosis of benign hyperplasia
in premenopause, hypotrophic-atrophic endometrium and postmenopausal adenocarcinoma.
Transvaginal ultrasound is a minimally invasive diagnostic and screening method in pre- and
postmenopausal endometrial pathology.
Keywords: Ultrasound, metrorrhagia, endometrial hyperplasia, endometrial adenocarcinoma, uterine leiomyofibroma

Introduction

Abnormal uterine bleeding affects between 10-30% of reproductive age women [1] and up to
50% of women in perimenopause [2, 3].
Uterine endometrial bleeding is more common in women over 40 [4, 5]. Their substrate is
most frequently represented by hormonal disorders that can lead to different variants of
endometrial hyperplasia (simple or complex hyperplasia without atypia, hyperplasia with simple
or complex atypia). Uterine bleeding in menopausal women has endometrial adenocarcinoma
substrate. Submucosal leiomyofibroma produces endometrium denudation with its elimination,
occurrence of uterine bleeding. Directly, being a connective tissue tumour, fibromyoma is not
characterized by metrorrhagia.
Hyperestrogenism affects both the endometrium, with the development of endometrial
hyperplasia and adenocarcinoma, and the myometrium, with the development of circumscribed
or diffuse uterine fibromatosis [6, 7].

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The objective of the study consists in correlating uterine, endometrial and myometrial
ultrasound imaging, biopsy curettage and histopathological examination of hyperplasia and
adenocarcinoma.

Material and Method

The study was conducted over a period of one year and included patients aged between 40
and 60 who presented uterine fibromatosis correlated with abundant bleeding in the form of
metrorrhagia, menorrhagia or meno-metrorrhagia.
The clinical examination of the patients included gynaecological examination, cardiology
examination and ECG, specialized examination for nutrition and metabolism diseases.
The hematologic, biochemical and urinary tests performed were: complete blood count, blood
group and Rh, glycaemia, urea, creatinine, uric acid, hepatic tests (SGOTT), total, direct and
indirect bilirubin, coagulogram – INR, Quick time, Howell time, platelets, fibrinogen, urinal
summary test.
To support the diagnosis, transvaginal ultrasound, endo-uterine curettage for haemostatic and
biopsy purposes with histopathological examination were used.
Transvaginal ultrasound highlighted the structure, size and shape of the uterus, myometrium,
endometrium thickness, cervix and ovarian condition.
We studied 110 patients: group I of 72 patients aged 40 to 50 years and group II of 38 patients
aged 51 to 60 years.
Haemostatic and biopsy uterine curettage was performed and the collected materials were sent
for histopathological examination, which revealed proliferative endometrial lesions without
simple or complex atypia, hyperplasia with simple or complex atypia, endometrial carcinoma.
Patients with uterine fibromatosis associated with simple or complex hyperplasia without
atypia were treated with progesterone preparations, while patients with atypical hyperplasia and
those with endometrial carcinoma received radical surgical indication.

Results and Discussions

The group I of patients aged 40 to 50 years, consisting of 72 cases (65%), is net superior to
the group II of patients aged 51 to 60 years, consisting of 38 patients (35%).
The transition from ovulatory cycles to menopause begins after 40 years. The decrease in the
anti-Müllerian hormone (AMH) with aging is preceding by a few years an increase in FSH and
therefore offers many precise indications of the transition to menopause [8]. Initially, FSH grows
slightly and causes a high follicular ovarian response, increase in oestrogen levels, and decrease
in progesterone [9, 10, 11]. Tardily, folliculogenesis disturbances and increased incidence of
anovulation occur as well as increased FSH levels. Ovarian follicular quality decreases, and also
inhibition secretion decreases until the follicle reserve is depleted [12, 13]. This is a good
indicator of the menopause period.
At the endovaginal ultrasound, we considered the thickness of the endometrial mucous
membrane visualized by the ultrasound. This imagistic method allowed, depending on the size of
the endometrium, the classification of the incidence of cases of hypotrophy-atrophy below 4 mm,
6 cases (5%), endometrial hyperplasia 4-10 mm, 86 cases (78%), endometrial adenocarcinoma
over 12 mm, 18 cases (17%). Anechogenic images found at the endometrium-myometrium limit
suggested the presence of submucosal fibroma. The oestrogen-progesterone balance is changing

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in favour of oestrogen after the age of 40. Initially, relative oestrogenemia by decrease in
progesterone, and then absolute oestrogenemia through the complete absence of progesterone,
cause proliferative lesions and lesions in the endometrium at the level of the myometrium with
sight of uterine fibromatosis [14].
Hormone therapy was beneficial in cases of simple or complex hyperplasia without atypia.
Total hysterectomy with bilateral adnexectomy was the indication of choice in patients with
hyperplasia with simple or complex atypia, in cases of over 45 years with associated uterine
fibromatosis and in patients with endometrial carcinoma.

Conclusions

The ultrasound findings compared with the endometrium sampled by biopsy curettage and
histopathological examination accounted for over 90% of cases with histopathological positive
diagnosis of benign hyperplasia in premenopause, hypotrophic-atrophic endometrium and
postmenopausal adenocarcinoma.
Transvaginal ultrasound is a minimally invasive diagnostic and screening method in pre- and
postmenopausal endometrial pathology.

REFERENCES

1. Brăila M, Brăila A, Neacşu A, Gogănău A. (2017). Treatment of Pelvigenital Pain Syndrome in External
Endometriosis. Clinical Study for a Period of 3 Years. Proceedings of the 14th National Congress of
Urogynecology and the National Conference of the Romanian Association for the Study of Pain. Filodiritto
Editore – Proceedings, pp. 328-330.
2. Haynes PJ, Hodgson H, Anderson AB. (1977). Measurement of menstrual blood loss in patients
complaining of menorrhagia. Br J Obstet Gynecol 84, p. 763.
3. Prentice A. (2000). When does heavy flow merit treatment?. Practitioner 244. pp.174.
4. Braila M, Brăila A, Neacsu A, Gogănău A. (2017). Treatment of Dysmenorrhea in Adenomyosis. Clinical
Study for a Period of 3 Years. Proceedings of the 14 th National Congress of Urogynecology and the National
Conference of the Romanian Association for the Study of Pain. Filodiritto Editore – Proceedings, pp. 325-
327.
5. Brăila AD,Brăila M,Cornițescu F et al. (2008). Benign ovarian tumors. Anatomo-clinical, diagnosis, and
therapeutical aspects. Gineco.eu, 4(3), pp. 178-185.
6. Brăila A D, Vaniova Klimentova D, Damian CM, Brăila M. (2012). Endometrial proliferative lesions
associated with uterine fibromatosis. RJME 56(3), Supp. pp. 743-747.
7. Vaniova Klimentova D, Brăila AD, Simionescu C, Ilie I, Brăila M. (2012). Clinical and paraclinical study
regarding the macro and microscopic diagnosis of various anatomo-clinical forms of operated uterine
fibromyoma. RJME 53(2), pp. 369-373.
8. Pacu I, Ionescu C, Vladareanu S, Banacu M, Neacsu A, Calin A. (2017). Predictive Value of the AMH
Level and Serum Estradiol for Ovarian Hyperstimulation Syndrome in the Assisted Human Reproduction.
Revista de Chimie 68 (5), pp. 1118-1121.
9. Jain A, Santoro N. (2005). Endocrine mechanisms and management for abnormal bleeding due to
perimenopausal changes. Clin Obstet Gynecol 48, p. 295.
10. Klein NA, Illingworth PJ, Groome NP. (1996). Decreased inhibin B secretion is associated with the
monotropic FSH rise in older, ovulatory women: a study of serum and follicular fluid levels of dimeric
inhibin A and B in spontaneous menstrual cycles. J Clin Endocrinol Metab 81, p. 2742.
11. Santoro N, Lasley B, McConnell D. (2004). Body size and ethnicity are associated with menstrual cycle
alterations in women in the early menopausal transition: the Study of Women s health across the nation
(SWAN) Daily Hormone Study. J Clin Endocrinol Metab 89(6), p. 2622.
12. Reyes FI, Winter JS, Faiman C. (1977). Pituitary-ovarian relationships preceding the menopause. I. A cross-
sectional study of serum follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and
progesterone levels. Am J Obstet Gynecol 129, p. 557.

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13. Santoro N, Brown JR, Adel T. (1996). Characterization of reproductive hormonal dynamics in the
perimenopause. J Clin Endocrinol Metab 81, p.1495.
14. Neacşu A, Marcu ML, Stānicā CD, Brāila AD, Pacu I, Ioan RG, Grigorescu CC, Ionescu CA. (2018). Early
Diagnosis of Endometrial Cancer. RJME, 59(2).

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Utrasound Aspects in Uterine Tumour Pathology

STĀNICA Cātālina Diana1, BOBEI Tina2


1 Department of Obstetrics and Gynecology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, (ROMANIA)
2 St. John Emergency Hospital, Bucur Maternity, Department of Obstetrics and Gynecology, Bucharest (ROMANIA)

Abstract

Transabdominal and transvaginal ultrasound has numerous indications in the assessment of


the uterine body. While transabdominal ultrasound gives us an overview of the uterine
fibromatosis, transvaginal ultrasound visualizes the endometrium in detail in both hyperplasia
and endometrial cancer. The pathology of the uterine body can be appreciated by transabdominal
and transvaginal ultrasound, taking into account the size and shape of tumours, the location and
the composition, as well as the homogeneous or non-homogeneous echographic appearance. The
colour Doppler provides important information on blood flow in patients with leiomyomas,
polyps and endometrial disorders such as hyperplasia and endometrial carcinoma.
The objective of the study is to assess the pathology of the uterine body by transabdominal,
transvaginal and colour Doppler ultrasound depending on the size and shape of the tumours, the
location and the composition, as well as the homogeneous or non-homogeneous ultrasound
appearance and blood flow information in patients with leiomyomas and endometrial disorders
of hyperplasia and endometrial carcinoma type.
Keywords: uterine body, transabdominal ultrasound, transvaginal ultrasound

Introduction

Transabdominal and transvaginal ultrasound has numerous indications in the assessment of


the uterine body. While transabdominal ultrasound gives us an overview of the uterine
fibromatosis, transvaginal ultrasound visualizes the endometrium in detail in both hyperplasia
and endometriosis and endometrial cancer. [1].
Leiomyomas are benign smooth muscle tumours originating in the myometrium and due to
their high content in collagen they have fibrous consistency. They have an incidence of 70-80%
taking into account histological and ultrasound criteria [2, 3, 4].
Most endometrial cancers occur as a result of progression of hyperplasic lesions [5, 6]. Risk
factors are associated with the creation of an oestrogen-free environment. Excessive adipose
tissue increases the peripheral aromatization of androstenedione in the oestrus. Coexisting
medical conditions such as diabetes mellitus and arterial hypertension are commonly associated
with endometrial cancer [7, 8]. These medical pathologies are frequent sequelae of obesity and of
an environment featuring chronic excess of oestrogen.
In some cases, gynaecological cancers can cause totally abnormal and chaotic metastases , so
a systemic imaging investigation to target these distant sites is always welcome [9, 10, 11].
The objective of the study is to assess the pathology of the uterine body by transabdominal,
transvaginal and colour Doppler ultrasound depending on the size and shape of the tumours, the
location and the composition, as well as the homogeneous or non-homogeneous ultrasound

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appearance and blood flow information in patients with leiomyomas and endometrial disorders
of hyperplasia and endometrial carcinoma type.

Material and Method

The research included 57 patients aged between 35 and 60 years who presented for uterine
fibromatosis and abundant uterine bleeding in the form of metrorrhagia, menorrhagia or meno-
metrorrhagia.
The clinical examination of the patients included gynaecological examination, cardiology
examination and ECG, specialized examination for nutrition and metabolism diseases.
Hematologic, biochemical and urinary tests performed were: complete blood count (for
assessing the degree of anaemia secondary to uterine bleeding), blood group and Rh, glycaemia,
renal tests (urea, creatinine, uric acid), hepatic tests (SGOT, SGPT, total, direct and indirect
bilirubin), coagulogram (INR, Quick time, Howell time, platelets, fibrinogen), urinal summary
test. Paraclinic investigations were performed to support the positive diagnosis and for
differential diagnosis of other pathologies with genital bleeding or tumour masses with pelvic
location. In premenopausal patients, transvaginal ultrasound was performed before the 10th day
of the menstrual cycle.

Results and Discussions

The ultrasound appearance of uterine leiomyosibromas (23 cases, 40%) is generally moderate
in echogenic terms, with variations from hyper-echogenic to hypo-echogenic, depending on the
prevailing tissue, fibrous or muscular. Also, the ultrasound appearance was influenced by the
presence and type of fibroids degenerescence: hyaline, calcar, cystic, myxoid, or haemorrhagic.
Necrosis and degenerescence often develop in leiomyomas due to their limited vascularisation
[12]. Leiomyomas have a low blood density compared to the myometrium around them. The
absence of organized vascularisation makes these tumours vulnerable to hypoperfusion and
ischemia [13, 14].
The colour Doppler has highlighted a marginal vascularisation and several vessels that enter
the centre of the fibroma. The benefit from Doppler investigation was the differentiation of an
extrauterine leiomyoma from other pelvic masses or a submucosal leiomyoma of an endometrial
or adenomyous polyp, as also reported in other scholarly studies [15, 16, 17].
Endometrial hyperplasia (13 cases, 23%) can be suspected when endometrial thickness is
greater than 8mm. In terms of ecostucture, the thickened endometrium is homogeneous. The
colour Doppler ultrasound highlighted a relative increase in local vascularisation.
Polyps are common in patients with meno-metrorrhagia with an incidence of 10-30% [18, 19].
Endometrial polyps (9 cases, 16%) depleted the uterine cavity with an irregularly echogenic
appearance as an elongated formation in the endometrial cavity. The polyps were unique or
multiples, measured from a few millimetres to a few centimetres, and were sessile, with a broad
base of implantation or pediculated, the appearance also being described in the scholarly
literature [20]. Glare cystic spots corresponding to dilated endometrial glands can be noticed
[21]. Visualisation of the polyps by colour Doppler has identified a single feeding vessel [15].
The thickened endometrium by over 4-5 millimetres, with heterogeneous ecostructure
suggested malignancy (12 cases, 21%). Endometrial invasion in endometrial carcinoma

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determined irregularities in the subendometrial halo, with thickening and irregularity of the
central endometrial interface. The colour Doppler revealed an increase in local vascularisation.

Conclusions

The pathology of the uterine body can be appreciated by transabdominal and transvaginal
ultrasound, taking into account the size and shape of tumours, the location and the composition,
as well as the homogeneous or non-homogeneous echographic appearance.
The colour Doppler provides important information on blood flow in patients with
leiomyomas, polyps and endometrial disorders such as hyperplasia and endometrial carcinoma.

REFERENCES

1. Brăila M, Brăila A, Neacşu A, Gogănău A. (2017). Treatment of Pelvigenital Pain Syndrome in External
Endometriosis. Clinical Study for a Period of 3 Years. Proceedings of the 14 th National Congress of
Urogynecology and the National Conference of the Romanian Association for the Study of Pain, Filodiritto
Editore – Proceedings, pp. 328-330.
2. Buttram VC Jr, Reiter RC. (1981). Uterine leiomyomata: etiology, symptomatology, and management. Fertil
Steril 36 (4). p. 433.
3. Cramer SF, Patel A. (1990). The frequency of uterine leiomyomas. Am J Clin Pathol 94 (4). p. 435
4. Day Baird D, Dunson DB, Hill MC. (2003). High cumulative incidence of uterine leiomyoma in black and
white women: ultrasound evidence. Am J Obstet Gynecol 188(1), p. 100.
5. Brăila A D, Vaniova Klimentova D, Damian C M, Brăila M. (2012). Endometrial proliferative lesions
associated with uterine fibromatosis. Romanian Journal of Morphology and Embryology 56(3), Supp, pp.
743-747.
6. Neacşu A, Marcu ML, Stānicā CD, Brāila AD, Pacu I, Ioan RG, Grigorescu CC, Ionescu CA. (2018). Early
Diagnosis of Endometrial Cancer, Romanian Journal of Morphology and Embryology, 59(2).
7. Morimoto LM, Newcomb PA, Hampton JM. (2006). Cholecystectomy and endometrial cancer: a marker of
long-term elevated estrogen exposure? Int J Gynecol Cancer 16(3), p. 1348.
8. Soliman PT, Oh JC, Schmeler KM. (2005). Risk factors for young premenopausal women with endometrial
cancer. Obstet Gynecol 105(3): pp. 575.
9. Marcu M L, Neacşu A, Stoica C, Bacalbaşa N, Contolenco A, and Radu E. (2017). Clinical and pathological
features of splenic metastasis from cervical squamous cell carcinoma. Romanian Journal of Morphology and
Embryology. 58(4), pp. 1157-1164.
10. Liu Q, Yu Q-Q, Wu H, Zhang Z-H, and Guo R-H. (2015). Isolated gastric recurrence from ovarian
carcinoma: A case report. Oncol. Lett. 9(3), pp. 1173-1176.
11. Gunay Y, Demiralay E, and Demirag A. (2012). Pancreatic Metastasis of High-Grade Papillary Serous
Ovarian Carcinoma Mimicking Primary Pancreas Cancer: A Case Report. Case Rep. Med., vol. 2012, pp. 1-
3.
12. Vaniova Klimentova D, Brăila AD, Simionescu C, Ilie I, Brăila M. (2012). Clinical and paraclinical study
regarding the macro and microscopic diagnosis of various anatomo-clinical forms of operated uterine
fibromyoma. Romanian Journal of Morphology and Embryology , 53(2), pp. 369-373.
13. Farrer-Brown G, Beilby JO, Tarbit MH. (1970). The vascular patterns in miomatous uteri. J Obstet
Gynaecol Br Commonw 77(11): p. 976.
14. Forssman L. (1976). Distribution of blood flow in myomatous uteri as measured by locally injected 133
Xenon. Acta Obstet Gynecol Scand 55 (2). p. 101.
15. Fleischer AC, Shappell HW. (2003). Color Doppler sonohysterography of endometrial polyps and
submucosal fibroids. J Ultrasound Med 22 (6): p. 601.
16. Brāila M, Brăila A, Neacsu A, Gogănău A. (2017). Treatment of Dysmenorrhea in Adenomyosis. Clinical
Study for a Period of 3 Years, Proceedings of the 14 th National Congress of Urogynecology and the National
Conference of the Romanian Association for the Study of Pain, Filodiritto Editore – Proceedings, pp. 325-
327.

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17. Brăila AD, Brăila M, Cornițescu F et al., (2008). Benign ovarian tumors. Anatomo-clinical, diagnosis, and
therapeutical aspects. Gineco.eu, 4(3), pp. 178-185.
18. Bakour SH, Khan KS, Gupta JK. (2000). The risk of premalignant and malignant pathology in endometrial
polyps. Acta Obstet Gynecol Scand 79: p. 317.
19. Goldstein SR, Monteagudo A, Popiolek D. (2002). Evaluation of endometrial polyps. Am J Obstet Gynecol
186, p. 669.
20. Kim KR, Peng R, Ro JY. (2004). A diagnostically useful histopathologic feature of endometrial polyp: the
long axis of endometrial glands arranged parallel to surface epithelium. Am J Surg Pathol 28: p. 1057.
21. Nalaboff KM, Pellerito JS, Ben Levi E. (2001). Imaging the endometrium: disease and normal variants.
Radiographics 21: p. 1409.

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Fibular Hemimelia – Case Report and Review of the Literature

ȘTEFĂNESCU Bogdan Ioan1,2, MITREA Geta1,3


1 University “Dunarea de Jos” Galati, Faculty of Medicine (ROMANIA)
2 Obstetrics and Gynecology Department, Clinical Emergency Hospital “Sf. Ap. Andrei” Galati (ROMANIA)
3 Neonatology Department, Clinical Emergency Hospital “Sf. Ap. Andrei” Galati (ROMANIA)

Emails: [email protected], [email protected]

Abstract

Fibular hemimelia is defined by a constellation of abnormalities regarding the lower


extremity. Although fibular hypoplasia or aplasia is the main feature of the syndrome, other
skeletal anomalies are frequently associated.
Fibular hemimelia is the most common congenital absence of long bone of the extremities.
Most cases are diagnosed at birth, based on limb shortening associated in most situations with
foot deformity. Our reported case was diagnosed prenatally during 2nd trimester morphological
screening.
Keywords: Fibular hemimelia, lower limb malformation

Introduction

Fibular hemimelia is the congenital deficiency or absence of the fibula. The syndrome is also
called femur-fibula-ulna syndrome, intercalary hemimelia of the fibula, congenital short tibia
with absent or dysplastic fibula and more recently, postaxial hypoplasia of the lower extremity
[1].
The last term emphasize that fibular hemimelia is not characterized by only a single anatomic
feature but a constellation of abnormalities of the lower extremity.
The incidence of this condition is reported between 5.7 to 20 cases per 1 million births. Also it
is twice more common in boys than in girls. Unilateral involvement occurs in two-thirds of cases
with the right fibula being affected more often than the left one. Bilateral involvement is
extremely rare.

Case report

A 27 years old woman, G2 P1, was referred for a second opinion regarding a possible lower
limb fetal malformation. She had no significant medical history and the pregnancy was
uneventful except for a mild upper respiratory tract infection occurred in the first trimester.
First trimester screening, performed in other institution, based on nuchal translucency
associated with free -human chorionic gonadotropin and pregnancy-associated plasma protein
A levels revealed a low risk for trisomies 21 and 18.
All next ultrasound scans revealed a normal developing fetus, normal amount of amniotic
fluid as well as normal placentation.

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Ultrasound morphological evaluation performed at 24 weeks of gestation revealed total


absence of right fibula associated with hypoplastic right tibia and unilateral clubbing foot with 3
metatarsal bones (Fig. 1, 2).

Fig. 1. Absence of the fibula and hypoplastic right Fig. 2. Clubbing foot with 3 metatarsal bones
tibia

Also, 3D reconstruction of the fetal lower limb revealed the deformity and was very useful in
describing and understanding this malformation (Fig. 3, 4).

Fig. 3. 3D reconstruction of the right lower limb Fig. 4. 3D reconstruction showing abnormal
implantation of the foot

No other skeletal anomalies were identified. The long bones of the left lower limb as well as
from the upper limbs were within normal limits. Despite the fact that there was also identified a
3.5 mm perimembranous ventricular septal defect, all skeletal anomalies observed sugested the
diagnosis of fibular hemimelia probably type II.
The couple received genetic counseling and amniocentesis was performed. The fetal
karyotype was normal as well as amniotic -fetoprotein level.
The pregnancy continued without complications. The baby boy was born by vaginal delivery
at 38 weeks of gestation with a weight of 2800 grams and Apgar score 8.
Neonatal clinical evaluation showed a short right lower extremity with a clubbing foot
associated with agenesis of the 4th and 5th fingers and syndactyly of the first 2 fingers (Fig. 5, 6).

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The front and lateral views X-rays performed afterwards confirmed the diagnosis (Fig. 7, 8)
and the baby was refered to a pediatric orthopedic surgery unit for further evaluation.

Fig. 5. Short right lower limb with clubbing foot Fig. 6. Agenesis of the 4th and 5th fingers

Fig. 7. X-ray showing the absence of the Fig. 8. X-ray profile showing anterior bowing of the
right fibula and hypoplastic tibia right tibial bone

Discussions

This malformation is the most common congenital anomaly regarding the long bones of the
extremities and is associated with serious leg shortening [2, 3]. The anomaly has a wide
spectrum of appearance ranging from mild fibular hypoplasia to fibular aplasia. Also, ipsilateral
tibia could be normal, bowed or hypoplastic [4]. Other associated anomalies could be proximal
focal femoral deficiency or deficiencies of the lateral aspect of the foot. In some cases, this
condition is part of a malformation syndrome.
Although sporadic, some reports suggested a possible autosomal recessive familial
transmission [5, 6].
The embryonic insults most commonly occur between four to seven weeks of gestation.
Although not clear, this insult could be represented by teratogenic environmental exposures,
embryonic trauma, maternal viral infections or vascular dysgenesis.

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Prenatal diagnosis, although rare, is possible. Upper and lower limb buds are usually clearly
seen by the end of 8th week of pregnancy. Subsequently, there is a rapid growth and, by the end
of 10th week of pregnancy, the limbs are fully developed [7]. Moreover, the fetal long bones can
be measured by the end of 12th week of pregnancy [8].
Numerous classification systems have been proposed (Coventry 1952, Letts 1993, Stanitski
2003) but the most reliable are the classifications of Achterman-Kalamchi (1979) and Birch
(2011).
Generally, three types of fibular hemimelia have been recognised: type I (10%) – represents
cases with partial absence of the fibula and mild or no bowing of the tibia; type II (35%) –
represents cases with unilateral absence of the fibula, anterior bowing of the tibia, foot deformity
and marked shortening of the leg; type III (55%) – represents cases with unilateral or bilateral
absence of the fibula associated with multiple other skeletal defects [9].
The prognosis is influenced by the severity of limb malformation and the possibility of
orthopedic surgery. Mental development is not affected.

Conclusions

Fibular hemimelia is a spectrum of deformity whose landmarks are shortening of the affected
limb, anomalies of the foot and ankle, absence of the ligamentous structures of the knee.
Fortunately, most cases are sporadic. Nevertheless, ultrosonografic evaluation of the
developing fetus should be performed with great responsability. Moreover, morphologic
evaluation performed at 12 weeks of gestation should always emphasize the existence and
simetry of the 3 segments of the limbs.

REFERENCES

1. Stevens PM, Arms D. Postaxial hypoplasia of the lower extremity. J Pediatr Orthop 2000; 20(2): 166-72.
2. Eze KC, Akhigbe AO, Awosanya GO. Fibular hemimelia: a case report. Niger J Clin Pract 2007; 10(3):
259-61.
3. Achterman C, Kalamchi A. Congenital deficiency of the fibula. J Bone Joint Surg 1979; 61B: 133-137.
4. Fordham LA, Applegate KE, Wilkes DC, Chung CJ. Fibular Hemimelia: More Than Just An Absent Bone.
Semin Musculoskelet Radiol. 1999; 3(3): 227-238.
5. Gupta AK, Berry M, Verma IC. Congenital absence of both fibulae in four siblings. Pediatr Radiol 1994;
24(3): 220-1.
6. Kohn G, Veder M, Schoenfeld A, el Shawwa R. New type of autosomal recessive short-limb dwarfism with
absent fibulae, exceptionally short digits, and normal intelligence. Am J Med Genet 1989; 34(4): 535-40.
7. Monteagudo A, Dong R, Timor-Tritsch IE. Fetal fibular hemimelia: case report and review of the literature.
J Ultrasound Med 2006; 25(4): 533-7.
8. De Biasio P, Prefumo F, Lantieri PB, Venturini PL. Reference values for fetal limb biometry at 10-14 weeks
of gestation. Ultrasound Obstet Gynecol 2002; 19(6): 588-91.
9. Cuillier F, Cartault F, Lemaire P. 2004-03-25-14 Absence of fibula, type II. www.thefetus.net

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Polycystic Ovaries and the Polycystic Ovary Syndrome

STELEA Lavinia1,2, PETRE Izabella1,2, RAPCEA Raluca2, NEAMTU Radu2,


CRAINA Marius1,2
1 University of Medicine and Pharmacy “V. Babes” Timisoara, (ROMANIA)
2 Universitary Clinic of Obstetrics and Gynecology “Bega”Timisoara, (ROMANIA)

Abstract

Polycystic Ovary Syndrome (PCOS) is the commonest endocrine disorder of women in their
reproductive years. Polycystic ovaries are present in 22% of randomly selected women and that
is estimated to affect 5% to 10% of reproductive-age women. When initially described by Stein
and Leventhal in the 1930s, the hallmarks of PCOS werw reported to be hirsutism,
oligomenorrhea, obesity, and the histopathologic finding of cystic ovaries. A recent consensus
has led to the formulation of unifying diagnostic criteria for the definition of PCOS. This criteria
rely on the presence of two of the following symptoms: oligo/anovulation, clinical/biochemical
evidence of hyperandrogenism and the presence of polycystic ovaries.
It is a condition that may not requaire medical treatment as the symptoms may be amelioreted
by simply employing lifestyle measures such as weight loss [1], however, current medical
treatments consist of the use of insuline sensitizing agents, [2]aromatase inhibitors [3] and
antiandrogens in conjunction with the oral contraceptive pill, with the occasional addition of an
insulin sensitizing agent [4], or occasionally, the use of laparoscopic surgery. [5]
Although the etiology of this condition is unknown, hypotheses include a dysregulated
hypothalamic-pituitary axis, abnormal ovarian responsiveness, excess adrenal androgen
production, and peripheralinsulin resistance. PCOS is a disgnosis of exclusion after other causes
of hyperandrogenism are eliminated. In addition, PCOS is a signifiacant cause of infertility,
largely owing to absence of ovulation. [6]
Keywords: PCOS

Clinical Presentation

PCOS includes a variety of potential singns and symptoms, including oligo-ovulation,


biochemical or clinical hyperandrogenism, polycystic ovaries, and hyperinsulinemia, but no
single diagnostic criterion is recommended for the diagnosis of PCOS.
PCOS is associated with an increased risk of type 2 diabetes and cardiovascular
events.Insuline resistance and elevated serum luteinizing hormone (LH) levels are also common
features in PCOS [7]. Among different criteria, hyperandrogenemia, specifically elaveted
bioavailable testosteron, and the recognition of oligo-ovulation are academically conducice in the
diagnosis.
Many support a combination of hyperandrogenemia and olig-ovulation as diagnostic criteria
in the absence of known causes, while many others use ovarian morphology to identify and
diagnose the syndrome [8]. To help solving this issue, the Rotterdam consensus conference

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proposed to include the ultrasonographic (USG) follicle count as a new diagnostic creiterion, in
addition to hyperandrogenism and oligo-anovulation [9].
Overall, the three recommended criteria are: oligomenorrhea, any form of
hyperandrogenemia, either clinical (hirsutism and acnee) or endocrine (the hormonal diagnosis
of high androgen levels), and the ultrasound picture of polycystic ovaries. These are the major
three criteria, but in order to make the diagnosis it would be necessary to fulfil only to out of
three criteria. This makes PCOS a heterogeneous disorder [9]. Normal ovulatory women with
polycystic ovaries (PCO), who excibit only the ovarian morphology, are not considered to have
PCOS. A subgoup of this women may, however, have subtle abnormalities resembling PCOS.

Oligomenorrhea

Oligomenorrhea or dysfunctional bleeding is a frequently early and dominant symptom of the


anovulatory component of PCOS. Menstrual irregularity in PCOS is chronic and can be
manifested in several different ways. Irregular menstruation due to anovulation is perhaps the
most common. Some women with PCOS have long lasting amenorrhea associated with
endometrial atrophy. Some women have regular cycles at first and experience menstrual
irregularity in association with weight gain, while sometimes, the onset of PCOS is peripubertal
[10].

Infertility and PCOS

Infertility was included in the original description of PCOS by Stein and Laventhal [11]. The
prevalence of infertility, caused mainly by anovulation in PCOS women varies between 35% and
94% [12]. According to one retrospective study, however, women with PCOS are as likely to
have children as healthy women, although often, after infertility treatment [13, 14, 15]. Some
studies have also described an increased miscarriage rate in PCOS, the mechanism of wich is
inadequately understood. It has been suggested that high follicular phase concentrations of LH
have a harmful effect on conception rates and may cause miscarriage [16, 17].

Hyperandrogenism

Hyperandrogenism is the second essential characteristic of PCOS. Clinically, the most


common sign of hyperandrogenism in PCOS is hirsutism, which can be defined as the growth of
coarse hair on a woman in a male pattern ( upper lip, chin, chest, upper abdomen and back).
Thus, an adolescent female with moderate to severe acne should be investigated for PCOS. It
has also been shown that hyperandrogenism may be related to overt signs of virilisation [18], i.e.
male pattern balding, alopecia, increased muscle mass, a deepening voice or clitoromagaly, but
these signs partly resolve before menopause in women with PCOS [19].

Gonadotropin secretion

Compared with the follicular phase of the normal menstrual cycle, women with PCOS exhibit
an unreasonably high LH secretion with comparatively constant low follicle stimulating hormone
(FSH) secretion. An elevated LH/ FSH ratio of 2-3:1 is commonly used to indicate abnormal

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gonadotropin secretion. The prevalence of increased serum LH in PCOS ranges from 30% to
90% [20, 21].

Ultrasonographic finding of PCOS

In clinical practice, ultrasonography has replaced the histologic evaluation of PCO and many
parameters have been used for its definition. Their criteria [22] were as follows: the presence of
either at least 10 follicles, usually between 2-8mm in diameter, distributed uniformly arround the
ovarian periphery with an increased amount of stroma, or multiple small cysts 2-4 mm in
diameter distributed throughout abundant stroma [22]. Overall, the USG findings are not
sufficient for the diagnosis of PCOS. In fact, the typical USG findings of PCO are demonstrated
in 8% to 25% of normal women. This USG picture can also be found in 14% of the women on
oral contraceptives.

Conclusions

1. PCOS is a common endocrinophaty characterized by menstrual irregularity and


hyperandrogenism that estimated to affect 5% to 10% of reproductive age women.
2. Diagnosis is based on clinical findings of menstrual irregularity and evidence of androgen
excess.
3. The finding of polycystic ovaries on ultrasound is nonspecific and should not be
usedalone to make a diagnosis of PCOS because 25% of normal women may have
polycystic appearing ovaries on ultrasound.

REFERENCES

1. Norman RJ, Davies MJ, Lord J, Moran LJ. (2002). The role of lifestyle modification in polycystic ovary
syndrome. Trends Endocrinol Metab. 13(6), pp. 251-257.
2. Harborne L, Fleming R, Lyall H, Norman J, Sattar N. (2003). Deascriptive review of the incidence for the
use of metformin in polycystic ovary sindrom. Lancet. 361(9372), pp. 1894-1901.
3. Mitwally MF, Casper RF. (2005). Single-dose administration of an aromatase inhibitor for ovarian
stimulation. Fertil Steril. 83(1), pp. 229-231.
4. Ibanez L, de Zegher F. (2005). Flutamide-metformin plus ethinilestradiol-drospinerone for lipolysis and
antiatherogenesis in young womenwith ovarian hyperandrogenism: the key role of metformin at the start
and after more than one year of therapy. J Clin Endocrinol Metab. 90(1), pp. 39-43.
5. Hart R, Magos A. (1997). Polycystic Ovarian Syndrome. Seminars in Laparoscopic Surgery. 4, pp. 210-
218.
6. Jensen JR, Alvero R. (2007). Polycystic Ovarian Syndrome. Reproductive Endocrinology and Infertility. 7,
pp.66.
7. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. (1999). Prevalence of impaired
glucose tolerance and diabetes in womenwith polycystic ovary syndrome. Diabetes Care. 22, pp. 141-146.
8. Legro RS. (2003). Diagnostic criteria in polycystic ovary syndrome. Semin Reprod Med. 21(3), pp. 267-
275.
9. The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. (2004). Revised 2003
consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).
Hum Reprod. 19(1), pp. 41-47.
10. Chakrabarty S, Miller BT, Collins TJ, Nagamani M. (2006). Ovarian dysfunction in peripubertal
hyperinsulinemia. J Soc Gynecol Investig. 13(2), pp. 122-129.
11. Stein IF, Leventhal ML. (1935). Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet
Gynecol. 29, pp. 181.
12. Franks S. (1995). Polycystic ovary syndrome. N Engl J Med. 333, pp. 853-861.

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13. Dahlgren E, Johansson S, Lindstedt G, Knutsson F, Oden A, Janson PO et al., (1992). 57, pp. 505-513.
14. Capatina, C; Radian, S; Baciu, I; Ghinea, A; Deciu, D; Dumitrascu, A; Ciubotaru, V; Poiana, C.
Spontaneous conception and term delivery in a woman with uncontrolled acromegaly and
hypogonadotropic hypogonadism. ACTA ENDOCRINOLOGICA-BUCHAREST, Vol: 12, Issue: 4, Pages:
481-484, DOI: 10.4183/aeb.2016.481, Published: OCT-DEC 2016.
15. Pacu I, Ionescu C, Vladareanu S, Banacu M, Neacsu A, Calin A. Predictive Value of the AMH Level and
Serum Estradiol for Ovarian Hyperstimulation Syndrome in the Assisted Human Reproduction. REVISTA
DE CHIMIE Volume: 68 Issue: 5 Pages: 1118-1121 Published: MAY 2017.
16. Homburg R, Armar NA, Eshel A, Adams J, Jacobs HS. (1988). Influence of serum luteinising hormone
concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome. BMJ.
297, pp. 1024-1026.
17. Balen AH, Tan SL, McDougall J, Jacobs HS. (1993). Miscarriage rates following IVF are increased in
women with PCO and reduced pituitary desisitization with buserelin. Hum Reprod. 8, pp. 959-964.
18. Poiana, Catalina; Virtej, Ioana, Mara; Banceanu, Gabriel; Sajin, Maria; Stanescu, Bogdan; Ioachim,
Dumitru; Hortopan, Dan; Coculescu, Mihail. Virilising Sertoli-Leydig cell tumour associated with thyroid
papillary carcinoma: case report and general considerations. GYNECOLOGICAL ENDOCRINOLOGY,
Volume: 26, Issue: 8 , Pages: 617-622, DOI: 10.3109/09513591003686361, Published: AUG 2010.
19. Elting MW, Korsen TJM, Rekers-Mombarg LTM, Schoemaker J. (2000). Women with polycystic ovary
syndrome gain regular menstrual cycles when ageing. Hum Reprod. 15, pp. 24-28.
20. Conway GS, Honour JW, Jacob HS. (1989). Heterogeneity of the polycystic pvary syndrome: clinical,
endocrine and ultrasound features in 556 patients. Clin Endocrinol. 30, pp. 459-470.
21. Franks S. (1989). Polycystic ovary syndrome: a changing perspective. Clin Endocrinol. 31, pp. 87-120.
22. Adams J, Franks S, Polson DW, Mason HD, Abdulwahid N, Tucker M, et al., (1985). Multifollicular
ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet.
2(8469-70), pp. 1375-1379.

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Syphillis in Pregnancy

STERIU Liliana1, NICULESCU Costin1, IZVORANU Silvia1, PENCIU Roxana1,


MOCANU Diana1, POSTOLACHE Iulia1
1Emergency Hospital of Constanta, (ROMANIA)
Email: [email protected]

Abstract

Introduction
Syphilis is an infectious disease caused by Treponema pallidum, which is transmitted by
sexual contact or vertically, from the mother to the fetus, after 20 gestational weeks.

Objective
The study aimed to determine the incidence of syphilis in pregnant women in Constanta over
a short period of time and the effects of this disease on the fetus and the newborn.

Methods
The study was conducted over a period of 6 months on pregnant and, subsequently, puerperal
women, who were admitted to the Obstetrics and Gynecology I Clinic of the Saint Andrew
Emergency Clinical County Hospital of Constanta.
All patients were serologically tested for syphilis, by using the rapid plasma reagin (RPR)
test. In patients for which the RPR was found to be positive, the result was confirmed with the
Treponema pallidum particle agglutination assay (TPHA), a more specialized test for syphilis.
Pregnant women with positive syphilis serology were evaluated by monthly ultrasounds
(including Doppler measurements). Fetal well-being and the bone system status were also
assessed in the respective fetuses and newborns.
The puerperal women diagnosed with syphilis were promptly reevaluated through
interdisciplinary consults after delivery, and all newborns received antibiotic therapy.

Conclusions
The incidence of syphilis in pregnant and puerperal women, in our series, is slightly higher
than that reported in the literature. This disease continues to be present in our patients. It became
a major source of perinatal morbidity and mortality.

Introduction

Syphilis is a sexually transmitted disease with possibly severe consequences.


The incidence of syphilis in Romania has decreased in the past 10 years, but still remains one
of the highest in Europe.
In the year 2016, the incidence of syphilis was: 4,83/100.000.
The incidence is increased for the age groups 20-34 years old.

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In 2016, 109 cases of syphilis in pregnant patients and 4 congenital syphilis cases were
registered [1].
Syphilis can be transmitted to the fetus: transplacental, which is the most common way or
during labor, through direct contact with genital lesions.

Material and methods

We analyzed data from all patients diagnosed with syphilis who were admitted in the
Obstetrics-Gynecology Department of SCJU “Saint Andrew” Emergency Clinical County,
Constanta over a period of 6 months, January the 1th, 2017-June the 31th, 2017.
In our hospital, all pregnant patients admitted are screened with the non-treponemal test RPR.
A positive result is confirmed by the treponemal test TPHA.

Results

Sixteen patients tested RPR positive. In 10 patients, the diagnosis was confirmed and they
received treatment with Benzathine Benzylpenicillin. None has had ovarian tumors, genetic
syndromes, surgical interventions, surgical or medical assisted reproductive techniques [2], [3],
[4], [5]. None was HIV-positive [6]. None had other pregnancy-related pathologies – like
tumors, biliary pathology, hypertension [7], [8], [9]. They, all, delivered vaginally, with different
partograms [10]. None needed surgery or amniocentesis during their pregnancies [11]. Four
patients were already treated for syphilis. Two patients left the hospital before receiving
treatment.
All but two cases had pregnancies, diagnosed at term. The other two cases were diagnosed
postpartum.

Image 1. Distribution of the patients studied by age groups

Discussions

Syphilis in pregnancy can cause: premature birth (not related, we think, with the ADP/Ca2+
myometrial system [12]), non-immune hydrops, still birth, IUGR, neonatal infection [13].

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The US Preventative Services Task Force recommends screening all pregnant patients for
syphilis [14]. WHO guideline recommends screening all patients for syphilis at the antenatal
visit.
The risk of fetal morbidity is minimal if the mother is properly treated during early pregnancy
– ideally, in the first trimester [15].
Most of our cases were diagnosed in the third trimester.
The chances of fetal infection decrease as the time from the primary infection increases – 40%
in primary latency and 10% in secondary latency [16], [17], [18].
Most of our cases were diagnosed as syphilis with undetermined duration.

Image 2. Prenatal care

Most of the patients in our study had late or no prenatal care, were not legally married (and
therefore were not subjected to premarital screening tests) and were usually diagnosed with
latent syphilis when they presented to the hospital, in labor. Their new-borns were subjected to
antibiotic treatments from the first day of life.

Conclusions

Even if the treatment for syphilis is well established, affordable and effective, this disease
continues to be frequent in women with low education and poor socio-economic status.

Image 3. Education levels of the patients

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Image 4. Patient residence

It is important to promote sexual education, to encourage pregnant patients to seek prenatal


care as early as possible in order to prevent maternal and fetal morbidity caused by syphilis.

REFERENCES

1. Institutul National de Sanatate Publica. (2016). CNSCBT. Analiza evolutiei bolilor transmisibile aflate în
supraveghere, Raport pentru anul 2016.
2. Tica I, Tica OS, Nicoară AD, Tica VI, Tica A-A. Ovarian teratomas in a patient with Biedl Bardet
syndrome, a rare association. Rom J Morphol Embryol 2016, 57(4): 1403-1408.
3. Tica V. Primary ovarian pregnancies. Gineco. ro 2011; 7(26):179-180.
4. Tica V. Laparoscopic ovarian drilling. Gineco. ro 2011; l7(25):119-120.
5. Tica V, Hedon B, Eid J, Audibert F, Benos P, Boulot P, Laffargue F, Viala JL. Determination of adverse
reactions to the stimulation of ovulation in vitro fertilization. [Effets secondaires de la stimulation
ovarienne dans le cadre de la fécondation in vitro.] Contraception Fertilité Sexualité. 1991; 19(7-8): 580-
582.
6. Cocu M, Thorne C, Matusa R, Tica V, Florea C, Asandi S, Giaquinto C. Mother-to-child transmission of
HIV infection in Romania: results from an education and prevention programme. AIDS Care. 2005; 17(1):
76.
7. Tica AA, Tica OS, Saftoiu A, Camen D, Tica VI. Large Pancreatic Mucinous Cystic Neoplasm during
Pregnancy: What Should Be Done? Gynecol Obstet Invest. 2013; 75(2): 132-138.
8. Tica I, Tica VI, Teren O. Pregnancy, parity and maternal age – predictive factors for occurrence of billiary
pathology (gallstones and sludge)? Gineco.ro 2010, 6(22): 218-222.
9. Tica V. Preeclampsia – an unsolved prophylaxis chapter. Gineco.ro 2012; 8(27): 3-4.
10. Galazios G, Tica V, Vrachnis N, Vlachos G, Zervoudis S, Ceausu I, Trypsianis G, Zographou C, Tsikouras
P. Assessment of labor using a new type partogram compared to the classical Fisher partogram. J Matern
Fetal Neonatal Med. 2015; 28(1): 82-7.
11. Tica V. One small step/one giant leap in the rate of fetal loss after amniocentesis. Gineco.ro 2011, 7(24).
12. V. I. Tica, V Cojocaru, Oana SorinaTica, Sabina Berceanu, A. A. Tica. Cyclic-ADP-ribose/Ca 2+ system in
uterine smooth muscle cells. Gineco.ro 2011, 7(26): 193-194.
13. Oswal, S., Lyons, G. Syphilis in pregnancy. (2008). Contin Educ Anaesth Crit Care Pain.
14. U.S. Preventive Services Task Force. (2009). Screening for syphilis infection in pregnancy, Ann Intern
Med 2009.
15. Kuznik, A. et al., (2015). Antenatal syphilis screening using point-of-care testing in low- and-middle-
income countries in Asia and Latin America: a cost efectiveness analysis. PLoS One. 2015.
16. Sanchez et al., (1993). Evaluation of molecular methodologies and rabbit infectivity testing for the
diagnosis of congenital syphilis and central nervous system invasion by Treponema pallidum, J Infect Dis,
1993.
17. Wendel, G.D. (1988). Gestational and congenital syphilis, Clin Perinatol.
18. Fiumara, N.J. (1951). The incidence of prenatal syphilis at the Boston City Hospital, N Engl J Med.

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On Thin Ice: Counselling in Minor Congenital Anomalies

TUDORACHE Stefania1,2, DRAGUSIN Roxana2, ILIESCU Dominic Gabriel1,2,


SOROP-FLOREA Maria2, DINU Marina2, MARINAS Cristian1,2,
TANASE Florentina1,2, STOICA Alin1,2
1University of Medicine and Pharmacy Craiova, (ROMANIA)
2University Emergency County Hospital Craiova, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected], [email protected]

Abstract

Many clinical ethics dilemmas have emerged as a result of advances in the ultrasound prenatal
diagnosis. Professionals are increasingly involved in performing high quality early anomaly
scans, applying genetic screening programs and practicing invasive procedures. These allowed
an unparalleled performance in diagnosis accuracy and establishing the probable neonatal and
childhood outcome. However, they also revealed a wider range of diagnosable diseases and
symptoms never reported before, or rarely described in the prenatal life. Therefore, we are
confronted occasionally with cases in which the best estimates of prognosis turn out to be wrong.
The postnatal symptoms/evolution may be less severe or more severe than anticipated based
on prenatal assessment. We present a case series in which the prenatal diagnosis identified so-
called “minor” structural anomalies, and in which the prenatal counselling proved to be
particularly challenging. Many cases requested a complex work-up program. In about half of
them, the same ultrasound feature has been associated with divergent outcome. Based on our
case series, we may state that in minor anomalies counsellors should prove particularly
thoughtful. They should be specifically trained and should maintain their skills, in a continuously
and rapidly developing field. Also, we noticed that the parental psychological impact has an
extremely large spectrum, couples facing same anomalies having completely different reactions.
Keywords: counselling, ultrasound, minor congenital structural anomaly

Background

Obstetric ultrasound (US) is widely used in all European countries, including the low-income
ones. The use of obstetric US have ingrained in obstetric care also in developing countries,
including Romania. There have been reported a growing availability of high resolution systems.
Many steps forward have been made, we use more often modern ultrasound on-line and off-
line processing techniques [1-4], in an attempt to confirm normality [1], diagnose the abnormal
[5], and even assess functional aspects [6]. Although there is to date no supporting evidence that
routine scans in early or late pregnancy may improve the mothers’ or babies’ outcome if used in
low-risk or unselected populations [7], obstetric US scans are popular among expectant parents
and the vast majority of women will gladly participate in scans offered during pregnancy. Lately,
the first trimester (FT) anomaly scan became the pillar of antenatal care [5]. Finding major
anomalies will probably alter the demographics [3, 4, 8-11], signaling placental and umbilical

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cord anomalies has the potential of altering the ante-/intrapartum management [12]. Yet, there
are minor findings that occasionally raise the difficulty in prenatal counseling and/or widens the
prenatal work-up [13-19].

Methods

We have been involved in a long-term prospective study having the aim to assess the
diagnosis accuracy of the FT anomaly scan. We used as reference methods the follow-up second
trimester (ST) scans, the perinatal autopsy of the intact specimens and the postnatal clinical and
imaging assessment. We selected and enrolled the minor anomalies that appeared isolated at the
moment of the diagnosis. We defined them as defects having a presumable low impact on the
quality of life and not changing the intrapartum/postpartum pregnancy management.

Results

We present below paired or matched case series, having discordant outcome. The trigger for
enrolling them was roughly the same “minor” ultrasound anomaly.
We detail below two cases in which the operator signaled repeated movements of tongue
protrusion. The first one had a completely normal evolution postnatally and in childhood. 6-years
old now, he has had a perfectly normal neurodevelopment, and a constitutionally large tongue
(Fig. 1). The second was diagnosed prenatally, in spite of the normal anomaly and genetic scan,
with Down syndrome. The parents opted for continuing the pregnancy, and the postnatal
evolution was consistent with the syndrome (Fig. 2).

Fig. 1. Constitutionally large tongue: a – fetal profile, third trimester, 2D conventional US. The tip of the tongue is
protruding between the bony anterior palate and the mandible (arrows indicating the bony landmarks). b, c and d –
fetal face reconstructions in 3-dimensional US, in surface rendering mode. In all three images the tongue may be
observed between the two lips. e and f – postnatal images, at 3 days and 2 years of age.

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Fig. 2. Repeated movements of protrusion of the tongue in a Down syndrome fetus and neonate

The first row consists in a series of fetal profile images, showing different moments in a
videoclip stored. The first image in the second row is a reconstructed image in 3-dimensional
US, in surface rendering mode. The characteristic dysmorphic features of trisomy 21 may be
observed. The following images are obtained in the neonatal period. The resemblance with the
prenatally acquired images may be seen, and also, the protrusion of the tongue movements
(reproduced with parental signed consent).
We enrolled two cases of isolated postaxial polydactyly. One of them evolved with
spontaneous prenatal amputation [20]. The other one suffered complex surgical interventions in
both hands, with suboptimal long-term results.
Furthermore, we enrolled five cases of persistent right umbilical vein, diagnosed at 16-18
weeks of amenorrhea. One case had a normal prenatal and postnatal evolution. In the second,
despite the subsequently diagnosed maternal gestational diabetes, and the large for gestational
age growing curve, the baby had a normal development. In the third case, a follow-up scan
diagnosed, one week later, the uncorrected transposition of great arteries suspected initially. The
forth case exhibited third trimester features of aortic coarctation [21]. This case was diagnosed
antenatally, referred to a tertiary center having neonatal surgery facilities, and evolved
uneventfully after the corrective surgery. In the last baby in this case series we diagnosed
associated tetralogy of Fallot, and subsequently – a 22q11 deletion syndrome (DiGeorge
syndrome), by means of Fluorescence In Situ Hybridization (FISH) technique. This latter case is
an evolving pregnancy at the time of writing.
We enrolled also several cases with isolated single umbilical artery. We had a case with a
normal evolution, a case evolving with late intrauterine restriction, a case diagnosed postnatally
with descending colon atresia and an imperforate anus (Fig. 3), requesting a complex surgical
intervention, and a case diagnosed with a minor form of hypospadias (Fig. 4).

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Fig. 3. Single umbilical artery syndrome (SUAS). In the prenatal period it was considered isolated. Postnatally, the
association with a descending colon complex anomaly was diagnosed. a – first trimester diagnosis (at 12 weeks
anomaly scan). b – postnatal aspect of the perineal area. c – detail of the sectioned umbilical cord.

Fig. 4. Single umbilical artery syndrome (SUAS). In the first and early second trimester it was considered isolated.
In the third trimester, a minor form of hypospadias was suspected. The postnatal aspect was consistent with penile
glanular hypospadias (absent parental consent for publishing the postnatal features). a – FT diagnosis, establishing
the laterality of SUAS. b – ST confirmation. c – third trimester 2D conventional US, showing the abnormal shape of
the penis. d – 3D surface rendering mode applied, detailing the external aspect of the short and abnormal glans.

Finally, we enrolled also two cases with bilateral congenital cataract, diagnosed in the second
trimester. One case had a neonatal surgical intervention, with a favorable outcome, and the other
developed in the third trimester dilated cardiomyopathy. Regardless the intensive care and
treatment, the neonate perished at two months of age.

Discussions

Our small case series is not enough to draw definite conclusions. Yet, we acknowledge that
the minor structural anomaly cases implied more time consuming sessions for teams involved in
perinatology, if compared with the ones diagnosed with isolated/multiple major anomalies.
Almost all cases required repeated scans, multiple multidisciplinary professional meetings and
repeated parental counseling sessions. We confirmed that the parental consumption facing a fetal
anomaly is intense, and it depends more on the personal views about family and personal life
concepts, than on the significance of the specific anomaly [22].
Medical stuff involved have to realize that the counseling must be adjusted for this group of
particularly sensitive patients, who rate their decision making support as very important. Inviting
the mothers together with their partner for prenatal counseling is paramount.
The technical advances in US equipment is increasing ethical dilemmas in obstetric practice.
The fetal diagnostics and treatment will continue to advance. This requires careful
consideration and further investigation in each case diagnosed with minor congenital structural

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anomalies. As reported before [23], our subjective impression was that pregnant women with
fetal anomalies experience the highest psychological stress levels at the initial suspicion, and
then, during pregnancy, their level of stress decreases. This reality should tailor the counselor’s
utterance in bringing the undesirable news to the parents.

Conclusions

In our view any minor anomaly detected should trigger a thorough search for associated
structural anomalies and a as complete as possible work-up, to rule-out an underlying syndrome.
The professionals involved in prenatal counselling should gather in large multidisciplinary
teams, in an attempt to cover all possible aspects consistent with the specific defect diagnosed.
Moreover, they should be involved in continuing medical education programs, due to working
in a rapidly changing field.

REFERENCES

1. Tudorache, S; Cara, ML; Iliescu, DG; Novac, L; Cernea, N. (2013) First trimester two- and four-
dimensional cardiac scan – intra and interobserver agreement, Ultrasound Obstet Gynecol,6 (42), 659-668.
2. Dragusin, R; Florea, M; Iliescu, DG; Cotarcea, S; Tudorache, S; Novac, L; Cernea, N. (2012) The
contribution and the importance of modern ultrasound techniques in the diagnosis of major structural
abnormalities in the first trimester – case reports. Curr Health Sci J. 38(1): 20-4.
3. Muresan, D; Popa, R; Stamatian, F; Rotar IC. (2015) The use of modern ultrasound tridimensional
techniques for the evaluation of fetal cerebral midline structures – a practical approach, Med Ultrason.
17(2): 235-40.
4. Ionescu, C; Gheorghiu, D; Davitoiu, B; Pacu, I; Vladescu, T (2009) Visualization of the atrioventricular
valve plane in fetuses with atrioventricular defect using STIC technique. GINECO RO 5(4), 210-215.
5. Iliescu, D; Tudorache, S; Comanescu, A; Antsaklis, P; Cotarcea, S; Novac, L; Cernea, N; Antsaklis, A.
(2013) Improved detection rate of structural abnormalities in the first trimester using an extended
examination protocol. Ultrasound Obstet Gynecol. 42(3): 300-9.
6. Kurjak, A; Antsaklis, P; Stanojevic, M; Vladareanu, R; Vladareanu, S; Neto, RM; Barisic, LS; Porovic, S;
Delic T. (2017) Multicentric studies of the fetal neurobehavior by KANET test. J Perinat Med. 28; 45(6):
717-727.
7. Whitworth, M; Bricker, L; Neilson, JP; Dowswell, T. (2010) Ultrasound for fetal assessment in early
pregnancy. Cochrane Database Syst Rev.; 4, CD007058.
8. Herghelegiu, D; Ionescu, CA; Pacu, I; Bohiltea, R; Herghelegiu, C; Vladareanu, S. (2017) Antenatal
diagnosis and prognostic factors of aneurysmal malformation of the vein of Galen A case report and
literature review Medicine (Baltimore). 96(30) e7483.
9. Marginean, C; Marginean, MO; Muresan, D; Zahiu, L; Horváth E. (2016) The TRAP (twin reversed
arterial perfusion) sequence – case presentation. Rom J Morphol Embryol. 57(1): 259-65.
10. Marginean, C; Gozar, L; Marginean, CO; Suciu, H; Toganel, R; Muntean, I; Muresan MC. (2018) Prenatal
diagnosis of the fetal common arterial trunk. A case series. Med Ultrason. Feb 4; 1(1): 100-104.
11. Iliescu, D; Comanescu, A; Antsaklis, P; Tudorache, S; Ghilusi, M; Comanescu, V; Paulescu, D; Ceauşu, I;
Antsaklis, A; Novac, L; Cernea, N. (2011) Neuroimaging parameters in early open spina bifida detection.
Further benefit in first trimester screening? Rom J Morphol Embryol. 52(3): 809-17
12. Bohîlțea, RE; Cîrstoiu, MM; Ciuvica, AI; Munteanu, O; Bodean, O; Voicu, D; Ionescu, CA. (2016)
Velamentous insertion of umbilical cord with vasa praevia: case series and literature review. J Med Life.
9(2): 126-9.
13. Iliescu, DG; Cara, ML; Tudorache, S; Antsaklis, P; Novac, LV; Antsaklis, A; Cernea, N. (2014) Agenesis
of ductus venosus in sequential first and second trimester screening. Prenat Diagn. 34(11): 1099-105.
14. Iliescu, DG; Comanescu, AC; Tudorache, S; Cernea, N. (2012) Right aortic arch with patent right ductus
arteriosus and normal heart. Ultrasound Obstet Gynecol. 40(1): 115-6.

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15. Marginean, C; Molnar-Varlam, C; Melit, LE; Mărginean, MO; Sasaran, VS; Muresan, D. (2016) Isolated
anomalies of the fetal hand – two case reports and a review of the literature. Rom J Morphol Embryol.
57(4): 1415-1419.
16. Marginean, C; Marginean, CO; Muntean, I; Toganel, R; Melit, LE; Marginean, MO; Gozar L. (2016 )
Ultrasonographic features of the persistence of superior left vena cava and pathological cardiac associations
in fetus. Case series. Med Ultrason. Jun; 18(2): 214-7.
17. Muntean, I; Marginean, C; Stanca, R; Toganel, R; Pop, M; Gozar, L. (2017) Prenatal diagnoses of an
uncommon isolated obstructed supracardiac total anomalous pulmonary venous connection – case report
and review of the literature (CARE compliant), Medicine, 96:5, e6061
18. Marginean, C; Marginean, CO; Muntean, I; Toganel, R; Voidazan, S; Gozar, L. (2015) The role of
ventricular disproportion, aortic, and ductal isthmus ultrasound measurements for the diagnosis of fetal
aortic coarctation, in the third trimester of pregnancy. Med Ultrason. 17(4): 475-81.
19. Zorila, GL; Tudorache, S; Barbu, EM; Comanescu, MC; Capitanescu, RG; Marinas, MC; Florea, M;
Cernea, N, Iliescu, DG. (2016) Outcome of fetuses with abnormal cavum septi pellucidi. Experience of a
tertiary center. J Clin Gynecol Obstet 5(4): 112-116.
20. Tudorache, S; Dragusin, RC; Florea, M; Patru, CL; Novac, M; Iliescu DG. (2016) Reversional unilateral
postaxial polydactyly type I in fetal life: a case report; Obstetrica și Ginecologia, nr. 4.
21. Tudorache, S; Iliescu, DG; Cara, ML; Burada, F; Ioana, M; Simionescu, C; Novac, L; Cernea, N; Cernea,
D. (2014), OC02.01: First trimester 2D cardiac assessment for congenital heart diseases. Ultrasound Obstet
Gynecol, 44: 3-3.
22. Tudorache, S; Iliescu, DG. Parental attitude to participate in follow-up research studies of their children’s
development after diagnosis of fetal abnormalities in a tertiary center in Romania Obstetrica și Ginecologia,
nr.4, 2016.
23. Kaasen, A; Helbig, A; Malt, UF; Næs, T; Skari, H; Haugen, G. (2017) Maternal psychological responses
during pregnancy after ultrasonographic detection of structural fetal anomalies: A prospective longitudinal
observational study. PLoS One. 2017 Mar 28; 12(3): e0174412.

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Abnormal Placenta

CEAUȘESCU Andreea1, DINU Marina1, DRAGUȘIN Roxana1,2,


TUDORACHE Ștefania1,2
1Emergency University Hospital Craiova, (ROMANIA)
2University of Medicine and Pharmacy Craiova, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

The placenta is an essential organ in developing a normal healthy pregnancy. It has multiple
functions: nutrient uptake, termo-regulation, waste elimination, gas exchange, immunity and
hormones’ production. Placental disorders are involved in fetal growth restriction, preeclampsia,
placental abruptio. The abnormal cord insertion is the primary cause of fetal death in many cases
[1].
The cesarean scar pregnancy threatens to became an epidemic, being the underlying condition
in a number of maternal and fetal complications. The management of these situations is often
difficult. This paper present a case series. It highlights the importance of the prenatal diagnosis
of abnormal placenta and its role in improving the intrapartum management.
Keywords: abnormal placenta, ultrasound, fetal death

Introduction

One of the consequences of increasing cesarean delivery rates is the increase in placental
implantation abnormalities. Low lying placenta, placenta praevia, abnormal ivasive placenta
(accreta, transcreta), vasa praevia, and velamentous cord insertion may have catastrophic
complications for both the mother and fetus. Efforts have been made for reducing the maternal
and fetal risk. The early diagnosis has the potential to change counselling and perinatal
management. In order to increase complications’ control, a planned caesarian section is often
preferred, and this may result in iatrogenic preterm delivery. Following ischemic placental
disease, placental implantation abnormalities are the second most common cause for indicated
preterm delivery, accounting for 5.6-8.7% of them. The ultrasound evaluation is the single most
important tool in detecting all placental and umbilical cord abnormalities.

Methods

We present below a case series from the archive of the Prenatal Diagnosis Unit in Emergency
County Hospital Craiova.
The first case is a caesarean scar pregnancy (CSP), diagnosed in the early first trimester of
pregnancy (Fig. 1). The couple was counseled about the whole spectrum of third trimester and
intrapartum complications, and declined a termination of pregnancy intervention. The
abnormally invasive placenta was diagnosed in the second trimester. The short interval follow-up
was performed. The patient delivered by elective, carefully planned Cesarean section, at 37

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weeks. Despite it, the complete hysterectomy was required for massive intraoperatory
hemorrhage. In the current literature, as CSP is a life-threatening type of abnormal placenta,
accounting for 6% all ectopic pregnancies, and multiple therapeutic options are available [2, 3].
Local methotrexate therapy (under ultrasound or hysteroscopy guidance), systemic
methotrexate, dilatation and curettage, excision of trophoblastic tissues using laparotomy or
laparoscopy, bilateral hypogastric artery ligation under laparoscopic guidance, followed by
dilatation and evacuation and selective uterine artery embolization (UAE) are valid solutions,
after a multidisciplinary approach of the condition. However, all patients should give an
informed consent, acknowledging the risks and benefits of each type of management. In that
matter, the early diagnosis of CSP by means of transvaginal ultrasound is paramount when
discussing preservation of fertility. The late diagnosis of the condition (at the labor onset or
during the surgery) can be associated with serious life threatening obstetric complications
(uterine rupture, massive hemorrhage and emergency hysterectomy).

Fig. 1. Details first case: a. ultrasound image of incipient scar pregnancy, in grey Scale (4 weeks + 5 days of
amenorrhea); b. ultrasound duplex image (grey-scale and HD flow) at 8 weeks, showing the complete coverage of
the internal cervical os by the placenta; c. same case, 23 weeks of amenorrhea; d. the specimen (uterus) after surgery

In the second case, vassa previa (VP) was diagnosed by means of transabdominal and
transvaginal ultrasound in the second trimester (Fig. 2). The patient had an uneventful evolution
during pregnancy and a cesarean section delivery at 37 weeks was offered, according to current
guidelines. The postpartum clinical exam of the placenta confirmed the velamentous insertion of
de umbilical cord and the vassa praevia. VP refers to aberrant chorionic vessels which can either
connect the chorionic plate to a velamentous cord (type I) or a succenturiate or accessory lobe to
the main placental mass (type II). It is reported to occur in around 1 in 2500 deliveries [4] and is
responsible for fetal blood loss, with significant neonatal morbidity or death in case of
spontaneous rupture of membranes or amniotomy. The prenatal diagnosis is achievable with a

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high accuracy by ultrasound. A sensitivity of 100% and a specificity of 99-99,8% is reported, if


transvaginal color Doppler examination is used [5]. A recent study has shown a higher resistance
to blood flow in the umbilical arteries of velamentous cords [6]. These findings suggest that the
insertion of the umbilical cord outside the chorionic placental plate may lead to abnormal
umbilical-placental blood flows and secondary fetal growth restriction. There are recent reports
of two main associations: velamentous insertions and vessels crossing between lobes in
succenturiate or bilobate placentas [7].

Fig. 2. a. transvaginal ultrasound image with HD flow (directional Power Doppler) showing the vassa praevi; b. the
postpartum aspect of velamentous insertion of the umbilical cord on the fetal surface (white arrow) and vasa praevia
(red arrow); c. the maternal surface, same details

Various kinds of placental shape abnormality have been reported in literature. They include
bi-discoidal, lobed, placenta membranaceea, placenta succenturiata, fenestrated placenta,
circumvallate and circummarginate placentae [8]. Infections can also be responsible for placental
anomalies such as hypertrophy or calcification. In the following, we present a case of
intraamniotic cytomegalovirus infection, diagnosed by means of amniocentesis. At 29 weeks’
gestation the placenta was described as maturity Grannum 3 (Fig. 3). The multiple calcifications
aspect persisted until delivery and was confirmed postpartum by clinical and pathological exam.

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Fig. 3. ultrasound image with Grannum 3 placenta

Below we present a case of circumvallate placenta. The patient self-presented in our Prenatal
Diagnosis Unit for the first trimester screening. The ultrasound revealed normal features, both in
the fetus and the adnexa. In the early second trimester the fetus was diagnosed with voluminous
localized cystic hygroma. After multidisciplinary counselling, the couple opted for termination
of pregnancy [9]. A circumvallate placenta was suspected during the scans (Fig. 4) and
confirmed post abortion. Circumvallate placenta is known as an extrachorial placenta, defined as
an annularly-shaped placenta with raised edges, composed by a double fold of chorion, amnion,
degenerated decidua, and fibrin deposits. The diagnosis is difficult during pregnancy and
circumvallate placenta is often detected by placental examination after delivery. The incidence of
circumvallate placenta has been reported in 0,5% to 18% of placentae examined after delivery
[10, 11].
The prenatal diagnosis of circumvallate placenta may have implications for detection of
patients at risk for complications. It may be suspected as a peripheral rim of chorionic tissue
appearing as an echo dense ridge (placental shelf), with a “tire sign” appearance on the 3D exam.
The cause of circumvallation is controversial: reduced amniotic fluid pressure, circumferential
hemorrhage, and superficial or deep implantation have been cited. The circumvallation is
considered complete if the entire circumference of the placenta is involved and partial if it is
incompletely involved.
Complete circumvallate placenta is rare (-1% of pregnancies) but clinically significant. Partial
circumvallate placenta is much more common (approximately 10-20 times more frequent) but is
not considered to be clinically significant [11].

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Fig. 4. The 3D-ultrasound aspect of the fetus (voluminous localized facial and neck cystic hygroma), compared with
the postabortum specimen (the first row). The early second trimester ultrasound aspect and the postabortum aspect
of the placenta (the second row)

Finally, we present a case of bilobed placenta. The diagnosis was reached at the second
trimester screening ultrasound (Fig. 5). Subsequently, the patient self-presented to the
Emergency University Hospital Craiova, at 33 weeks of gestation, complaining of reduced fetal
movements. The fetal well-being ultrasound parameters were confirmed, but the
cardiotocography revealed a non-reactive tracking. A caesarean section was eventually
performed and a healthy neonate, weighing 2450g was extracted. The bilobate placenta was
confirmed. Bilobate placenta is present in 2% to 8% of all placentas [12].
The diagnosis of bilobed placenta is made by ultrasound assessment when two separate
placental discs of nearly equal size are noted. In cases of bilobed placenta there is no increased
risk of fetal anomalies.
This type of placental abnormality can be associated with first-trimester bleeding,
polyhydramnios, abruption and retained placenta.

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Fig. 5. a. the 2D-ultrasound duplex (2D/2D color) at the second trimester scan; the anterior uterine wall lobe and the
posterior wall lobe may be observed; the association with velamentous cord insertion was suspected (white arrow);
b. the maternal surface of the placenta; c. the fetal surface of the bilobed placenta

Conclusions

Timely detection of placental abnormalities can optimize the clinicians’ management


decisions. Thus, it has the potential to improve both the maternal and the fetal morbidity and
mortality [13].
Most placenta abnormalities can be diagnosed by means of ultrasound examinations [14]. In
some cases, a transvaginal color Doppler examination may be beneficial.
The guidelines of the International Society of Ultrasound and Gynecology (ISUOG)
recommend that the position of the placenta, the relation to the internal cervical bone and its
appearance, should be specified at the second trimester routine scan [15]. Our results highlight
the importance of applying theses recommendations in clinical practice.

REFERENCES

1. Benirschke K, Kaufman P Ptaıenta1 shape aberrarims.In: Benirschke K. Kaufman P. eds. Pathology of the
human placenta. 3rd ed. New York: Spiinger-Verlag, 1995: pp. 394-398.
2. Dragusin RC, Cernea N, Constantin C, Hertzog D, Deaconu A, et al., (2016). Indications and Outcome of
Uterine Artery Embolization (UAE) in Gynaecological Conditions: Up-to-Date and the Results of our
Experience. Emerg Med (Los Angel) 6: p. 342.
3. Iliescu, D, Tudorache, S, Nemescu, D, Constantin, C, Dragoescu, A, Diroescu, A, Ciurea, R. and Dragusin,
R. (2017), OP11.01: Outcome of ectopic uterine pregnancy (EUP) treated with methotrexate (MTX)
associated with uterine artery embolisation (UAE). Ultrasound Obstet Gynecol, 50: 80-80.
4. Velamentous insertion of umbilical cord with vasa praevia: case series and literature review. Bohîlțea RE,
Cîrstoiu MM, Ciuvica AI, Munteanu O, Bodean O, Voicu D, Ionescu CA. J Med Life. 2016 Apr-Jun; 9(2):
pp. 126-9. Review.
5. McCarthy J. Thurmond AS, Jones MK. et al. Circumvallate placenta: sonographic diagnosis.
www.ajronline.org June 1997 Ultrasound Med 1995; 14:21-26 1995; 14: pp. 21-26.
6. Yerlikaya G, Pils S, Springer S, Chalubinski K, Ott J. Velamentous cord insertion as a risk factor for
obstetric outcome: a retrospective case-control study. Arch Gynecol Obstet 2016; 293: pp. 975-81.
7. Vintzileos AM, Ananth CV, Smulian JC. Using ultrasound in the clinical management of placental
implantation abnormalities. Am J Obstet Gynecol 2015; 213:S70-77.
8. Sudha R, Sivakumar V, Christilda FJ. Study of shape of placenta and its relation to placental weight in
normal and complicated pregnancies. National Journal of Basic Medical Sciences. 2012; 2(4): pp. 307-11.
9. Olaru Gabriel Octavian, Antoniu Crangu Ionescu, Anca Lesnic, George Alexandru Filipescu, Liana Ples.
Ethical and medico-legal aspects of the therapeutic abortion – our experience. Journal of Romanian Legal
Medecine 26(1), pp. 82-85

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10. Maqueo-Topete M, Chavez-Azuela J, Valenzuela-Lopez S, Espinosa-Hernandez J, Placenta accreta and


circumvallate (extrachorialis), Obstet Gynecol. 1968 Sep; 32(3):397-401.
11. Ziel H. Circumvallate placenta, a cause of antepartum bleeding, premature delivery, and perinatal mortality.
Obstet Gynecol 1963; 22: 798-802.
12. Fujikura T, Benson RC, Driscoll SG. The bipartite placenta and its clinical features. Am. J. Obstet. Gynecol.
1970; 107(7): 1013-7.
13. Iliescu D, Dragusin R, Patru CL, Sorop-Florea M, Marinas C, Zorila L, Sorop BV, Capitanescu R, chapter
16 Abnormalities of the Placenta, Congenital Anomalies Book, InTechOpen, 2018, ed. Tudorache S.
14. Pleș L, Sima RM, Moisei C, Moga MA,Dracea LA.(2017) Abnormal Ultrasound Appearance of the
Amniotic Membranes-diagnostic and significance: a pictorial essay. Medical Ultrasonography 19(2): pp.
211-215.
15. Salomon, L. J., Alfirevic, Z., Berghella, V., Bilardo, C., Hernandez‐Andrade, E., Johnsen, S. L., Kalache,
K., Leung, K., Malinger, G., Munoz, H., Prefumo, F., Toi, A., Lee, W. and (2011), Practice guidelines for
performance of the routine mid‐trimester fetal ultrasound scan. Ultrasound Obstet Gynecol, 37: 116-126.

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Genetic Diagnosis and Counselling Challenges in Prenatal Life

DOCEA Andreea1, DINU Marina2, ILIESCU Dominic Gabriel1,2,


TUDORACHE Stefania1,2
1University of Medicine and Pharmacy Craiova, (ROMANIA)
2University Emergency University Hospital Craiova, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

The prenatal diagnosis is a very important field of clinical genetics and obstetrics, being in
fact, the result of theoretical and clinical medicine integration. Genetic counselling “deals with
the human problems associated with the occurrence, or the risk of occurrence, of a genetic
disorder in the family” [1]. It is a specialized and complex medical process, aiming to help the
patients to better understand medical facts: the diagnosis, the risk factors, the evolving pattern,
the prognosis, the risk of recurrence, the options for treatment and the reproductive alternatives.
The counselling should be followed by an informed decision making process in regards to the
pregnancy management or to the best adjustments/improvement of the specific condition.
Published studies showed that genetic screening tests, aiming in fact to reassure the health of
the fetus, are involved in raising the parental anxiety levels. This is why the pre-test counselling
is paramount. In the reported case series we highlight the particular challenges of the genetic
counselling process during pregnancy.
Keywords: genetic, prenatal diagnosis, counselling

Introduction

The genetic prenatal diagnosis includes all methods adjusted to gain information about the
fetus, but it is basically based on combination of tests. The standard prenatal care includes
screening by means of ultrasound (US) “genetic markers” and serologic data [2]. The last
decades brought major development in cytogenetic, molecular genetics and prenatal US
diagnosis. These techniques became milestones in the prenatal diagnosis field, providing earlier,
more precise and reliable diagnosis of chromosomal abnormalities. Nowadays we have the
opportunity to diagnose a wide range of genetic conditions, using complex, invasive and non-
invasive screening tests. The on-going technological development allow the prenatal diagnosis of
subtle fetal central nervous system abnormalities [3]. Modern US protocols are able to identify
the morphometric abnormalities of the first trimester posterior brain, identifying open spina
bifida [4]. Other scanning techniques such as spatial-temporal image correlation (STIC) –
rendering and STIC with tomographic ultrasound image (STIC-TUI) acquisition are able to
refine the diagnosis of atrioventricular septal defects [5, 6]. In many cases, these techniques
allow us not only to reach a precise diagnosis, but also to establish the functional prognosis, and
as a result – to provide a more accurate parental counselling. Due to technical advances, the first
trimester scan became the widely used first anomaly scan [7, 8, 9].

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About 4% of all neonates present fully or partially genetic conditioned disorder. Abnormal
US findings and positive screening tests for genetic anomalies may have a huge psychological
impact on the parents. Thus, the genetic counselling became imperative, as the final act of
prenatal diagnosis. The most important challenge is balancing the amount of scientific genetic
information in understanding the specific genetic condition and to personalize the discussion in
regards to what this information means to the parents. In continuing pregnancies, the final goal is
to help them to cope with the diagnosis. A complete documentation of the counselling process is
important. The information is to be delivered in an explicit and comprehensive manner. The
screening/diagnostic tests must always be offered as “an option”.

Counselling in hyper IgM syndrome


A 25 years old pregnant women, belonging to the low risk group, addressed to our unit for a
complete prenatal care in her first pregnancy. She delivered by planned C-section a 4300g male.
The new-born was apparently perfectly healthy. At 8 month of age, he developed recurrent
pyogenic bacterial infections of the upper and lower respiratory tract (pneumonia), recurrent
otitis media and conjunctivitis. The increased risk for unusual “opportunistic” infections required
a complete work-up, having as result the final diagnosis of immunodeficiency with hyper IgM
type 1: a c.614 T>C missense mutation in exon 5 of the CD40LG gene. Genomic DNA
sequencing of the mother showed that she was heterozygous for this mutation. The genetic
counselling was assured, and invasive prenatal diagnosis in future pregnancies was
recommended.
The patient self-referred in our unit in her second pregnancy. Despite the completely normal
first trimester genetic and anomaly scan (Fig. 1), chorionic villus sampling (CVS) and testing for
CD40LG gene mutation was performed. The results turned back positive for the mutation, and a
medical termination of pregnancy was requested by the parents.

Fig. 1. Details from the first trimester US scan in the second pregnancy: normal fetal profile, present nasal bone,
normal facial angle, normal nuchal translucency, normal tricuspid valve and ductus venousus results at interrogation
with spectral Doppler

The couple needed repeated counselling sessions in order to accept a new pregnancy project.
Feelings of guilt and helplessness prevented them to attempt it for 7 years. Eventually, the couple
assumed a new pregnancy, and another CVS procedure was performed at 12 weeks of
amenorrhea. The results came back negative and the pregnancy evolved to term uneventfully.

Counselling in mosaicism 45,X[22]/46,XY


A 35 years-old pregnant women was referred to our unit in the Emergency University
Hospital Craiova, having a high obstetrical risk. She had a history of late second trimester
intrauterine fetal demise. The first and early second genetic and anomaly scans were reassuring,
and the male sex of the fetus was stated on the ultrasound form. Yet, an amniocentesis was

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performed on maternal request. A rare disorder of sex development in humans was diagnosed:
45,X/46,XY mosaicism (Fig. 2). The couple was informed about the abnormal genetic findings
and their significance, about the various phenotypical aspects found at birth and also-about the
their options.

Fig. 2. The two cellular lines cultured: the 45 XO line (40%), and the normal line (60%)

The prenatal genetic counselling was performed repeatedly, and the parents were informed
that X0/XY mosaicism and mixed gonadal dysgenesis is associated with sex chromosome
aneuploidy and mosaicism of the Y chromosome. The clinical manifestations are highly variable,
ranging from partial virilisation and ambiguous genitalia at birth, to patients with a completely
male or female gonads. The phenotypic spectrum of males with a 45,X/46,X(r)Y karyotype and
bilaterally descended testes varies greatly, from males with short stature and spermatogenic
failure, to males without short stature and less severely affected spermatogenesis.
The couple decided to continue the pregnancy.
Due to the phenotypical variation sex anomalies, the geneticists’ team requested detailed
prenatal scans of the fetus genitalia. The prenatal aspect was consistent with normal development
of male genitalia (Fig. 3). A term normal baby boy, with normal phenotypical features, was
delivered (Fig. 3).

Fig. 3. 2D image of the normal genitalia (20 weeks of amenorrhea), 3D image of the normal genitalia (36 weeks)
and the normal macroscopic appearance at birth

Counselling in prenatally diagnosed cri-du-chat syndrome


The case presented in the following was referred after a positive combined screening test. The
sequential US scans revealed many “minor” markers: an intracardiac hyperechogenic focus (the
left ventricle), hyperechogenic bowels, mild retrognathia, high prenasal oedema, small
cerebellum (for the gestational age), borderline pyelectasis and short corpus callosum (Fig. 4).

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Fig. 4. 2D US images in the second trimester: the fetal profile (mild retrognathia, high prenasal oedema), axial
cranial oblique posterior view (small cerebellum for the gestational age), short corpus callosum, and borderline
bilateral pyelectasis.

Amniocentesis was performed at 17 weeks of gestation and revealed (in all the metaphases
analysed) a partial deletion on the short arm of chromosome 5 – a cri-du-chat syndrome (Fig 5).
After extensive counselling, the couple requested medical termination of the pregnancy.

Fig. 5. Details from the karyotype file in a cri-du-chat syndrome. The short arm of chromosome 5 marked by arrows

Discussions

X-linked hyper-IgM syndrome (XHIM) is a rare congenital immunodeficiency disorder,


characterised by a defect in both humoral and cellular immune responses, secondary to the
deficiency of a membrane ligand that is expressed on activated T-cells, causing a defect immune
responses [10]. Patients with XHIM present severe, recurrent infections, predominantly of the
respiratory and gastrointestinal tract. Prenatal screening and diagnosis had known indeed great
development in the past decades, but there are still many limitations [10, 11]. As in our case, the
diagnostic is usually a retrospective one, being impossible to suspect it antenatally, if missing a
hereditary context. The females are asymptomatic (being carriers of the allele), because the trait
is recessive. Male offspring of these women have a 50% chance of inheriting their mother’s
mutant allele. The genetic diagnosis is based on molecular genetic testing of the CD40LG gene
(also known as TNFSF5 or CD154) in order to identify the only mutation known to cause x-
linked HIGM. Diagnosing an offspring with these disease requires familial genetic
investigations.
In this condition, an important aspect is the genetic counselling, which has the role to inform
the parents about the diagnostic, about the risk of future off springs to inherit the disease, about
the type of prenatal testing, and also about their options.
Patients with mosaic 45, X/46,X(r)Y karyotype are characterised by a wide phenotypical
range, from females with Turner-like phenotypes, phenotypic males and females with mixed

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gonadal dysgenesis, to almost phenotypic normal males [12, 13]. This phenotypical variation
depends on the percentage of monosomic cells in different tissues and cells.
Phenotypic sex seems to be determined by the presence of the 45,X vs. SRY-bearing cells and
depends more on the number of copies of the SRY gene rather than on the percentage of 45,X
cells, in the gonads [12, 13].
There had been studies reporting cases of male phenotype with subtle signs of Turner
syndrome. Even with absence of Turner stigmata, cardiac and renal anomalies must be excluded
in all such cases. It is also important to check for gonadal dysgenesis in these patients as it is
associated with increased risk of gonadoblastoma. Informing parents about the meaning of this Y
chromosome anomaly is vital, first of all because that will enable them to make an informed
decision concerning the pregnancy, and also to help them better understand therapeutic options
and subsequent management.
The cri-du-chat syndrome diagnosis in prenatal life is extremely rare. The condition, caused
by a deletion of the distal end of the short arm of chromosome 5, includes: low birth weight,
slow growth, a catlike cry, mental deficiency, hypotonia, microcephaly, and other craniofacial
features [14]. Approximately 85% of cases represent spontaneous de novo deletions, whereas
15% arise secondary to unequal segregation of a parental translocation. In 80% of cases the
deleted chromosome has a paternal origin. In these cases the recurrence risk is very low, being
higher in balanced familial translocations. The risk for male and female carriers is similar.
The novo 5p- antenatal diagnosis is rare [14, 15]. It is usually diagnosed secondary to
abnormal non-specific findings or high risk screening tests, or when performing amniocentesis
due to advanced maternal age.

Conclusions

Our case series highlights once more the importance and the difficulty of the genetic
counselling process. This is a highly complex medical process, and it should be performed by
trained professionals. Counselling means offering some medical facts. It means also
recommending further personalised investigation options, function of a multitude of issues,
including the legal ones [16]. Yet, the counsellors must acknowledge that any bad news about
the baby induces a wide spectrum of new feelings and emotional reactions to the parents. Despite
facing many challenges, the counsellors should exercise empathy, caution and a completely non-
judgemental stand.

REFERENCES

1. Borle K,Morris E, Inglis A, Austin J. Risk communication in genetic counseling: Exploring uptake and
perception of recurrence numbers, and their impact on patient outcomes. Clin Genet. 2018 May 16.
2. Park SY, Jang IA, Lee MA, Kim YJ, Chun SH, Park MH. Screening for chromosomal abnormalitiesm using
combined test in the first trimester of pregnancy. Obstet Gynecol Sci. 2016 Sep; 59(5): pp. 357-66.
3. Muresan D, Popa R, Stamatian F, Rotar IC. The use of modern ultrasound tridimensional techniques for the
evaluation of fetal cerebral midline structures – a practical approach. Med Ultrason. 17(2): pp. 235-40.
4. Tudorache S, Iliescu DG, Turcu A, Florea M, Dragusin R, Novac L, Cernea N, First Trimester Anomaly
Scan-The Last Redoubt Won: Open Spina Bifida, Donald School J Ultrasound Obstet Gynecol 2015; 9(1):
pp. 80-90.
5. Ionescu, D. Gheorghiu, B. Davitoiu, I. Pacu, T. Vlădescu Visualization of the atrioventricular valve plane in
fetuses with atrioventricular defect using STIC technique GINECO RO Volume: 5 Issue: 4, pp. 210-215.
6. Muresan D, Marginean C, Zaharie G, Stamatian F, Rotar IC. Complete atrioventricular septal defect in the
era of prenatal diagnosis. Med Ultrason 2016, Vol. 18, no. 4, pp. 500-507.

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7. Tudorache S, Cara M, Iliescu DG, Novac L, Cernea N, First trimester two- and four-dimensional cardiac
scan-intra and interobserver agreement, Ultrasound Obstet Gynecol 2013, Nr. 6, Vol.42, pp. 659-668.
8. Sosoi S, Streata I, Tudorache Stefania, Burada F, Siminel M, Cernea N, Ioana M, Iliescu DG, Mixich F.
Prenatal and postnatal findings in a 10.6 Mb interstitial deletion at 10p11.22-p12.31. Journal of Human
Genetics 60, pp. 183-185.
9. Burada F., S. Sosoi, D. Iliescu, M. Ioana, D. Cernea, Ștefania Tudorache. A rare occurrence of three
consecutive autosomal trisomic pregnancies in a couple without offspring. Clinical and Experimental
Obstetrics & Gynecology; 2016; 43(2): pp. 287-90.
10. Erdos M, Alapi K, Maródi L. Retrospective diagnosis of X-linked hyper-IgM syndrome in a family with
multiple deaths of affected males. Haematologica. 2007 Feb; 92(2): pp. 281-2.
11. Hubbard N, Hagin D, Sommer K, Song Y, Khan I, Clough C, Ochs HD, Rawlings DJ, Scharenberg AM,
Torgerson TR. Targeted gene editing restores regulated CD40L function in X-linked hyper-IgM syndrome.
Blood. 2016 May 26; 127(21): pp. 2513-22.
12. Hooke E. Rates of chromosome abnormalities at different maternal ages. Obstet Gynecol. 1981; 58: pp. 282-
285.
13. Layman LC, Tho SP, Clark AD, Kulharya A, McDonough PG. Phenotypic spectrum of 45,X/46,XY males
with a ring Y chromosome and bilaterally descended testes. Fertil Steril. 2009 Mar; 91(3): pp. 791-7.
14. Eswarachari V, Kadam P, Movva S, Lingaiah S, Akther RM, Kidangan FX, Gowda KC, Golakoti RRK, Lall
M, Mahajan S, Saviour P, Puri R, Verma IC, Vedam RL. Noninvasive prenatal testing (NIPT) detects
variant of Turner syndrome not detectable by fluorescent in situ hybridization. J Matern Fetal Neonatal Med.
2018.
15. Macayran Nguyen J, Gamble C, Smith JL, Raia M, Johnson A, Czerwinski J. Prenatal diagnosis of 5p
deletion syndrome in a female fetus leading to identification of the same diagnosis in her mother. Prenat
Diagn. 2014 Nov; 34(11): pp. 1115-8.
16. Olaru GO, Ionescu Cringu A, Lesnic A, Filipescu GA, Ples L. Ethical and medico-legal aspects of the
therapeutic abortion – our experience. Journal of Romanian Legal Medecine 26(1), pp. 82-85.

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Counselling in Minor Fetal Abnormalities – Large First Trimester


Choroid Plexus Cyst, Persistent Left Superior Vena Cava and Single
Umbilical Artery in Vanishing Twin Syndrome – A Case Report

NAGY Rodica Daniela1, ILIESCU Dominic Gabriel1,2,


PATRU Ciprian Laurentiu1,2, DRAGUSIN Roxana1, TUDORACHE Stefania1,2
1 University Emergency County Hospital Craiova, (ROMANIA)
2 University of Medicine and Pharmacy Craiova, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

Ultrasound in pregnancy is the most important tool used to detect fetal malformations.
Nowadays, the first trimester scanning is able to detect most structural and chromosomal
anomalies, and also to identify minor anomalies of uncertain significance, known as ‘soft
markers’. However, routine antenatal ultrasound have a potential to induce high levels of anxiety
to the couple. An appropriate timing of routine ultrasound screening can reduce the false positive
results. The current technology and available equipment provide high quality images. Yet, it is
paramount that healthcare professionals and clinicians who perform the scans to be trained in
performing also the subsequent counselling. We present a case of vanishing twin syndrome in
the first trimester. The surviving twin presented with multiple soft markers and minor defects
during pregnancy. Counselling is often difficult, especially when diagnosing multiple minor
abnormalities.
Keywords: minor abnormalities, counselling, ultrasound, vanishing twin

Introduction

The importance of ultrasound (US) in obstetrics has been extensively studied and there is no
doubt about its applicability in all pregnancies’ assessment [1, 2, 3]. Nowadays the fetal US is
used as an essential part of antenatal care, and it is usually highly appreciated by the couple.
However, we often find in couples a lack information or misunderstandings about the purpose
of US examinations and its technical limitations. Thus, in the situation of an abnormal scan
result, the parents are often unpleasantly surprised and even resentful. US has known limitations
and we should exercise caution and empathy when communicating unfavorable results. If
needed, a counselling following the multidisciplinary assessment is preferred. The aim of fetal
anomaly screening is: to identify potential problems so that parents can make an informed
choice, and to optimize a safe delivery [4]. When counselling the parents for fetal abnormalities,
they may experience many negative feelings, such as anxiety, grief, anger, loneliness,
hopelessness, prostration and guilt.
With the increase of US use and the evolving technology, questions about the appropriate
counselling in cases with minor fetal abnormalities have arisen as well. Depending on the

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specific US findings, the options for obstetric management vary, from standard care to
aggressive care, with termination of pregnancy. Counseling is, by its definition, a process of
communication and education. It should be done by trained professionals and its purpose is to
help individuals or the family. Counselling should not be “giving advice”, should not be
judgmental, should not attempt to sort out the problems of the patient. The counselor should not
look at a patient’s problems from his/her own perspective, based on own value system [5].

Case report

A 33-year-old low risk pregnant woman presented to our Clinic in the County Emergency
University Hospital of Craiova, for the dating scan. The diagnosis was dichorionic diamniotic
twin pregnancy, 7 weeks and 2 days of gestation. In the last two days, the patient experienced
mild vaginal bleeding. Despite a concordant growth, a significant discordance between the twins’
embryonic heart rates was recorded (Fig. 1). In the after scan counselling process, the poor
prognosis of the early embryonic bradyarrhythmia was mentioned, also highlighting the absence
of its influence on the cotwin baby.

Fig. 1. The discordance between the embryonic heart rates at the dating scan

Two weeks later, following another episode of vaginal bleeding, the embryonic single demise
was confirmed (Fig. 2). The pregnancy evolved with vanishing twin syndrome.

Fig. 2. The single twin early demise

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At the first trimester genetic and anomaly scan, the surviving fetus presented with no major
structural anomalies, but had a slight asymmetry of the arterial arches, a unilateral voluminous
cyst at the anterior border of the right choroid plexus, single umbilical artery and hypoplastic
nasal bone (Fig. 3).

Fig. 3. Details from the first trimester genetic and anomaly scan:
- unilateral voluminous cyst at the anterior border of the right choroid plexus;
- the fetal profile (the hypoplastic nasal bone and the thin nuchal translucency seen);
- the single umbilical artery, left sided by the bladder;
- 3D static US surface rendering mode, the volume dataset highlighting the integrity of the upper lip

The combined test showed an intermediate risk (the adjusted risk for trisomy 21 was 1:162),
with free β-HCG (β-human chorionic gonadotropin) – 2.78 MoM (multiple of the median), and
PAPP-A (pregnancy-associated plasma protein A) – 0.436 MoM.
The patient opted for an invasive procedure in the second trimester. Amniocentesis was
performed at 17 weeks of gestation, and a normal fetal karyotype was confirmed.
In the following months, all first trimester findings were confirmed, and every new scan
revealed new soft US markers or difficult to interpret images.
At 18 weeks of gestation, a minor apical interventricular septal defect was diagnosed. At 20
weeks, a persistent left superior vena cava was confirmed. In the third trimester a mild arterial
arches discordance became visible, with a structurally normal heart (Fig. 4) and the Z-scores
were consistent with suspicion of aortic coarctation. In addition, fetal growth curve was
suboptimal (Fig. 4).

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Fig. 4. Normal 4 chamber view (lateral view) grey scale; suboptimal growth curve

Delivery was scheduled at 39 weeks of gestation, having a complete team for postnatal care,
and prostaglandins E1 available. An apparently normal baby girl, weighing 2360g, was extracted
by planned Cesarean section. Postnatally, the pediatric cardiologist confirmed two minor
ventricular septal defects (with no functional hemodynamic significance), confirmed also the
persistent left superior vena cava and excluded the aortic coarctation (Fig. 5). The new-borne
was repeatedly scanned, until the arterial canal complete closure.
At 3 months of age, the baby had a complete negative detailed echocardiography, with normal
functional parameters.

Fig. 5. Postnatal echocardiography, confirming the ventricular septal defect and normal contractility, as well as
normal veno-atrial, atrio-ventricular and vetriculo-arterial concordance

Discussions

First trimester screening includes measuring the serum level of free beta human chorionic
gonadotropin hormone (free-β-hCG) and pregnancy associated plasma protein A (PAPP-A). The
risk of fetal aneuploidies is calculated based on the biochemical and ultrasound markers (nuchal

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translucency, presence of nasal bone) and on the age of pregnant women [6, 7]. Absence or
hypoplasia of fetal nasal bone in the first or second trimester scans is correlated in many studies
with an increased risk for trisomy 21. There is proof that the use of isolated absent or hypoplastic
nasal bone in the second trimester US scan for Down syndrome screening may not be as
effective. Amniocentesis is indicated for fetuses with structural abnormality or additional soft
markers, which should be carefully searched by an experienced examiner [7]. Delayed
ossification is associated with a lower risk of trisomy 21 than the absence of nasal bone [8].
Congenital heart diseases are the most common form of birth defect [9]. Congenital heart
defects range from mild to very severe. Some require surgical repair in the newborn period and
some may resolve on their own with time. If a cardiac anomaly occurs, a more thorough
examination of the fetal heart is indicated because minor anomalies may be present. [1, 9].
Although there are several studies which have demonstrated the correlation of fetal choroid
plexus cyst (CPC) and the risk of congenital anomalies, few ones have discussed isolated CPC
(with no other abnormal sonographic finding). Choroid plexus cysts (CPCs) are found in second
trimester screening sonography and may be single/multiple or unilateral/bilateral. Most of them
are resolved until the end of the second trimester being considered “a benign condition” but they
may be caused by presence of a chromosomal abnormality, mostly Trisomy18. Most probably,
isolated CPC is a benign regressive condition with no clinical significance, especially when
mother serum screening is in normal range. Parents can be reassured that the cysts will regress
by 28th week of gestation. Yet, they are extremely rare reported in the first trimester, like in the
case reported. Further investigations such as amniocentesis are helpful in situations in which
serum screening reveals higher risk of abnormalities [11, 12, 13].
The significance of finding a single umbilical artery (SUA) in first trimester ultrasound is not
well established [14, 15]. Some studies showed that there is an association of SUA syndrome
with intrauterine growth restriction, preterm delivery, fetal poor obstetric outcomes, and
congenital anomalies. The most frequently associated congenital anomalies are genitourinary and
cardiac. The association with chromosomal defects occurs in approximately 10% of fetuses with
SUA, the most common being the Trisomy 18. Trisomy 21 does not appear to be associated with
this anomaly. Finding of a single umbilical artery does not justify an amniocentesis, unless there
are other associated ultrasound abnormalities. SUA is more common in twin pregnancies,
velamentous insertion, extreme maternal ages, smoking, diabetic or hypertensive disorders. It is
important to assess the number of cord vessels during the 12th week scan because an isolated
SUA requires a thorough search for associations at the second trimester US [14, 15].

Conclusions

This case shows the importance and the difficulties in counseling for minor anomalies. The
anxiety caused by all our findings during scanning is associated with psychological trauma.
Thus, we must acknowledge it in each case with minor anomalies. While normal findings at
US examination have strong beneficial psychological effects [16], the couple is often ill prepared
for bad news about their unborn child. The parental psychological reactions may vary in a wide
spectrum, and these reactions are often discordant with the severity of the anomaly reported [16].
This is particularly true if the US examination is carried out without an appropriate
counselling. Informing the parents should be done by trained professionals, having
multidisciplinary communication. This approach avoids the unnecessary parental stress.

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REFERENCES

1. Iliescu D, Tudorache S, Comanescu A, Antsaklis P, Cotarcea S, Novac L, Cernea N, Antsaklis A. Improved


detection rate of structural abnormalities in the first trimester using an extended examination protocol.
Ultrasound Obstet Gynecol. 2013 Sep; 42(3): pp. 300-9.
2. Tudorache S, Cara M, Iliescu DG, Novac L, Cernea N, First trimester two- and four-dimensional cardiac
scan-intra and interobserver agreement, Ultrasound Obstet Gynecol 2013, Nr. 6, Vol.42, pp. 659-668.
3. Salomon LJ, Alfirevic Z, Berghella V, Bilardo C, Hernandez-Andrade E, Johnsen SL, Kalache K, Leung
KY, Malinger G, Munoz H, Prefumo F, Toi A, Lee W; ISUOG Clinical Standards Committee. Practice
guidelines for performance of the routine mid-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol.
2011 Jan; 37(1): pp. 116-26.
4. NICE Clinical Guidelines, No. 62. National Collaborating Centre for Women’s and Children’s Health (UK).
London: RCOG Press; 2008 Mar. Antenatal Care: Routine Care for the Healthy Pregnant Woman.
5. Hilmar H. Bijma & Agnes van der Heide & Hajo I. J. Wildschut :Decision-making after ultrasound
diagnosis of fetal abnormality.
6. Ples L, Sima RM, Stanescu AD, Olaru OG. The Importance of a National Congenital Anomalies Registry –
the Role of the Prenatal Diagnosis. (2017) Proceeding paper for the 5 TH ROMANIAN CONGRESS OF THE
ROMANIAN SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY, pp. 505-510.
7. Navolan D, Ionescu CA, Carabineanu A, Birsasteanu F, Cretu O, Szasz F, Vladareanu S, Ciohat I, Gidea R,
Nemescu D, Farcas S, Andreescu N, Simu S, Stoian D. Influence of Weight of Pregnant Women on First
Trimester Biochemical Markers Values. REVISTA DE CHIMIE Volume: 68 Issue: 12, pp.2836-2838.
8. Oosterhuis JJ, Gillissen A, Snijder CA, Stiggelbout A, Haak MC. Decision-making in the referral process of
sonographers in primary care screening centers. Prenat Diagn. 2016 Jun; 36(6): pp. 555-60.
9. Tudorache Stefania, Cara M, Iliescu DG, Novac L, Cernea N, First trimester two- and four-dimensional
cardiac scan-intra and interobserver agreement, Ultrasound Obstet Gynecol 2013, Nr. 6, Vol. 42, pp. 659-
668.
10. Cicero S, Curcio P, Papageorghiou A, Sonek J, Nicolaides K. Absent of nasal bone in fetuses with trisomy
21 at 11-14 weeks of gestation: an observational study. Lancet 2001; 358: pp. 1665-1667.
11. Shohreh Irani, Firoozeh Ahmadi, Maryam Javam, Ahmad Vosough Taghi and Fatemeh Niknejad: Outcome
of isolated fetal choroid plexus cyst detected in prenatal sonography among infertile patients referred to
Royan Institute: A 3-year study.
12. Cheng PJ, Shaw SW, Soong YK. Association of fetal choroid plexus cysts with trisomy 18 in a population
previously screened by nuchal translucency thickness measurement. J Soc Gynecol Investig. 2006; 13: pp.
280-284.
13. DiPietro J, Costigan K, Cristofalo E, Lu Y, Bird CW, McShane CA, et al. Choroid plexus cysts do not affect
fetal neurodevelopment. J Perinatol. 2006; 26: pp. 622-627.
14. Hua M, Odibo AO, MacOnes GA, Roehl KA, Crane JP, Cahill AG. Single umbilical artery and its
associated findings. Obstetrics and Gynecology. 2010; 115(5): pp. 930-934.
15. Gornall AS, Kurinczuk JJ, Konje JC. Antenatal detection of a single umbilical artery: does it matter?
Prenatal Diagnosis. 2003; 23(2): pp. 117-123.
16. Tudorache, S., Coleta, E., Capitanescu, R. and Cernea, N. (2015), OC20.07: Parental attitude to participating
in follow‐up research studies of their children’s development after diagnosis of abnormalities. Ultrasound
Obstet Gynecol, 46: pp. 45-45.

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Changes in Markers of Ovarian Reserve and Doppler Velocimetry


After Laparoscopic Surgery

VARLAS Valentin1,2,*, IONESCU Oana2, BOSTAN Georgiana2


1 Carol Davila University of Medicine and Pharmacy, Bucharest, (ROMANIA)
2 Filantropia Clinical Hospital, Bucharest, (ROMANIA)
* Correspondence to: Valentin Varlas, Filantropia Hospital, 11-13 Ion Mihalache, Bucharest, Romania

Email: [email protected]

Abstract

Background
Operative laparoscopy is the main technique used for the ovarian cysts treatment. Many of the
patients with ovarian cysts are young women with desire of future pregnancy and as a result, the
changes in the ovarian reserve after surgery are of great concern.

Objective
The aim of this study was to analyze the main indicators of ovarian reserve (antimullerian
hormone – AMH, antral follicle count – AFC and ovarian volume) as well as the changes in the
ovarian artery flow (pulsatility index – PI and resistance index – RI determined by color Doppler
analysis) before and after laparoscopic surgery for different pathologies.

Patients and methods


It is a prospective observational study which included 42 patients who underwent
laparoscopic surgery for different pathologies (endometriotic cyst, non-endometriotic cyst and
diagnostic laparoscopy for infertility). The ovarian reserve parameters and the blood flow in the
ovarian artery were examined 1 month before surgery and 2 and 4 months after surgery. The size
of the cysts was between 3 and 8 cm.

Results and conclusions


The preoperative AMH level, AFC and ovarian volume showed a significant correlation with
patient’s age. There was a strong correlation between the rate of serum AMH decline and the
diameter of the cyst as well as the preoperative serum AMH level. In addition, the rate of serum
AMH decline was larger for bilateral cysts than for unilateral cysts. The changes of RI and PI in
the ovarian artery before and after the surgery were not correlated with the diameter or the type
of the cyst. There were no significant changes of the biochemical markers and Doppler
velocimetry before and after surgery in the group of patients that underwent diagnostic
laparoscopy for infertility.
Keywords: laparoscopic surgery, ovarian reserve, Doppler velocimetry

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Introduction

Benign ovarian cysts have a high incidence among women of reproductive age. Most tumors
are functional ovarian cysts. Endometriosis is a benign, an estrogen-dependent, inflammatory
disease that affects women during their reproductive age, and is represented by the presence of
endometrial glands and stroma outside the uterine cavity. The lesions are found especially in the
pelvis but can be located at multiple sites including the bowel, diaphragm, and pleural cavity.
Endometriosis can cause dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility.
Symptoms can range from mild to severe and are not well correlated with the degree of
anatomic involvement.
The prevalence of endometriosis is approximately 7%-10%, but among infertile women, it
increases up to 50%. Endometrioma is a cyst within the ovary with ectopic endometrium tissue
lining and is found in 17%-44% of patients with endometriosis. The high incidence of this
pathology among reproductive age group has led to a concern regarding the decrease of ovarian
reserve after surgical treatment. [1]
The treatment of endometriosis involves the destruction of all lesions, adhesiolysis and
restoration of the normal anatomical structure, prevention of recurrences, and the increase of
conception rates in patients with subfertility. Operative laparoscopy is the main technique used
for the ovarian cysts treatment. [1]
Compared with laparotomy, laparoscopy is feasible in the vast majority of cases and has the
advantage of a shorter hospitalization, faster recovery, less pain, and lower costs. [2]
Laparoscopic excision by the stripping technique is considered the gold standard surgical
approach for endometrioma. [1]
However, the safety of laparoscopy with respect to the degree of damage to ovarian reserve
has been questioned. Ovarian reserve is a marker of the good function of the ovary and reflects
the number and quality of the ovarian follicles. [2]

Methods

This is a prospective observational study which included 42 patients who were admitted to
Filantropia Clinical Hospital and underwent laparoscopic surgery for benign ovarian pathology.
The aim of this study was to assess the degree of ovarian damage after surgery. Patients were
divided in three groups according to the final pathological diagnosis. Group A included 14
patients who underwent laparoscopy for endometriotic cyst, group B included 14 patients who
underwent surgical intervention for non-endometriotic benign cyst and group C included 14
patients who underwent diagnostic laparoscopy for infertility. We examined ovarian reserve
parameters (AMH, AFC, ovarian volume, Doppler evaluation of ovarian vascularization) 1
month before surgery and 2 and 4 months after surgery.
The ovarian pathology was identified and the cysts were measured using transvaginal
ultrasound. There were several other risk factors for a reduced ovarian reserve which took into
consideration at the moment of analysis of the results: patient’s age over 35 years, a family
history of early menopause, a personal history of radiotherapy or chemotherapy or a personal
history of ovarian stimulation techniques failure.
The inclusion criteria were as follows: 1) non-pregnant patients; 2) age under 40 years with a
regular menstrual cycle; 3) cysts measuring between 3 and 8cm; 4) absence of any submucosal
leiomyoma or intramural leiomyoma >5cm in diameter; 5) absence of endocrine disorders which

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interfere with normal fertility such as thyroid disease, hyperprolactinemia and Cushing’s
syndrome; 6) no previous history of surgery for ovarian cyst; 7) absence of a malignant ovarian
tumor or a previous history of radiotherapy or chemotherapy for any neoplasm; 8) no history of
hormonal treatment within the previous 3 months. None of the patients underwent postoperative
hormonal therapy in the first 4 months after surgery. In the cases with bilateral ovarian cysts, the
total diameter was calculated as the sum of the diameters of both cysts.
The surgical technique was represented by laparoscopy ovarian cystectomy. In the case of
endometrioma the stripping technique was used (a cleavage plane between the cyst wall and
ovarian cortex was identified; after removing the cyst from the abdominal cavity, selective
minimal bipolar coagulation for bleeding control was performed, without excessive coagulation
to avoid damaging of the remnant ovary). There were no complications during or after surgery
and there was no need to shift from laparoscopy to laparotomy. The pathology results performed
in all cases confirmed the benign type of the excised ovarian tumors.

Results

Mean age of the patients at the moment of diagnosis was 324.6 years. Mean body mass
index of the patients was 222.4 kg/m2 with no patient suffering from obesity. There were 6
cases of bilateral ovarian cysts (3 of them proved to be endometriomas and 3 of them proved to
be non-endometriotic benign cysts). Preoperative ovarian reserve markers showed the following
results: mean serum AMH level (group A – 1.90.4 ng/mL, group B – 2.10.4 ng/mL, group C –
20,4 ng/mL), AFC on each ovary (group A – 71, group B – 82, group C – 82).
It was observed a mild variation of AMH level and AFC according to the size of the cyst, to
the age of the patient and to the bilaterality of the tumor. AMH values were higher in younger
compared to older patients (median AMH 2.10.4 ng/mL in women less than 30 years and
1.70.2 ng/mL in women between 30 – 39 years). AMH and AFC values were higher in the case
of smaller tumors (median AMH 2.10.1 ng/mL and AFC – 72 in the case of tumors between 3
– 5cm; median AMH – 1.90.4 ng/mL and AFC – 61 in the case of tumors between 6 – 8 cm).
Bilateral tumors were associated with lower values of AMH and AFC (median AMH – 20.1
ng/mL and AFC – 82 in the case of unilateral tumors; median AMH – 1.60.1 ng/mL and AFC
– 61 in the case of bilateral tumors). (chart 1)

9
8
7
6 bilateral tumors
5
unilateral tumors
4
tumors between 3-5 cm
3
tumors between 6-8 cm
2
1
0
AMH (ng/mL) AFC

Chart 1. The distribution of AMH and AFC according to the size of the cyst and to the bilaterality of the tumor

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Preoperative measurement of the ovarian volume was done only for the patients who
underwent diagnostic laparoscopy for infertility and proved to be within normal ranges (mean
ovarian volume of 6.60.3 cm3 in women less than 30 years; 6.10.4 cm3 in women between 30
– 39 years). (chart 2)

Chart 2. The distribution of pre- or postoperative AMH among the three groups

Postoperative evaluation of ovarian reserve markers was done at 2 and 4 months after surgery
in order to assess the degree of recovery of ovarian function after surgery. The analysis of the
results led to the following conclusions:
- there was a decrease of AMH level after surgery for ovarian cyst with a higher decrease
in the case of treatment for endometrioma (postoperative mean serum AMH level in the
group A – 1.60.1ng/mL compared to 1.80.1 ng/mL in the group B);
- there was no significant change of AMH in group C (postoperative mean serum AMH
level 20,2 ng/mL);
- there was a more severe decrease of AMH value in the case of bilateral cystectomy
compared with unilateral cystectomy (postoperative mean serum AMH level 1.70.1
ng/mL in the case of unilateral cystectomy compared to 1.50.1 ng/mL in the case of
bilateral cystectomy);
- the other markers of ovarian reserve were also lower in the case of bilateral cystectomy
(AFC on each ovary 71 after unilateral cystectomy and 61 after bilateral cystectomy;
ovarian volume 5.20.3 cm3 after unilateral cystectomy and 4.80.2 cm3 after bilateral
cystectomy). (chart 3, chart 4)
AMH levels at 4 months were significantly correlated with the values at 2 months; AFC
proved to be a less reliable marker after surgery.

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Chart 3. The distribution of AMH, AFC and ovarian volume according to unilateral/bilateral cystectomy

Some cases with a decreased postoperative AMH were associated with a higher postoperative
compared to preoperative AFC. This fact can be explained especially in the case of large cysts by
the poor visualization and measurement of the follicles. Postoperative ovarian volume at 2 and 4
months in groups A and B proved to be slightly decreased compared to normal values for a
determined age (mean ovarian volume of 50.3 cm3 in women less than 30 years; 4.50.4 cm3 in
women between 30-39 years). There was no change in ovarian volume, AMH and AFC in group
C.
The changes of RI and PI in the ovarian artery before and after the surgery were not correlated
with the diameter or the type of the cyst. There were no significant changes of Doppler
velocimetry before and after surgery in group C.

Chart 4. The distribution of normal and postoperative ovarian volume according to the whole groups

Discussions

Evaluation of ovarian reserve is based on both ultrasonography and endocrine tests.


Biochemical indicators of ovarian reserve include follicle stimulating hormone (FSH),
estradiol (E2), inhibin B, antimullerian hormone (AMH) and FSH/LH ratio. They are measured
on the third day of the menstrual cycle. [6]

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In the presence of a good ovarian function and an adequate ovarian reserve the values of FSH
on day 3 of the menstrual cycle are less than 10 mIU/mL and the serum level of E2 is less than
<80 pg/mL. FSH levels of 10 to 15 mIU/ml are considered borderline. Normal values of FSH
and E2 on day 3 of the menstrual cycle are predictive of a good response to ovarian stimulation
techniques.
A high serum E2 level on day 3 of the menstrual cycle can be suggestive of an abnormal
follicular development. Elevated E2 levels are due to premature follicle recruitment that occurs
in women with poor ovarian reserve. A high serum E2 level reduces the pituitary secretion of
FSH and causes a false-negative FSH testing. This is why the levels of FSH should be correlated
with E2 values (both E2 and FSH levels should be within normal ranges in the case of good
ovarian function). FSH levels depend on the age of the patient and are well correlated with antral
follicle count.
Anti-müllerian hormone (AMH) is produced by the granulosa cells of the preantral and early
antral follicles. Of all the biochemical factors the changes in AMH level best reflect ovarian
function. In adults, AMH levels gradually decline with age so that at menopause AMH is
undetectable. The AMH level modifies earlier than FSH or E2 values (ovarian reserve may be
reduced in some patients with normal values of FSH and E2 on day 3 of the menstrual cycle). In
patients undergoing IVF, AMH level is well correlated with the number of oocytes retrieved
after stimulation, and is the best marker for predicting poor and excessive ovarian response.
AMH <0.5 ng/mL predicts reduced ovarian reserve with poor response to ovarian stimulation
techniques. AMH between 1.0 ng/mL and 3.5 ng/mL is associated with a good response to
ovarian stimulation. AMH >3.5 ng/mL is suggestive of a good ovarian reserve and predicts a
sustained response to ovarian stimulation and a high risk of ovarian hyperstimulation syndrome
(in this cases ovarian stimulation techniques should be avoided). In contrast to FSH and E2,
AMH can be measured in any phase of the menstrual cycle, as the values have minimal
intercycle and intracycle variability. However, interpretation of the results of biochemical
markers is laboratory assay-dependent and there is no international standard. [4, 6]
Ultrasound markers of ovarian reserve include antral follicle count (AFC), ovarian volume
(OV), and ovarian blood flow. AFC represents the number of follicles measuring 2 to 10 mm
determined on days 2-4 of the menstrual cycle. [6] The measurement is done using transvaginal
ultrasound. The size of the follicle is the mean of two perpendicular diameters, one of which
should be the largest dimension of each follicle. A normal AFC is considered when 5-10 follicles
measuring 2 to 10 mm are identified in each ovary. The AFC depends on the age of the patient.
The annual decrease of AFC is approximately 5% per year before 37 years. Afterward the
reduction of AFC is accelerated. A low AFC is suggestive of a poor ovarian reserve and a poor
response to ovarian stimulation. However, it is less predictive of oocyte quality, the ability to
conceive with IVF, and pregnancy outcome. [4, 6]
Ovarian volume is determinate by measuring the ovary in three dimensions (length, width and
depth) during the early follicular phase of the menstrual cycle. Ovarian size depends on age,
pregnancy status, and phase of the menstrual cycle. In women of reproductive age the mean
ovarian volume is 9.8 cm3 with higher volumes during the preovulatory phase of the menstrual
cycle and lower volumes during the luteal phase. Ovarian volume decreases after 30 years (in
one study ovarian volume was 6.6 cm3 under 30 years and only 1.85 cm3 after 70 years). There is
no relation between ovarian volume and weight. However, there is a linear relationship between
ovarian volume and height of the patient (there is an increased ovarian volume in tall women).
[11]

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An ovarian volume of less than 3cc is associated with a higher rate of failure of IVF
procedures. The determination of ovarian volume can be predictive for the good or worse
response to ovarian stimulation (it is considered that the predictive value of ovarian volume is
superior to the determination of FSH and E2 during day 3 of the menstrual cycle but inferior to
AFC). [6]
The vascularization of the ovary is determined through the assessment of ovarian stromal
blood flow and of the velocimetry in the ovarian artery. VOCAL analysis of ovarian
vascularization and Doppler ultrasound examination have been used to examine the influence of
ovarian vascularization on ovarian reserve. Ovarian stromal PSV of less than 10 cm/s is
associated with a poor ovarian response and a lower number of retrieved oocytes. [6] In one
study, women with unexplained infertility had a significantly higher uterine and ovarian arteries
pulsation index. [12] However, a good insonation angle may be difficult to obtain and thus the
interpretation of the results may be impaired. In our study the changes of RI and PI in the ovarian
artery before and after the surgery were not correlated with ovarian reserve and were not
influenced by the diameter or the type of the cyst.
A study was conducted to establish the utility of the determination of FSH in patients with
otherwise normal ovarian reserve tests. An isolated elevated FSH level on day 3 of the menstrual
cycle was associated with decreased follicular development despite normal AMH and AFC.
Clinical pregnancy rate and live birth rate were not statistically different in the case of a single
ovarian cycle. However, there may be a cumulative impact on pregnancy rates and long-term
results. Taking into account these findings it is recommended a complete ovarian reserve
evaluation irrespective of the initial values of AMH and AFC. [3]
The decision of surgical treatment of ovarian cysts should always take into account the risks
and the benefits. In a study of 244 women with unilateral endometriomas, ovulation occurred at
similar rates from the normal ovary and the endometriotic ovary. This fact led to the conclusion
that an endometrioma itself does not alter ovarian function and has no effect on pregnancy or live
birth rates. However it may reduce the number of follicles recruited after ovarian stimulation. In
contrast, ovarian surgery to remove the endometrioma can reduce ovarian reserve. A meta-
analysis of eight studies reported that endometrioma cystectomy resulted in a 38 percent
reduction of AMH levels after ovarian cystectomy. Bilateral ovarian cystectomy may result in an
even greater reduction in AMH levels compared to unilateral ovarian cystectomy. Women
undergoing repeated surgery for ovarian cysts have lower values of AMH compared with women
undergoing a single surgical intervention. Our study confirms the results of this study. [5]
The causes of the reduced ovarian reserve after ovarian surgery are not fully understood.
There are no definitive data to establish whether the damage to the ovary is related to the
surgical procedure and/or to the previous presence of a cyst. A histological analysis reported that
the ovarian tissue surrounding the cyst wall in endometriomas is morphologically altered and
possibly not functional. A functional alteration of the ovarian tissue may already be present
before the surgical intervention (Muzii et al., 2002). The decrease of AMH may be the
consequence of surgical trauma or the removal of normal ovarian tissue. Another factor that must
be taken into account is the damage caused on the ovarian stroma and vascularization by
surgery-related local inflammation and electrosurgical coagulation during haemostasis. [7]
Laparoscopic excision of endometriotic ovarian cysts is associated with a higher reduction in
serum AMH levels during follow-up period compared with laparoscopic excision of
nonendometriotic cysts. This fact may be related to the surgical technique used for the excision
of endometriomas. Endometriomas are known to have adherent walls which are difficult to

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enucleate during surgery. The stripping technique may involve excessive removal of ovarian
tissue with loss of follicles. [2]
In spite of all concerns regarding removal of endometriomas, most studies indicate that
surgery is the treatment of election in the case of large (≥4cm) symptomatic ovarian
endometriomas in infertile women. [8]
There are conflicting reports on the changes in AFC after laparoscopic cystectomy of
endometriomas. These changes are not in line with the changes in the serum AMH level. AFC
may increase after surgery. This fact may be related to the difficulty in visualization of the antral
follicles in ovaries affected by endometrioma. As a consequence AFC is less reproducible and
reliable than AMH to assess the impact of surgery for ovarian cyst on ovarian reserve. [10]
The most important factors that predict a poor ovarian reserve after surgical removal of an
ovarian cyst are a low serum AMH level before surgery and the presence of the cysts on both
ovaries. [9]

Conclusions

Laparoscpic cystectomy is one of the most frequent surgical interventions in reproductive age
women. AFC is less reproducible and reliable than AMH to assess the impact of surgery for
ovarian cyst on ovarian reserve. The changes of RI and PI in the ovarian artery before and after
the surgery are not correlated with ovarian reserve and are not influenced by the diameter or the
type of the cyst. In all cases, the unilateral involvement of the ovary has a better prognosis for
future pregnancy. Dispite of the minimum damage to the ovarian structure made by the new
laparoscopic techniques, a postoperative reduction in ovarian reserve is unavoidable and care
should be taken to correctly select the patients who undergo surgical intervention.

REFERENCES

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Gynecology, 6th edition, 2017.
12. Mohamed Abdel Razik, Mohamed Abdel HadyFarag, Mohamed Sheta, Uterine and ovarian arteries blood
flow during the mid luteal phase in women with unexplained infertility, Middle East Fertility Society
Journal, Volume 20, Issue 3, 2015, pp. 209-212.

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The Degree of Correlation Between Prenatal Ultrasonography and


Fetal Autopsy Findings – A Retrospective Study

VARLAS Valentin1,2,*, BOSTAN Georgian 2


1 Carol Davila University of Medicine and Pharmacy, Bucharest, (ROMANIA)
2 Filantropia Clinical Hospital, Bucharest, (ROMANIA)
* Correspondence to: Valentin Varlas, Filantropia Hospital, 11-13 Ion Mihalache, Bucharest, Romania

Email: [email protected]

Abstract

Objective
We aim to compare the results of prenatal ultrasound (US) with those of the autopsy reports at
different gestational ages (GA) in order to assess the degree of correlation between the results
and its clinical impact. This is a retrospective study of 54 cases over an 8-year period (2009-
2016). Both US scans and the autopsies were made in Filantropia Clinical Hospital.

Methods
We analyzed 18 cases diagnosed in the third trimester (mean GA of 322,6 weeks) and 36
cases in the second trimester (224.1 weeks). Taking into account both the US and pathology
report, the majority of fetuses had either a nervous system malformation (31.48%) or multiple
anomalies (29.62 %) and a small number of malformations of other organs.

Results
The analysis of the data showed the following: 31 cases (54.38%) with full correlation, in 18
cases (31.57%) the autopsy confirmed US findings, but revealed supplementary malformations,
in 6 cases (10.52%) US partially correlates with the autopsy, and in 2 cases (3.5%) total
discrepancy between US and autopsy.

Discussion
The results confirm that in 80% of cases the malformation suspected by US examination was
confirmed by autopsy. In 31% of cases the pathologic examination revealed additional
malformations.

Conclusions
There is a high degree of correlation between the US and autopsy findings, especially when
only one organ is involved. Autopsy proves to be the best way to diagnose malformations.
Keywords: prenatal ultrasonography, malformations, autopsy

Introduction

Malformations are responsible for a large number of prenatal deaths (15-20% of stillbirths are
caused by a major structural malformation) and related to an elevated morbidity and mortality in

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the post-natal period. The relationship between the malformation and fetal death must be
supported by epidemiologic data (the malformation is rare in live-born and the newborn has little
chance of survival because of that malformation).
The rate of fetal demise caused by malformations varies according to the availability of
prenatal diagnosis, the experience of the examiner, the kind of machine used for the examination
and the availability of pregnancy termination. Couple malformations unrelated to chromosomal
abnormalities are associated with an increased risk of fetal demise such as neural tube defects,
abdominal wall defects, Potter syndrome, thanatophoric dysplasia, achondrogenesis, lethal
multiple pterygium syndrome, and amniotic band sequence. The pathologic examination of the
fetus is a reliable gold standard which can provide a complementary and sometimes more
accurate diagnosis than prenatal ultrasound examination. [1]
Women with a stillbirth in the first pregnancy have a five-time increased risk to experience
another stillbirth in their second pregnancy compared to women with a live newborn in their first
pregnancy. The recurrence risk of stillbirth is influenced by the cause of fetal demise and the
patient’s history. In 5% of cases the etiology of fetal demise is not determined. In those cases the
reported risk of recurrence is 7.8 to 10.5 per 1000 births, especially at less than 37 weeks of
gestation. The risk decreases afterwards, and incidence of stillbirth at term is 1.8 per 1000 births.
An accurate diagnosis of a malformation in a stillborn is correlated with a high risk of
recurrence in future pregnancies. There is a 7.6-fold increased risk of the same defect and a 1.5-
fold increased risk of a different defect in the second infant compared to those women who had a
structurally normal first infant. After many years of ultrasound scans, we observed a higher rate
of anomalies detection by ultrasound, especially due to the continuous training of sonographers
and the quality of the ultrasound equipment. However, ultrasound diagnosis of congenital
anomalies at earlier gestational ages and the presence of more subtle conditions challenge the
verification of congenital anomalies and require other premortem and postmortem examination
methods. [2]

Objective

The aim of this study was to compare the results of prenatal ultrasound and those of the
autopsy at different gestational ages and to assess the degree of correlation between the results
and its clinical impact. This is a retrospective study of 54 cases over an 8-year period (between
2009 and 2016). The ultrasound examination was made in the Department of Fetal Medicine and
the autopsies were made at the Department of Pathology, Filantropia Clinical Hospital,
Bucharest.

Methods

The ultrasound examination was made by experienced examiners using either a Voluson 730
Expert or a Voluson E8 Expert. We used SPSS 21.0 for statistical analysis and correlation
analyses were performed using independent samples t‐test. P < 0.05 was considered statistically
significant. We analyzed a series of 54 cases – 18 cases were diagnosed in the third trimester (at
a gestational age between 25 and 38 weeks with a mean gestational age of 322.6 weeks) and 36
cases were diagnosed in the second trimester (at a gestational age between 13 and 24 weeks with
a mean gestational age of 224.1 weeks). The ages of the patients varied between 16 and 42
years with a mean age of 304.5 years.

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Taking into account both the ultrasound and pathology report, the great majority of fetuses
had either a nervous system malformation (17 cases = 31.48%) or multiple anomalies (16 cases =
29.62%). We report a small number of malformations of other organs (4 cases of cardiovascular
malformations, 2 cases of gastrointestinal malformations, 6 cases of skeletal abnormalities, 5
cases of anomalies in the development of the genitourinary system and 4 cases of anomalies of
other systems or organs).(table 1, chart 1)

Detection rate (n (%)) at:


Primary diagnosis 13 + 0 to 24 + 6 weeks 25 + 0 to 37 + 6 weeks
(n = 36) (n = 18)
Central nervous system anomaly (17) 11 (30.55) 6 (31.33)
Cardiovascular system anomaly (4) 3 (8.33) 1 (5.55)
Multiple anomalies (16) 12 (33.33) 4 (22.22)
Gastrointestinal system anomaly (2) 1 (2.77) 1 (5.55)
Other (4) 2 (5.55) 2 (11.11)
Genital and urinary system anomaly (5) 3 (8.33) 2 (11.11)
Skeletal anomaly (6) 4 (11.11) 2 (11.11)
Table 1. Primary diagnosis and detection rate – n (%) – between 13 – 37 + 6 weeks

Chart 1. The distribution of major malformations according to the organ or system

Results

We classified the results into the following categories according to the degree of correlation
between the ultrasound examination and the pathology report: A (full correlation between
ultrasound and autopsy), B (autopsy confirmed all the ultrasound findings, but revealed one or
more additional malformations), C (ultrasound findings were only partially demonstrated after
fetal autopsy), D (complete disagreement between the ultrasound and autopsy report). The
analysis of the data showed the following result: 31 cases of category A (54.38%), 18 cases of
category B (31.57%), 6 cases of category C (10.52%), and 2 cases of category D (3.5%). (chart
2, table 2, chart 3)

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Chart 2. The distribution of major malformations according to the organ or system in whole categories

Correlation by primary diagnosis Number of cases


13 + 0 to 24 + 6 weeks 25 + 0 to 37 + 6 weeks
Category A: (full correlation between ultrasound and autopsy) 21 10
Category B: (autopsy confirmed all the ultrasound findings, 12 6
but revealed one or more additional malformations)
Categories A and B: Correct main diagnosis 33 16
Category C: (ultrasound findings were only partially 4 2
demonstrated after fetal autopsy)
Category D: (complete disagreement between the ultrasound 1 1
and autopsy report).
Table 2. Primary diagnosis and detection rate – n (%) – between 13 – 37 + 6 weeks.

Chart 3. The distribution of major malformations according to the organ or system

The category A includes especially anomalies of one system or organ. The main
malformations reported in category A include CNS (14), skeletal (3), gastrointestinal (2),
genitourinary (3) and cardiovascular anomalies (3). Multiple anomalies are less frequently
reported (6 cases). (table 3, chart 4) The degree of correlation between ultrasound and autopsy
decreases in the cases with multiple anomalies.

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Category A
Malformation Number of cases
CNS 14
Skeletal 3
Gastrointestinal 2
Cardiovascular 3
Multiple anomalies 6
Genitourinary 3

Table 3. Category A

Chart 4. The distribution of major malformations according to the organ or system in category A

The categories B, C and D include especially cases of multiple anomalies. (table 4, chart 5)
The pathologic report proved to be more accurate than ultrasonography for the detection of
multiple complex anomalies such as facial dysmorphism or skeletal malformations. The
limitations of the autopsy report are described especially by category C. In cases of minor
ultrasound defects or when stillbirth occurs days before delivery the quality of the pathologic
report suffers. In these cases, ultrasound proves more information than the autopsy. When we
take into account only major anomalies the degree of correlation between autopsy and ultrasound
examination is higher. If we take into account both major and minor ultrasound defects the
degree of correlation decreases.

Categories B, C and D
Malformation Number of cases
Multiple anomalies 13
Skeletal 3
CNS 3
Cardiovascular 1
Genitourinary 2
Other 4
Table 4. Categories B, C and D

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Chart 5. The distribution of major malformations according to the organ or system in categories B, C and D

In some cases the autopsy revealed a definitive diagnosis where the ultrasound evaluation was
impeded by fetal factors such as the diminished/absence of the amniotic fluid (ex.
unilateral/bilateral renal agenesis) or by the maternal factors (obesity or uterine fibroids). In spite
of correlation between prenatal ultrasound and autopsy, the fetal examination is important
because in some cases it reveals supplementary findings or modifies the final diagnosis in
accordance or not with genetic counselling.

Discussions

According to some studies, the sensitivity (known as the ability of the ultrasound examination
to detect the anomalies) ranges between 14% and 85%, while the specificity (known as the
ability of the ultrasound examination to correctly diagnose each malformation) varies from 93%
to 99%. The differences of sensitivity and specificity are made by the organ examined, the
experience of the examiner, the type of the machine used for the examination and the individual
characteristics of the pregnancy. [3]
Maternal causes of impaired acoustic window include: maternal obesity (the most important
factor that impedes a proper examination), the increased tone of abdominal wall muscles, large
abdominal scars from burns, the presence of striae rubrae from metabolic diseases, a previous
abdominoplasty. In the case of maternal obesity, it may be useful to examine the fetal anatomy
using the lateral regions of the abdomen or the suprapubic area (table 5). [8]

Factors that impeded proper ultrasound examination


Fetal factors Maternal factors
an unfavorable fetal lie (an anterior spine) maternal obesity
severe polyhydramnios increased tone of abdominal wall muscles
oligohydramnios
Table 5. Factors that impeded proper ultrasound examination

Fetal causes of impaired acoustic window include: an unfavorable fetal lie (an anterior spine
makes it difficult to examine the fetal heart and the fetal profile), fetal crowding (the difficulty of
the examination increases with the number of fetuses), oligohydramnios (in this case it is
especially difficult to examine the heart and the limbs) and severe polyhydramnios (in this case
the increased fetal movement and the increased distance between the transducer and the organ
examined make more difficult a proper evaluation). [8]

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The difference between the ultrasound and pathologic evaluation can be caused by the fact
that some malformations may only be identified by ultrasonography during the late second
trimester or during the third trimester. These malformations include microcephaly, agenesis of
corpus callosum (partial agenesis of corpus callosum can only be demonstrated by an
experienced examiner during the evaluation of the midsagital section of the fetal head), small
heart defects (ventricular septal defects account for 30-35% of all congenital heart disease
detected after birth because small muscular defects may not be seen during ultrasound
examination), diaphragmatic hernia (in some cases a diaphragmatic hernia is demonstrated only
after birth when intraabdominal pressure increases), hydrocephaly, esophageal atresia, duodenal
and ileo-jejunal atresia, hydro-ureteronephrosis, fetal tumors, vein of Galen aneurysm, premature
closure of ductus arteriosus. [8]
In some cases the differential diagnosis is only made after multiple examinations of the same
fetal anatomic region (Dandy Walker malformation can be suspected after the examination of the
transcerebelar view of the fetal head, but a complete and differential diagnosis can only be made
after a thorough examination of the midsagital view of the fetal head). It is important to realize a
differential diagnosis of the anomalies of the posterior fossa as the prognostic implications can
vary from very good outcome for isolated mega cisterna magna and Blake’s pouch cyst to poor
outcome in the case of Dandy Walker malformation. The examination of the midsagittal view of
the fetal head can evaluate the degree of vermis hypoplasia. The measurement of brainstem-
vermis and brainstem-tentorium angles and vermis dimensions, as well as the presence or
absence of primary fissure of the vermis can orientate the diagnosis.
Other CNS malformations such as lissencephaly can only be suspected after an ultrasound
examination made by an experienced examiner and can only be confirmed by fetal MRI.
Lissencephaly is a neuronal migration anomaly defined by a smooth brain surface with a total
absence of cortical convolutions. Lissencephaly cannot be suspected at a routine ultrasound
examination before 22-24 weeks of gestation. Mild isolated ventriculomegaly may raise the
suspicion of lissencephaly in the second trimester. In this case a careful examination of parieto-
occipital and Sylvian fissures should be made. A fetal MRI is also recommended. The great
challenge in these cases is the impossibility of an early diagnosis (the diagnosis is often made
when fetal viability is reached).
In some cases the diagnosis of cardiac malformations is difficult and in other cases can only
be made after birth. Atrial septal defects such as septum primum defect, coronary sinus type and
sinus venosus type can only be diagnosed after birth. Before birth the only atrial septal defect
that can be suspected is type II (ostium secundum). It is detected on the 4 chamber view of the
fetal heart as a wide foramen ovalae (>7-8 mm) with bidirectional flow on color Doppler.
Pulmonary stenosis is a progressive lesion. It may be recognized in the third trimester or may
be suspected in the second trimester and evolve to pulmonary atresia later during gestation.
Outlet ventricular septal defects can only be identified after the examination of the left
outflow tract view and are not visible on the 4 chamber view. Artefacts may impede the proper
examination of the fetal heart. If the interventricular septum is examined on the apical 4 chamber
view, an artefact may be caused by the absorption of ultrasound waves by the interventricular
septum. This artefact may be mistaken for an inlet VSD. This is why it is recommended to assess
the interventricular septum on the transverse 4 chamber view. [8, 9]
Renal pathology such as renal agenesis or cystic diseases may be missed by ultrasound
examination due to the reduced amniotic fluid. We report in our study 2 cases of bilateral renal
agenesis. Autosomal dominant polycystic kidney disease (ADPKD) is a frequent anomaly,

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reported in approximately 1 of 400 to 1000 live births. The typical age of clinical onset is in the
third to fifth decade of life. However, there are rare cases (<1%) when ADPKD can be diagnosed
during the prenatal ultrasound screening or during the neonatal period with ultrasound changes
similar to ARPKD. [6, 7]
Autosomal recessive polycystic kidney disease (ARPKD) is a rare disorder, with an incidence
of 1:20,000 live births. Fetal death may occur because of severe oligohydramnios, and neonatal
death may occur because of pulmonary insufficiency. When the diagnosis of cystic renal disease
is made, the genetic counselling is necessary. [7]
Some malformations will be identified during the first trimester ultrasound screening program
such as exencephaly, holoprosencephaly, spina bifida, congenital heart disease, omphalocele,
gastroschisis, megacystis and limb reduction defects. [4, 8]
When a fetal malformation is detected at the pathologic examination, it is recommended to
examine the placenta and umbilical cord. Other examinations that should be made include a fetal
radiography (it helps to detect skeletal dysplasia), and chromosomal analysis of the fetus.
Chromosomal analysis should be performed not only when a major malformation is detected,
but also when fetal demise is associated with other conditions such as hydrops, intrauterine
growth restriction or oligohydramnios. It is also necessary in the cases of a macerated fetus and
unexplained fetal loss. [5]
The results of our study confirm the fact that ultrasound is a good tool to detect fetal
malformations (in more than 80% of all cases the malformation suspected by ultrasound
examination was confirmed by autopsy). (table 6)

Degree of correlation between prenatal ultrasound and autopsy


Diagnosis Our study Literature*
Central nervous system anomaly 80,9% 79,4%
Skeletal anomaly 50% 76,6%
Genital and urinary system anomaly 78,1% 76,6%
Cardiovascular system anomaly 75% 75,5%
Multiple anomalies 37,5% 37%
Table 6. Degree of correlation between prenatal ultrasound and autopsy in our study versus literature

However, in approximately 31% of cases, the pathologic examination revealed additional


malformations that could not be observed during the ultrasound evaluation. The discordance can
be explained by the fact that some ultrasound examinations were made during the third trimester
when fetal morphology is more difficult to evaluate and by some other factors such as
oligohydramnios and maternal obesity. This fact reveals the importance of both examinations to
establish a definitive diagnosis. Ultrasound examination can determine more accurately small
structural defects that are not visible during a gross pathological examination.

Conclusions

This study shows a high degree of correlation between the ultrasound and autopsy findings
especially when only one organ or system is involved. Ultrasound examination may have some
limits caused by maternal factors, fetal factors or by the malformation itself. The patient must be
informed that some anomalies cannot be detected during the second trimester ultrasound
examination (some anomalies are only identified during the late second or third trimester or after
birth) and that in some cases fetal MRI may be recommended. A prenatal ultrasound

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examination and a subsequent detailed postmortem examination provide the basis for a correct
diagnosis in fetuses terminated due to congenital anomalies.
In current practice there is a risk of false‐positive diagnoses of congenital anomalies which
represent a major concern in prenatal diagnostics, when termination of pregnancy might be an
option. Verifying the ultrasound findings is important for the parents involved, the obstetrician,
genetic counselling and epidemiological analysis.

REFERENCES

1. Ruth C Fretts. Fetal death and stillbirth: Incidence, etiology, and prevention, Uptodate, 2017.
2. Amos Grunebaum, Frank A Chervenak, Fetal death and stillbirth: Maternal care, Uptodate, 2017.
3. Antonella Vimercati, Silvana Grasso, Marinella Abruzzese, Annarosa Chincoli, Alessandra de Gennaro,
Angela Miccolis, Gabriella Serio, Luigi Selvaggi, and Fabiana Divina Fascilla, Correlation between
ultrasound diagnosis and autopsy findings of fetal malformations, 2012 Apr-Jun; 6(2): pp. 13-17.
4. T Todros, E Capuzzo, P Gaglioti, Prenatal diagnosis of congenital anomalies, 2001 Apr-Jun; 3(2): pp. 3-18.
5. Shanmuga Priya S, Rajendiran S, Leena Dennis Joseph, Sai Shalini, Correlation of fetal autopsy with
prenatal ultrasound findings: Study in a tertiary care teaching hospital, 10.5958/2394-6792.2016. 00119.8.
6. Vicente E Torres, William M Bennett, Diagnosis of and screening for autosomal dominant polycystic
kidney disease, Uptodate, 2017.
7. Tulin Ozcan, Prenatal sonographic diagnosis of cystic renal disease, Uptodate, 2017.
8. Dario Paladini, Paolo Volpe, Ultrasound of Congenital Fetal Anomalies: Differential Diagnosis and
Prognostic Indicators, CRC Press, second edition, 2014.
9. Paula J. Woodward Anne Kennedy, Roya Sohaey, Diagnostic Imaging: Obstetrics, 3 rd Edition, Elsevier,
2016.

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Urinary Tract Anomalies – Prenatal Diagnosis and Prognosis

VARLAS Valentin1,2,*, BOSTAN Georgiana2, DRAGOȘ Georgescu1,3


1 Carol Davila University of Medicine and Pharmacy, Bucharest, (ROMANIA)
2 Filantropia Clinical Hospital, Bucharest, (ROMANIA)
3 St John Hospital, Bucharest (ROMANIA)
* Correspondence to: Valentin Varlas, Filantropia Hospital, 11-13 Ion Mihalache, Bucharest, Romania

Email: [email protected]

Abstract

Urinary tract anomalies are among the most frequent malformations found during the
ultrasound screening. The main aim of our retrospective study was to make a review of the
urinary tract anomalies detected in Filantropia Clinical Hospital, Bucharest between 2009 and
2016, taking into account the high incidence of these defects and their important impact on future
prognosis and quality of life. Second, we evaluated prenatal criteria of gravity for an accurate
diagnosis and an overall prognosis of the renal malformations. In this study we analyzed also, the
correlations between ultrasound findings and pathological data for fetuses with severe renal
damage and associated extrarenal malformations.
Out of the 103 cases of urinary tract malformations, more than 19% of fetuses presented
associated other malformations and very few cases were associated with an abnormal karyotype.
Ultrasound scans established the gravity of urinary tract malformations and evaluated the
overall fetal prognosis in accordance with the analysis of a multidisciplinary team.
In conclusion, urinary tract anomalies can range from severe cases with very bad prognosis
such as bilateral renal agenesis to mild cases with a good evolution and prognosis such as
unilateral ureterohydronephrosis. Prenatal differential diagnosis of renal malformations can be
challenging as many different diseases can have similar ultrasound features such as polycystic or
hyperechogenic aspect of the kidney.
Keywords: urinary tract anomalies, ultrasound scan, prognosis

Introduction

Malformations of the kidney and urinary tract represent 20 to 30 percent of all anomalies
identified during the prenatal ultrasound screening and count for 30 to 50 percent of all cases of
end-stage renal disease in children. They can be unilateral or bilateral and more than one defect
can exist in an individual child. The diagnosis of renal and urinary tract anomalies has a high
impact on future prognosis and quality of life. Anomalies involving the reduction in kidney
number or size are more likely to be associated with a poor prognosis. On axial ultrasound
images, normal fetal kidneys are hypoechoic ovoid paravertebral masses located in the renal
fossa corresponding to the level of the second lumbar vertebrae. [1]
The ratio between renal circumference and abdominal circumference is approximately 0,27-
0,30 and remains constant throughout pregnancy. [2]

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The renal cortex and medulla have different echogenicities and this fact is visible during the
second trimester ultrasound evaluation. Fetal renal length is a marker of renal growth. Normally,
the fetal ureters are not seen on ultrasonography. The urine-filled bladder is normally identified
during the first trimester ultrasound. The presence of urine in the bladder demonstrates that at
least one kidney has a good function. The bladder wall is normally thin. A thick wall of the
bladder is suggestive of urethral obstruction. The frequency of congenital anomalies of the
kidney and urinary tract in unselected populations is reported to be approximately 0.1 to 0.7
percent.
Studies report a sensitivity of antenatal screening for renal malformations as high as 82
percent at a mean gestational age of 23 weeks. First and second trimester ultrasound examination
make an early diagnosis of renal and urinary tract anomalies and allow completion of prenatal
diagnostic procedures such as fetal karyotype and legal termination of pregnancy if desired. [1]

Methods

This is a retrospective study of the cases of urinary tract malformations over an 8-year period
(between 2009 and 2016). The ultrasound examination was made in the Department of Fetal
Medicine and the autopsies were made at the Department of Pathology, Filantropia Clinical
Hospital, Bucharest. The ultrasound examination was made by experienced examiners using
either a Voluson 730 Expert or a Voluson E8 Expert. We analyzed a series of 103 urinary tract
anomalies identified during an ultrasound examination. The majority of cases were identified
during first and second trimester ultrasound examination and only in a minority of cases the
diagnosis was made during the third trimester. The ages of the patients varied between 18 and 43
years with a mean age of 304.7 years. Some severe cases were associated with fetal demise or
abortion. In these cases, we compared the results of the prenatal ultrasound and those of the
autopsy at different gestational ages and assessed the degree of correlation between the results
and its clinical impact.

Results

Renal and urinary tract malformations represented 15.41% of all malformations detected
during an ultrasound examination. Most anomalies were detected during second trimester
ultrasound (70.87%). 25.24% of cases were detected during the third trimester ultrasound
examination and only a minority of cases (3.88%) were identified during first trimester
screening. (chart 1) All anomalies detected during first trimester ultrasound screening were cases
of megacystis and the majority of cases detected during third trimester were unilateral or bilateral
hydroureteronephrosis. This fact underlines the idea that in many cases urinary tract anomalies
can only be seen late in pregnancy and the fact that a normal aspect of the kidneys and urinary
tract during the second trimester ultrasound cannot exclude a possible urinary tract disease.
We report the following distribution of renal and urinary tract malformations:
hydroureteronephrosis (27.18%), hydronephrosis (5.82%), polycystic and dysplastic kidneys
(33.98%), ureterohydronephrosis associated with megacystis (8.73%), fusion anomalies and
renal ectopia (7.76%), bilateral renal agenesis (9.7%) and unilateral renal agenesis (6.79%).
More than 19% of fetuses presented associated other malformations (most of which were
cardiac, CNS, skeletal and gastrointestinal malformations) and very few cases were associated
with an abnormal karyotype. (chart 2)

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Chart 1. The distribution of major malformations according to each trimester of pregnancy

Chart 2. The distribution of major renal and urinary tract malformations

The fetal mortality rate of all cases identified with renal or urinary tract anomalies was
29.12% and was determined by bilateral renal agenesis or the presence of multiple anomalies.
A pathologic analysis was made in order to establish the degree of correlation between
ultrasound findings and autopsy. We classified the results into the following categories according
to the degree of correlation between the ultrasound examination and the pathology report: A (full
correlation between ultrasound and autopsy), B (autopsy confirmed all the ultrasound findings,
but revealed one or more additional malformations), C (ultrasound findings were only partially
demonstrated after fetal autopsy), D (complete disagreement between the ultrasound and autopsy
report). The analysis of the data showed the following result: 20 cases of category A (66.66%), 7
cases of category B (23.33%) and 3 cases of category C (10%). Most cases reported as category
B or C represent fetuses with multiple birth defects. (chart 3)

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Chart 3. The degree of correlation between ultrasound findings and autopsy

(a) (b) (c)

(d) (e)
Fig. 1. Different types of renal and urinary tract malformations: (a) renal agenesis, (b) absent urinary bladder, (c, d)
polycystic kidney disease, (e) hydronephrosis.

Discussions

The differential diagnosis between the anomalies with similar ultrasound features is very
important as the recurrence risk is lower in the case of sporadic isolated malformations and
higher in the case of genetic syndromes. An absent kidney on ultrasound can be caused by
unilateral renal agenesis or by renal ectopia (the kidney is found in most cases in the pelvis,
presacral area or iliac fossa). It can be also determined by a fusion anomaly (both kidneys are
found on the same side and are fused). The differential diagnosis of a hyperechoic kidney is
challenging and must take into consideration the size of the kidney and the associated
malformations. In the case of small hyperechoic kidneys the most probable diagnosis is cystic
renal dysplasia Potter type IV. It is caused by the early and severe obstruction of the urinary
tract.
In the case of hyperechoic enlarged kidneys the following diagnoses must be taken into
account: polycystic kidneys, a genetic syndrome such as Bardet Biedl, Beckwith Wiedemann,
Meckel Gruber, Zellweger or Perlman syndrome. Autosomal dominant polycystic kidney disease

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is in most cases associated with a normal amount of amniotic fluid while autosomal recessive
polycystic kidney disease is more frequently associated with reduced or absent amniotic fluid.
A genetic syndrome is especially suspected in the presence of other extrarenal anomalies.
Meckel Gruber syndrome is a genetic disorder with autosomal recessive inheritance pattern
which consists of three classic signs: occipital cephalocele, cystic renal dysplasia and postaxial
polydactyly. CNS anomalies (Dandy Walker malformation, hydrocephaly) and gastrointestinal
anomalies (exomphalos, asplenia, splenomegaly, and imperforate anus) can also be associated.
The diagnosis of Beckwith Wiedemann syndrome is suspected in the following case: the
association of exomphalos, macroglossia, gigantism and polycystic kidneys. [2]
Zellweger is a rare lethal condition with an autosomal recessive pattern of inheritance. The
average survival is less than 1 year. It is defined by hypotonia, facial dysmorphism (long and
narrow forehead, Brushfield spots in the iris, hypoplastic supraorbital ridges, epicanthal folds),
abnormal brain gyri, and seizures. Renal anomalies include cystic dysplasia, horseshoe kidney
and urethral duplication. Bardet-Biedl syndrome is defined by the association of retinitis
pigmentosa, obesity, renal dysplasia, polydactyly, learning disability, and hypogenitalism. [7]
When an extrarenal anomaly is found VACTERL association should be considered.
VACTERL association refers to a group of birth defects as follows: vertebral anomalies
(scoliosis or hemivertebrae), anal atresia, cardiac defects, oesophagal atresia with tracheo-
oesophagal fistula, renal anomalies (agenesis, ectopia, horseshoe kidney, hydronephrosis), and
limb abnormalities (most frequently aplasia radii).
Hydronephrosis, hydroureteronephrosis and bladder dilatation can be determined or not by
obstruction of the urinary tract. The most frequent causes include pelvic ureteric junction
obstruction, vesico-ureteric junction obstruction, megaureter, cloacal dysgenesis, complicated
duplex kidney, vesicoureteral reflux, megacystis-microcolon-intestinal hypoperistalsis syndrome,
posterior urethral valves. Hydronephrosis (pelvicalyceal dilatation) is one of the most common
urinary tract anomalies detected in the fetus, accounting for approximately 50% of all renal
anomalies detected during a prenatal ultrasound examination. The moment of onset and the
degree of obstruction are very important for the prognosis of the fetus. [2]
Most experts use the following cut-off values to define hydronephrosis in the second
trimester: >4 mm at 15-19 weeks of gestation, >5 mm at 20-29 weeks of gestation and >7 mm at
30-40 weeks of gestation. [3]
Mild renal pelvic dilation (RPD), known as pyelectasia, is defined as an RPD of ≥4 to 10 mm
in the second trimester. Most cases of mild renal pelvic dilation resolve spontaneously and do not
interfere with neonatal renal development. Transient causes of fetal hydronephrosis are
represented by maternal-fetal overhydration or relaxation of the smooth muscle of the urinary
tract due to the high levels of maternal hormones. However, there are reports of persistent cases
that require postnatal intervention. RPD >10 mm in the second trimester is associated with an
increased risk of significant congenital anomalies of the kidney and urinary tract [3, 4]
The diagnosis of hydroureteronephrosis can be made both in the second and third trimester.
The fetal outcome is better in the case of unilateral obstruction with a late onset during
gestation and is worse for bilateral obstructions and those with an early onset during gestation.
Bladder anomalies include non-visualisation of the bladder and megacystis. Non-visualisation
of the bladder can have different causes which range from the normal transient emptying of the
bladder to more severe anomalies such as bilateral renal agenesis, severe FGR, bladder
exstrophy, autosomal dominant and recessive polycystic kidney disease and cystic renal
dysplasia Potter type IV. The amount of amniotic fluid may be normal in the case of autosomal

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dominant polycystic kidney disease, bladder exstrophy and is always reduced in the case of
severe FGR, cystic renal dysplasia Potter type IV and bilateral renal agenesis. [2]
Bladder dilatation is defined as a longitudinal bladder diameter >7 mm during the first
trimester, >30 mm during the second trimester and >60 mm during the third trimester of
pregnancy. [5]
When the diagnosis is made during the first trimester of pregnancy the risk of a chromosomal
anomaly is increased and the determination of the fetal karyotype is mandatory. However, in the
case of normal karyotype and a bladder diameter of 7-15 mm spontaneous resolution occurs in
more than 90% of cases. Bladder dilatation can be due to obstructive causes such as posterior
urethral valves, urethral stenosis or atresia or can be caused by non-obstructive causes such as
chromosomal disorders, megacystis-microcolon-intestinal hypoperistalsis syndrome or bilateral
vesico-ureteral reflux. The most severe case known as prune belly syndrome is the result of a
complete urethral obstruction determined by complete posterior urethral valves or urethral
atresia. [2]
Posterior urethral valves are considered the most common cause of lower urinary tract
obstruction in male infants and fetuses. Posterior urethral valves cause oligohydramnios, a
distended urinary bladder, bilateral hydroureteronephrosis, and obstructive renal dysplasia
(Potter type IV). The high intraabdominal pressure determines atrophy of the abdominal wall
muscles. As a result the abdomen is covered only by skin and peritoneum and an extremely
atrophic muscular layer. These fetuses have cryptorchidism and intestinal malrotation secondary
to the distended bladder that impedes normal bowel positioning and testicular descent. Survival
depends on the degree of pulmonary hypoplasia caused by severe oligohydramnios. [6, 7]
Consequently megacystis caused by a complete obstruction has a worse prognosis.
There are some renal anomalies associated with late-onset renal insufficiency such as
autosomal dominant polycystic kidney disease which may be discovered only during adulthood
(at a median age of 30-50 years). [2]
Other anomalies such as renal ectopia and fusion anomalies may remain asymptomatic during
the entire life. The most common fusion anomaly is the horseshoe kidney. However, postnatal
follow-up is recommended as some cases are complicated by urinary tract infections, hematuria
and vesico-ureteral reflux. Renal ectopia and fusion anomalies may be associated in female
fetuses with genital tract malformations. [8]
Another factor that must be taken into account is the risk of recurrence. Genetic syndromes
associated with renal anomalies have in many cases an autosomal recessive inheritance pattern
and the recurrence risk is 25%. Other conditions such as autosomal dominant polycystic kidney
disease have a 50% recurrence risk. When autosomal dominant or recessive polycystic kidney
disease is suspected, the family history must be investigated and renal ultrasound assessment of
the parents is recommended. Sporadic cases are associated with a low recurrence risk. [2]

Conclusions

There are some lethal malformations of the urinary tract such as bilateral renal agenesis,
cystic renal dysplasia Potter type IV or prune belly syndrome. Prognostic factors for the
postnatal evolution include the degree of obstruction (complete obstruction has a worse outcome
compared to incomplete obstruction), the anatomic site of the obstruction (urethral
stenosis/atresia and bilateral lesions are associated with a worse prognosis compared to unilateral
lesions), the associated malformations (genetic syndromes or VACTERL association have a

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worse prognosis compared to isolated urinary tract anomalies), the presence of a chromosomal
anomaly, the moment of diagnosis (malformations that are discovered in the third trimester or
during the postnatal period are usually mild and have a better outcome). Pathologic examination
confirms in most cases the ultrasound findings and in other cases reveals the presence of
additional malformations. When abortion or fetal demise occurs, the pathologic report is a
complementary useful tool to establish a final diagnosis.

REFERENCES

1. Norman D Rosenblum, Overview of congenital anomalies of the kidney and urinary tract (CAKUT),
Uptodate, 2018.
2. Dario Paladini, Paolo Volpe, Ultrasound of Congenital Fetal Anomalies: Differential Diagnosis and
Prognostic Indicators, CRC Press, second edition, 2014.
3. Gianluigi Pilu, Kypros Nicolaides, Renato Ximenes and Phillipe Jeanty, The 18-23 weeks scan, ISUOG
and Fetal Medicine Foundation, 2002.
4. Laurence S Baskin, Overview of fetal hydronephrosis, Uptodate, 2017.
5. Ayush Goel, Yuranga Weerakkody, Fteal megacystis, Radiopaedia 2005-2018.
6. Paula J. Woodward Anne Kennedy, Roya Sohaey, Diagnostic Imaging: Obstetrics, 3 rd Edition, Elsevier,
2016.
7. Maria M. Rodriguez, Congenital Anomalies of the Kidney and the Urinary Tract (CAKUT), 2014, 33(5-6):
pp. 293-320.
8. Norman D Rosenblum, Renal ectopic and fusion anomalies, Uptodate 2017.

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Thyroid Ultrasound – Between Endocrinology and Gynaecology

VASILIU Cristina1, CARSOTE Mara2, VALEA Ana3, ALBU Simona Elena1


1 Carol Davila University of Medicine and Pharmacy, & University Emergency Hospital, Bucharest, (ROMANIA)
2 Carol Davila University of Medicine and Pharmacy & Constantin I. Parhon National Institute of Endocrinology, Bucharest,
(ROMANIA)
3 Iuliu Hatieganu University of Medicine and Pharmacy & Clinical County Hospital, Cluj-Napoca, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected]

Abstract

Thyroid ultrasound is a key element in endocrine assessment of different conditions situated


at the border between endocrinology and gynaecology like premature ovarian failure or various
climacteric vasomotor symptoms. We aim to introduce specific echographic aspects in two adult
female cases from a gynaecological endocrinology point of view. Method: these are case reports.
This is 64-year old female, with negative medical family history, who is admitted for
vasomotor symptoms 15 years after physiological menopause was registered. She is known with
chronic persistent B hepatitis without specific therapy. Current gynaecological evaluation was
within normal limits but an endocrine check-up was recommended. The blood assays of TSH
(Thyroid Stimulating Hormone), TPO (anti-thyroperoxidase antibodies), and calcitonin were
normal. Thyroid ultrasound showed a large multinodular goitre. Right lobe has 2.3 by 3 by 5.1
cm and left lobe of 3.2 by 2.8 by 6.1 cm (centimetre). Right lobe has 3 nodules as a
conglomerate of maximum diameters each up to 2.5 cm. The isthmus has a nodule of 3.6 cm.
The left lobe is entirely displayed by a large nodule of 3.1 cm and another large nodule of 3.8
cm is situated at inferior, pre-tracheal left side. Large, compressive goitre indicates total
thyroidectomy which the patient currently delays. The second case is a 47-year old female
known with autoimmune hypothyroidism with negative blood antibodies against thyroid based
on highly suggestive pattern ultrasound (hypo-echoic, inhomogeneous). She is diagnosed since
last 6 years with premature ovarian insufficiency with induced menses under estro-progestatives.
Currently, she stopped any medication and secondary amenorrhea is registered due to
autoimmune hepatitis which contraindicates estrogens. Take-home messages for the first case are
the facts that local compressive symptoms associated with a large multi-nodular goitre as
dyspnoea, difficulties of breathing or eating in addition to anxiety and excessive sweating may
mimic vasomotor syndrome and anatomic thyroid check, not only the function assays, is
essential for differential diagnosis. As for the second case, the conclusion is ultrasonographic
pattern may help to establish the diagnosis of autoimmune thyroid condition if specific blood
tests are negative while the association of different autoimmune diseases as ovarian, thyroid and
hepatic (as seen in Schmidt syndrome) diseases requires a pluridisciplinary approach.
Keywords: thyroid, ultrasound, menopause

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Introduction

Thyroid ultrasound is the best tool to evaluate the thyroid anatomy, especially in cases with
multinodular goitre or autoimmune background. [1], [2], [3] It serves both for gynaecology and
endocrinology. [1], [2], [3] Accidentally discovered thyroid nodules display the scenario of a
typical endocrine incidentaloma, as seen at the levels of other glands as ovaries, adrenal or
pituitary gland; thyroid is not a typical site of secondary malignancy involvement. [4], [5] The
specific aspects of thyroid incidentaloma are the fact that they are the most frequent and they
may be directly explored trough fine needle aspiration which provides a cytological exam. [4]
We aim to introduce specific echographic aspects in two adult females from a gynaecological
endocrinology point of view.

Methods

These are case reports. Both patients agreed to anonymously use their medical records. They
were followed in different tertiary centres of endocrinology and gynaecology from Romania.
Thyroid evaluations based on ultrasound and blood assays are introduced.

Case presentation 1
This is 64-year old female, with negative medical family history, who is admitted for
vasomotor symptoms 15 years after physiological menopause was registered. She has
intermittent dyspnoea, difficulties of eating for some types of food, sweat episodes in association
with anxiety (with normal blood pressure). She is known with chronic persistent B hepatitis
without specific therapy. Current gynaecological evaluation was within normal limits but an
endocrine check-up was recommended. The blood assays of TSH (Thyroid Stimulating
Hormone), TPO (anti-thyroperoxidase antibodies), and calcitonin were normal. (Table 1)

Table 1. The thyroid assays for a 64-year old female complains of dyspnoea, sweat, and anxiety
Parameter Value Normal limits Units
TSH 1.2 0.5-4.5 µUI/mL
(Thyroid Stimulating Hormone)
FreeT4 12 10.3-24.4 pmol/L
(Free levothyroxine)
TPO 14 0-35 U/L
(anti-thyroperoxidase antibodies)
calcitonin 2 1-11.8 ng/mL

Thyroid ultrasound showed showed a large multinodular goitre. Right lobe has 2.3 by 3 by 5.1
cm and left lobe of 3.2 by 2.8 by 6.1 cm (centimetre). Right lobe has 3 nodules as a
conglomerate of maximum diameters each up to 2.5 cm. (Fig. 1)

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Fig. 1. Thyroid ultrasound on a 64-year old female with compressive symptoms. Right lobe (longitudinal aspect)
presents conglomerate of several nodules

The isthmus has a nodule of 3.6 by 2.1 by 3 cm. (Fig. 2.)

Fig. 2. Nodule of the thyroid isthmus: 3.6 by 2.1 by 3 cm

The left lobe is entirely displayed by a large nodule of 3.1 cm. (Fig. 3)

Fig. 3. Nodule of the left thyroid lobe: 3.6 by 2.1 by 3 cm

Also, the left thyroid lobe has a nodule of 3.8 by 2.8 by 4 cm which is situated at inferior, pre-
tracheal left side. (Fig. 4)

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Fig. 4. Nodule of the left thyroid lobe: 3.8 by 2.8 by 4 cm

Large, compressive goitre indicates total thyroidectomy which the patient currently delays.
Further functional and ultrasound follow-up is necessary. No specific medical therapy
represents a practical alternative if surgery is refused. Fine needle aspiration is useful only to
differentiate the malignancy risk not as therapy if no cyst is presented.

Case presentation 2
The second case is a 47-year old female known with autoimmune hypothyroidism with
negative blood antibodies against thyroid based on highly suggestive pattern ultrasound (hypo-
echoic, inhomogeneous). (Fig. 5)

Fig. 5. Thyroid ultrasound on a 47-year old female with autoimmune hypothyroidism but negative antibodies against
thyroid; specific pattern for autoimmune condition is based on hypo-echoic and inhomogeneous aspects; she
associates a small hypoechoic nodules of 3 mm at the level of inferior right lobe which has no clinical significance

Blood thyroid assays are normal (under daily levothyroxine). (Table 2)

Table 2. The thyroid assays for a 47-year old female with poly-glandular autoimmune syndrome
Parameter Value Normal limits Units
TSH 3.4 0.5-4.5 µUI/mL
(Thyroid Stimulating Hormone)
FreeT4 10.9 10.3-24.4 pmol/L
(Free levothyroxine)
TPO 23 0-35 U/L
(anti-thyroperoxidase antibodies)
calcitonin 3 1-11.8 ng/mL

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She is diagnosed since last 6 years with premature ovarian insufficiency with induced menses
under estro-progestatives. Currently, she stopped any medication and secondary amenorrhea is
registered due to autoimmune hepatitis which contraindicates estrogens.

Discussions

Multi-nodular goitre often induces local symptoms but they may mimic various conditions
including climacteric syndrome. [1], [6], [7] This particular aspect may be investigated by
endocrinologist or gynaecologist. Current gynaecological conditions, including ovarian tumours
found in menopause, are incidentally associated with thyroid nodules, including thyroid
carcinoma but a specific pattern is not clear yet. [6], [7] Thyroid exploration also serves for the
diagnosis of autoimmune chronic thyroiditis, especially in those rare cases with positive TSH
blocking antibodies that are not routinely assessed in clinical practice. [8] In this particular case,
the other thyroid antibodies as anti-thyroperoxidase and anti-thyroglobuline, if negative, do not
help the positive diagnosis thus the value of thyroid ultrasound. [8], [9]

Conclusions

Take-home messages for the first case are the facts that local compressive symptoms
associated with a large multi-nodular goitre as dyspnoea, difficulties of breathing or eating in
addition to anxiety and excessive sweating may mimic vasomotor syndrome and anatomic
thyroid check, not only the function assays, is essential for differential diagnosis. As for the
second case, the conclusion is ultrasonographic pattern may help to establish the diagnosis of
autoimmune thyroid condition if specific blood tests are negative while the association of
different autoimmune diseases as ovarian, thyroid and hepatic (as seen in Schmidt syndrome)
diseases requires a pluri-disciplinary approach.

REFERENCES

1. Paschou, SA, Vryonidou, A, Goulis, DG. (2017). Thyroid nodules: Α guide to assessment, treatment and
follow-up. Maturitas. 96, pp. 1-9.
2. Gharib, H, Papini, E, Valcavi, R, Baskin, HJ, Crescenzi, A, Dottorini, ME, Duick, DS, Guglielmi, R,
Hamilton, CR Jr, Zeiger, MA, Zini, M; AACE/AME Task Force on ThyroidNodules. (2006). American
Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for
clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract. 12(1), pp. 63-102.
3. Burch, HB, Burman, KD, Cooper, DS, Hennessey, JV, Vietor, NO. (2016). A 2015 Survey of Clinical
Practice Patterns in the Management of Thyroid Nodules. J Clin Endocrinol Metab. 101(7), pp. 2853-62.
4. Gheorghisan-Galateanu, AA,Carsote, M, Valea, A. (2017). Incidentaloma: from general practice to specific
endocrine frame. J Pak Med Assoc. 67(6), pp. 917-922.
5. Poiana, C, Carsote, M, Ardeleanu, C, Terzea, D, Avramescu, ET, Neamţu, MC, Miulescu, RD. (2011). The
value of the immunohistochemistry in a case of gastric neuroendocrine tumor and thyroid metastasis. Rom
J Morphol Embryol. 52(1), pp. 187-92.
6. Poiana, C, Virtej, I, Carsote, M, Banceanu, M, Sajin, M, Stanescu, B, Ioachim, D, Hortopan, D, Coculescu,
M. (2010). Virilising Sertoli-Leydig cell tumour associated with thyroid papillary carcinoma: case report
and general considerations, Gynecol Endocrinol. 26(8). pp. 617-622.
7. Chowdhury, S, Mukherjee, S, Mukhopadhyay, S, Mazumder, R. (2006). The thyroid nodule evaluation and
management. J Indian Med Assoc. 104(10), pp. 568-70.
8. Walsh JP. (2016). Managing thyroid disease in general practice. Med J Aust. 205(4), pp. 179-84.
9. Radetti G. (2014). Clinical aspects of Hashimoto's thyroiditis. Endocr Dev. 26: pp. 158-70.

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Thyroid Nodules on Female Patients of Reproductive Age – The


Importance of Ultrasound

VASILIU Cristina1, ALBU Simona Elena1, GHEMIGIAN Adina2, VALEA Ana3,


CARSOTE Mara2
1 Carol Davila University of Medicine and Pharmacy, & University Emergency Hospital, Bucharest, (ROMANIA)
2 Carol Davila University of Medicine and Pharmacy & Constantin I. Parhon National Institute of Endocrinology, Bucharest,
(ROMANIA)
3 Iuliu Hatieganu University of Medicine and Pharmacy & Clinical County Hospital, Cluj-Napoca, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected]

Abstract

Thyroid nodules may be affected by reproductive period of time or by pregnancy especially


via hyper-vascularisation and endothelial changes. We aim to introduce different scenarios
related to thyroid nodules detected at reproductive age. Method. This is a cases series of females
within their forth decade of life. Case 1. This is a 34 year old female known with menarche since
age of 14, no births, she was under oral contraceptives (intermittent administration) but not
currently. She has spontaneous menses. Recently, she accused progressive increase of thyroid
gland without apparent trigger. Thus, she came to our attention. Normal thyroid function and
autoimmunity was associated. Iodine 131 thyroid scintigram showed bilateral inhomogeneous
uptake with multiple “cold” areas. Thyroid ultrasound showed a conglomerate with irregular
shape at the level of right lobe of 4.5 by 2.2 by 2 cm. Left lobe is highly increased and a nodular
conglomerate displays it up to the isthmus level, of 4.7 by 4.4 by 7 cm with intense
vascularisation and tracheal local effect. Fine needle aspiration showed non-specific follicular
aspects. Total thyroidectomy was done and confirmed benign aspects. Case 2. This is a 30-year
old female. She is known since last two years with multinodular goitre of 1.7 cm maximum
diameter. She had 2 births, and currently is evaluated after second one. Blood thyroid assays are
normal, and thyroid ultrasound showed a left thyroid nodule with significant increase to 2 cm
associating a hypo-echoic halo. Total thyroidectomy is recommended. Case 3. This is a 34-year
old female with a history of two births. She came to our attention 3 month postpartum when a
thyroid nodule of 3.8 cm was detected at right lobe with some cyst-like area inside. Three more
months later the nodule displayed similar characteristics, indicating gland removal. The take-
home messages: thyroid ultrasound is essential for diagnosis and follow-up of nodules on women
of reproductive age.
Keywords: thyroid, ultrasound, menses

Introduction

Thyroid nodules may be affected by reproductive period of time or by pregnancy especially


via hyper-vascularisation/angiogenesis and endothelial changes. [1], [2], [3] Thyroid ultrasound
is recognised as the best tool to assess thyroid anatomy, under normal and pathological

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circumstances. [1], [2], [3] The potential of growth is caused by direct actions of estrogens at the
level of thyroid follicular cells via genomic and non-genomic actions through its membranes
receptor (MAPK/PI3K) signal transduction pathways. [2], [3]

Aim

We aim to introduce different scenarios related to thyroid nodules detected at reproductive


age.

Methods

These are case presentations. All the subjects agreed to introduce their medical records under
anonymous base; they signed the informed written consent. They were admitted in different
Romanian tertiary centres of endocrinology/gynaecology.

Case presentation 1
This is a 34-year old female known; she is known with menarche since age of 14, she has no
pregnancies, births, she was under oral contraceptives (intermittent administration) but not
currently. She has spontaneous regular menses. Her medical history is negative, so is the medical
family history. Recently, she accused progressive increase of thyroid gland without apparent
trigger. Thus, she came to our attention. Normal thyroid function and negative autoimmunity was
associated, as normal calcitonin. (Table 1)

Table 1. The thyroid assays for a 34-year old female with large compressive goitre
Parameter Value Normal limits Units
TSH 0.9 0.5-4.5 µUI/mL
(Thyroid Stimulating Hormone)
FreeT4 14 10.3-24.4 pmol/L
(Free levothyroxine)
TPO 20 0-35 U/L
(anti-thyroperoxidase antibodies)
TRAb 0.3 0-1 UI/L
(anti-receptor TSH antibodies)
calcitonin 1.6 1-11.8 ng/mL

Thyroid ultrasound showed a conglomerate with irregular shape at the level of right lobe of
4.5 by 2.2 by 2 cm. Total diameters of right lobe are 5.2 by 3.3 by 2.4 cm. (Fig. 1)

Fig. 1. Thyroid ultrasound on a 34-year old female:


enlarged right lobe with a nodular conglomerate of 4.5 by 2.2 by 2 cm

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Left lobe has also highly increased diameters, and a nodular conglomerate entirely displays it
(of irregular shape, with increased vascularisation) extended up to the isthmus level, of 4.7 by
4.4 by 7 cm with local tracheal effect. (Fig. 2)

Fig. 2. Thyroid ultrasound on a 34-year old female:


enlarged left lobe with a large nodule of 4.7 by 4.4 by 7 cm

Also, left lobe has anther smaller nodule of 1.2 cm. (Fig. 3)

Fig. 3. Thyroid ultrasound on a 34-year old female:


a left lobe with a second smaller nodule of 1.2 cm

The isthmus is entirely occupied by the large nodule originating from left nodule. Overall,
tracheea is partially narrowed by the nodules. No local lymph nodes involvement is detected.
Iodine 131 thyroid scintigram showed bilateral inhomogeneous uptake with multiple “cold”
areas. (Fig. 4)

Fig. 4. Thyroid scintigrame based on 131 iodine uptake: large, inhomogeneous aspect

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Fine needle aspiration showed non-specific follicular aspects. Total thyroidectomy was done
and confirmed benign aspects like aniso- follicular goitre, area with hyperplasic epitheliums,
haemorrhage, siderophagia, sclerosis and dystrophic calcifications. Lifelong levothyroxine
therapy is offered to the patient.

Case presentation 2
This is a 30-year old female. She is known since last two years with multi-nodular goitre of
1.7 cm maximum diameter for the largest nodule. She had 2 births, and currently she is evaluated
after the second one. Blood thyroid assays are normal as presented below. (Table 2)

Table 2. The thyroid assays for a 30-year old female with goitre evaluated after her second birth
Parameter Value Normal limits Units
TSH 1.3 0.5-4.5 µUI/mL
(Thyroid Stimulating Hormone)
FreeT4 12 10.3-24.4 pmol/L
(Free levothyroxine)
TPO 10 0-35 U/L
(anti-thyroperoxidase antibodies)
calcitonin 1.6 1-11.8 ng/mL

Thyroid ultrasound showed a left thyroid nodule with significant increase to 3 by 1.8 by 2.4
cm, associating a hypo-echoic halo. (Fig. 5)

Fig. 5. Thyroid ultrasound on a 30-year old female (postpartum aspect):


a large left lobe nodule which registered a postpartum increase

Computed tomography confirmed that thyroid had multiple nodules, with a different
structures and pattern from pre-partum aspects. (Fig. 6)

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a. b.
Fig. 6. Thyroid computed tomography on a 30-year old female (postpartum aspect):
multinodular goitre with postpartum increase (6A-transversal aspect, 6B-coronal section)

Total thyroidectomy is recommended due to local compressive effects (which is soon to be


done).

Case presentation 3
This is a 34-year old female with a history of two births. She came to our attention 3 month
postpartum when a thyroid nodule of 3.8 by 2.5 cm was detected at right lobe with some cyst-
like area inside causing a inhomogeneous pattern, and small hypoechoic hallo. (Fig. 7A)

a. b.
Fig. 7. Thyroid ultrasound:
large inhomogeneous nodule of right lobe (a. sagittal section, 3 month postpartum; b. 6 months postpartum)

Three more months later the nodule displayed similar characteristics (of 3.02 by 1.8 by 2.4
cm, inhomogeneous, well shaped), indicating complete gland removal. (Fig. 7B)

Discussions

Non-autoimmune thyroid conditions as nodules or nodular goitre, regardless accidentally


detected or associating severe compressive symptoms, may be related to hormonal changes
during menstrual cycle or during/after pregnancy. [3], [4], [5], [6] Overall, a thyroid nodule may
be usually found in 5% of women of reproductive age up to 70% according to incidentaloma
series. [3], [4], [5], [6] The risk of malignancy is described in 1 to 15 % of subjects; there is not a
very well described relationship regarding estrogens exposure and cancer risk. [3], [4], [5], [6]

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Conclusions

Thyroid ultrasound is essential for diagnosis and follow-up of nodules on women of


reproductive age in addition to function and autoimmunity profile. Even the exact pathogenic
link with estrogens is less clear up to this moment; practitioners related to gynaecological
endocrinology field should pay attention to these particular aspects.

REFERENCES

1. Gharib, H, Papini, E, Valcavi, R, Baskin, HJ, Crescenzi, A, Dottorini, ME, Duick, DS, Guglielmi, R,
Hamilton, CR Jr, Zeiger, MA, Zini, M; AACE/AME Task Force on ThyroidNodules. (2006). American
Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for
clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract. 12(1), pp. 63-102.
2. Paschou, SA, Vryonidou, A, Goulis, DG. (2017). Thyroid nodules: Α guide to assessment, treatment and
follow-up. Maturitas. 96, pp. 1-9.
3. Derwahl, M, Nicula, D. (2014). Estrogen and its role in thyroid cancer. Endocr Relat Cancer. 21(5):T273-
83.
4. Burch, HB, Burman, KD, Cooper, DS, Hennessey, JV, Vietor, NO. (2016). A 2015 Survey of Clinical
Practice Patterns in the Management of Thyroid Nodules. J Clin Endocrinol Metab. 101(7), pp. 2853-62.
5. Gheorghisan-Galateanu, AA, Carsote, M, Valea, A. (2017). Incidentaloma: from general practice to
specific endocrine frame. J Pak Med Assoc. 67(6), pp. 917-922.
6. Chowdhury, S, Mukherjee, S, Mukhopadhyay, S, Mazumder, R. (2006). The thyroid nodule evaluation and
management. J Indian Med Assoc. 104(10), pp. 568-70.

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Thyroid Ultrasound On Patients Within 5th Decade Of Life

VASILIU Cristina1, ALBU Simona Elena1, GHEMIGIAN Adina2, VALEA Ana3,


CARSOTE Mara2
1 Carol Davila University of Medicine and Pharmacy, & University Emergency Hospital, Bucharest, (ROMANIA)
2 Carol Davila University of Medicine and Pharmacy & Constantin I. Parhon National Institute of Endocrinology, Bucharest,
(ROMANIA)
3 Iuliu Hatieganu University of Medicine and Pharmacy & Clinical County Hospital, Cluj-Napoca, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected]

Abstract

Menopause related vasomotor symptoms are heterogeneous, thus dyspnoea or others


compressive accuses related to anterior cervical area need to be evaluated from an
endocrinological as well as gynaecological point of view. Our purpose is to introduce different
aspects of thyroid ultrasound in women of 5th decade of life, pre and/or peri-menopausal status in
order to analyze the thyroid anatomy in relationship to potential menopause- associated clinical
picture. Method and patients: Case reports of adult females. Case 1 is a 46-year old subject,
known with non-autoimmune hypothyroidism which is currently treated with 100 µg of
levothyroxine per day since last 10 years. She accuses bradimenorrhea since 6 months in
association with insomnia, suffocation, intermittent sensation of regurgitation. Gynaecological
evaluation detected a mild FSH (Follicle Stimulant Hormone) increase with normal TSH
(Thyroid Stimulating Hormone). Further on, thyroid examination via ultrasound was done. The
procedure identified a mild enlargement of thyroid (right lobe of 5.3 cm largest diameter, and left
lobe of 4 cm largest diameter); the right lobe had a inhomogeneous nodule of 0.8 by 0.6 by 0.7
cm, while on the left, there are 2-3 nodules with hypoechoic pattern of maximum 0.6 by 0.3 by
0.5 cm. The dominant nodule is situated on the right lobe, of 2.68 by 1.78 by 2.59 cm
(hypoechoic, with peripheral calcification of “egg-shell” aspects and mild tracheal deviation to
the left). Due to mass effect, surgery is recommended. Case 2 is a 47-year old female with a
history of hypethyroidism treated with thiamazol for a few months, one year ago. She currently
accuses palpitations, suffocation, and she associates secondary amenorrhea since last two years
because of total hysterectomy without ovarian remove. Thyroid assessment shows: multiple
thyroid nodules, suppressed TSH indicating thyrozol therapy (normal thyroid antibodies, and
calcitonin). Case 3 is a 44-year old female with headache, intermittent breathing accuses, and
recent span-menorrhea. She had a subtotal right thyroidectomy for a benign nodule, and surgical-
induced hypothyroidism is treated with levothyroxine. Thyroid ultrasound indicated right
remnants with 5-6 nodules of maximum 0.6 cm, which need to be followed-up. Conclusion: the
first case has accidental overlap between premenopausal symptoms and large, compressive
goitre; the second case: hyperthyroidism may be mistaken as climacteric syndrome; the third
case: despite partial thyroidectomy, the patient will need periodic ultrasound check-up.
Keywords: ultrasound, menopause, thyroid

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Introduction

Menopause related vasomotor symptoms are heterogeneous, thus dyspnoea or others


compressive accuses related to anterior cervical area need to be evaluated from an
endocrinological as well as gynaecological point of view. [1], [2], [3] The presence of the thyroid
nodule may be accidental (incidentaloma) or it may be associated with menses disturbances. [4]

Purpose

We aim to introduce various thyroid ultrasound aspects in women of 5th decade of life in
association with menstrual anomalies

Methods & patients

Case reports of adult females (who signed the informed written consent during their
hospitalisation at three Romanian tertiary centres of endocrinology/gynaecology).

Case report 1
This is a 46-year old subject, known with non-autoimmune hypothyroidism which is currently
treated with 100 µg of levothyroxine per day since last 10 years. She accuses bradimenorrhea
since 6 months in association with insomnia, suffocation, intermittent sensation of regurgitation.
Gynaecological evaluation detected a mild FSH (Follicle Stimulant Hormone) of 20 mUI/mL
(clear menopausal level is above 40 mUI/mL) increase with normal TSH (Thyroid Stimulating
Hormone). (Table 1)

Table 1. The thyroid assays for a 46-year old female with treated hypothyroidism and menses anomalies
Parameter Value Normal limits Units
TSH 1.2 0.5-4.5 µUI/mL
(Thyroid Stimulating Hormone)
FreeT4 11.9 10.3-24.4 pmol/L
(Free levothyroxine)
TPO 10 0-35 U/L
(anti-thyroperoxidase antibodies)

Further on, thyroid examination via ultrasound was done. The procedure identified a mild
enlargement of thyroid (right lobe of 5.3 cm largest diameter, and left lobe of 4 cm largest
diameter). The right lobe had a inhomogeneous nodule of 0.8 by 0.6 by 0.7 cm, while on the left,
there are 2-3 nodules with hypo-echoic pattern of maximum 0.6 by 0.3 by 0.5 cm. (Fig. 1)

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Fig. 1. Thyroid ultrasound on a 46-year old female: enlarged gland and multiple small nodules

There is also a dominant nodule which is situated on the right lobe, of 2.68 by 1.78 by 2.59
cm (hypo-echoic pattern, with peripheral calcification of “egg-shell” types and mild tracheal
deviation to the left). (Fig. 2)

Fig. 2. Thyroid ultrasound pointing a large macro-nodule of the right lobe with “egg shell” calcifications

Due to mass effect, surgery is recommended and total thyroidectomy is soon to be done. The
menses anomalies were considered independent of thyroid changes and cyclic administration of
progestative (10 days per month) is recommended. Lifelong therapy with levothyroxine will also
be offered to the patient after adjustment based on TSH levels.

Case report 2
This is a 47-year old female with a history of hypethyroidism treated with thiamazol for a few
months, one year ago. She currently accuses palpitations, suffocation, and she associates
secondary amenorrhea since last two years because of total hysterectomy without ovarian
remove. Thyroid assessment shows: multiple thyroid nodules, suppressed TSH indicating
thyrozol therapy (normal thyroid antibodies, and calcitonin). Fig. 3a+b reveal 3 nodules at the
level of right thyroid lobe of 1.1 by 0.5 cm, 0.8 by 0.4 cm, respective of 1 by 1.02 cm.

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a. b.
Fig. 3. Thyroid ultrasound on a 47-year old female with hyperthyroidism-associated multinodular goitre. a. right
lobe, longitudinal section (1/3 medium level); b. right lobe, superior pole, longitudinal section

Also, at the level of left lobe there is a dominant nodule of 4.2 by 2 by 3.2 cm with necrosis
areas inside and microcalcifications with a higher level of suspicion regarding a potential
papillary malignancy (but with “hot” nodules on iodine 1131 thyroid scintigrame). (Fig. 4)

Fig. 4. Thyroid ultrasound shows a left lobe nodule of 4.2 cm maximum diameter with microcalcifications

After achieving normal thyroid function through medication, the patient was referred to
surgery. Post-operatory pathological report after total thyroidectomy showed benign aspects, and
no confirmation of papillary thyroid malignancy was done. Further long time levothyroxine
substitution therapy will be necessary under TSH surveillance.

Case report 3
This is a 44-year old female admitted for non-specific headache, intermittent breathing
accuses, and recent span-menorrhea. She had a subtotal right thyroidectomy for a benign nodule
2 years ago, and surgical-induced hypothyroidism is currently treated with levothyroxine with
normal TSH values. Thyroid ultrasound indicated right remnants with 5-6 nodules of maximum
0.6 cm, which need to be followed-up, mainly via cervical ultrasound. (Fig. 5)

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Fig. 5. Thyroid ultrasound aspect 2 years after subtotal thyroidectomy for benign nodules (left lobe)

Discussions

The cases we mention introduce three specific aspects regarding thyroid conditions and
menses anomalies on women to whom menopause showed be taken into account as differential
diagnosis. [5], [6], [7] First, the complete evaluation from a gynaecological endocrinology point
of view includes thyroid function and ultrasound. A large nodule as seen in first case may cause
local compressive symptoms and potentially anxiety and flushes, as seen in vasomotor accuses.
[5]
Secondary, also hyperthyroidism need to be differentiated from menopause-related clinical
picture. [6] Third aspect is a very practical one: in case with subtotal or partial or near total
thyroid remove the residual anatomical parts still need consideration for periodic check-up
including ultrasound. Also, in most cases, thyroid substitution is necessary, while no specific
precautions are necessary in peri-menopausal women (neither including bone profile). [7] Some
observations supported the idea that period of time when a patient has menses increases the risk
of developing thyroid nodules, not necessarily thyroid cancer, and that the number of
pregnancies and abortions also increases the risk of adding new nodules. [8]

Conclusion

The first case has accidental overlap between premenopausal symptoms and large,
compressive goitre; the second case introduces the idea that hyperthyroidism may be sometimes
mistaken as climacteric syndrome, while the third case points that, despite partial thyroidectomy,
the patient will need periodic ultrasound assessment.

REFERENCES

1. Chowdhury, S, Mukherjee, S, Mukhopadhyay, S, Mazumder, R. (2006). The thyroid nodule evaluation and
management. J Indian Med Assoc. 104(10), pp. 568-70.
2. Paschou, SA, Vryonidou, A, Goulis, DG. (2017). Thyroid nodules: Α guide to assessment, treatment and
follow-up. Maturitas. 96, pp. 1-9.
3. Gharib, H, Papini, E, Valcavi, R, Baskin, HJ, Crescenzi, A, Dottorini, ME, Duick, DS, Guglielmi, R,
Hamilton, CR Jr, Zeiger, MA, Zini, M; AACE/AME Task Force on ThyroidNodules. (2006). American
Association of Clinical Endocrinologists and Associazione Medici Endocrinologi medical guidelines for
clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract. 12(1), pp. 63-102.
4. Gheorghisan-Galateanu, AA, Carsote, M, Valea, A. (2017). Incidentaloma: from general practice to
specific endocrine frame. J Pak Med Assoc. 67(6), pp. 917-922.
5. Sadeghian, A, Rouhana, H, Oswald-Stumpf, B, Boh, E. (2017). Etiologies and management of cutaneous
flushing: Nonmalignant causes. J Am Acad Dermatol. 77(3), pp. 391-402.

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6. Derwahl M, Nicula D. Estrogen and its role in thyroid cancer. Endocr Relat Cancer. 2014 Oct; 21(5): T273-
83.
7. Tunca, F,Senyurek, YG, Terzioglu, T, Tanakol, R, Tezelman, S. (2009). Impact of total versus subtotal
thyroidectomy on calcium metabolism and bone mineral density in premenopausal women. J Laryngol
Otol. 123(4), pp. 434-8.
8. Wang, K, Yang, Y, Wu, Y, Chen, J, Zhang, D, Liu, C. (2015). The association of menstrual and
reproductive factors with thyroid nodules in Chinese women older than 40 years of age. Endocrine. 48(2),
pp. 603-14.

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Breast Ultrasound on Young Patient with Mastodynia

VASILIU Cristina1, ALBU Simona Elena1, GHEMIGIAN Adina2, VALEA Ana3,


CARSOTE Mara2
1 Carol Davila University of Medicine and Pharmacy, & University Emergency Hospital, Bucharest, (ROMANIA)
2 Carol Davila University of Medicine and Pharmacy & Constantin I. Parhon National Institute of Endocrinology, Bucharest,
(ROMANIA)
3 Iuliu Hatieganu University of Medicine and Pharmacy & Clinical County Hospital, Cluj-Napoca, (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected]

Abstract

Mastodynia on young patients may underline many diagnoses from mammary dysplasia,
fibro-cystic dysplasia to fibroadenomas, etc. The management includes a part from typical
endocrine and gynaecological evaluation, breast ultrasound which is elective for women of
reproductive age. We aim to introduce mammary echography aspects on patients of reproductive
age who were admitted for mastodynia (non-related to menstrual cycle). Method. This is a 2
cases series presentation. Case 1. This is an 18-year old female with spontaneous menarche at
age of 12 years, and regular menses since then, and no oral contraceptives exposure. She accuses
left unspecific mastodynia since last weeks. Clinical exam is nonspecific. Endocrine tests
showed normal TSH (Thyroid Stimulating Hormone) and prolactin. Thyroid ultrasound is
normal while mammary echography showed fibro-glandular structure, a solid lesion at left
breast, super-intern level (10.oo) without axially lymph nodes involvement (BIRADS 3).
Conservative approach is indicated and follow-up trough ultrasound. Case 2. This is a 37-year
old female with spontaneous menarche at age of 14 years, she gave birth 15 years ago, and she
was exposed to oral contraceptives for 2 years, a decade ago. Currently, she has regular
spontaneous menses. At age of 27 she had non-specific bilateral mastodynia with normal
endocrine profile at that moment. Breast ultrasound identified a solid nodule at right breast of 1
cm (BIRADS 3). Two years later, this lesion was stationary, yet another lesion at 4 mm under the
skin was identified as a solid nodule of 1.1 by 1 by 0.5 cm, and another one at the level of left
breast of 0.6 by 1.2 by 1.3 cm. (BIRADS 3). Currently, all three nodules are stationary on a
background of multiple bilateral cysts (fibro-cystic dysplasia). Ultrasound follow-up is
necessary. Both patients received symptomatic pain medication and no hormonal therapy.
Conclusion: breast ultrasound represents the first step after mastodynia is presented in women
of reproductive age, but also, in cases with conservative decision, representing the best tool for
follow-up. Fibro-epithelial lesions involve a dual proliferation of unknown cause, a frequent
diagnosis at this age.

Introduction

Mastodynia on young patients may underline many diagnoses from mammary dysplasia,
fibro-cystic dysplasia to fibroadenomas, mastitis, breast cancer, intra-ductal papiloma, and, also,
premenstrual syndrome if the pain is correlated with the phases of menstrual cycle. [1], [2], [3]

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The management includes a part from typical endocrine and gynaecological evaluation, breast
ultrasound which is elective for women of reproductive age. [1], [2], [3] If mammary secretion is
positive outside breastfeeding period, the differential diagnosis with prolactinoma and/or
galactocele should also be taken into account. [4]

Purpose

We aim to introduce mammary echography aspects on patients of reproductive age who were
admitted for mastodynia (non-related to menstrual cycle).

Methods & patients

This is a 2 cases series presentation. The patients agreed to anonymously use their medical
data and history. Both of them were admitted at different Romanian tertiary centres of
endocrinology/gynaecology.

Case report 1
This is an 18-year old female with spontaneous menarche at age of 12 years, and regular
menses since then, and no oral contraceptives exposure. She accuses left unspecific mastodynia
since last weeks. Clinical exam is nonspecific. Endocrine tests showed normal TSH (Thyroid
Stimulating Hormone) and prolactin. (Table 1)

Table 1. The endocrine assays on a 18-year old female admitted for mastodynia
(with non-specific pattern, independent of menstrual cycle)
Parameter Value Normal limits Units
TSH 1.3 0.5-4.5 µUI/mL
(Thyroid Stimulating Hormone)
Prolactin 11.9 10-21 ng/ml
TPO 10 0-35 U/L
(anti-thyroperoxidase antibodies)

Thyroid ultrasound is normal while mammary echography showed fibro-glandular structure, a


solid lesion at left breast, super-intern level (10.oo), without axially lymph nodes involvement
(BIRADS 3). The nodule has 1.8 by 0.8 by 0.4 cm. Conservative approach is indicated and
follow-up trough ultrasound. (Fig. 1)

Fig. 1. Breast ultrasound on an 18-year old female; the arrows indicate a nodule at the level of left mammary gland

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Case report 2
This is a 37-year old female with spontaneous menarche at age of 14 years, she gave birth 15
years ago, and she was exposed to oral contraceptives for 2 years, a decade ago. Currently, she
has regular spontaneous menses. At age of 27 she had non-specific bilateral mastodynia with
normal endocrine profile at that moment. Breast ultrasound identified a solid nodule at right
breast of 1 by 0.9 by 0.5 cm (BIRADS 3). The nodule is oval, well shaped, with homogenous
structure, without vascularisation (hour 2.oo). (Fig. 2)

Fig. 2. Breast ultrasound on a 27-year old female; a nodule at the level of right mammary gland of 1 by 0.9 by 0.5cm

Two years later, this lesion of the right breast was stationary, of 1.1 by 1 by 0.6 cm (2. oo).
(Fig. 3)

Fig. 3. Breast ultrasound on a 29-year old female;


the same pattern and size of the nodule from right mammary gland (as first identified 2 years ago)

Another lesion, also at the level of right breast, was revealed 4 mm under the skin, displayed
as a solid, retro-areolary nodule of 1.1 by 1 by 0.5 cm. (Fig. 4)

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Fig. 4. Breast ultrasound on a 29-year old female: a newly identified small nodule at right breast,
of 1.1 by 1 by 0.5cm

Moreover, another nodule at the level of left breast of 0.6 by 1.2 by 1.3 cm was revealed
under the skin, at 5 mm from the nipple. (BIRADS 3) (Fig. 5)

Fig. 5. Breast ultrasound on a 29-year old female: a newly identified small nodule at left breast,
of 0.6 by 1.2 by 1.3 cm

Currently, at age of 37, the subject has all three nodules that were priory identified with
stationary pattern, on a background of multiple bilateral cysts (fibro-cystic dysplasia),
microcalcifications, ductal dilatations, etc. (BIRADS 3 for both mammary glands) Further on
follow-up based on ultrasound is necessary. (Fig. 6)

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A B

C
Fig. 6. Breast ultrasound by the age of 37. A. background of fibro-cystic dysplasia; B. right breast with 2 nodules of
1 cm; C. left breast with a nodule of 1 cm

Discussions

Ultrasound follow-up is necessary since this represents the best tool. Both patients received
symptomatic pain medication without hormonal therapy since a clear endocrine anomaly was not
registered. Mastodynia may be the only symptom of a benign breast disease which usually
requires conservative approach based on echographic features. [5], [6] Typically the hormonal
profile is required regardless clinical circumstances. Fibro-cystic dysplasia, as well as
fibroadenomas in young women require as major tool ultrasound. [5], [6] Most of cases associate
incidental mastodynia. The breast cancer arising within a fibroadenoma is the next logical
parameter related to the condition (also called BcaFAD) with a reported rate of 0.002% up to
0.125%. [7], [8], [9]

Conclusions

Breast ultrasound represents the first step after mastodynia is presented in women of
reproductive age, but also, in cases with conservative decision, representing the best tool for
follow-up. Fibro-epithelial lesions involve a dual proliferation of unknown cause, a frequent
diagnosis at this age. Usually the decision is these cases require either a gynaecologist or an
endocrine evaluation or both and, also, an imagist.

REFERENCES

1. Berens, PD. (2015). Breast Pain: Engorgement, Nipple Pain, and Mastitis. Clin Obstet Gynecol. 58(4), pp.
902-14.

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2. Bagenal, J, Bodhinayake, J, Williams, KE. (2016). Acute painful breast in a non-lactating woman. BMJ.
353, pp. i2646.
3. Coskun, AK, Harlak, A, Mentes, O. (2014). Breast clinic referrals: can mastalgia be managed in primary
care? Ir J Med Sci. 183(3), pp. 509.
4. Poiana, C, Chirita, C, Carsote, M, Hortopan, D, Goldstein, A. (2009). Galactocele and prolactinoma – A
pathogenic association?, Maturitas, An international journal of midlife health and beyond, Official Journal
of the European Menopause & Andropause Society. 62(1), pp. 98-102.
5. Iddon, J, Dixon, JM. (2013). Mastalgia. BMJ. 347:f3288.
6. Amin, AL, Purdy, AC, Mattingly, JD, Kong, AL, Termuhlen, PM. (2013). Benign breast disease. Surg Clin
North Am. 93(2), pp. 299-308.
7. Wu, YT, Chen, ST, Chen, CJ, Kuo, YL, Tseng, LM, Chen, DR, Kuo, SJ, Lai, HW. (2014). Breast cancer
arising within fibroadenoma: collective analysis of case reports in the literature and hints on treatment
policy. World J Surg Oncol. 12, pp. 335.
8. Saimura, M, Koga, K, Anan, K, Mitsuyama, S, Tamiya, S. (2018). Diagnosis, characteristics, and treatment
of breast carcinomas within benign fibroepithelial tumors. Breast Cancer.2018 Feb 19. doi:
10.1007/s12282-018-0847-7.
9. Limite, G, Esposito, E, Sollazzo, V, Ciancia, G, Formisano, C, Di Micco, R, De Rosa, D, Forestieri, P.
(2013). Lobular intraepithelial neoplasia arising within breast fibroadenoma. BMC Res Notes. 6, pp. 267.
doi: 10.1186/1756-0500-6-267.

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Training in Fetal Echocardiography – the Development of a


Multidisciplinary Approach in Prenatal Imaging

VEDUTA Alina1, DUTA Simona1, PETCA Razvan3, PETCA Aida2


1 Filantropia Clinical Hospital, Bucharest (ROMANIA)
2 Elias University Hospital, Bucharest; “Carol Davila” University of Medicine and Pharmacy, Bucharest (ROMANIA)
3 “Theodor Burghele” Clinical Hospital, Bucharest; “Carol Davila” University of Medicine and Pharmacy, Bucharest

(ROMANIA)
Emails: [email protected], [email protected], [email protected]; [email protected]

Abstract

Heart defects are the most common fetal structural anomalies. Ultrasound has become very
accurate in detecting and describing congenital heart disease (CHD). As detection of CHD in the
routine obstetrical ultrasound settings increases, the demand for fetal echocardiography grows as
well. Fetal echocardiography is the most important tool of fetal cardiology – a new
multidisciplinary field of fetal medicine. Fetal cardiology emerges as a multidisciplinary
specialty where the high-risk obstetrician, the fetal medicine specialist and the pediatric
cardiologist care together for fetuses with structural heart disease or cardiovascular dysfunction.
We present details on the content of the fetal echocardiogram and on the guidelines for
training in fetal echocardiography.
Keywords: Congenital heart disease, prenatal ultrasound, fetal echocardiography

Introduction

Heart defects are the most common fetal structural anomalies [1]. Ultrasound has become
very accurate in detecting and describing the structural anomalies of the fetal heart, from early
stages in pregnancy [2]. The optimal care in pregnancies with congenital heart disease (CHD)
relies on the input of fetal medicine specialists, geneticists, obstetricians, neonatologist and,
ultimately, on detailed cardiologic examination and pediatric cardiology counseling.
Fetal echocardiography represents the detailed ultrasonic evaluation of the fetal
cardiovascular system. Many important fetal medicine, pediatrics and cardiology associations
and boards produced opinions and guidelines on the content of a thorough echocardiogram. In
2008, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) published
a document with an explicit title: ‘ISUOG consensus statement: what constitutes a fetal
echocardiogram?’ [3]. The Fetal Cardiology Working Group of the European Association of
Pediatric Cardiology (AEPC) [4], the American Heart Association (AHA) [2], the American
Society of Echocardiography [5] and the American Institute of Ultrasound in Medicine (AIUM)
[6] also published papers on the subject.
As detection of CHD in the routine obstetrical ultrasound settings increases, the demand for
fetal echocardiography grows as well. The most frequent reason of referral for fetal
echocardiography is the suspicion of a heart defect during the routine fetal ultrasound
examination. Other common scenarios for referral are: CHD in a previous pregnancy [2, 3];

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increased nuchal translucency at the 11-14 week scan [3, 7]. Fetuses with extra-cardiac structural
defects as well as fetuses of mothers with specific medical conditions would benefit from
specialist heart examination. More or less extensive lists of indications for fetal
echocardiography have been issued [8]; in practice, referral for fetal echocardiography is limited
by the reduced availability of the service.
Availability of specialist examination of the fetal heart is generally reduced because of the
small number of doctors trained to undertake it. The European Association of Pediatric
Cardiology (AEPC) [4, 9] as well as the American College of Cardiology and the American
Heart Association (ACC/AHA) [2] produced guidelines on training in fetal echocardiography.
In Romania, a system of training in fetal echocardiography has to be developed; all the same,
an integrated national system of perinatal care in cases of CHD is to be developed. Taking into
account the disparity between the demand and the small number of providers in Romania, we
think that patients would greatly benefit from fetal medicine specialists as well as pediatric
cardiologists and neonatologists training in fetal echocardiography.
We present details on the content of a fetal echocardiogram and on the guidelines for training
in fetal echocardiography.

The content of the fetal echocardiogram

There are slight variations between the recommendations of different professional bodies and
associations on the content of a fetal echocardiogram, but these recommendations are overall
consistent [3-6]. At a minimum, fetal echocardiography involves the thorough subjective
segmental analysis of the cardiovascular structures from the upper abdomen to the upper
mediastinum. Quantitative analysis (measuring) is compulsory if any suspicion of abnormal size.
Color Doppler analysis is important for detailed evaluation of the ventricular septum and of
the heart valves. The anatomical structures of the fetal heart are usually evaluated using
transverse views, but both transverse and sagittal scanning planes have to be used if necessary.
The ISUOG consensus paper states that the specific views are less important as long as the
relevant cardiac structures are satisfactorily visualized [3].
We show, in comparison, the European – AEPC, ISUOG, TABEL 1 [2, 3] and the US –
American Society for Echocardiography, TABEL 2 [5] recommendations on the components of
the fetal echocardiogram.

Training in fetal echocardiography

To become competent in fetal echocardiography, one has to have a relevant and sufficient
background (pediatric cardiology, fetal medicine, obstetrical radiology) [2, 4, 5] and to go
through a training program that allows the acquisition of at least basic knowledge of both
obstetrical ultrasound/fetal medicine and echocardiography/pediatric cardiology. Ideally, the
training program should be tailored on the individual background of the candidate. The time
needed to acquire the skills for fetal echocardiography varies from case to case. The aims of the
training are described by both the European board AEPC and the American Society of
Echocardiography [4, 5, 9]. In order to perform fetal echocardiography and correctly interact
with patients in cases where anomalies are diagnosed, a specialist should:
- recognize the full spectrum of simple and complex CHD and be familiar with the
manifestation and natural history of CHD throughout gestation and after birth;

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- recognize the limitations of fetal echocardiography in diagnosing CHD;


- recognize the limitations of the own knowledge and experience;
- be able to apply all modalities of echocardiography, including 2-dimensional, M-mode,
pulsed wave, continuous wave and color Doppler flow mapping, volumetric techniques
(STIC, spatio-temporal image correlation);
- have good knowledge of the anatomy and physiology of the cardiovascular system
through the stages of fetal development and understand the differences between the fetal
and the postnatal circulation;
- have a good understanding of maternal – fetal physiology and be aware of the maternal
conditions that may affect the fetus;
- be familiar with the latest developments in obstetrical diagnosis and in genetic diagnosis;
- be familiar with the growing field of fetal therapy/fetal surgery;
- be familiar with the latest developments in pediatric cardiology and pediatric cardiac
surgery;
- be able to examine the fetal heart early, at 12 weeks of gestation.
Programs of systematic training in fetal echocardiography are already running in many
countries, all over the world [2-5].
In Romania, an integrated national system for prenatal detection and perinatal management of
heart defects has to be organized; this would contribute towards better postnatal outcomes. Local
clinical and training programs have already achieved good results [10-12]. Foreseeable, a
national training program in fetal echocardiography and, eventually, a national Certificate of
Competence in Fetal Cardiology will help creating a system of integrated perinatal care in cases
of CHD. Bringing together pediatric cardiologists, fetal medicine specialists, obstetricians,
neonatologists in the same training program will enhance the quality of treatment for the children
born with heart defects.
Ultimately, fetal echocardiography is a tool for fetal cardiology – the care of the tiniest
patients with heart disease. Fetal cardiology emerges as a multidisciplinary specialty where the
high-risk obstetrician, the fetal medicine specialist and the pediatric cardiologist work together to
manage the fetuses with structural heart disease or cardiovascular dysfunction [2].

Table 1. [2, 3]
Recommendations for a complete fetal echocardiogram – AEPC and ISUOG
cardiac axis and situs
- normal arrangement of the aorta and the inferior cava in the abdomen
- stomach and heart on the left side of the fetus
four chamber view
- size, position
- two atriums of approximately equal size
- foramen ovale in the middle third of the atrial septum, with the flap of the valve in the left atrium
- two ventricles of approximately equal size
- intact ventricular septum
- ventricular morphology and contractility
- intact crux of the heart with the off-setting of the atrioventricular (AV) valves
- two AV valves opening during diastole (color Doppler for regurgitation)
- pulmonary veins to the left atrium, with at least one visualized by color Doppler
- systemic veins to the right atrium
- pericardial effusions
venous-atrial, atrioventricular and ventriculoarterial connections of the heart
size and relationships of the left and right ventricular outflow tracts
- pulmonary trunk crossing over the aortic arch

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semilunar valves (color Doppler for regurgitation)


ductal and aortic arches
- arterial duct lying caudal to the aortic arch
- unaliased color flow through the ductal and aortic arches
heart rate and rhythm

Table 2. [5]
Essential components of fetal echocardiography – the American Society for Echocardiography
Anatomic Biometry Cardiac views Doppler Cardiac Examination of
overview examination measurements rhythm
fetal number and cardiothoracic four chamber umbilical artery AV valve M-mode for wall
position ratio view diameter motion
stomach biparietal five chamber pulmonary veins semilunar valve Doppler
position, diameter view diameter examination of
situs flow
femur length left outflow in ductus venosus main pulmonary
long axis
right outflow in foramen ovale ascending aorta
long axis
short axis sweep AV valves branch
and 3-vessels pulmonary
view arteries
caval long axis semilunar valves transverse aortic
view arch
ductal arch transverse aortic ventricular
arch length
aortic arch umbilical vein ventricular
short-axis
dimensions

REFERENCES

1. Hoffman JI, Kaplan S (2002). The incidence of congenital heart disease. J Am Coll Cardiol; 39: pp. 1890-
900.
2. Donofrio MT, Moon-Grady AJ et al., (2014). American Heart Association. Diagnosis and treatment of fetal
cardiac disease: a scientific statement from the American Heart Association. Circulation; 129(21): pp.
2183-242.
3. Lee W, Allan L et al., ISUOG Fetal Echocardiography Task Force (2008). ISUOG consensus statement:
what constitutes a fetal echocardiogram? Ultrasound Obstet Gynecol; 32(2): pp. 239-42.
4. Allan L, Dangel J, Fesslova V, Marek J, Mellander M, Oberhänsli I, Oberhoffer R, Sharland G, Simpson J,
Sonesson SE (2004). Association for European Paediatric Cardiology. Recommendations for the practice of
fetal cardiology in Europe. Cardiol Young; 14(1): pp. 109-14.
5. Rychik J, Ayres N, Cuneo B, Gotteiner N, Hornberger L, Spevak PJ, Van Der Veld M (2004). American
Society of Echocardiography guidelines and standards for performance of the fetal echocardiogram. J Am
Soc Echocardiogr; 17(7): pp. 803-10.
6. Fetal Echocardiography Task Force; American Institute of Ultrasound in Medicine Clinical Standards
Committee; American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine
(2011). AIUM practice guideline for the performance of fetal echocardiography. J Ultrasound Med; 30(1):
pp. 127-36.
7. Carvalho JS, Moscoso G, Tekay A, Campbell S, Thilaganathan B, Shinebourne EA (2004). Clinical impact
of first and early second trimester fetal echocardiography on high-risk pregnancies. Heart; 90: pp. 921-926.
8. Small M, Copel JA (2004). Indications for fetal echocardiography. Pediatr Cardiol; 25: pp. 210-222.

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9. Fetal Working Group of AEPC (2008). Recommendations from the Association for European Paediatric
Cardiology for training in Fetal Cardiology.
https://www.aepc.org/@Bin/23122/fwg_training_guidelines_2008.pdf
10. Marginean C, Gozar L, Mărginean CO, Suciu H, Togănel R, Muntean I, Mureșan MC (2018). Prenatal
diagnosis of the fetal common arterial trunk. A case series. Med Ultrason; 1(1): pp. 100-104.
11. Mărginean C, Mărginean CO, Muntean I, Togănel R, Meliț LE, Mărginean MO, Gozar L (2016).
Ultrasonographic features of the persistence of superior left vena cava and pathological cardiac associations
in fetus. Case series. Med Ultrason; 18(2): pp. 214-7.
12. Mărginean C, Mărginean CO, Muntean I, Togănel R, Voidăzan S, Gozar L (2015). The role of ventricular
disproportion, aortic, and ductal isthmus ultrasound measurements for the diagnosis of fetal aortic
coarctation, in the third trimester of pregnancy. Med Ultrason; 17(4): pp. 475-81.

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Cystic Cerebral Lesions in Newborn Infants Diagnosable by


Ultrasound Examination

BLAGA Ligia1, OANCEA Mihaela2, VIDRA Camelia3, FUFEZAN Otilia4,


URESAN Marta3, HASMASANU Monica1, MATYAS Melinda1,
DICULESCU Doru2
1 Neonatology Department, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca (ROMANIA)
2 Obstetrics-Gynecology Department, “Iuliu Haţieganu” University of Medicine and Pharmacy, Cluj-Napoca (ROMANIA)
3 Neonatology Department, “Dominic Stanca” Obstetrics-Gynecology Clinical Hospital, Cluj-Napoca (ROMANIA)
4 Children’s Clinical Hospital, Cluj-Napoca (ROMANIA)

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

Introduction
Cerebral ultrasound is the most frequently used method for evaluating intracranial structures
of the newborn infants. The two fontanellae – anterior and posterior – and the cranial sutures
represent optimal ultrasound windows, which allow a good evaluation of median structures of
the central nervous system, cerebral hemispheres and cerebral circulation. Sonography has high
sensitivity and specificity in diagnosing major cerebral lesions, and it alows long-term follow-up,
so it became a part of the newborn care process in the NICU. Cystic cerebral lesions can be
congenital or acquired (perinatally or postnatally). They can be located in the posterior fossa,
supratentorial periventricularly or at some distance to the lateral ventricles, intra or extraaxial.

Methodology
We present ultrasound features of cystical intracerebral lesions that can be found in the
neonatal period, some of which are common, others rare. The images we present were taken at
seriate transfontanelar ultrasound exams that have been done in our service.

Results
We will analyse anatomical variants, developmental congenital cysts, cystic lesions following
perinatal hypoxia-ischemia or intracerebral haemorrhage, rare vascular lesions. We emphasize
those ultrasound features which are useful for the differential diagnosis.

Conclusions/Discussion
Although initially the images may seem non-specific, evaluating the lesion’s ultrasound
features and its location may orient the diagnosis. Ultrasonography is though limited with
regards to posterior fossa and cerebral hemisphere’s convexity examination.
Keywords: Newborn infants, Untrasound, Cerebral lesions, Cysts

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Introduction

Cerebral ultrasound is the most frequently used method for evaluating intracranial structures
of the newborn infants. It still represents an indispensable means for the routine care of all
newborn infants, but especially of severely ill and unstable preterm infants in the neonatal
intensive care units (NICUs). Knowing the ultrasound anatomy and normal developmental
features, correct use of the technology and variable frequencies transducers, multiple ultrasound
windows in the newborn (anterior and posterior fontanellae, unosiffied cranial sutures), allow for
a good evaluation of median structures of the central nervous system (CNS), cerebral
hemispheres and cerebral circulation. [1, 2] Sonography has high sensitivity and specificity in
diagnosing major cerebral lesions affecting the anatomy and structure of the cerebral
parenchyma and ventricular system, but also cerebral haemorrhages, hypoxic-ischemic lesions
and periventricular leucomalacia, or central nervous system infections. It also allows for long-
term follow-up, so it became a part of the newborn care process in the NICU. Ultrasonography is
though limited with regards to posterior fossa and cerebral hemisphere’s convexity examination;
it is unable to evaluate ischemic lesions in term newborns in the first 24 hours postnatally or
neuronal migration anomalies, so MRI is the only alternative means for the evaluation of these
pathologies. [1, 2]
Cystic cerebral lesions can be congenital or acquired (perinatally or postnatally). They can be
located in the posterior fossa, supratentorial periventricularly or at some distance to the lateral
ventricles, intra or extraaxial. Although initially the images may seem non-specific, accurate
evaluation of the lesion’s anatomical location and ultrasound features may orient the diagnosis.
Combining Doppler and B-mode examination is useful for evaluating, characterizing and
locating cystic lesions and for the differential diagnosis. [3, 4]

Methodology

The aim of this paper is to present ultrasound features of cystical intracerebral lesions that can
be found in the neonatal period, some of which are common, others rare, that have been found at
transfontanelar cerebral ultrasound. The images we present were taken at seriate transfontanelar
ultrasound exams that have been done in our service with a 7.5 MHz convex transducer, on term
or preterm infants. The first exam has been taken in the first 72 hours, then repeated as per
protocols for each type of pathology that has been found.

Results

Conatal cysts or lateral ventricle coarctation


Conatal cysts or lateral ventricle coarctation (Fig. 1a) have an incidence of 0.7%. Long time
considered as secondary to antenatal factors affecting fetal developing brain (viral infections or
chromosomal anomalies), in present they are considered anatomical variants. Ultrasound features
are thin walled cystic lesions, located in the superior lateral region of the frontal horns of lateral
ventricles, anterior to Monro’s holes. They can be single or multiple and regress in time.
Differential diagnosis includes periventricular leucomalacia or germinal matrix cysts. [3, 5, 6,
7]

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Subependimal cysts
Subependimal cysts (Fig. 1b) are tear shaped cyst of 2-11 mm diameter, located at the level of
the thalamocaudate groove or anteriorly to the caudate nucleus. They appear as a result of the
liquefaction of haemorrhages occurred in the subependimal region, their prognosis being benign.
They are more frequently found in preterm infants of 25-34 gestational weeks. Those that are
found at birth, in newborns without pathological events, are benign lesions; they can also be
secondary to hypoxic-ischemic lesions or congenital infections (CMV or rubella), but these have
a poor prognosis, being associated to neurodevelopmental delay. Subependimal cysts have also
been correlated to some metabolic diseases (Zellveger syndrome) or with cocaine use during
pregnancy. [5, 8, 9]

Arachnoidian cyst
Arachnoidian cyst (Fig. 1c, d) is a benign congenital lesion of the arachnoid membrane
containing cerebrospinal fluid (CSF); it represents 1% of all space-replacing cerebral lesions in
the newborn infant. 25% are located in the posterior fossa. These are well demarcated transonic
lesions, with thin wall, without Doppler signal, more frequently located retrocerebellar, and
sometimes can compress the cerebellum vermis. They can also be located at the level of the 4th
ventricle or cerebellopontine cistern. They are associated to Aycardi syndrome, unbalanced X9
translocation, type I glutaric aciduria, mucopolysaccharidoses, Marfan syndrome. [5, 10, 11, 12]

Fig. 1. Conatal cyst (a), subependimal cyst (b), arachnoid cyst (c, d)

Neuroglial cyst
Neuroglial cyst (Fig. 2a, b) is a benign congenital lesion derived from the embrionar elements
of the neural tube that have been sequestrated during white matter development. They represent
less than 1% of all cystic cerebral lesions. The tipical location is in the frontal lobe, within the
white matter. These are round transonic lesions, with regular borders, usually uniloculated and of
variable sizes. The differential diagnosis is mandatory with enlarged perivascular space or
infections of the CNS. [4, 5]

Galen malformation
Galen malformation (Fig. 2c, d) is a rare brain vessel abnormality, in which there is an
aneurysmal dilatation and a direct communication between the arterial and cerebral venous
system. It results from persistent shunting of primitive choroidal vessels into the median of the
prosencephalic vein of Markowsky. It appears in the 6th-11th week of gestation. It represents 1-
2% of intracranial vascular malformations and 0.5-5% of all cerebral aneurysms. It is considered
to be the most frequent arterio-venous malformation in the newborns, although its real incidence
is unknown. Echographically it is described as a cystic or tubular lesion that is located posterior
to the 3rd ventricle, on the middle line of the brain, or in the pineal gland region. Doppler
ultrasound reveals a turbulent venous and/or arterial flow. When there are thrombi at this level,

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the ultrasound image is izo or hypoechogenic. There may be associated hydrocephalus. Forms
that have congestive heart failure as onset have poor prognosis. [13, 14, 15]

Fig. 2. Neuroglial cyst (a, b); Galen malformation (c, d)

Postnatally acquired cystic lesions

Periventricular leucomalacia
Periventricular leucomalacia, also known as hypoxic-ischemic encephalopathy (HIE) of the
preterm infant, is a periventricular white matter disorder due to hypoxic-ischemic events
especially, but also to infections or vasculitis. It is found in 33% of preterm infants with
gestational age less than 33 weeks and birth weight below 1500 g. In the incipient phase, its
echographic feature is the increased periventricular echogenicity, more intense than that of the
choroid plexus, and persisting more than 7 days. In this stage, it has to be differentiated from the
echogenic periventricular halo, as normal variant, located posterosuperior to the ventricular
trigone. It also has to be differentiated from the haemorrhages located at this level. In the 2nd, 3rd
and 4th stages, there are cystic lesions of variable extent. In stages III and IV, these lesions
become confluent and extend in the occipital and frontoparietal zones, and eventually in the
depth of the white matter, forming subcortical cysts (Fig. 3). [3, 16, 17]

Fig. 3. Periventricular leucomalacia – stage II, III and IV

Multicystic encephalomalacia
Multicystic encephalomalacia (Fig. 4) reffers to areas of necrosis secondary to severe asphixia
or arterial hypotension, which evolve towards cysts. It is the result of the evolution of the HIE in
term newborns over time, being the most known cause of the cerebral palsy, with an incidence of
2-9 in 1000 live newborns. It has also been described following meningoencephalitis or twin-
twin transfusion. Seriate cerebral ultrasound show cysts of variable dimensions, with thin
avascular walls, that replace the normal cerebral parenchyma. The parenchyma is reduced to thin
septae which separate these cysts. The lesions form in 2-3 weeks after the hypoxic-ischemic
insult. In the first 7-10 days the diagnosis is made by cerebral MRI. Neurologic prognosis of
these lesions is severe, they evolve over time towards cortical atrophy. [5, 18, 19]

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Fig. 4. Multicystic encephalomalacia

Porencephalic cyst
Porencephalic cyst (Fig. 5) is a cystic lesion containing CSF, located anywhere in the cerebral
parenchyma, secondary to ischemia, haemorrhage or infection located at this level. It may
communicate with the ventricular system. The cerebral parenchyma area is replaced by CSF. In
the first stage it appears like a hyperechogenic area, which over time is centered by a
hypo/anechogenic area, and eventually becomes transonic. Calcification areas in the walls of the
lesion may appear sometimes. It is found in 2.5% of newborn infants that suffered perinatal
cerebral injuries. Differential diagnosis includes neuroglial cysts, but these do not communicate
with the ventricular system, or the arachnoidian cyst, from wich it differs by location and the
normal appearance of the cerebral parenchyma adjacent to the arachnoidian cyst. [4, 5, 20]

Fig. 5. Porencephalic cyst

Conclusions

The progress of the scanning technology, use of Doppler examination and the presence of
multiple cranial windows led to spectacular improvement of the images obtained at the cerebral
ultrasound examination, allowing for evaluation of cerebral anatomy, accurate description of
different lesions and also evaluation of cerebral circulation. Thus, lesions such as subependimal
or choroid plexus cysts, periventricular leucomalacia, multicystic encephalomalacia and
porencephalic cysts can be diagnosed and monitored by ultrasonography alone. Still, severe
lesions such as those secondary to HIE require MRI evaluation.

REFERENCES

1. Franca, K Neal Lewis, Neonatal cranial ultrasound; current perspectives. Reports in Medical Imaging,
2013:6 93-103.
2. Rumack CM, Drose JA. Neonatal and infant brain imaging. In: Rumack CM, Wilson SR, Charboneau JW,
eds. Diagnostic ultrasound. 3rd ed. St. Louis, Mo: Elsevier Mosby, 2005; pp. 1623-1701.
3. Beek, F. Groenendal, Neonatal brain ultrasound, Radiollogy Assistant, 1 apr. 2006.
4. G Osborne, M. T Preece, Intracranial Cysts: radiologic, Pathologic Correlation and Imaging Approach,
Radiology: june 2006; vol 239. No 3.

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5. M. Epelman, A. Daneman, S. Blaser, C. Ortiz-Neira, O. Konen, J Jarrin, O M Navarro, Differential


diagnosis of intracranial cystic lesions at head US; Correlation with CT and MR Imaging, RadioGraphics,
2006; vol 26, Nr.1 173-196.
6. Rosenfeld DL, Schonfeld SM, Underberg-Davis S. Coarctation of the lateral ventricles: an alternative
explanation for subependymal pseudocysts. Pediatr Radiol 1997, 27: pp. 895-897.
7. JH Lu, D Emons, S. Kowalewski, Connatal periventricular pseudocysts in the neonate, Pediatr. Rad, 1992,
22(1) pp. 55-8.
8. Larcos g, Gruenwald SM, Lui K. Neonatal subependimal cysts detected by sonography: prevalence,
sonographyc findings and clinical significance, AJRAM J Roentgenol , 1994, apr 162(4), pp. 953-6.
9. Saskia MW, Fekete, Michele Monset Couchard, ligia MSS Rugolo, Odile de Bethmann, A Jose Crocci,
Diagnosis of subependymal cysts by brain ultrasound, J Pediatr (Rio J), 2002; 76(5): pp. 373-82.
10. Hacking, F. Gaillard end all Aracnoid cysts –, Radiopaedia.
11. Nelson MD Jr, Maher K, Gilles FH. A different approach to cysts of the posterior fossa. Pediatr Radiol
2004; 34: pp. 720-732.
12. Suzuki H, Takanashi J, Sugita K, Barkovich AJ, Kohno Y. Retrocerebelar arachnoid cysts in siblings with
mental retardation and undescended testis. Brain Dev 2002; 24: pp. 310-313.
13. Jones BV, Ball WS, Tomsick TA, Millard J, Crone KR. Vein Galen aneurismal malformation: diagnosis
and treatment of 13 children with extended clinical follow-up. AJNR Am J Neuroradiol 2002;2 3: pp.
1717-1724.
14. Raj D. Sheth, Amy Nao, Ann M. Neumeyer, Vein of Galen Malformation, https//emedicine.medscape.com,
Ian.03.2018.
15. Jeremy Jones, Donna D’Souza. Vein of Galen aneurismal malformation radiology, Radiopaedia.org.
16. Blumenthal I. periventricular leucomalacia: a review. Eur J Pediatr 2004; 163: pp. 435-442.
17. LM Procopciuc, G. Caracostea, G. Zaharie, et al. Maternal/newborn VEGH-C936T interaction and its
influence on the risk, severity and prognosis of preeclampsia as well as on the maternal angiogenic profile,
Journ of Maternal-Fetal & Neonatal Medicine, nov 2014; vol27, Issue 17, pp. 1754-1760.
18. G. Frigieri, B. Guidi, S. C. Zaccarelli, C. Rossi, G. Muratori, F. Ferrrari, GB Cavazzuti. Multicystic
encephalomalacia in term infants. Child’s Nervous System, dec. 1996, Vol 12, Issue 12, pp. 759-764.
19. IL Barbosa Pereira, LA Freitas de Albuquerque, Gerival Vieira Jr, BS Costa, J Bras N, Post Infectious
Multicystic encephalomalacia Neurocirurg 2014; 25(2): pp. 144-146.
20. Moinuddin A, McKinstry RC, Martin KA, Neil JJ. Intracranial hemorrhage progressing to porencephaly as
a result of congenitally acquired cytomegalovirus infection: an illustrative report. Prenat Diagn 2003; 23:
pp. 797-800.

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Does Romanian Pregnant Teenage Girls Find First and Second


Trimester Ultrasound Exams and Follow Up Important?

VIEZUINĂ Roxana1, SOCEA Bogdan1,2, CONSTANTIN Vlad Denis1,2,


GHEORGHIU Nicolae2, CĂLIN Florin Daniel1,2, DAVIȚOIU Bogdan Andrei1,
ROȘU George-Alexandru1, AL AZAWI Alla1, GHEORGHIU Diana Claudia1
1“Sf Pantelimon” Clinical Emergency Hospital, Pantelimon Blvd, no 340-342, 021661, Bucharest (ROMANIA)
2Carol Davila University of Medicine and Pharmacy, Dionisie Lupu St, no 37, 020021, Bucharest (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

The object of our study is to show the exact importance that Romania’s pregnant adolescents
give to the rightly follow-up of their pregnancy and to obstetric ultrasound examination
performed during the follow-up visits, we have conducted a prospective observational study in
the Department of Obstetrics and Gynecology from “Saint Pantelimon” Clinical Emergency
Hospital, Bucharest (tertiary maternity center), between June 18, 2017 and July 19, 2017. We
have recorded a total of 74 teenagers who gave birth, which corresponded to a 21.02% birth rate
among adolescent girls, a percentage related to the total births number registered in this
department in that period of time. 25 of these 74 teenagers were under the age of 18, the age that
defines full age in the Romanian legislation (7,1% minor, aged between 14 and 17 years). 73.0%
of adolescents included in our study said they have had their current pregnancy followed-up and
44.6% of them had more than 6 pregnancy follow-up visits for the pregnancies that we have
studied. Only 66.2% of these adolescent girls have had obstetrical ultrasound examination
performed on them because they have been to the obstetrician during pregnancy.
Keywords: pregnancy in adolescents, obstetric ultrasound examination, pregnancy follow-up, medical education, reproductive
health, quality of life

Introduction

Modern obstetrical diagnosis [1-22] and the gynecological one [23-27], cannot be conceived
in the absence of obstetrical-gynecological ultrasound is already well-known. Also, the fact that
a good reproductive health reflects a better quality of women's lives and that these are closely
correlated with a high level of healthcare are almost axiomatic statements today [28]. The utility
of quarterly obstetric ultrasound examination is today postulated by most guides and studies on
rightly pregnancy follow-up [1-14].
In addition, it is also well-known that Romania occupies the first place in Europe and the EU
in the top of births among adolescents and minors [19].
Wanting to find out how many of these adolescents who are getting pregnant and give birth
know the real importance of proper follow-up of their pregnancy and obstetric ultrasound
examination performed on this occasion, we developed a retrospective, populational-based study

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(conducted by means of volunteering and anonymity) between June and September 2017, which
included a number of 74 pregnant teenage girls (under the age of 21) admitted for birth
assistance to the Department of Obstetrics and Gynecology from “Saint Pantelimon” Clinical
Emergency Hospital, Bucharest, in that time period.

Methods

This retrospective, populational-based study (conducted by means of volunteering and


anonymity) included 74 pregnant teenage girls (under the age of 21) (N=74) admitted for birth
assistance to the Department of Obstetrics and Gynecology from “Sf Pantelimon” Clinical
Emergency Hospital, Bucharest (tertiary maternity center – a centre of excellence, which offers
tertiary care services and has complex capabilities, handling cases from both the capital and the
rest of the country), in the period between June 19th, 2017-September 18th, 2017 (meaning a
three-calendar month period) [19].
The study involved questioning of anonymous, voluntary, unpaid (or rewarded in any way)
patients through an anonymous questionnaire that included a series of statistical questions.
The inclusion criteria did not allow discrimination of the study participants in any way
(depending on education, schooling, ethnicity, nationality, age, social origin, marital status,
economic status, religion, political beliefs, occupation, race etc.)
In order to achieve this goal, after we explained to patients, in layman's terms, what are the
objectives, usefulness and stages of the study, any patient who wanted to participate
anonymously, voluntarily and unpaid in the study was accepted after expressing her free consent
for participation. The only exclusion criterion from the study (applied immediately) was the
verbal refusal to participate. In order to be as objective as possible and for patients to participate
voluntarily (without feeling that they would be discriminated against or disadvantaged in any
way if they refuse), they were interviewed about their willingness to participate in the study and
the questionnaire was given to them for filling in on the day (calendar day) immediately
following that in which they gave birth.

Results and Discussions

This retrospective, populational-based study included 74 pregnant teenage girls admitted for
birth assistance (and which gave birth during the same hospitalization) to the Department of
Obstetrics and Gynecology from “Sf Pantelimon” Clinical Emergency Hospital, Bucharest
(tertiary maternity center), in the period between June 19th, 2017-September 18th, 2017, which
corresponded to a 21.02% birth rate among adolescents (a percentage based on a total number of
352 births recorded in our clinic during the three-month study period). 25 of these 74 teenagers
were under the age of 18, which is the age of majority in Romanian legislation (a proportion of
7.1% of minor patients aged 14-17 years old) [25].
Simultaneously with this retrospective, populational-based study carried out by us in 2017 at
the Department of Obstetrics and Gynecology from “Sf Pantelimon” Clinical Emergency
Hospital, Bucharest, we also analyzed the data provided by the department’s birth records from
2015 to 2017 and centralized in Table no. 1 data on the proportion of births recorded among
teenage and minor girls in that time period.

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Table 1. Births recorded among teenage and minor girls between 2015 and 2017
(in Department of Obstetrics and Gynecology from “Saint Pantelimon” Clinical Emergency Hospital, Bucharest)
2015 2016 2017 Total
Total number of births 1374 1474 1302 4150
Pregnant teenage girls that gave birth (under the age of 21) 222 240 285 747
Percentage of teenage girls that gave birth from total number of
16.15% 16.28% 21.88% 18.00%
births
Pregnant minor girls that gave birth (under the age of 18) 90 93 112 295
Percentage of minor girls that gave birth from total number of 6.55% 6.30% 8.60% 7.10%
births (% from the total number of teenage girls) (40.54%) (38.75%) (39.29%) (39.49%)

Returning to the anonymous, interview-based study we conducted in 2017, we found that


51.4% of the adolescents come from urban areas and 79.5% of their families are not what we
usually call disorganized families (parents are not divorced or separated, nor have they gone
abroad “to work” and the family is living together with the adolescent girl interviewed) [19].
23.0% of the teenage girls we studied have had at least an other pregnancy before the
pregnancy we analyzed. In order to fill in the image these teenage girls have about their
pregnancy and the way a pregnant woman should behave, we asked additional questions in our
questionnaire. So, we found that: 17.6% of adolescents interviewed by us consumed alcohol even
though they knew they were pregnant and 45.9% of them smoked during the pregnancy we
studied. In the study group, there were even teenagers who claimed to have taken drugs during
pregnancy (5.4%). 97.3% of adolescents included in our study believe that they have the support
of their family to carry out the pregancy that we studied until birth [19].
The cesarean delivery rate in the teenage girls group was 71.6% (comparable to that of the
control batch, which was 71.3%), the mean gestational age at which adolescents from the study
group gave birth was 37.79 weeks, the average weight of their newborns at birth was 2989.19
grams and the average APGAR score was 8.8. The average gravidity in the teenage girls group
we studied was 1.67 (gravidity between 1 and 7) and the average parity was 1.25 (parity between
1 and 3). 97.3% of newborns studied were alive and 58.1% of the teenage girls’s newborns were
boys. Two of the 74 births resulted in twins. 73.0% of the adolescent girls included in the study
said that they have had their current pregnancy followed-up by a physician and 44.6% of them
had more than 6 follow-up visits during the pregnancy we studied (reasonable pregnancy follow-
up). 35.1% of the teenage girls included in the study have had their pregnancy followed-up only
by the obstetrician, 1.4% of the pregnancies were followed-up only by a general practitioner and
31.1% of adolescents have had their pregnancy followed-up by both the obstetrician and the
family physician. 23.0% of the patients we interviewed said they have had 10 or more pregnancy
follow-up visits during the pregnancy that we studied.
Only 66.2% of these adolescents have had one or more obstetric ultrasound examination
performed during their current pregnancy, because they addressed the obstetrician for pregnancy
follow-up [19].

Conclusions

20 out of 74 (27%) teenage patients interviewed anonymously by us have never been to a


doctor during the pregnancy we studied (they did not make any medical follow-up visit during
current pregnancy), that is, an almost double proportion of this inadequate behavior to its own
pregnancy compared to that of the control batch (14.7% of the control group patients).

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33 out of 74 (44.6%) of those adolescent patients interviewed anonymously by us have


received a reasonable number of medical visits for following-up their pregnancy (6 or more
follow-up visits) versus a proportion of 64.7% of the phenomenon in the control group.
The obstetrician and obstetrical ultrasound examination were involved in the follow-up of
66.2% of these analyzed pregnancies, compared to a proportion of 82.3% of the phenomenon in
the control batch.
These figures clearly demonstrate an extremely precarious medical education and scanty
medical care during pregnacy and must motivate medical staff of any level and institutions that
have jurisdiction in the field to promote as much as possible and intensively health education
among children and adolescents. All the more so when these tennagers become pregnant.

REFERENCES

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2015; 9(1): pp. 80-90.
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659-668
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consecutive autosomal trisomic pregnancies in a couple without offspring – Clinical and Experimental
Obstetrics & Gynecology; 2016; IF 0.52, 43(2):287-90.
9. Liana Pleș, Romina-Marina Sima, Cristina Moisei, Marius Moga, Laura Dracea – Abnormal ultrasound
appearance of the amniotic membranes – diagnostic and significance: a pictorial essay – Med Ultrason
2017:0, 1-5 ISSN 2066-864.
10. L. Pleș, V. Beliș, A. Rîcu, R. M. Sima – Medico-legal issues of the nuchal cord at birth – Journal of
Romanian Legal Medecine 24(4)289-293(2016).
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Maternal Blood – Maedica – A Journal of Clinical Medicine 2015; 10(4): pp. 382-385.

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12. Herghelegiu, D, Ionescu, CA, Pacu, I, Bohiltea, R, Herghelegiu, C, Vladareanu, S – Antenatal diagnosis
and prognostic factors of aneurysmal malformation of the vein of Galen A case report and literature
review. MEDICINE Volume: 95 Issue: 30, 2017.
13. Crîngu Antoniu Ionescu, Dan Navolan, Alina Călin, Alexandra Matei, Roxana Bohîlțea, Mihai Dimitriu,
Corina Ilinca, Liana Pleș – Hormonal contraception in postpartum patients with gestational diabetes
mellitus – Revista de Chimie, www.revistadechimie.ro, REV.CHIM. (Bucharest), 69, No. 2, 2018, Vol. 69,
No. 2, February, 2018, pag. 478-483, ISSN 0034-7752, ISSN-L 1582-9049, ISSN CD-ROM 2537-5733,
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Maria Vlădăreanu, Irina Voican, Mihai Dimitriu, Natalia Turcan – Primary myelofibrosis and pregnancy
outcomes after low molecular-weight heparin administration – a case report and literature review –
MEDICINE, Vol. 96, Issue 46, Article number e8735, DOI: 10.1097/MD.0000000000008735, Published:
NOV 2017, Accession Number: WOS:000417630400083, PubMed ID:29145319, ISSN:0025-7974,
eISSN:1536-5964.
15. Crîngu Antoniu Ionescu, Liana Pleș, Mihail Bănacu, Elena Poenaru, Eugenia Panaitescu, Mihai Cornel
Traian Dimitriu – Present tendincies of elective caesaerean delivery in Romania: Geographic, social and
economic factors – Journal of Pakistan Medical Association (J Pak Med Assoc), Vol. 67, No. 8, Aug 2017,
pag. 1248-1253, ISSN:0030-9982, Accession Number: WOS:000405943300020, PubMed ID:28839313.
16. Crîngu Ionescu, Mihai Dimitriu, Elena Poenaru, Roxana Viezuină, Cristian George Furău – Fetal-maternal
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Medicine – Rom J Leg Med [25] 82-88 [2017], Volumul 25, Nr. 1(Martie)/2017, pag 82-88, Romanian
Society of Legal Medicine – DOI:10.4323/rjlm.2017.82 – ISSN (print): 1221-8618, ISSN (on-line): 1844-
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Mehedintu, C; Vladareanu, S; Ciohat, I; Craciunescu, M; Nemescu, D – The Effect of Chemical
Compounds from Cigarettes Smoke on First Trimester Biochemical Markers – REVISTA DE CHIMIE
Volume: 68 Issue: 9 Pages: 2122-2124, SEP 2017.
18. Navolan, D; Birsasteanu, F; Carabineanu, A; Cretu, O; Badiu, DL; Ionescu, CA; Mehedintu, C;
Vladareanu, S; Craina, M; Boia, M; Ciohat, I; Craciunescu, M; Simu, S; Nemescu, D – Does Active
Smoking Influence the Second Trimester Biochemical Markers Concentrations? – REVISTA DE CHIMIE
Volume: 68 Issue: 10 Pages: 2234-2236.
19. Mihai Dimitriu, Mihail Bănacu, Ina Popescu, Roxana Viezuină, Alexandra Matei, Crîngu Ionescu –
Nașterea la adolescente – o problemă de sănătate publică în România – Forum Ginecologia.ro 2018, Ediția
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Ultrasound Obstetr & Gynecol 5TH ROMANIAN CONGRESS OF THE ROMANIAN SOCIETY OF
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Filodiritto International Proceedings, First Edition June 2017, ISBN 978-88-95922-88-1, pag. 199-202,
Accession Number: WOS: 000406419700034 – © Copyright 2017 Filodiritto Publisher
filodirittoeditore.com, inFOROmatica srl, Via Castiglione, 81, 40124 Bologna.
25. Bogdan Socea, Laura Ileana Socea, Ovidiu Gabriel Bratu, Bogdan Mastalier, Mihai Dimitriu, Alexandru
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Are There Cesarean Section Indications Without Ultrasound Exam


Nowadays?

VIEZUINĂ Roxana1, SOCEA Bogdan1,2, CONSTANTIN Vlad-Denis1,2,


GHEORGHIU Nicolae2, CĂLIN Florin Daniel1,2, DAVITOIU Bogdan Andrei1,
ROȘU George1, MATEI Alexandra1, GHEORGHIU Diana Claudia1
1“Sf Pantelimon” Clinical Emergency Hospital, Pantelimon Blvd, no 340-342, 021661, Bucharest (ROMANIA)
2Carol Davila University of Medicine and Pharmacy, Dionisie Lupu St, no 37, 020021, Bucharest (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected], [email protected],
[email protected]

Abstract

Nowadays obstetrics is changing every day and obstetricians must adapt. C-section rates have
gone through the roof in some countries around the globe and we are wondering if natural birth
will be soon obsolete. Romania finds itself in the second place in Europe after Italy with a rate of
C-sections over 35% and in Bucharest 75% of all births are through C-sections making the
capital not only one of the leaders in total C-sections, but also a trend setter for obstetricians
around the country.
The normal question that arises from this transformation of birth into a surgical act is: How
many of the C-section indications are absolute ones and how can ultrasound exam be helpful in
indicating C-section? Can we put a C-section indication without using ultrasound exam
nowadays? This is in fact the question we intend to answer, analyzing not only the modern
spectrum of c-section indications but also the absolute ones that we like to call “the classic
indications”.
Keywords: cesarean indications, ultrasound exam, pregnancy, absolute, relative, surgical birth

Introduction

Nowadays obstetrics is changing every day and obstetricians must adapt. C-section rates have
gone through the roof in some countries around the globe and we are wondering if natural birth
will be soon obsolete. Romania is found in the second place in Europe after Italy with a rate of
C-sections over 35% and in Bucharest 75% of all births are through C-sections making the
capital not only one of the leaders in total C-sections, but also a trend setter for obstetricians
around the country [1-2].
Scientific and social progress, different cultural and ethnic aspects, but also many legal
implications have led to a radical change in the attitude and indications, choosing the right
moment and technique of the cesarean surgery [1-2].
The normal question that arises from this transformation of birth into a surgical act is: How
many of the C-section indications are absolute ones and how can ultrasound exam be helpful in
indicating C-section? Can we put a C-section indication without using ultrasound exam, today?

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This is in fact the question we intend to answer, analyzing not only the modern spectrum of c-
section indications but also the absolute ones that we like to call “the classic indications”.
The general agreement involving cesarean indications has taken a rather quick shift in the last
decades in many countries, including psychosocial factors like anxiety towards the moment of
birth and the actual delivery, or even the mother’s wish to give birth through cesarean without
having a medical indication [1-2]. The reasons that led to this liberal attitude towards cesarean
section are diverse, making this a hard problem to quantify and also making the
medical/obstetrical indications of cesarean section very difficult to gauge [1-2].
The modern obstetrical diagnosis [1-26] and the gynecological one [27-31] cannot be
conceived today in the absence of ultrasound examination is already very well-known. Another
known fact is that a good reproductive health reflects a good quality of a women’s life and that
this is strong related to a high level of medical assistance [26]. The utility of obstetrical
ultrasound in pregnancy follow-up and choosing the way of birth are today stated in most
guidelines [1-2].

Method and material

Nowadays there is no international classification system for cesarean operation that can give
us the possibility of collecting and analyzing real data and to compare the indications and
incidence of cesarean indications in different countries, cities and regions [1-2]. That is why
WHO (OMS) recommends the use of Robson classification as being a global standard
(classification used in most evolved countries in the last years).
Therefore Robson defines these ten categories based on five obstetrical characteristics that are
usually identified in all maternities worldwide, and have the advantage of being simple,
clinically relevant and extremely valuable at a prospective level [2]: 1. Parity (no matter how
many cesarean sections the patient has in her history); 2. Gestational age (premature, term,
postmature); 3. Form of labor (spontaneous, induced, cesarean section before labor); 4. Fetal
presentation; 5. Number of fetuses ( singleton or multiple).
Using this five extremely simple criteria, we can define the ten Robson categories [2]: 1.
Primipara with singleton cephalic, more than 37 weeks of amenorrhea in spontaneous labor; 2.
Primipara with singleton cephalic, more than 37 weeks of amenorrhea with induced labor or
cesarean section before labor; 3. Multiparous without uterine scar in their medical history,
singleton cephalic over 37 weeks of amenorrhea and spontaneous labor; 4. Multiparous without
uterine scar in their medical history, singleton cephalic over 37 weeks of amenorrhea with
induced labor or cesarean section before labor; 5. Multiparous with uterine scar in their medical
history, singleton cephalic presentation, over 37 weeks; 6. All nulliparous breech; 7. Multiparous
breech with uterine scar; 8. All multiple pregnancies with uterine scar in their medical history; 9.
All pregnancies with singleton transverse or oblique with uterine scar in their medical history;
10. All singleton cephalic under 37 weeks with uterine scar.
Before any database is formed, most obstetrical gynecology societies divide medical
indications of cesarean surgery in absolute and relative indications [2]. Elective cesarean sections
(patient requested without medical indication) are considered for now a separate entity which
should be discussed within legal grounds.
Until these goals are fulfilled, absolute indications for cesarean section are [2]:
• Chephalopelvic disproportion;
• Maternal pelvic abnormalities;

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• Failure of induced labor;


• Chorioamnionitis;
• HELP syndrome and eclampsia;
• Umbilical cord prolapse;
• Praevia placenta;
• Abnormal placentation;
• Premature abruption of normal insered placenta;
• Fetal presentation incompatible with spontaneous labor (transverse and frontal);
• Uterine rupture;
• Curable fetal abnormalities ( hydrocephaly and myelomeningocele);
• Benign or malignant obstructive tumors located at the birth canal, urogenital maternal
malformation;
• Active genital herpes infection;
• Abdominal cerclage.

The relative indications are the following [2]:


Breech; Multiple pregnancy; Pathological aspects of cardiotocographic tracing; Abnormal
labor progression; Preexistent uterine scar; Colporrhaphy; Maternal infection (HCV, HBV, HIV)
[2]. To find out the essential role of ultrasound exam in cesarean section indications we have
taken every absolute and relative indication and assigned it a role: absolute, relative or absent.

Results and discussions

We have made the following correlations between the obstetrical ultrasound examination (and
its role) and the type of cesarean indication:
• Chephalopelvic disproportion, maternal pelvic abnormalities – absolute role in evaluating
fetal measurements;
• Failure of induced labor – relative role in evaluation of the fetus;
• Chorioamnionitis – absolute role in fetal evaluation;
• HELP syndrome and eclampsia - absolute role in fetal evaluation;
• Umbilical cord prolapse – relative role in fetus evaluation (usually there is no time for
evaluation);
• Praevia placenta, abnormal placentation – absolute role;
• Premature abruption of normal inserted placenta – absolute role;
• Fetal presentation incompatible with spontaneous labor (transverse and frontal) – relative
role in evaluating the fetus, the presentations and the associated factors of presentation
dystocia;
• Uterine rupture – relative role in evaluating the fetus and the uterus (usually there is no
time for the evaluation);
• Curable fetal abnormalities ( hydrocephaly and myelomeningocele) – absolute role;
• Benign or malignant obstructive tumors located at the birth canal, urogenital maternal
malformation – relative role in evaluating the fetus and the birth canal;
• Active genital herpes infection – relative role in evaluating the fetus;
• Abdominal cerclage – relative role in evaluating the fetus;

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• Breech – relative role in evaluating the fetus and the factors that led to the breech
presentation;
• Multiple pregnancy – absolute role;
• Pathological aspects of cardiotocographic tracing – absolute role in evaluating the fetus
and the causes of dystocia;
• Abnormal labor progression – relative role in evaluating the fetus and the causes of
dystocia;
• Preexistent uterine scar – absolute role in evaluating the role and the uterine scar;
• Colporrhaphy – relative role in evaluating the fetus;
• Maternal infection (HCV, HBV, HIV) – absolute role in evaluating the fetus;

Conclusions

Practically we have not found any guideline of cesarean indication (relative or absolute) that
eludes unequivocally the ultrasound examination before formulating the cesarean indication. We
have found two absolute cesarean indications that need immediate OR management in which
ultrasound examination can be time wasting (umbilical cord prolapse and uterine rupture). Half
of the cesarean indications analyzed by us involve compulsory ultrasound examination before
cesarean section is completed and in the other half ultrasound has a relative role, for tactical
update.

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andevidence/databases/european-health-for-all-database-hfa-db.
22. World Health Organisation: WHO Statement on caesarean section rates. Human Reproductive Programe -
www.who.int/reproductivehealth.
23. Novac, Liliana; Tudorache, Stefania; Manolea, Magda; et al. Edited by: Vladareanu, S; Marginean, C;
Vladareanu, R – The Use of Doppler Ultrasound as Early Parameter for Detection of Fetal Compromise in
Restricted Fetuses – 5th Romanian Congress of the Romanian Society of Ultrasound in Obstetrics and
Gynecology Location: Targu Mures, APR 20-22, 2017, Pag: 445-449.
24. Novac, Liliana; Niculescu, Mihaela; Manolea, Maria Magdalena et al. – The vasculogenesis – a possible
histological identification criterion for the molar pregnancy; ROMANIAN JOURNAL OF
MORPHOLOGY AND EMBRYOLOGY 2011, Volume: 52 Issue: 1, Pages: 61-67.

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25. Olaru Gabriel Octavian, Cringu Ionescu, Anca Lesnic, George Alexandru Filipescu, Liana Ples – Ethical
and medicolegal aspects of the therapeutic abortion – our experience, Rom Journal Leg Med 2018, (26)
82-85.
26. Mocuță Dorina, Popvici Laura Roxana, Dumitriu Anca Silvia, Burlibașa Liliana, Ionescu Crîngu Antoniu,
Sfeatcu Ruxandra – Life quality – condition of social welfare – Metalurgia International, Volume: 14,
Pages: 62-64, 2009, Accession Number: WOS:000272155900013ISSN: 1582-2214.
27. Crîngu Antoniu Ionescu, Ina Popescu, Mihail Bănacu, Mihai Dimitriu – Lifestyle Changes and Weight
Loss: Effects in PCOS (Cap. 4) in “Debatable Topics in PCOS Patients” – Edited by Neeraj Kumar
Agrawal and Kiran Singh, InTech, ISBN 978-953-51-3812-9, Print ISBN 978-953-51-3811-2, publicated in
February 14, 2018 under CC BY 3.0 license – DOI: 10.5772/intechopen.68300;
http://dx.doi.org/10.5772/intechopen.73298.
28. Ionescu Crîngu, Bănacu Mihail, Popescu Ina, Ionescu Andra, Vlădăreanu Simona, Dimitriu Mihai –
Ultrasound diagnosis of endometrial cancer in asymptomatic menopausal women – 5th Congress of the
Romanian Society of Ultrasound in Obstetrics and Gynecology, Târgu Mureș, 20-22 april 2017, Filodiritto
International Proceedings, ISBN 978-88-95922-88-1, pag. 199-202, Accession Number: WOS:
000406419700034.
29. Bogdan Socea, Laura Ileana Socea, Ovidiu Gabriel Bratu, Bogdan Mastalier, Mihai Dimitriu, Alexandru
Carap, Vlad Denis Constantin – Recurrence Rates and Mesh Shrinkage After Polypropylene vs. Polyester
Mesh Hernia Repair in Complicated Hernias – Materiale Plastice (Bucharest),
http://www.revmaterialeplastice.ro, Chem. Abs.:MPLAAM 55 (1) (1-136), ISSN 0025-5289, Vol. 55, no. 1
March, 2018, pag. 79-81.
30. Crîngu Antoniu Ionescu, Simona Vlădăreanu, Liana Pleș, Mihai Cornel Traian Dimitriu, Gheorghe Oto
Furău, Teodora Camelia Vlădescu, Alina Mihaela Călin, Nuți Daniela Oprescu – Synchronus bilateral
primary ovarian carcinoma – case presentation – Romanian Journal of Morphology and Embryology –
Rom J Morphol Embryol 2017, 58(1):219-223, Volume 58 Number 1, 2017 (New series), pag. 219-223,
ISSN (print): 1220-0522, ISSN (online): 2066-8279, Accession Number: WOS: 000402584100032,
PubMed ID: 28523322.
31. Socea Bogdan, Alexandru Carâp, Smaranda Alexandru, Moculescu Cezar, Bobic Simona, Dimitriu Mihai,
Socea Laura, Vlad Denis Constantin- Delayed Recognition of a Sigmoid Colon Iatrogenic Lesion
Following Total Abdominal Hysterectomy in a Patient with a Previous Episode of Acute Diverticulitis –
13th National Congress of Urogynecology UROGYN 2016, România – Urogyn 2016 – Filodiritto
International Proceedings, First Edition, November 2016, ISBN 978-88-95922-78-2, Accession Number:
WOS: 000389054300009.

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Specific Long-Term Complications After a C-Section

VINTEA Alexandra1,2, DRAGOMIR Ramona2, DRAGAN Ioana2,


DRAGODAN Anda Viviana2, BĂNCEANU Gabriel1
1“Carol Davila” University of Medicine and Pharmacy, Bucharest (ROMANIA)
2“Alessandrescu-Rusescu” National Institute for Mother and Child Health, Polizu Department, Bucharest (ROMANIA)
Email: [email protected]

Abstract

The incidence of caesarean section has increased during the last decades both in developed
and developing countries. Multiples studies showed both the benefits and the risks associated
with the procedure. Some authors consider this type surgery as one with significant and
sometimes permanent complications, especially in services where there is a lack of the facilities
or capacity to properly manage the procedure. The complications that can appear after a C-
section can be categorised between intraoperative, short or long-term ones. Many authors proved
and explained the different mechanisms that are responsible for their occurrence and described
the different approaches to minimise the risk of adverse effects. But there are some
complications, such as scar ectopic pregnancy or abnormal adherent placenta that, despite the
correct management and follow up of a C-section, their incidence is mainly related to a scarred
uterus.
Keywords: C-section, complications, scar pregnancy, abnormal adherent placenta

Introduction

The incidence of caesarean section (C-section) has increased during the last decades and the
reasons for this are not clearly understood. According to World Health Organisation (WHO), the
international consensus regarding the ideal rate for a C-section in 1985 was between 10-15% (1).
Nowadays, there are countries where the caesarean rate is about 60-80%. A C-section has
multiple benefits both for mother and foetus and sometimes it can also be lifesaving. But a lot of
studies proved no evidence of advantages of caesarean delivery for women who require the
procedure. As with any surgery, this operation is associated with both short and long-term
complications that can influence the prognosis of future pregnancies. This paper will analyse
some specific complication that may appear after a C-section, as their incidence has become
more and more frequent along with the increasing rate of this type of surgery.

Vaginal birth after C-section

One complication that occur after the C-section is the need for another surgery in the
subsequent pregnancy. From the beginning of the century, Edwin Cragin described in his paper
that the next mode of delivery for future pregnancy in case of C-section, will also be a C-section:
“once a Caesarean, always a Caesarean” (2). Of course, the indications for surgery in that period
was to save the mother, fetal compromise not even being taken into consideration and surgery

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was considered crude and dangerous (3). Cragin stated that the women who were candidates for
surgery in first pregnancy, would also deliver via C-section in the future pregnancy.
Nowadays, with the availability of modern antepartum and intrapartum tests and the presence
of different drugs to interact with the course of labour, things have changed. There are a lot
specialised centres where women can deliver vaginally after a C-section (4). In well developed
countries, the national and international societies tried to set different algorithms for identifying
the candidates for vaginal birth after C-section (VABC). Of course, the indication must be very
well analysed, and a multidisciplinary team should be available in case of complications. The
first indication for surgery must be taken into consideration and if it is not recurrent, like
malpresentations, pre-eclampsia, premature rupture of membranes, the chances of success are
very high (3). Every women should be offered labour analgesia, as there are different types to
achieve it (5, 6). The selection of patients for VABC should be vigorously evaluated and the
decision for a mode of delivery (caesarean vs vaginal delivery) should be made by the patient in
consultation with the obstetrician (5).

Adherent placenta

Another long-term complication that can appear after a C-section is the placental pathology in
subsequent pregnancies. The various degrees of adherent placenta (accreta, increta, percreta)
have increased during the last decades and it strongly corelates with the rising rate of C-sections
(7).
There are a lot of studies that analysed the risk of peripartum hysterectomy because of
placental pathology and the previous uterine surgeries (C-section, myomectomies, curettage,
hysteroscopies) for different pathologies. Most of them identified the C-section as the main risk
factor for adherent placenta and abnormal localisation (8). There are many cases when abnormal
adherent placenta occurred in unscarred uterus, but it is important to mention that these patients
had a history of surgical termination of pregnancy. It is important to note the subsequent risk of
placental pathology in cases of intrauterine procedures, without caesarean section (8). The
maternal morbidity in these cases is significantly high because of the increased risk of
postpartum haemorrhage after forced removal of the placenta. With massive bleeding being the
major complication, it is necessary an antenatal investigation of the placenta. The ultrasound
evaluation based on typical characteristics (loss of the clear retroplacental space, placental gaps,
bladder wall interruption) can rise the suspicion of an abnormal adherent placenta (9, 10). In
cases of high suspicion of placental invasiveness, MRI or cystoscopy should be offered for
additional screening (11-14). The multidisciplinary approach is important, the reduction in
maternal morbidity and mortality being the standard of care. The implementation of a national
imagistic protocol for evaluation of the placenta, ultrasound being the method of first choice,
would significantly reduce the complications of undiagnosed placental pathology. Based on the
data that certify the substantial increase of the C-section rate, the necessity of this kind of
practice, beside of a national registry of congenital anomalies (including the placental anomalies)
is not only an option, but a necessity (15).

Caesarean scar pregnancy

Caesarean scar pregnancy (CSP) is another long-term complication that can influence the
outcome of future pregnancies. CSP is one of the rarest form of ectopic pregnancy and its

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incidence has increased due to the rise in C-section rate. If left untreated, it is a serious life
threating condition which can lead to massive haemorrhage and uterine rupture, with increased
risk of maternal death. Some studies analysed the possible pathophysiology mechanism in CSP
appearance but the some of them are not clearly understood. It is suggested that the trophoblast
cells abnormally penetrate the uterine myometrium through the fibrous scar via a microscopic
dehiscence (16). The defect may appear after uterine surgery, C-section being the most frequent.
Some studies tried to analyse the relationship between different techniques in closing of the
uterine wall and the pathophysiology of the CSP, but the lack of data in the literature cannot
prove benefits of any of them (17). The importance of the CSP rise form the difficulties in
diagnosis in an unexperienced obstetrician and the life threating complications that can arise if
left untreated. The management is challenging because there is no international consensus
regarding the treatment and it depends on the gestational age and the symptoms and it can be
both medical and surgical. The suspicion index must be very in high in case of an empty uterine
cavity and a gestational sac between the bladder and the anterior isthmic wall (16-18).
Ultrasound remains an important tool in CSP diagnosis and evaluation of uterine scar after a
C-section has drawn attention to different practitioners who observed a wall defect at the level
uterine isthmus in some patients with history of uterine surgery (19). The definition of uterine
niche or isthmocele is being more and more accepted and it became widely analysed.

Abdominal wall endometriosis

Another complication that it is not so generally accepted is the abdominal wall endometriosis
that can arise after a C-section. The etiology of these foci is thought to be iatrogenic secondary to
the transfer and implantation of the endometrial cell into the soft tissue during open uterine
surgeries like C-sections (20, 21). The incidence varies from 0,3% to 3,5% (22) and the
diagnosis is usually made after surgical excision and histological examination of the
endometriomas. The main symptom is chronic pelvic pain which can be harmful enough to cause
functional incapacity. The etiology of the chronic pain is often difficult to assess (23). The cyclic
appearance of the pain and the increase in intensity during menstruation can suggest
endometriosis, but this characteristic of the pain is not always present. The abdominal wall
endometriosis can occur years after a C-section and sonographic findings are not
pathognomonic. The location of the pelvic mass close to the caesarean section scar should be of
prime consideration in the differential diagnosis (21).

Conclusions

Of course, these are other complications with increased incidence after a C-section. The aim
of this paper was to highlight some of the complications that, in general, are secondary to this
surgery. The relation between the scarred uterus and their appearance is becoming more and
more evident, so that their specificity cannot be ignored.

REFERENCES

1. WHO Statement on Caesarean Section Rates Caesarean section rates at the hospital level and the need for a
universal classification system.
2. EB C. Conservatism in Obstetrics. N Y Med J. 1916; 104: pp. 1-3.

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3. Bangal VB, Giri PA, Shinde KK, Gavhane SP. Vaginal birth after cesarean section. N Am J Med Sci. 2013
Feb; 5(2): pp. 1404.
4. Martel M-J, MacKinnon CJ. No. 155-Guidelines for Vaginal Birth After Previous Caesarean Birth. J Obstet
Gynaecol Canada. 2018 Mar; 40(3): pp. e195-207.
5. Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 184. Obstet Gynecol. 2017 Nov; 130(5):
pp. e217-33.
6. Toader Oana, Vintea Alexandra, Suciu Nicolae VA. Techniques of analgesia during labour. In: Proceedings
of the National Conference of the Romanian Association for the Study of Pain. Filodiritto Editore-
Proceedings; 2017. pp. 629-32.
7. Belfort MA, Shamshirsaz AA, Fox KA. The diagnosis and management of morbidly adherent placenta.
Semin Perinatol. 2018 Feb; 42(1): pp. 49-58.
8. Cheng KK, Lee MM. Rising incidence of morbidly adherent placenta and its association with previous
caesarean section: a 15-year analysis in a tertiary hospital in Hong Kong. Hong Kong Med J. 2015 Nov 6;
21(6): pp. 511-7.
9. Collins SL, Ashcroft A, Braun T, Calda P, Langhoff-Roos J, Morel O, et al., Proposal for standardized
ultrasound descriptors of abnormally invasive placenta (AIP). Ultrasound Obstet Gynecol. 2016 Mar;
47(3): pp. 271-5.
10. Bohâlțea Roxana Elena, Turcan Natalia, Ionescu Crîngu Antoniu, Mehedințu Claudia, Nastasia Serban,
Toader Oana, Munteanu Octavian CMM. Ultrasound Diagnosis of Abnormal Adherent Placenta-Literature
Review. In: Proceedings of 5th Congress Of The Romanian Society Of Ultrasound In Obstetrics And
Gynecology. Filodiritto Editore-Proceedings; pp. 113-9.
11. Tanimura K, Yamasaki Y, Ebina Y, Deguchi M, Ueno Y, Kitajima K, et al., Prediction of adherent
placenta in pregnancy with placenta previa using ultrasonography and magnetic resonance imaging. Eur J
Obstet Gynecol Reprod Biol. 2015 Apr; 187: pp. 41-4.
12. Shetty MK, Dryden DK. Morbidly Adherent Placenta: Ultrasound Assessment and Supplemental Role of
Magnetic Resonance Imaging. Semin Ultrasound, CT MRI. 2015 Aug; 36(4): pp. 324-31.
13. Liu Y, Fan D, Fu Y, Wu S, Wang W, Ye S, et al., Diagnostic accuracy of cystoscopy and ultrasonography
in the prenatal diagnosis of abnormally invasive placenta. Medicine (Baltimore). 2018 Apr; 97(15):e0438.
14. Norris BL, Everaerts W, Posma E, Murphy DG, Umstad MP, Costello AJ, et al., The urologist’s role in
multidisciplinary management of placenta percreta. BJU Int. 2016 Jun; 117(6): pp. 961-5.
15. Ples, Liana; Sima, Romina Marina; Stanescu ADOO-G. The Importance of a National Congenital
Anomalies Registry – the Role of the Prenatal Diagnosis. In: Proceeding paper for the 5 TH ROMANIAN
CONGRESS OF THE ROMANIAN SOCIETY OF ULTRASOUND IN OBSTETRICS AND
GYNECOLOGY. Filodiritto Editore-Proceedings; 2017. pp. 505-10.
16. Toader O, Vintea A, Voichitoiu A, Suciu N, Cirstoiu M, Esanu S, et al. Caesarian scar ectopic pregnancy.
A case report. 2017; 13(471).
17. Ash A, Smith A, Maxwell D. Caesarean scar pregnancy. BJOG An Int J Obstet Gynaecol. 2007 Feb 13;
114(3): pp. 253-63.
18. Patel MA. Scar Ectopic Pregnancy. J Obstet Gynaecol India. 2015 Dec;65(6): pp. 372-5.
19. Toader Oana, Fetecau Andreea-Catalina, Suciu Nicolae, Voichițoiu Andrei, Cîrstoiu Monica, Bohîlțea
Roxana FA-R. Cesarean Scar Defects – An Underdiagnosed Cause for Abnormal Uterine Bleeding and
Other Gynecologic Complications. In: Proceedings of 5th Congress Of The Romanian Society Of
Ultrasound In Obstetrics And Gynecology. Filodiritto Editore-Proceedings; pp. 660-3.
20. Bozkurt M, Çil AS, Bozkurt DK. Intramuscular abdominal wall endometriosis treated by ultrasound-guided
ethanol injection. Clin Med Res. 2014 Dec; 12(3-4): pp. 160-5.
21. Hensen J-HJ, Van Breda Vriesman AC, Puylaert JBCM. Abdominal Wall Endometriosis: Clinical
Presentation and Imaging Features with Emphasis on Sonography. Am J Roentgenol. 2006 Mar 23; 186(3):
pp. 616-20.
22. Leite GKC, Carvalho LFP de, Korkes H, Guazzelli TF, Kenj G, Viana A de T. Scar endometrioma
following obstetric surgical incisions: retrospective study on 33 cases and review of the literature. Sao
Paulo Med J. 2009 Sep; 127(5): pp. 270-7.
23. Toader Oana, Vintea Alexandra, Suciu Nicolae VA. Mapping of the chronic pelvic pain in women and
therapeutic approach. In: Proceedings of the National Conference of the Romanian Association for the
Study of Pain. Filodiritto Editore-Proceedings; pp. 624-8.

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Ultrasound Endometrial Changes in Perimenopause and


Menopausal Transition

VOINEA Bogdan1, VELEA Rodica1, LUNGULESCU C1


1University of Medicine and Farmacy Craiova (ROMANIA)
Email: [email protected]

Introduction

Menopausal transition relates to the period in the later reproductive years,begins with
irregular menstrual cycles and stretches one year after the permanent termination of menstrual
periods.
In the period of early menopausal transition,the menstrual cycles are regulated,but the interval
between cycles can be modified with over 7 days,the duration of menstrual cycles also shortens,
the ovarian inhibin secretion lowers,the level of FSH is high and the level of estrogens can
increase in folicular early phase,the normal ovulatory cycles can be intercalated by anovulatory
cycles.Although the menstrual cycles are regulate,the level of progesterone is lower than women
on reproductive age [1].
Late menopausal transition is characterised by two or more absent menses and at least one
intermenstrual interval at least 60 days due to longer anovulation duration [2]. foliculogenesis
disorders and increased incidence of anovulation; the follicle reserve depletes, rises the level of
FSH and declines the capacity of older follicles to secrete inhibin [3, 4]. The antimullerian
hormone correlate with the number of early antral follicle and can be used as marker for ovarian
reserve [5, 6, 7].The level of AMH decline marked and progressive during the menopausal
transition [8].
Abnormal uterine bleeding affects up to 50-70% among women on perimenopause.
In premenopause,anovulation and changes who take place at the level of the hypothalamo-
hypophysis-ovarian axis are responsable of methroragy and menomethroragy [9].
The incidence of leiomyoms and endometrial polyps rise with age and can determine bleeding
like menorhagia,metrorhagia and menometrorhagia [10].
Every bleeding wich appears on menopause indicate a possible neoplasm, especially
endometrial carcinom [11]. Estrogen-secretory ovarian carcinom can determine endometrial
hyperplasia with uterine bleeding.
The objective of the study is to early tracking and monitoring the endometrial changes
through transvaginal ultrasound as non invasive method.
keywords: endovaginal ultrasound,endometrium,perimenopause

Material and method

The study was made on a lot of 36 patients with ages between 40 and 50 years.The patients
presented for complaints like menorhagy, methroragy, menomethroragy, dysmenorhea,
dispareunia, hot flashes, sleep disorders iritability or depression, urinary incontinence and have

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been investigated clinic and paraclinic through usual hematologic analysis, hormonal deliveries
of estradiol and FSH and urinary exam,transvaginal ultrasound and complementary exams like
cardiologic exam and EKG ,nutrition disease and metabolism investigation.
The investigations made underlined diferrent grades of low anemia (11 cases, 31%), medium
(7 cases, 19%), severe (4 cases, 11%) and in 14 cases (39%) there were nochanges in Hb
(hemoglobin), or Ht (hematocrit). HTA (arterial hypertension 9 cases, 25%), overweight patients
(12 cases, 33%) obesity first grade (6 cases, 17%), the rest of 18 cases (50%) were
normoponderal, increase resistence on insulin (8 cases 22%).
Estradiol was low and FSH high was in 29 cases (80%) and in 7 cases (20%) estradiol and
FSH were in normal parametres.

Results and Discussions

The evaluation of abnormal uterine bleeding through the transvaginal ultrasound view of the
ovaires,endometrium and miometrum support the diagnosis and allow monitoring the involved
pathology [12, 13, 14].
The thickness and the aspect of the endometrial lining is an important landmark in diagnosis
of the endometrium hyperplasia and endometrial carcinoma.
The cases with endometrial hyperplasia had the endometrial lining between 6 and 10mm with
omogen aspect (17 cases 47%).

Fig. 1. Endometrial hyperplasia

The patients with endometrial proliferation on malign cause (2 cases, 6%, 1 case with
endometrial cancer and 1 case with ovarian carcinoma) had the endometrium thickness bigger
than 12mm and irregular aspect.

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Fig. 2. Endometrial cancer

The hipoecogen and hiperecogen areas from the endometrium can indicate neoplasia.
The endometrial polyps (3 cases 8%) appear like a lengthened formation in the endometrial
cavity with or without bright cystic points.

The aspect of leiomyoma (14 cases 39%) varies from hipoecogen to hiperecogen.

Fig. 4. Uterine leyomiom

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Conclusions

Endovaginal ultrasound has an increased compliance from the patients compared with
invasive methods.
Early tracking of the endometrial changes and their monitoring is important and it can achieve
easy by transvaginal ultrasound.

REFERENCES

1. Santoro N, Lasley B, Mc Connell D: Body size and ethnicity are associated with menstrual cycle alterations
in women in the early menopausal transition: the Study of Women’s health across the Nation (SWAN)
Daily Hormone Study. J Clin Endocrinol Metab 89 (6): 2622, 2004.
2. Soules MR, Sherman S, Parrott E: Executive summary: stages of reproductive aging workshop (STRAW).
Fertil Steril 76: 874, 2001.
3. Reyes FI, Winter JS, Faiman C: Pituitary-ovarian relationships preceding the menopause. I. A cross-
sectional study of serum follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and
progesterone levels. Am J Obstet Gynecol 129: 557, 1977.
4. Santoro N, Brown JR, Adel T: Characterisation of reproductive hormonal dynamics in the perimenopause. J
Clin Endocrinol Metab 81: 1495, 1996.
5. Kwee J, Schats R, Mc Donnell J: Evaluation of anti-Mullerian hormone as a test for the prediction of
ovarian reserve. Fertil Steril 90(3): 737, 2008.
6. La Marca A, Sighinolfi G, Radi D: A nti-Mullerian hormone (AMH) as a predictive marker in assisted
reproductive technology (ART). Hum Reprod Update 16 (2): 113, 2010.
7. Pacu I, Ionescu C, Vladareanu S, Banacu M, Neacsu A, Calin A. (2017).Predictive Value of the AMH
Level and Serum Estradiol for Ovarian Hyperstimulation Syndrome in the Assisted Human Reproduction.
Revista de Chimie. 68 (5), pp. 1118-1121.
8. Hale GE, Zhao X, Hughes CL: Endocrine features of menstrual cycles in middle and late reproductive age
and the menopausal transition classified according to the staging of Reproductive Aging Workshop
(STRAW) staging system. J Clin Endocrinol Metab 92 (8): 3060, 2007.
9. Brăila A D, Vaniova Klimentova D, Damian CM, Brăila M: Endometrial proliferative lesions associated
with uterine fibromatosis, RJME 56(3), Supp, 743-747, 2012.
10. Vaniova Klimentova D, Brăila AD, Simionescu C, Ilie I, Brăila M: Clinical and paraclinical study
regarding the macro and microscopic diagnosis of various anatomo-clinical forms of operated uterine
fibromyoma, RJME 53(2), 369-373, 2012.
11. Neacşu A, Marcu ML, Stānicā CD, Brāila AD, Pacu I, Ioan RG, Grigorescu CC, Ionescu CA, Early
Diagnosis of Endometrial Cancer, RJME, 59(2), 2018.
12. Braila M, Brăila A, Neacsu A, Gogănău A (2017), Treatment of Dysmenorrhea in Adenomyosis. Clinical
Study for a Period of 3 Years, Proceedings of the 14 th National Congress of Urogynecology and the
National Conference of the Romanian Association for the Study of Pain, Filodiritto Editore – Proceedings,
pp. 325-327.
13. Brăila M, Brăila A, Neacşu A, Gogănău A (2017),Treatment of Pelvigenital Pain Syndrome in External
Endometriosis. Clinical Study for a Period of 3 Years, Proceedings of the 14th National Congress of
Urogynecology and the National Conference of the Romanian Association for the Study of Pain, Filodiritto
Editore – Proceedings, pp. 328-330.
14. Brăila AD,Brăila M,Cornițescu F et al., (2008). Benign ovarian tumors. Anatomo-clinical, diagnosis, and
therapeutical aspects. Gineco.eu, 4(3), p. 178-185.

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Premature Placental Abruption. Ultrasound Aspects

VOINEA Bogdan1,VELEA Rodica1, LUNGULESCU C1


1University of Medicine and Farmacy Craiova, (ROMANIA)
Email: [email protected]

Introduction

Hemorhagia represents a major factor for maternal mortality in Great Britain,represent the
cause of maternal death in over 17% on 4200 pregnancies in United States [1], in private
American sector represents 12% from maternal deaths [2] and represents the essential reason for
mothers to be interned in the intensive therapy departament [3, 4, 5, 6].Hemorhagia represents
one of the most important causes of mother death in the world.The obstetrical hemorhagia is
responsible of approximately half of maternal postpartum death [7, 8]. Modernisation of
obstetrics lead to the improvement of the rate of mortality because of hemorhagia in pregnancy,
reaching 6% between 1972 and 2000 [9]. Hemodynamics stabilization and fast blood
administration are absolutely necessary in hemorhagia of obstetrical cause [10, 11]. Obstetrical
hemorhagia can start antepartum in placenta praevia and premature placental abruption or
postpartum in hypotonia and uterine atony and in urinary tract lesions. Every pregnancy with
antepartum bleeding determine a high risk for unfavorable evolution [12]. Most of the blood
originated from premature placental abruption has origin from the mother. Premature placental
abruption begins by bleeding at the level of basal decidua. After that, it can stop spontaneously
or it can extend, leading to partial or total placental abruption. The bleeding occured in the
second and third trimester of pregnancy can determine an unfavourable obstetrical prognosis
[13].
The objective of the study is the correlation of the hemorhagia data with the feto-maternal
condition and complexity and rapidity of the establishment of therapeutic behaviour for a good
vital materno-fetal and functional prognosis.
keywords premature placental abruption,antepartum bleeding,unfavourable prognosis

Material and method

The study comprised 17 cases of premature placental abruption in trimester II and III. The
patients had ages between 30 and 45 years IIIG-VIIG, IIIP-VP. The pregnant women were
hospitalized, made usual hematologic and urinary investigations, ultrasound exam for the
assesment of the fetus and fetal anexes. In the second trimester there were 4 pregnant women
who presented premature placental abruption, the rest of 13 patients suffered the obstetrical
accident in the third trimester. All the patients were monitorized and were surprised in easy and
medium form of retroplacentar hematoma. Risk factors associated with premature placental
abruption were identified by supplementary investigations, the presence of MTHFR gene, PAI,
factor V Leyden, S protein, C protein, homocystein, TA monitoring, cardiologic exam,
oftalmologic, neurologic, complete urinary exam, nefrologic exam.

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Results and Discussions

Of the 17 cases taken in study, 1 case was in the group aged 30-35 years, 7 pregnant women
in the age group 36-40 years and 9 patients between 41-45 years.Excepting 1 case aged 32 years
the other patients had ages between 36 and 45 years. The incidence of premature placental
abruption grow with the age of the pregnancy, being 2.3 times more frequent after 40 years
compared with the pregnancies under 35 years [14].
The ultrasound view between maternal basal plate of the placenta and the uterine wall of an
anechogen area indicated the diagnosis of premature placental abruption.

Fig. 1. Placental hematoma

The inhomogenous ultrasound view,viewed in case of an early bleeding is more difficult to


view and differentiate from the uterine wall.
The risk factors associated with premature placental abruption were preeclampsia [15],
trombophilia, HTA before pregnancy, age over 36 years, high gestation and high parity.
The guidance in completion the gestation is determined by the severity of bleeding, the size of
the retroplacental hematoma and the gestational age [16, 17].
The fetal prognosis was hopeless in 5 cases, three cases in the second trimester and two cases
in the third trimester. The maternal prognosis, vital and functional was good in all the cases.

Conclusions

The treatment of the pregnant women with premature placental abruption depends on the
volume of hemorhagia,gestational age,fetal viability and the clinical state of the mother.
Premature placental abruption represents a severe patology in obstetrics through the viability
and fetal distress and also by the vital and functional maternal prognosis.

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REFERENCES

1. Geberding JL: Centers for Disease Control and Prevention: Update: Pregnancy-related mortality ratios by
year of death-United States 1991-1999, MMWR 52:1, 2003.
2. Clark SL, Bedfort MA, Dildy GA: Maternal death in the 21st century: causes prevention and relationship to
cesaren delivery. Am J Obstet Gynecol 199: 36e1, 2008.
3. Zwart JJ, Richters JM, Ory F: Severe maternal morbidity during pregnancy delivery and puerperium in the
Netherlands: a nationwide population-based study of 371.000 pregnancies. BJOG 115: 842, 2008.
4. Gilberrt TT, Smulian JC, Martin AA: Obstetric admission to the intensive care unit: outcomes and severity
of illness, Obstet Gynecol 102: 897, 2003.
5. Zeeman GG, Wendel Jr GD, Cunningham FG: A blueprint for obstetric critical care. Am J Obstet Gynecol
188: 532, 2003.
6. Hazelgrove JF, Price C, Pappachan VJ: Multicenter study of obstetric admissions to 14 intensive care units
in Southern England. Crit Care Med 29: 770, 2001.
7. Lalonde A, Daviss BA, Acosta A: Postpartum hemorrhage today: ICM/FIGO initiative 2004-2006. Int J
Obstet Gynaecol 94: 243, 2006.
8. McCormick ML, Sanghvi HC, McIntosh N: Preventing postpartum hemorrhage in low-resource settings.
Int J Gynecol Obstet 77: 267, 2002.
9. Ho EM, Brown J, Graves W: Maternal death at an inner-city hospital, 1949-2000. Am J Ostet Gynecol 187:
1213, 2002.
10. BrăilaM, Neacșu A, VeleaR, Brăila A (2017). Caesarian Section And The Forceps Use -5 Year Study In
Craiova Scju Maternity Section ,Filodiritto International Proceedings, Congress of the Romanian-German
Society of Obstetrics-Gynecology, pp. 91-94.
11. Braila AD, Brăila M, Nawaf Alkrayem, Gogănău A (2017). Uterine Haemostasis In Puerperality By
Radical And Conservative Surgical Procedures, Filodiritto International Proceedings, Congress of the
Romanian-German Society of Obstetrics-Gynecology, pp. 81-83.
12. Braila AD, Marinov Krastev B, Mihai-Zamfir E, Caraveteanu DC, Nawaf Al Krayem, Braila M, Velea R,
Neacsu A, Uteroplacental apoplexy associated with invasive cervical neoplasm, RJME 58(4), 2017, 1465-
1470.
13. Brăila AD, Gluhovschi A, Neacșu A, Lungulescu C, Brăila M, Cotoi BV, Goganau A (2018) Placental
abruption. etiopathogenic aspects, diagnostic and therapeutic implications, RJME 59(1).
14. Cleary-Goldman J, Malone FD, Vidaver J: Inpact of maternal age on obstetric outcome. Obstet Gynecol
105: 983, 2005.
15. Brăila AD, Forțofoiu C, Zamfir EM, Velea R, Brăila M (2017). Eclampsia And Epilepsy. Differential
Diagnosis. Associated Diagnosis, Filodiritto International Proceedings, Congress of the Romanian-German
Society of Obstetrics-Gynecology, pp. 84-87.
16. Brăila A, Gogănău A., Brăila M., Neacşu A (2017). Caudal analgezia continues in controled birth. 5 year
clinical study, Proceedings of the 14th National Congress of Urogynecology and the National Conference of
the Romanian Association for the Study of Pain, Filodiritto Editore – Proceedings, pp.323-324.
17. Brăila AD, Brăila M, Velea R, Neacșu A (2017). Delivery Management: Past, Present And Perspective,
Filodiritto International Proceedings, Congress of the Romanian-German Society of Obstetrics-
Gynecology, pp. 77-80.

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Perinatal Outcome of Intra – Versus Retroplacental Hematomas

VRABIE Sidonia Cătălina1, NOVAC Liliana1, DIJMĂRESCU Anda Lorena1,


MANOLEA Maria Magdalena1, SANDULESCU Sidonia1, ILIESCU Dominic1,
NOVAC Marius2
1 Department of Obstetrics & Gynecology, University of Medicine and Pharmacy Craiova, (ROMANIA)
2 Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy Craiova, (ROMANIA)
Emails: [email protected], [email protected], [email protected], [email protected],
[email protected], [email protected]

Abstract

Introduction
Placental hematoma generated in the second trimester is an important complication with
tremendous and sometimes unpredictable evolution. This study aims to assess the risk profile of
these pregnancies by location.

Methods
35 patients were diagnosed by ultrasound with placental hematomas between 16 and 20 weeks
of gestation. Perinatal outcome was evaluated. Of these, 18 cases had central retroplacental
hematoma, 12 peripheral retroplacental hematoma, 5 cases with intraplacental hematoma.

Results
Pregnancies complicated with peripheral placental hematomas had the best prognosis, 8 of
them with growth restriction, 4 with premature birth, all with good neonatal adaptation.
Intraplacental hematomas developed placental insufficiency in most cases, with the highest
rate of complications: spontaneous abortion in the second trimester in 3 cases and fetal death in
utero in 2 cases. Retroplacental hematomas allowed pregnancy evolution until the onset of
trimester 3 in 5 cases, completed by bleeding and premature labor between 32 and 34 weeks with
difficult neonatal adaptation; 2 cases resulted in abrupted placenta and intrauterine fetal death in
utero at 29 and 31 weeks, 4 miscarriages at 17 weeks of gestation and IUGR in 7 cases.

Conclusions
In conclusion, the occurrence of placental hematoma can dramatically alter the progression
and prognosis of a pregnancy, especially in the intraplacental development, with significant
damage to the vasculature followed by the introduction of fetal hypoxia and sometimes death in
utero.
Keywords: placental hematomas, fetal outcome, ultrasound

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Introduction

The extensive use of ultrasonography in obstetrical practice has allowed the identification of
marginal or retroplacental hemorrhages. The aim of our study was to evaluate the impact of
second trimester placental hematomas on pregnancy evolution.

Methods

The study analyses 35 patients diagnosed by ultrasound with placental hematomas between 16
and 20 weeks of gestation at Filantropia Clinical Hospital, Craiova. The study group included
primi gravida with singleton pregnancies who were informed about the study and appropriately
counselled.
The criteria for inclusion in the study were the presence of a placental hematoma (PH)
diagnosed by ultrasound during 16-20 weeks of pregnancy and the presence of a viable fetus in
the primary ultrasound examination. Exclusion criteria were multiple pregnancies and cases of
detected congenital anomalies.
For each patient, the whole placenta was scanned using both gray-scale ultrasound and color-
flow mapping. Parameters evaluated were the size, the volume of PH and its location and stage
of development.
The size of the hematoma was determined by measuring the transverse, anterior-posterior,
longitudinal dimensions. The position of the hematoma relative to the placental site was
described as peripheral, retroplacental and intraplacental.
Intraplacental hematomas (IPH) were described as hypoechoic masses, with no Doppler flow,
located in the intervillous cavity of the placenta. Central and peripheral retroplacental
hematomas (RPH) were defined as an hypoechoic area located behind the placenta. Patients
underwent regular follow-up examinations at least every 2 weeks.
As outcome parameters, we analyzed pregnancy complications like: placental insufficiency,
intrauterine growth retardation; intrauterine fetal death; early preterm delivery before 32 weeks
and complete placental abruption which was defined as a complete separation of the placenta
from the uterus.

Results

All cases had normal uterine artery Doppler studies and normal placental morphology.
Intraplacental hematomas developed placental insufficiency in most cases, with the highest
rate of complications: spontaneous abortion in the second trimester in 3 cases and fetal death in
utero in 2 cases. (Table. 1)

PREGNANCY PLACENTAL HEMATOMAS


COMPLICATIONS RETROPLACENTAL INTRAPLACENTAL PERIPHERAL
A. IUGR
Yes 7 (38,8%) 0 (0%) 8 (66,6%)
No 11 (61,1%) 5 (100%) 4 (33,3%)
B. PREMATURE DELIVERY
Yes 5 (27,7%) 0 (0%) 4 (33,3%)
No 13 (72,2%) 5 (100%) 8 (66,6%)

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C. IUFD
Yes 0 (0%) 2 (40%) 0 (0%)
No 18 (100%) 3 (60%) 12 (100%)
D. MISCARRIAGES
Yes 4 (22,2%) 3 (60%) 0 (0%)
No 14 (77,7%) 2 (40%) 12 (100%)
Table 1. Incidence of pregnancy complications according to the hematoma localisation

The incidence of second-trimester miscarriage was highest in the intraplacental hematoma


group. Missed miscarriage was observed in 60% women with IPH and in 22,2% of retroplacental
hematomas (Fig. 1).

Fig. 1. Intraplacental hematoma, 21 weeks of gestation

Fig. 2. Intrauterine hematoma folowed by fetal demise

IUFD occurred in 40% of with intraplacental hematoma (Fig. 2, Fig. 3)

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Fig. 3. Large intrauterine hematoma and fetal demise

Retroplacental hematomas allowed pregnancy evolution until the onset of trimester 3 in 5


cases, completed by bleeding and preterm labor between 32 and 34 weeks with difficult neonatal
adaptation; 2 cases resulted in abrupted placenta and fetal death in utero at 29 and 31 weeks, 4
miscarriages at 17 weeks of gestation and IUGR in 7 cases (Fig. 4).

Fig. 4. Retroplacental hematoma – Doppler exam

One of the life-threatening consequence of placental pathology is placental abruption, defined


as partial or total separation of the placenta before delivery. This entity folowed by fetal demise
complicated 5% of cases, being present only in RPH group.
For all outcome parameters, retroplacental hematomas significantly increased the risk for the
development of the complication.
Pregnancies complicated with peripheral placental hematomas had the best prognosis, 8 of
them with intrauterine growth restriction, 4 with premature birth, all with good neonatal
adaptation (Fig. 5).

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Fig. 5. Peripheral retroplacental hematoma – Doppler exam

The presence of peripheral placental hematomas increased the chance of IUGR 66(%)
compared with RPH group (38%).Preterm labor occured in 27,7% of RPH cases and 33% of
peripheric forms (Fig. 6). Fetal growth restriction was defined by a birth weight of less than the
tenth percentile for gestational age and sex.

Fig. 6. Peripheral retroplacental hematoma

Discussions

The literature lacks studies about outcomes based on hematoma localization.


Intrauterine hematomas are a common pregnancy complication and can occur at any time
during the entire pregnancy. [1] The most common localizations of intrauterine hematomas are
retroplacental and subchorionic, with little data on the evolution and prognosis of intra-central
hematomas.
Our study confirms that an intrauterine hematoma identifies a gestation at risk for antepartum
complications.
Based on our findings, the presence of intrauterine hematomas might be an indication for
sonographic evaluation for fetal wellbeing and grow charts characteristics. Preterm delivery is

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the most frequently investigated outcome. Our report of a 25,71% rate of preterm delivery is
lower than the 32% preterm delivery rate reported by Tower. [2]
In utero fetal demise can be considered the ultimate expression of abnormal placentation. Our
findings of an increased risk of intrauterine demise is consistent with previous reports. [3]
Occurrence of an intrauterine hematoma can alter the perinatal outcome by putting the
affected women at an increased risk for pregnancy-related complications. The frequency of
postnatal complications like low Apgar scores, meconium staining and admission at intensive
care unit may be due to the increased rates of preterm delivery, fetal growth restriction and
placental abruption associated with intrauterine hematomas.
Our study concluded that pregnancies complicated by intraplacental hematomas carry a
different risk profile than hematomas with other localization; the risks for growth retardation,
preterm labor, and preterm delivery are significantly higher.
Preterm labor was common in women with retroplacental hematomas. Many studies
suggested that these events are accompanied by the release of cytokines which could trigger
preterm labor [4].
The location of the hematomas and the degree of placental involvement were significantly
correlated with the incidence of perinatal complications. Although data from literature suggests
that gestational age at the time of diagnosis can predict the occurrence of associated risks, our
study highlights the importance of the type of hematoma in evaluating the perinatal outcome. [5]
Patients diagnosed in the second part of pregnancy with intraplacental hematoma presented
the worst prognosis.
Our study demonstrates that pregnancies complicated with intrauterine hematomas had a
higher risk for fetal growth restriction. Dates of literature also highlights the theory that
abnormal placentation may be the consequence of intrauterine hematomas and fetal growth
restriction.

Conclusions

Intra- and retroplacental hematomas have different risk profiles for the affected pregnancy and
act as independent risk factors. The occurrence of placental hematomas may dramatically alter
the progression and prognosis of a pregnancy, particularly in the case of intraplacental
development, with significant alteration of the materno-fetal vascularization followed by the
onset of fetal hypoxia and sometimes death in utero.
Due to the frequent objection of an intrauterine hematoma in routine ultrasound monitoring,
knowing and appreciating the outcome of these entities is essential in perinatal medicine.

REFERENCES

1. Leite J, Ross P, Rossi AC, Jeanty P (2006). Prognosis of very large first-trimester hematomas. J Ultrasound
Med. 2006; 25: pp. 1441-5.
2. Tower CL, Regan L. (2005) Intrauterine hematomas in a recurrent miscarriage population. Hum Reprod
2001;16: p. 7
3. Mandruzzato GP, D’Ottavio G, Rustico MA, Fontana A, Bogatti P. (1989) The intrauterine hematoma:
Diagnostic and clinical aspects. J Clin Ultrasound; 17: pp. 503-10.
4. Kraus FT Redline RW, Gersell DJ, Nelson DM, Dicke JM. (2004) Placental pathology. Atlas of non-tumor
pathology; pp. 117-57.
5. Nagy et al., Clinical significance of subchorionic and retroplacental hematomas detected in the first
trimester of pregnancy Obstetrics & Gynecology, (2003) vol. 102, no. 1.

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Perspective of the Prematures Infants Below 28 Weeks of Gestation

ZAHARIE Gabriela1,*, HASMASANU Monica1,*, OBADA Veronica1,*,


MURESAN Daniel4,*, BLAGA Ligia1,*, ZAHARIE Alexandru Teodor3,*,
DRUGAN Tudor2,*, BOIA Marioara5,*, ROTAR Ioana4,*, MATYAS Melinda1,*
1 Iuliu Haţieganu University of Medicine and Pharmacy, Department of Neonatology, Cluj-Napoca, (ROMANIA)
2 Iuliu Haţieganu University of Medicine and Pharmacy, Department of Medical Informatics and Biostatistics, Cluj-Napoca,
(ROMANIA)
3 Medical University of Vienna, Department of Radiation Oncology, Vienna, (AUSTRIA)
4 Iuliu Haţieganu University of Medicine and Pharmacy, Department of Obstetrics and Gynecology, Cluj-Napoca, (ROMANIA)
5 University of Medicine and Pharmacy “Victor Babeş”, Department of Pediatrics, Timişoara, (ROMANIA)
* All authors have equal contribution as the first author.

Emails: [email protected], [email protected], [email protected],


[email protected], [email protected], [email protected], [email protected],
[email protected], [email protected], [email protected]

Abstract

Prematurity is the single most important cause of death in the first month of life and it’s a
factor in over 75% of pediatric deaths in the neonatal period (1), making it the 8th most frequent
cause of death (2).Survival has increased over the last period, but the complications and
outcomes remain the same. Due to these facts, prematurity constitutes a global heath problem.

Aim
The purpose of this study is to evaluate the dynamics of the premature neonates under 28
weeks of gestation between 2011-2016 in a tertiary center, in Romania, and the immediate
outcome of these premature infants. The study group consists of premature infants under 28
weeks of gestation born or referred to the Ist Neonatology NICU Cluj between january 2011 and
december 2016.
We evaluated the incidence in evolution, early complications, retinopathy of prematurity
(ROP) and bronchopulmonary dysplasia (BPD) for late complications and mortality.

Material and methods


The study group is represented by premature infants below 28 weeks of gestation admitted to
the NICU of the Ist Neonatology department, Emergency County Hospital, Cluj, during jannuary
2011 and december 2016. We evaluated the dynamics of the admissions, prevalence of
prematurity, the risk factors of the premature birth, the early and late complications and the
mortality rate. Statistical analysis was performed using SPSS V25. All the premature infants
admitted had the informed consent signed.

Results
We enrolled 111 prematures infants; from which 92 were delivered by C-section, with the
GA=26.79±1.47weeks and BW=933.16g±155.351 and 19 were delivered spontaneously with
GA=26.53±1.305 weeks and BW=944.35±226.353g. There is a notable increase of extreme
prematurity from 1.53% in 2011 to 3.31% in 2016.

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The most important causes of extreme prematurity in the study group were: 25% rupture of
membranes, 13% chorioamnionitis, 14% UTI of the mother, 14% IVF (in vitro fertilization) and
15% placenta praevia. All the included neonates needed resuscitation in the delivery room,
including ventilation on NeoPuff followed by intubation. No significant statistical differences
were found between the two groups (p=0,67). The pO2 in the delivery room was significantly
higher in the spontaneous group vs. the C-section group (p=0.04). The severity of respiratory
distress syndrome was significantly increased in the C-section group (p=0.05). Early and late
complications show no significant differences between the two groups. The mortality rate was
not influenced by the delivery-mode.

Conclusions
The severity of RDS was significantly greater in the C-section group (p=0.05) Mortality was
not influenced by delivery mode. The main risk factors for extreme premature birth in our study
were: preeclampsia, chorioamnionitis, fever, FIV. Neither CS nor spontaneous delivery had a
significant impact on the incidence of early or late complications.
Keywords: Extreme premature infant, 28 weeks gestational age, early coplications, mortality

Introduction

In 2010 more than 10% out of the 15 milion born children were premature. Prematurity is the
single most important cause of death in the first month of life and contributed to over 75% of
pediatric deaths in the neonatal period (1). It represents the second cause of death in children
under 5 years old. So, we accept that prematurity remains a global health problem. Prematurity
and birth asphyxia are in the top ten causes of deaths (2).
Gestational age exerts the greatest influence on outcomes for preterm births. In the 1970s,
before the widespread of assisted ventilation, more mature newborns died because of surfactant
deficiency. In the mid 1990, survival greatly improved for this group, including very preterm
newborns before 28 weeks of gestation. Survival at 22 weeks is rare but rates increase with GA:
up to 40% at 23weeks, 40-60% at 24 weeks, 60-80% at 25weeks and 70-80% at 26 weeks of
gestation (3, 4). Data published for newborns delivered in the United States, England, and
Australia within the past decade have indicated rates of survival to discharge of 23-27% for
births at 23 weeks, 42-59% for births at 24 weeks, and 67-76% for births at 25 weeks of
gestation (5, 6). The overall survival of extremely preterm infants was related to pro-active
obstetric policy with use of tocolytics, antenatal corticosteroids, and cesarean section. Obstetric
factors, except for vaginal breech delivery, were not associated with neuro-developmental delay
at 2.5 years of age (7). In Romania, the incidence of prematurity varies from region to region
from 5.9% to 15% (8). In Europe the prevalence of prematurity varies between 5.9% to 14.7%;
Romania´s is around 9% (8).
The natality structure of CNSIP-2016 based on gestational age of the newborn in 2016 was
10,3% under 28weeks, 19,6% at 28-31 weeks, 22,1% at 32-35weeks; 30,6% at 36-39weeks and
over 10,5% for over 40weeks of gestation. Seven percent of the population had no data. Human
viability in Romania begins with the 24th week of gestation. The limit varies from country to
country based on the association of gestational age with a 50% chance of survival, without
providing medical care. On average, this rate is estimated at approximately 22-24 weeks in
developed countries versus approximately 34 weeks in low to middle income countries. Despite
technological advances, the extremely premature infants at less than 28 weeks of gestation and

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the extremely low birth weight infant(ELBW) with less than 1000g remain at high risk for death
and disability with a mortality rate of 30-50% and a 25-50% risk of morbidity. (10, 11, 12, 13,
14, 15, 16).

Aims

This retrospective study aims to analyse the management of preterm babies below 28 weeks
of gestation, to evaluate their early complications, morbidity and mortality on extreme preterm
newborns admitted in NICU at the Ist Neonatology Department, Emergency County Hospital
Cluj-Napoca between 2011 and 2016.

Material and methods

The study was conducted at the Ist Department of Neonatology Cluj Napoca, Romania,
between 2011 and 2016 and has included 111 premature infants below 28 weeks of gestation.
We split the groups based on delivery mode into spontaneous delivery and C-section group.
We also included the transferred infants, which were admitted in the service. For every patient
we have assessed the following parameters: anthropometric data (weight, length, and head
circumference), delivery modality, antenatal cortisone prophylaxis, the severity of respiratory
distress syndrome, resuscitation maneuvers, blood gases, early complications and mortality rate.
The severity of respiratory distress syndrome we assesed by the Silverman score. We
quantified the resuscitation maneuvers: 1 for routine care, 2 CPAP ventilation and 3 for invasive
resuscitation in the delivery room. The blood gas analysis was determinated with an X-lab
machine. Echocardiography assessment was done on day 3 and 4 of life with 12 Hz probe on
VIVID 5 GE ultrasound machine. The statistical analysis was performed with SPSS v5. All
patients signed an informed consent.

Results

We enrolled 111 prematures infants; 92 which were delivered spontaneously, with a GA of


26.53±1.305weeks and a BW of 944.35±226.353g and 19 which were delivered by C-section
with a GA of 26.79±1.47weeks and a BW of 933.16±155.351g. The rate of extreme prematurity
increased from 1.53% in 2011 to 3.31% in 2016. We identified a variety of factors involved in
the causality of extreme premature birth: 25% premature rupture of membrane, 13%
chorioamnionitis, 14% UTI of the mother, 14% IVF, 15% placenta praevia, 10% preeclampsia,
12% polyhydramnios, oligohydramnios 10%. Only 51% of pregnancy were correctly followed.
All the prematures needed resuscitation, ventilation on NeoPuff or intubation in the delivery
room. No significant statistical differences were found between the two groups (p=0,67). The
maneuvers used in the delivery room were quantified at 2.18±0.62 versus 2.28±0.66 in the C-
section group.
The mean Apgar score at minute one was 4.47±2.11 in the spontaneous group and 4.67±2.24
in the C-section group without significant differences. The value of the pH was 7.25±0.11 versus
7.29±0.10 in the C-section group (p=0.45). The lactate value was high in both groups 12.96±2.5
and 6.57±3.17. The pO2 in the delivery room was significantly higher in the spontaneous group
vs C-section group (p=0.04). The severity of respiratory distress syndrome was significantly
increased in the C-section group, measured by the Silverman score: 6.67±2.14 versus 6.20±2.21

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(p=0.05). The antenatal prophylaxis with steroids was administered as followed: completely in
31.69%; incomplete in 34.95%; absent in 35.15%. Sixty nine cases presented with a severe form
of respiratory distress syndrome and required more then one month of oxygen therapy. Early and
late complication rates show no significant differences between the two groups. The most
frequent complication was the persistent ductus arteriosus with an incidence of 6.30% in CS
group and 30.63% in SPN group. Necrotic enterocolitis was diagnosed in 2.7% in CS and
15.31% in SPN group. Bronchodysplasia was diagnosted in 24 cases in the spontaneous delivery
group versus 3 cases in the CS group. Retinopathy of prematurity was identified in 4 cases of the
CS group and 17 cases of the SPN group. The mortality rate showed no difference: 26.31 in the
CS group and 25% in the SPN group (p=0.47). Overall survival was 25.22%. Mortality
decreased dramatically from 47% in 2011 to 22% in 2015. There were no deaths in 2016.

Disscusions

Extreme prematurity remains a global health problems. Perinatal care of pregnant women at
risk for preterm delivery and of preterm infants born at 22-26 completed weeks of gestation
requires a multidisciplinary team to improve the outcomes of these “special group”. In our
center, extreme prematurity rate has had a tendency to increase in the last five year. The
incidence increased from 1.53% in 2011 to 3.31% in 2016. From the beginning these babies
generated debates between the obstetrician and the neonatologist. One of the discussion points
was the delivery mode. In the literature this issue remains open. Berger et al., consider that
between week 22 0/6 and week 23 6/7 obstetric intervention for fetal indications such as
Caesarean section delivery are usually not indicated (17). In our study the incidence of C-section
is low, with 17,11%. One study in Denmark indicates C-section starting with a gestational age of
26 weeks (18).
A large panel of etiologies were identified in the study. There is still 49% of unfollowed
pregnancies. The main factors involved in the premature birth were: 25% premature rupture of
membranes, 14% placenta praevia, 15% IVF, 14% UTI during pregnancy, 14% cerclage, 13%
chorioamnionitis, 11% fever and 10% preeclampsia. Guidance regarding the impact of delivery
mode on the outcome of the premature infants can be obtained only by analysing retrospective
studies. Hogberg et al., showed that infants born in cephalic position at the age between week 25
0/7 and week 25 6/7, with no maternal or fetal risk factors by C-section do not have any benefit
regarding survival or complication rate (19, 17).
Antenatal corticotherapie is recognized to have a positive impact on the perinatal
complication rate of the premature infants. In our study, the prophylaxis was done only for 51
out of 111 cases. Regarding these babies, the severity of respiratory distress syndrome was
6,67±2.12 for the C-section group and 6.20±2.21 for spontaneous group with significant
statistical differences (p=0.05). Respiratory distress is the main issues of neonates at this
gestational age.
Fetal maturity at identical gestational age can also vary, meaning that situations like these can
influence their therapeutic requirements and even affect individual mortality and morbidity (17).
Antenatal prophylaxis reduces the incidence of RDS and overall mortality for preterms
between the 29 and 34 weeks of gestation. For the 24-28 weeks of gestation only the extent of
RDS was positively impacted. At the same gestational age a reduction of incidence and mortality
for intraventricular hemorrhage was noted (20). The incidence of pneumothorax was only 9.9 %
in the spontaneous group and 1.2% in the C-section group.

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All the premature babies needed interventions in the delivery room but with no differences
regarding delivery mode. The complication rate was similar in both groups. PDA remains the
major complication with an incidence of 30.63%. That could be considered within normal values
at this gestational age. Regarding the decision of the duct closure, our protocol is to perform
echocardiography between the 3-th and fourth days of life. The hemorrhagic complications were
27,01% digestive and 21,61% pulmonary. Necrotic enterocolitis was diagnosed in 2.7% in CS
and 15.31% in SPN group.
Most of the cases presented a severe form of respiratory distress syndrome.Sixty nine cases
required more than one month of oxygen therapy. Bronchopulmonary dysplasia was diagnosed
in 24 cased in the spontaneous delivered group and 3 casesin the CS delivered group. Scriam et
al., concluded that ventilation for 14 ore more days for a premature below 28 weeks tended to
attenuate the severity of bronchopulmonary dysplasia associated with hypoxemia and
hypercapnia (20). In our study we applied the European guidelines 2016 for the management of
RDS but we consider that also our high percent of absent antenatal prophylaxis influenced the
incidence of bronchopulmonary dysplasia.
Retinopathy of prematurity (ROP) was identified in 4 cases in the CS delivered group and 17
cases in the SPN delivered group. Overall 18,1% premature babies presented different grades of
ROP, but only 3 cases needed laser therapy. The incidence of ROP is different from country to
country, especially from middle income countries to low income ones. The resuscitation with
suboptimal standards, oxygen therapy and maternal care are important factors involved in the
risk for ROP. Also in Romania the percent is very different from region to region, showing
variable tendency from 11.72% for lasertherapy in our region (21) to 2.7% in our study.
Infants born at an extremely low gestational age have a high mortality rate and are at risk of
having neurodevelopmental disabilities. Estimated gestational age of delivery has shown strong
association with neurodevelopmental outcome and it serves as the basis for antenatal counselling
(22).
In our study the mortality rate was 25.22%. The delivery mode had no influence in the
mortality rate.
Interventions that are done in the first 60 min of postnatal life have the highest impact on the
outcome both at premature babies and newborn at term. This lead to “Golden hour” concept (22,
23). The multiple pregnancies also increase the morbidity of premature babies (24). In our study
the mortality rate decreased in the study period from 47% in 2011 to 22% in 2015.

Conclusions

Outcome of the extreme premature infant depends on gestational age. In our study, mortality
rate was not influenced by the delivery mode. The main risk factors for extreme premature birth
in our study were: 25% premature rupture of the membrane, 14%placenta praevia, 15% IVF,
14% urinary tract infections during pregnancy, 14% cerclage, 13% chorioamnionitis, 11% fever
and 10% preeclampsia. The severity of RDS was significant greater in the C-section group
p=0.05.
Neither CS nor spontaneous delivery had a significant impact on the incidence of early or late
complications. Mortality rate decreased constantly in this period.

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REFERENCES

1. Hannah C. Glass, MDCM, MAS, et al., (2016). Outcomes for Extremely Premature Infants.Anesth
Anal.june;120(6), pp. 1337-1351.
2. http://new.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death).
3. Lex W. Doyle and Saroj Saigal. (2009). Long-term Outcomes of Very Preterm or Tiny Infants Neoreviews
10(3), pp. e130-137.
4. Doyle LW, Rogerson S, Chuang SL, James M, Bowman ED,Davis PG. Why do preterm infants die in the
1990s?. Med J Aust 170, pp. 528-532.
5. Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, et al., Neonatal outcomes of
extremely preterm infants from the NICHD Neonatal Research Network. (2010). Pediatrics 126, pp. 443-
456.
6. Bolisetty S, Legge N, Bajuk B, Lui K. Preterm infant outcomes in New South Wales and the Australian
Capital Territory. New South Wales and the Australian Capital Territory Neonatal Intensive Care Units’
Data Collection. (2015). J Paediatr Child Health, doi: 10.1111/jpc.12848.
7. Nordic Federation of Societies of Obstetrics and Gynecology.(2015). Acta Obstetricia et Gynecologica
Scandinavica 94, pp. 1203-1214.
8. National statistic center and information in public health (CNSIP), 2014 and 2016.
9. ORDIN Nr. 359/2012 privind criteriile de înregistrare şi declarare a nou-născutului M.Of. nr. 237 din
9.4.2012.
10. Preterm Birth, Fact Sheet No363, Geneva www.sciepub.com/reference/148957
11. www.who.int/pmnch/media/news/2012/201204_borntoosoon-report.pdf
12. Saigal S, Doyle LW.(2008). An overview of mortality and sequelae of preterm birth from infancy to
adulthood. Lancet. 371(9608), pp. 261-269 [PubMed: 18207020].
13. Hamilton BE, Hoyert DL, Martin JA, Strobino DM, Guyer B. Annual summary of vital statistics: 2010-
2011(2013). Pediatrics.131(3), pp. 548-558 [PubMed: 23400611].
14. Engle WA. Age terminology during the perinatal period. (2004). Pediatrics. 114(5), pp. 1362-1364
[PubMed: 15520122].
15. 15.Spong CY.(2013). Defining “term” pregnancy: recommendations from the Defining “Term” Pregnancy
Workgroup. JAMA. 309(23), pp. 2445-2446 [PubMed: 23645117].
16. Hăşmăşanu MG, Bolboacă SD, Baizat MI, Drugan TC, Zaharie GC.(2015). Neonatal short-term outcomes
in infants with intrauterine growth restriction. Saudi Med J 36(8), pp. 947-953.
17. Thomas M. Berger, Vera Bernet, Susanna El Alama, Jean-Claude Fauchère, Irène Höslie, Olivier Irion,
Christian Kind, Bea Latal, Mathias Nelle, Riccardo E. Pfister, Daniel Surbek, Anita C. Truttmann, Joseph
Wisser, Roland Zimmermann. (2011). Perinatal care at the limit of viability between 22 and 26 completed
weeks of gestation in Switzerland.Review article. Swiss Med Wkly.141(13280), pp.1-13.
18. Aroba Ahmad Quazi and Maymunah Ghulam A. (2015). Approach to infants born before gestational week
26:Method of delivery, complication risks and health of the preterm neonate. Norsk Nyfødtmedisinsk
kvalitetsregister,University of Oslo.11.07. V11.
19. Hogberg U, Holmgren PA. Infant mortality of very preterm infants by mode of delivery,institutional
policies and maternal diagnosis. (2007). Acta Obstet Gynecol Scand.86, pp. 693-700.
20. M. E. Tsimis, N. Abu Al-Hamayel, H. Germaine, And I. Burd. Prematurity: Present And Future.(2015).
Minerva Ginecol. 67(1), pp. 35-46.
21. Nicoara, Simona-Delia; Cristian, Cristina; Irimescu, Iulian; et al., (2014). Diode Laser Photocoagulation
for Retinopathy of Prematurity: Outcomes After 7 Years of Treatment Journal Of Pediatric Ophthalmology
& Strabismus 51(1), pp. 39-45.
22. Deepak Sharma. Golden hour of neonatal life: Need of the hour.(2017). Matern Health Neonatol Perinatol.
3, 16 doi: 10.1186/s40748-017-0057-x.
23. M. Boia, I. Daniela,M.Aniko,M. Dima, D. Ragobete.(2013). Multiple pregnancies- Risk factor for the
grown in newborn death.kow, June 19-22, 2013, Abstract bookJ.Perinat.Med 41, ISSN:1619-3997.

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Distal Arthrogryposis in Newborns with Turner Syndrome

ZAHARIE Gabriela1, MURESAN Daniel2, MICLEA Diana3,


HASMASANU Monica1, MATYAS Melinda1
1 Neonatology Department ,University of Medicine and Pharmacy, Cluj-Napoca, (ROMANIA)
2 Iuliu Haţieganu University of Medicine and Pharmacy, Department of Obstetrics and Gynecology, Cluj-Napoca, (ROMANIA)
3 Iuliu Haţieganu University of Medicine and Pharmacy, Department of Genetics, Cluj-Napoca, (ROMANIA)

Emails: [email protected], [email protected], [email protected],


[email protected], [email protected]

Abstract

Arthrogryposis multiplex congenital represents a heterogeneous group of disorders


characterized by severe joint contractures with multiple locations. The incidence of this disease
is 1/3000 live newborns. Etiology is varied and involves teratogenic factors, intrauterine
compression, fetal blood supply disorders, maternal muscle diseases – myasthenia gravis,
maternal medication, maternal viral infections. There are forms of congenital arthrogryposis that
associate genetic abnormalities, but the association with Turner syndrome is not very frequent.
[1, 2, 7]
In this paper, we present the case of a newborn with arthrogryposis diagnosed postpartum, in
which the karyotype performed evidenced Turner syndrome. The patient had no clinical
elements suggestive of Turner syndrome at birth. Subsequently, the FISH test on oral mucosal
cells was carried out, which showed the same aspect of X monosomy.
Keywords: arthrogryposis, Turner syndrome, newborn, FISH test

Introduction

Athrogryposis is a disease characterized by multiple joint contractures. In the literature, the


term arthrogryposis multiplex congenita – AMC is also used, which is characterized by
contracture of several joints. More than 400 forms of arthrogryposis have been described. Some
forms of arthrogryposis are associated with genetic abnormalities, but the most frequent form is
sporadic arthrogryposis. All forms of arthrogryposis are associated with fetal akinesia. The
causes of fetal akinesia are various: myopathy, neuropathy, neuromuscular disorders, fetal blood
flow abnormalities, compression of the fetus, maternal exposure to toxic substances, connective
tissue diseases, genetic or metabolic abnormalities. The longer its duration, the more severe are
its consequences on the fetus. It may associate other abnormalities: polyhydramnios, pulmonary
hypoplasia, facial abnormalities – micrognathia, hypertelorism, palatoschisis. [4, 7, 8] Turner
syndrome is a chromosomal disease with an incidence of 1/2000-2500 live-born females. It is
characterized by X chromosome monosomy. However, there are forms of Turner syndrome
characterized by tissue mosaicism. These forms cannot be evidenced by the blood karyotype.
Also, these forms of mosaicism may associate the presence of Y chromosome derivatives in
the tissues. In these forms of Turner syndrome, the incidence of gonadoblastoma is higher. In the
literature, an incidence of 12% up to 30% is reported [2, 3, 6].

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Case report

A female patient, born from the followed up pregnancy of a 33-year-old mother, who was a
heavy smoker during the first two months of pregnancy (20 cigarettes/day) and had an obstetric
history of abortion (fetal hydrops, ectasia, pyelon, hydrocephalus, oligoamnios). The baby was
born at 41 gestational weeks by cesarean section for acute fetal distress, with an Apgar score 8/9,
premature rupture of amniotic membranes at 26 hours antepartum, meconial amniotic fluid. The
newborn was vigorous and required no suction between vocal cords in the delivery room;
postnatal transition was good, but clinical examination at birth evidenced craniofacial
dysmorphism: upward and outward slanted palpebral fissures, retrognathia, slightly oblique ears,
ogival palate, bilateral single palmar crease, camptodactyly of the fingers and toes, elbow and
knee joints with extension contractures, difficult mobilization, genu varum. Neurologically,
generalized hypertonia and no archaic reflexes were found. The development curves showed a
development adequate for the gestational age (the 95th percentile for weight and length, PI=1.95).
Postnatal lab tests evidenced post-asphyxia syndrome (CK, CK-MB, LDH reaction) which
remitted during hospitalization. pH gas values were within normal limits, at birth and after the
patient became stabilized.
Considering facial dysmorphism and the clinical aspect of distal arthrogryposis, imaging
investigations were performed and karyotype was collected, due to the known possible
association of arthrogryposis with genetic abnormalities. Transfontanelar ultrasound revealed no
pathological findings; cardiac ultrasound showed a 3-4 mm atrial septal defect with restrictive
left-to-right shunt in the middle area. Abdominal ultrasound evidenced no abnormalities. Hip
ultrasound evidenced type III b hip (predislocation stage), for which correction treatment was
initiated immediately after birth (abduction pants). Dynamic hip ultrasound is shown in the
following images (Fig. 1-4)

Fig. 1. Left hip ultrasound 1st week Fig. 2. Right hip ultrasound 1st week

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Fig. 3. Left hip -4th week Fig. 4. Right hip- 4th week

The karyotype evidenced 46XX/45X mosaicism. The same aspect was indicated by the FISH
test performed on oral mucosal cells. The FISH test on blood examined 200 interphases and 15
metaphases. The following were observed: 2 fluorescent signals corresponding to the centromere
of the X chromosome in 80% of the analyzed cells, 3 fluorescent signals corresponding to the
centromere of the X chromosome in 12% of the analyzed cells, and 1 fluorescent signal
corresponding to the X chromosome in 8% of the analyzed cells. Conclusion of the test:
45,X/46,XX.ishXp11.1q11.1(DXZ1x1)[8%]/Xp11.1q11.1(DXZ1x3)[12%]/Xp11.1q11.1(DX
Z1x2)[80].

Fig. 5. FISH analysis of oral cells Fig. 6. FISH analysis of blood cells

During the hospital stay, the evolution was favorable. After discharge, orthopedic treatment of
arthrogryposis, neurological follow-up, then physiotherapy were initiated. The evolution was
favorable during the first 12 months of life, with the gradual remission of distal joint contracture
and a good neurological course. Motor skills developed according to age. Also, extrauterine
growth in the first 12 months was adequate for age. The patient will be followed up
neurologically.

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Discussions and conclusions

Arthrogriposis comprises a wide variety of abnormalities characterized by limb contracture,


with a favorable evolution in the context of adequate treatment. The incidence of arthrogryposis
is 1 to 3000 live-born neonates. There are various forms of arthrogryposis. Some authors like
Hall et al., have described the presence of this contracture in association with other systemic
abnormalities such as: Freeman-Sheldon syndrome, Möbius syndrome, multiple pterygium
syndrome, popliteal pterygium syndrome, nail-patella syndrome, Sturge-Weber syndrome,
Marfan syndrome, osteogenesis imperfecta, neurofibromatosis type II, and the association of
limb contractures with central nervous system abnormalities (lethal multiple pterygium
syndrome, lethal X-linked arthrogryposis, pterygium syndrome with facial clefting, cerebro-
oculo-facial syndrome, fetal alcohol syndrome, Marden-Walker syndrome, Pena-Shokeir
syndrome, Zellweger syndrome, myelomeningocele, myotonic dystrophy, spinal muscular
atrophy, Turner syndrome, trisomies: 4p, 8, 9, 9q, 10q, 13, 15, 18, 21) [7, 12, 13]. Bamshad et
al., include multiple contractures in the course of distal arthrogryposis (DA), where the
contractures occur on the background of known genetic disorders [8, 9]. Normal neurological
examination associated with distal arthrogryposis is suggestive of the fetal origin of the
contracture. Some patients are mosaics: chromosomal aberrations can be detected in fibroblasts
and are absent in blood cells [7, 10, 11]. A phenotypically identical presentation of
arthrogryposis can sometimes be caused by mutations of different genes [8, 9]. In the presented
case, genetic abnormalities were found on the examination of both the blood karyotype and oral
mucosal cells. In the fetal period, there were no fetal ultrasound elements suggestive of Turner
syndrome (hygroma colli, fetal hydrops, cardiac defects or increased nuchal translucency). The
clinical elements characteristic of Turner syndrome are: edema of the dorsa of the hands and feet,
low birth weight, webbing of the neck, low hair line, small mandible, prominent auricle,
epicanthic fold, wide thorax, widely spaced nipples, high arched palate, short stature, cubitus
valgus, gonadal dysgenesis. The incidence of Turner syndrome is 1 in 2000 to 1 in 5000 live-
born phenotypic females. The clinical picture of the reported case was dominated by minimal
elements of facial dysmorphism and the aspect of arthrogryposis, without clinical elements
suggestive of Turner syndrome. Arthrogryposis diagnosed at birth determined the initiation of
the investigations performed, including karyotyping of this patient. X monosomy diagnosed by
karyotype examination was little expected due to the absence of clinical elements suggestive of
Turner syndrome, but given the known possible associations of arthrogryposis with genetic
abnormalities, this examination was carried out.
Considering this result and the importance of knowing tissue mosaicism, oral mucosal
samples were taken, which were examined by the FISH technique. Mosaicism involves a less
severe clinical picture, but is however associated with an increased risk of gonadoblastoma,
particularly in cases where the Y chromosome is involved. In the reported case, there is no
implication of the Y chromosome. This evaluation is correlated with the aspect of the ovarian
karyotype. As such, the risk of gonadoblastoma is high in this case. However, the presence of the
Y chromosome in the examination of the oral mucosa requires FISH analysis of lymphocytes in
order to evidence the possible presence of the Y chromosome (chromosome derivative) at this
level.
Recent studies highlight the fact that in addition to the increased incidence of cardiac
malformations in patients with Turner syndrome, there is also a high cardio-metabolic risk. [14,
15] At the adult age, the body mass index is higher compared to the control population. The risk

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of diabetes mellitus is 2-5 times higher and there is an increased risk of cardiovascular and
cerebral mortality at the adult age [5, 14, 16]. There is also a high risk of arterial hypertension
and altered cardiac variability, which is correlated with sympathetic vagal tone dysfunction.
The most frequent cardiac malformations are aortic stenosis, coarctation of the aorta, bicuspid
aortic valve. Mitral valve abnormalities and atrial septal defects can also be found. Over the past
years, the literature has described an increased incidence of aortic dissection in patients with
Turner syndrome. This is why the annual cardiac ultrasound monitoring of these patients is
recommended.
Other congenital abnormalities that can be associated with Turner syndrome are renal
abnormalities – most frequently horseshoe kidney, hypothyroidism, auricular abnormalities,
hearing loss, external auditory canal narrowing. This is why in childhood and adolescence there
will be frequent episodes of otitis media that will generate sensorineural hearing loss with time.
Its incidence will be favored by the frequently associated abnormalites – ogival palate and
Eustachian tube abnormalities [6].
The significantly higher incidence of recurrent otitis media compared to the general
population is determined by the particular anatomical characteristics as well as by the humoral
and cellular immune deficiency of patients with Turner syndrome. IgG and IgM immunoglobulin
levels are reduced, and the number of T and B lymphocytes is lower. Also, in correlation with
immune problems, there is an increased incidence of Hashimoto thyroiditis in the population
with Turner syndrome. [10, 11]
Hearing loss that occurs during evolution seems to be correlated with estrogen deficiency in
these patients. In the first 12 months of life, the presented patient had no episodes of otitis media.
Arthrogryposis in the reported case will require orthopedic treatment. The patient will also
need neurological and endocrinological follow-up because of the risks associated with Turner
syndrome: diabetes mellitus, arterial hypertension, thyroid dysfunctions. The risk of ovarian
gonadoblastoma is low because the Y chromosome was not involved, but the case will require
long-term follow-up.

REFERENCES

1. Darin N, Kimber E, Kroksmark AK, Tulinius M. Multiple congenital contractures. Birth prevalence,
etiology and outcome. J Pediatr 2002;140: pp. 61-67.
2. Gordon N. Arthrogryposis multiplex congenital. Brain Dev 1998; 20: pp. 507-511.
3. Riemersma S, Vincent A, Beeson D et al. Association of arthrogryposis multiplex congenital with maternal
antibodies inhibiting fetal acetylcholine receptor function. J Clin Invest 1998; 98: pp. 2358-2363.
4. Mennen U, van Heest A, Ezaki MB, Tonkin M, Gericke G. Arthro- gryposis multiplex congenita. J Hand
Surg Br 2005;30(5): pp. 468-74.
5. Gravholt CH, Juul S, Naeraa RW, et al. Morbidity in Turner syndrome. Journal of Clinical Epidemiology
1998; 51: pp. 147-158.
6. Beckman A, Conway GS, Cadge B. Audiological features of Turner’s syndrome in adults. Int. J. Audiol.
2004; 43(9): pp. 533-544.
7. Hall JG. Arthrogryposis multiplex congenita: etiology, genetics, classification, diagnostic approach and
general aspects. J Pediatr Orthop B 1997; 6: pp. 159-66.
8. Bamshad M, Van Heest AE, Pleasure D. Arthrogryposis: a review and update. J Bone Joint Surg Am 2009;
91(4): pp. 40-6.
9. Narkis G, Landau D, Manor E, et al. Genetics of arthrogryposis: linkage analysis approach. Clin Orthop
2005; 456: pp. 30-5.
10. Reed SD, Hall JG, Riccardi VM, et al. Chromosomal abnormalities associated with congenital contractures
(arthrogryposis). Clin Genet 1985; 27: pp. 353-72.

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11. Witters I, Moerman P, and Fryns JP. “Fetal akinesia deformation sequence: a study of 30 consecutive in
utero diagnoses,” American Journal of Medical Genetics 2002; 113(1): pp. 23-28.
12. Hyett J, Noble P, Sebire NJ, Snijders R, and Nicolaides KN. “Lethal congenital arthrogryposis presents
with increased nuchal translucency at 10-14 weeks of gestation.” Ultrasound in Obstetrics and Gynecology
1997; 9(5): pp. 310-313.
13. Bamshad M, Jorde LB, and Carey JC. “A revised and extended classification of the distal arthrogryposes”.
American Journal of Medical Genetics 1996; 65(4): pp. 277-281.
14. Goksen D, Darcan S, Coker M, et al. “Permanent neonatal diabetes with arthrogryposis multiplex
congenita and neurogenic bladder-a new syndrome?”. Pediatric Diabetes 2006; 7(5): 279-283.
15. Smith H, Galmes R, Gogolina E, et al. Associations among genotype, clinical phenotype, and intracellular
localization of trafficking proteins in ARC syndrome. Hum Mutat 2012; 33(12): pp. 1656-1664.
16. Hășmășanu MG, Bolboacă SD, Drugan TC, Matyas M, Zaharie GC. Parental Factors Associated with
Intrauterine Growth Restriction. Serbian Archives of Medicine 2015; 143(11-12): pp. 701-706.

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Prevalence and Early Out Come of Congenital Heart Disease

MATYAS Melinda1,*, KARI Orsolya2, OBADA Veronica3,


HASMASANU Monica1,*, BLAGA Ligia1, ZAHARIE Gabriela1,*
1 University of Medicine and Pharmacy, Cluj-Napoca, (ROMANIA)
2 County Children’s Hospital, Cluj-Napoca, (ROMANIA)
3 County Emergency Hospital, Cluj-Napoca, (ROMANIA)
* All authors have equal contribution as the first author.

Emails: [email protected], [email protected], [email protected], [email protected],


[email protected], [email protected]

Abstract

Congenital heart defects are the most common congenital diseases .The critical heart defects
require surgery or catheterization in the first year of life. There are environmental factors that
increase the risk for heart malformation like diabetes mellitus, positive family history,
preeclampsia.

Material and methods


The aim of our study was to evaluate the incidence of congenital heart disease in our region,
the association with other malformations and chromosomal disease, the role of the environmental
factors, treatment follow up and influence of pH gas value in predicting immediate evolution.

Results
The study group consist in 197 patients, more male than female. Gestational age in the study
group ranged between 24 and 42 weeks. In 33 cases we identified risk factors: artificial
technique of fertilization (15 cases), preeclampsia (8 cases), diabetes mellitus (9 cases) and
antiepileptic treatment ( 1 case). Of the 197 patients, 29 cases required surgery. Of the 64 (46%)
preterm newborns with PDA, 15 (23.5%) received ibuprofen for closure of the ductus arteriosus
(Chi2 p<0.0001, OR=22.65 [95% CI: 2.9-177.1]). The lactate value at birth was significantly
correlated with vital prognosis in the studied group (p=0.0085).

Conclusion
In the study conducted in our geographical area, the incidence of congenital heart disease
(CHD) was 3,18%. At 32 patients from study group chromosomal abnormalities or different
genetic syndromes were diagnosed. The study evidenced a higher frequency of CHD in
newborns of mothers with risk factors (33 cases). A future study extended to the whole country
would grant more relevant information about prevalence of the heart defects and there outcome.
Keywords: heart defect, new born, risk factors, pH gas value, lactate

Introduction

Congenital heart defects are the most frequent congenital diseases, having an incidence of 1.5
to 8 in 1000 live newborns [1]. Of all congenital heart defects, 25% are critical defects, requiring

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surgery or interventional cardiac catheterization in the first year of life [1, 2]. Ventricular septal
defect (VSD) is the most frequent malformation, about 20-30% of all heart defects [4, 5], being
followed by atrial septal defect (ASD) and patent ductus arteriosus (PDA), then tetralogy of
Fallot (9%), pulmonary artery stenosis, aortic stenosis and coarctation of the aorta (7%),
transposition of the great vessels (5%). [1] There are environmental factors that increase the risk
of heart defects; among these, a positive family history and maternal diabetes are the most
frequent. Some studies report a higher incidence of CHD in neonates born from pregnancies
obtained using assisted reproductive techniques [4, 5, 7, 30] and in pregnancies with
preeclampsia. In maternal and fetal circulation and in the fetal with CHD, there seems to be an
intrinsic imbalance between angiogenesis and antiangiogenesis [3, 4, 7, 8]. Auger et al.,
concluded that preeclampsia with onset before 34 gestational weeks is associated with critical
CHD [8, 9, 30]. The majority of the malformations occur as a result of complex interactions
between environmental and genetic factors. They are probably caused by susceptible genes that
can be influenced by epigenetic and environmental factors [1, 5, 6]. Prenatal diagnosis is an
important link in the evaluation of fetuses with a suspicion of congenital heart defect [25, 29].
Amniocentesis and chorionic villi biopsy for chromosomal diagnosis and fetal
echocardiography are the prenatal diagnostic methods [10, 11]. Pulse oximetry is an important
tool for the screening of CHD. However, it should be mentioned that non -cyanotic heart defects
cannot be identified by this method [20, 21].

Objectives

The aim of the study was to evaluate the incidence of CHD in patients from a level III
Neonatology Center in Romania. The study assessed the frequency of various congenital heart
defects and their association with other malformations, as well as the treatment administered to
cases diagnosed with CHD.

Material and method

We conducted a descriptive, retrospective, non-randomized study in the period January 2014-


December 2016, in Neonatology Department I, Cluj-Napoca, in North-Western region of
Romania. The study group included 197 newborns with congenital heart defects. The study
inclusion criteria were: diagnosis of CHD, born in the study unit or transferred for the purpose of
diagnosis and surgery. The following were analyzed in the study group: risk factors for CHD,
treatment used, diagnosis, presence of other malformations or chromosomal diseases, role of pH
gas values in predicting immediate evolution. Statistical analysis was performed using Microsoft
Office Excel 2010 and Stat Soft Statistics 12 software. The results were considered statistically
significant at p<0.05.

Results

The study group included 197 patients, of which 100 males, 96 females, and one patient with
sexual ambiguity. The rate of death in the study group was 9.6% (19 patients), in the period of
admission to the maternity ward, preoperatively. 25 patients were born from twin pregnancies.
Among twin pregnancies, in 5 cases both children had a CHD.

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Table 1. Incidence of CHD in the study period

Year CHD Total admission %


2014 57 1890 3,02
2015 82 1962 4,18
2016 59 2345 2,52

Gestational age in the study group ranged between 24 and 42 weeks (median: 38), with a
mean of 35.22±5.3 weeks [95% CI: 34.5-34.47].
The birth weight (g) of the study group varied between 500 and 4850g (median: 2765), with a
mean of 2496.48±1114.3g [95% CI: 2339.5-2339.50]. Percentile weight according to growth
curves ranged between 3.6% and 99.6% (median: 36.2%), with a mean of 41%±3% [95% CI:
4%-37%]. Z score was between -2.6836 and 2.641 (median: -0.353), with a mean of -0.33±1.1
[95% CI: -0.5-0.48].
In 139 cases of the studied group, patent ductus arteriosus was described by ultrasound. Patent
ductus arteriosus was described in 75 neonates born at term, of which 35 had PDA without other
ultrasound changes, and 40 had another associated malformation.
Of the 64 preterm newborns with PDA, 18 had different associated CHD. The incidence of
the different types of CHD in the studied group is shown in Figure 2.

Frequency of congenital hearth disease


pulmonary stenosis
Congenital malformation of unspecified cavities
common arterial trunk
left heart hypoplasia
common atrioventricular canal
Double outlet right ventricle
tetralogy Fallot
aortic valve stenosis
mitral insufficiency
DSA ostium secundum
DSV membranos
DSV
coarctation of the aorta
PCA

Fig. 1. GA of the study group 0 10 20 30 40 50 60 70 80 90

Fig. 2. Type and number of CHD diagnosed in the


studied group

In the studied group, 32 newborns had chromosomal abnormalities or other associated


malformations.
In 33 mothers, the presence of risk factors for CHD was detected, thus: in vitro fertilization
(15 cases), preeclampsia (8 cases), diabetes mellitus (9 cases) and antiepileptic treatment (1
case).
Postnatal evolution was monitored based on pH gas value parameters. pH values ranged
between 7 and 7.51 (median: 7.297), with a mean of 7.30±0.1 [95% CI: 7.3-7.27]. In 18.6% of
the cases, severe acidosis was present. Lactate at birth had values between 0.97 and 9.62
(median: 3.21), with a mean of 3.90±2.5 [95% CI: 3.0-3.04]. On an average, lactate values
tended to decrease at the following evaluations. In the study group, there was a statistically
significant correlation between the lactate value at birth and vital prognosis (p=0.0085).

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Fig. 4. Correlation of the


risk of death and lactate
Fig. 3. Frequency of associated abnormalities values

Of the 197 patients, 29 cases required surgery, which was performed in different
cardiovascular surgery centers The rate of death in the study group was 9.6% (19 patients), in the
period of admission to the maternity ward, before surgery.
Of the 64 (46%) preterm newborns with PDA, 15 (23.5%) received ibuprofen for closure of
the ductus arteriosus (Chi2 p<0.0001, OR=22.65 [95% CI: 2.9-177.1]), taking into account the
degree of prematurity (RS=0.42, p<0.0001) and gestational age (T test: p<0.0001, mean
difference=8.25 weeks). Prostaglandin treatment was administered to 17 newborns of the study
group. 25% of the newborns in the study group received mechanical ventilation. Of these, 37
(74%) were premature, and 13 (26%) were born at term. The correlation between gestational age
and mechanical ventilation was statistically significant (p<0.0001).

Discussions

Congenital heart defects have an incidence of 8 in 1000 births [29]. The majority of the cases
have a multifactorial cause: genetic and environmental [17, 24]. In our study 61% of the
newborns, birth occurred at term. Of the 77 preterm neonates, 46 had PDA alone (3 late preterm
between 35-36 weeks, 43 preterm under 34 weeks). Of the cases with PDA in the study group,
64 neonates were premature. In preterms, this abnormality is more frequent, prematurity being a
risk factor for PDA. In neonates born at term, the ductus arteriosus usually closes one week after
birth. In the study group, the higher frequency of PDA in newborns at term was correlated with
the presence of a residual shunt in the patent ductus arteriosus. This is a transient state of the
newborn at term. In the literature, PDA in neonates born at term is reported to be more frequent
in the female sex. In the studied group, there was a higher incidence in males. It is known that
VSD is the most frequent CHD (except for bicuspid aortic valve which is underdiagnosed at this
age), having a frequency of 20-30% [19]. In the studied group, VSD was present in 17.6% of the
cases, similarly to literature data.The second most frequent defect was ASD, with an incidence of
11.6%, similarly to literature data – 10%[5]. SAD predominantly occurs in the female sex [12,
13], but in the studied group, sex distribution was almost equal (F: 18 cases, M: 21 cases).
Coarctation of the aorta, tetralogy of Fallot and transposition of the great vessels are more
frequently reported in males [1]. In the studied group, tetralogy of Fallot was exclusively found
in male newborns, and transposition of the great vessels was detected in 4 males and 2 females.
At females, the most frequent anomalies are ASD, PDA and Ebstein’s anomaly [12, 14].
Maternal risk factors were present in 33 cases, the most frequent being in vitro fertilization
(46%). Iwashima et al., maintain that assisted reproductive techniques are not associated with an

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increased risk of CHD [26]. A study conducted in UK reached the same conclusion [27], while
Panagiotopoulou et al., concluded in their study that twins resulting from assisted reproductive
techniques have a moderately increased risk to develop CHD compared to spontaneously
conceived twins [28]. Maternal diabetes as a risk factor for CHD was evidenced in 9 cases.
Maternal diabetes is the most frequent exogenous cause of CHDand associate: double outlet
right ventricle, common arterial trunk, tetralogy of Fallot, and VSD. In our study we found
associated: PDA, ASD, VSD, tetralogy of Fallot, and transposition of the great vessels.
Preeclampsia was present in 8 cases. The literature reports the presence of interrelations
between CHD and maternal preeclampsia [4, 5, 6, 7]. Brodwall et al., describe a 15 times higher
risk of developing AVSD in newborns of mothers with preeclampsia [7, 8]. In the studied group,
the disorders present in neonates of mothers with preeclampsia were: PDA, VSD, ASD, and
tetralogy of Fallot.
In the study group, 17% of the cases had a prenatal diagnosis. The most frequent prenatally
diagnosed malformations were coarctation of the aorta, atrioventricular canal, double outlet right
ventricle, and tetralogy of Fallot. An increase of diagnostic accuracy was observed in cases
where other abnormalities were associated with the defect [16, 22]. Combining ultrasound
sections and monitoring pregnancy significantly increase the specificity of the method [18, 19,
22].
The evaluation of pH at birth evidenced severe acidosis in 18.6% of the cases (pH<7.2).
Lactate values at birth were correlated with hypoxia and tissue hypoperfusion. Lactate values
ranged between 0.97 and 9.62 mmol/L. A study conducted in 408 patients with CHD who
required surgery concluded that the prenatal diagnosis of the cardiac defect leads to the
minimization of the risk of metabolic acidosis and can be associated with a favorable prognosis
[15, 30]. The lactate value at birth was significantly correlated with vital prognosis in the studied
group (p=0.0085). In a study on patients with tetralogy of Fallot, Bhardwai et al., concluded that
serum lactate and base excess might be used as a prognostic marker of perioperative mortality in
this category of patients [9, 30, 31]. In 17 cases of the study group, prostaglandin therapy was
initiated to ensure survival until surgery. In 12 of these cases, surgery was performed, 3 patients
died in the clinic preoperatively, and other 2 cases died after they were transferred to another
service.

Conclusions

In the study conducted in our geographical area, the incidence of CHD was 3,18%. 32 patients
with CHD in the study group had chromosomal abnormalities or were diagnosed with different
genetic syndromes. The study evidenced a higher frequency of CHD in newborns of mothers
with risk factors (33 cases). pH and lactate values normalized during admission, after the
hemodynamic stabilization of neonates with CHD. The study revealed a significant correlation
between lactate values at birth and vital prognosis. In 29 of the newborns of the study group,
surgery was performed in the perinatal period. It would have been useful to know the
postoperative evolution of the cases, but post-surgical follow-up was carried out by other
services; consequently, only in few cases is long-term follow-up was possible. The aim of the
study was to analyze the situation of CHD in the perinatal period and to assess the incidence of
critical cases that require immediate surgery. It would be useful to extend the study and make a
national analyze of congenital heart disease to have a more relevant view of the local condition.

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Maternal and Newborn Health Research Network. Pre-eclampsia, eclampsia and adverse maternal and
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5. Boyd HA, Basit S, Behrens I, Leirgul E, Bungaard H, Wolfhart J et al. Association Between Fetal
Congenital Heart Defects and Maternal Risk of Hypertensive Disorders of Pregnancy in the Same
Pregnancy and Across Pregnancies. Circulation. 2017; 136(1): pp. 39-48.
6. Llurba E, Sánchez O, Ferrer Q, Nicolaides KH, Ruíz A, Domínguez C et al. Maternal and foetal angiogenic
imbalance in congenital heart defects. Eur Heart J. 2014; 35(11): pp. 701-7.
7. Sliwa K, Mebazaa A. Possible joint pathways of early pre-eclampsia and congenital heart defects via
angiogenic imbalance and potential evidence for cardio-placental syndrome. Eur Heart J. 2014; 35(11): pp.
680-2.
8. Auger N, Fraser WD, Healy-Profitós J, Arbour L. Association between Preeclampsia and Congenital Heart
Defects. JAMA. 2015; 314(15): pp. 1588-98.
9. Brodwall K, Leirgul E, Greve G, Vollset SE, Holmstrøm H, Tell GS et al. Possible Common Aetiology
behind Maternal Preeclampsia and Congenital Heart Defects in the Child: a Cardiovascular Diseases in
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10. Holland BJ, Myers JA, Woods JR. Prenatal diagnosis of critical congenital heart disease reduces risk of
death from cardiovascular compromise prior to planned neonatal cardiac surgery: a meta-analysis.
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11. Zhang YF, Zeng XL, Zhao EF, Lu HW. Diagnostic value of fetal echocardiography for congenital heart
disease: a systematic review and meta-analysis. Medicine (Baltimore). 2015; 94(42): pp. 1-11.
12. Khalil A, Nicolaides KH. Fetal heart defects: potential and pitfalls of first-trimester detection. Semin Fetal
Neonatal Med. 2013; 18(5): pp. 251-260.
13. Nelle M, Raio L, Pavlovic M, Carrel T, Surbek D, Meyer-Wittkopf M. Prenatal diagnosis and treatment
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14. Sotiriadis A, Papatheodorou S, Eleftheriades M, Makrydimas G. Nuchal translucency and major congenital
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24. WHO/CDC/ICBDSR. Birth defects surveillance: a manual for programme managers. Geneva: World
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Prenatal Diagnosis of Kabuki Syndrome

ZVANCA Mona Elena1, PETCA Aida1, BOȚ Mihaela1, MUNTEANU Alexandra1,


NEDELEA Florina Mihaela2
1 Elias University Hospital, Obstetrics & Gynecology Department, University of Medicine and Pharmacy “Carol Davila”,
Bucharest,(ROMANIA)
2 Clinical Hospital Filantropia Bucharest, Human Genetics Department, University of Medicine and Pharmacy “Carol Davila”,

Bucharest,(ROMANIA)
Emails: [email protected]

Abstract

Introduction
The prenatal diagnosis of genetic conditions is focused on the detection of the most frequent
aneuploidies (trisomies 21, 18 and 13) and it is based on a standardized combination including
maternal age, fetal ultrasound measurements and maternal biochemical markers (β-hCG and
pregnancy associated plasma protein A-PAPP-A). In the screening process for aneuploidies,
different fetal pathologies may be detected and a genetic diagnosis is of vital importance in most
cases.

Clinical report
We present the case of a IIG pregnant woman with a fetus which displayed a series of
abnormal findings on serial ultrasound examinations between 11-21 weeks (increased nuchal
translucency and edema, vermian hypoplasia, pelvic kidney, single umbilical artery,
brachicephaly, cardiac malformation, early onset growth retardation). Cell-free fetal DNA in
maternal blood, chorionic villi sampling and micro-array CGH were performed and the results
were normal. At 21 weeks the invasive testing was repeated and Whole Exome Sequencing
(WES) was performed. The results were indicative of type 1 Kabuki syndrome (c.7169C>T
p.(Pro2390Leu); Chr12(GRCh37):g.49434384G>A), but in the laboratory database this mutation
is marked as VOUS (Variant of Unknown Significance). However, the association with multiple
structural anomalies suggests a significant finding. The parents decided for termination of
pregnancy.

Discussion
The technical progress of both the ultrasound examination and genetic technologies has
enabled the prenatal detection of a series of rare genetic conditions. However, findings must be
interpreted with caution and always correlating the ultrasound picture with the genetic result.
Our case is a first report of a prenatal diagnosis of Kabuki syndrome.
Keywords: Kabuki syndrome; prenatal diagnosis; Whole Exome Sequencing

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Introduction

The continuously increasing performance of the ultrasound examination during pregnancy


favors early detection of fetal structural anomalies and subtle dysmorphic features, which are
generically named “markers for genetic disorders”. A series of maternal characteristics (age,
racial origin, obstetric history), standardized ultrasound measurements (nuchal translucency,
nasal bone, the blood flow through tricuspid valve and ductus venosus) and maternal
biochemical markers (β-hCG and pregnancy associated plasma protein A-PAPP-A) have been
incorporated into an algorithm which estimates the individual risk for the most common
aneuploidies (trisomy 21, 18 and 13) at 11-14 weeks of gestation [1, 2, 3]. The management of
pregnancies according to their stratification of risk is also standardized, with minor differences
according to different regulatory bodies and hospital policies. However, in many cases a detailed
ultrasound may detect fetal abnormalities, sometimes multiple, which are highly suggestive of a
genetic condition, other than the most common aneuploidies. Sometimes the anomalies per se
are severe enough as to guide a decision regarding the management of pregnancy. Additional
genetic testing is still required to establish the recurrence risk for future pregnancies. In cases
where there is an association of minor defects or ambiguous ultrasound findings that can be
either normal variants or dysmorphic traits, genetic counseling and testing become essential.
Repeated ultrasound examinations with advancing gestational age and organ development,
sometimes serial invasive procedures (chorionic villi sampling, amniocentesis) become
necessary in these cases and the results are often frustratingly inconclusive.
We present a clinical case that illustrates the long journey from the ultrasound suspicion to the
antenatal diagnosis of a rare genetic disorder.

Clinical report

A 39 years old woman 15 weeks pregnant was referred to our Maternal and Fetal Medicine
Department for increased fetal nuchal translucency (5 mm) measured at 12 weeks during the
routine ultrasound investigation, part of the first trimester risk assessment for aneuploidies.
The patient had a previous pregnancy with suspected trisomy 18 on ultrasound and fetal cell-
free DNA from maternal blood. The pregnancy ended with a spontaneous miscarriage and no
further genetic testing was performed.
During the ongoing pregnancy a cell-free fetal DNA testing from the maternal blood was
carried out at 11 weeks and the results were screen-negative for trisomies 21, 13, 18 and they
were indicative of a male fetus.
The ultrasound examination performed in our unit revealed a fetus with an early delay in
general growth, with measurements of the head circumference and long bones (femur and
humerus) below the 10th centile. The nuchal fold was increased for gestational age (3.6-5.1 mm).
There was a single umbilical artery and the external genitalia were suggestive of a female
fetus. The fetal heart rate was 124 beats per minute (bpm), which represents the 5th centile. There
was bivalvular, tricuspid and aortic regurgitation and the myocardium was generally hyperechoic
and scattered with echogenic foci. Due to the small gestational age a full diagnosis of the heart
anomaly was not possible.
Considering the association of ultrasound anomalies we have decided for further genetic
investigations and we have performed, with patient’s agreement, an invasive procedure,

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chorionic villi sampling. The result of the molecular karyotype, array CGH, was normal (arr(1-
22)x2, (xy)x1).
We reexamined the patient two weeks later, at 17 weeks. The growth was consistent with
previous measurements, with head circumference and long bones around the 10th centile and
normal size of the abdominal circumference. Additional ultrasound findings were: right ectopic
kidney and hypoplastic cerebellar vermis. Even though the cerebellum is not completely
developed at 17 weeks, especially in a fetus with a delay in growth, vermian hypoplasia can be
suspected at the beginning of the second trimester based on the progresses made in visualizing
and understanding the fetal brain at early gestational ages [4, 5]. The nuchal fold continues to be
increased, with a jelly-like appearance and the occiput is flat. Imaging of the fetal heart is
improved and a muscular ventricular septal defect (VSD) becomes apparent. The heart rate is
maintained at 120-130 bpm, with 1 to 1 conduction. The left ventricular outflow cannot be
visualized and there is turbulent flow across the aortic valve. The fetal gender on ultrasound is
ambiguous, but with rather female traits.
After extensive counseling based on the genetic results and the ultrasound findings, the
parents decided for expectant management.
We rescan at 19 and 21 weeks. A summary of the fetal anomalies detected on ultrasound,
suspected during previous scans and confirmed at this gestational age are:
- Mild growth restriction
- Cerebellar hypoplasia with vermian hypoplasia
- Flat profile and brachicephaly (Fig. 1)
- Aortic stenosis and muscular VSD; mild bradiarythmia, progressive (113 bpm)
- Right ectopic kidney
- Single umbilical artery
- Small chest
- Ambiguous genitalia with sex reversal (Fig. 2)

Fig. 1. Ultrasound image of the fetal profile at 19 weeks.


The nasal bone is visible, but the chin is smaller than expected, without clear micrognathia or retrognathia

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Fig. 2. Ultrasound image – sagittal view of the fetal lower abdomen at 19 weeks.
The external genital tubercle is small, with an appearance suggestive of a female fetus

With a very high suspicion of a fetal genetic condition and after genetic counselling, the
parents have decided to continue investigations and amniocentesis was performed. Due to
overlapping structural anomalies with different genetic syndromes, limited availability of time
and taking into account the heterogeneity of genetic disorders, a comprehensive genetic testing
as Whole Exome Sequencing (WES) was achieved. The sample was sent to an external laboratory
for analysis. WES test is able to sequence all coding regions (exons) of human genome. It can
identify exonic mutations that represent the base for most of the genetic conditions. The results
are promising, with a metaanalisys which finds diagnostic rates between 62% and 80% [6].
However, the test is unable to identify mutations in introns, large gene duplications or
deletions. Moreover, it can reveal mutations with uncertain significance, the so-called Variants
of Unknown Significance, or VOUS. These situations are challenging, because they require
additional testing of parents or periodical reclassification according to published data.
WES test detected in our case a heterozygous variant in the KMT2D gene, c.7169C>T
p.(Pro2390Leu); Chr12(GRCh37):g.49434384G>A. According to OMIM classification the
mutation corresponds to Kabuki syndrome 1 (147920, AD). According to the laboratory
database, it is a first time detection of this variant, which was previously listed as variant of
uncertain significance (class 3), in concordance with the recommendations of ACMG (American
College of Medical Genetics and Genomics).
Although the mutation was listed as VOUS, in our case it cannot be considered an incidental
finding, taking into consideration the association of structural anomalies, which correlate with
the description of Kabuki syndrome. Considering the genetic results, the associated
malformations, the deteriorating fetal hemodynamic status with development of cardiac
insufficiency and progressive hydrops, the parents decided for termination of pregnancy [7, 8].
Severity of the natural evolution in our case guided parental choice. In other circumstances,
the decision based on VOUS mutation could have been more reticent. This is actually the most
difficult point in prenatal testing.
Further action includes the need to test the parents in order to demonstrate de novo character
of mutation and predict the recurrence risk.
The postabortum images reveal a particular facial dysmorphism with hypertelorism,
downslanting eyelids, low-set years, small chin, flat occiput and a special impression of “happy
face” (Fig. 3). The external genitalia confirmed the ambiguous appearance suspected on
ultrasound (Fig. 4). No other external anomalies were present.

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Fig. 3. Postabortum image of the fetus.


Widely spaced eyes, with down slanting palpebral fissures, broad nasal root and small chin are distinctive elements

Fig. 4. Postabortum image of the fetal external genitalia – partially fused scrotum and a small genital tubercle

Discussions

Kabuki syndrome is a rare genetic condition first described in 1981 in Japan by Niikawa and
Kuroki. The incidence in Japanese population is apparently higher than in other populations, 1 in
32,000 newborns [9] compared to 1 in 86,000 in Australia and New Zeeland [10]. A series of
clinical diagnostic criteria were established in 1988 [9] based on examination of a group of 62
patients with Kabuki syndrome. The genetic base of Kabuki syndrome was identified in 2010
using exome sequencing. The initial MLL2 gene was later renamed KMT2D [11] and mutations
in a different gene, KDM6A were described in association with type 2 Kabuki syndrome [12].
Until 2013 more than 350 cases were reported and the spectrum of clinical features became
more divers.
The initial summary of the clinical characteristics included five categories:
1. Typical facial features with elongated palpebral fissures and arched eyebrows (a constant
feature);
2. Minor skeletal anomalies (in 92% of cases);
3. Dermatoglyphic anomalies with persistence of high finger pads (93%);

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4. Mild to moderate intellectual disability (in 92%). In some cases the neurological
impairment has an underlying structural brain abnormality. Posterior fossa anomalies,
such as vermian hypoplasia and Dandy – Walker malformation have been described in
several cases [13, 14, 15];
5. Postnatal growth deficiency (83%).
However, the phenotype may display a variety of structural defects such as:
- congenital heart defects: aortic stenosis, coarctation of the aorta, tetralogy of Fallot, atrial
and ventricular septal defects [16];
- genitourinary anomalies
- cleft lip/cleft palate;
- ophthalmologic anomalies (ptosis, strabismus);
- gastrointestinal anomalies (feeding difficulties mainly related to hypotonia);
- dental anomalies (widely spaced teeth, hypodontia);
- large, prominent ears with ear pits;
- anomalies of the immune system with increased susceptibility to infections and
autoimmune diseases;
Many of these features may be detected antenatally by ultrasound, sometimes as early as the
first trimester. In our case particular features, as uncommon prenatal growth restriction and
ambiguous genitalia, additional to heart and cerebellar malformation, may correlate with a more
severe phenotype. We appreciate that these findings helped prenatal identification and parental
decision in this situation.
The progress in genetic testing and the introduction into clinical practice of techniques such as
whole exome sequencing opens the door to early diagnosis of many rare genetic conditions. The
most challenging aspect will remain the correct interpretation of the results in the context of a
good quality, detailed ultrasound scan and within the limited window of time for decisive
management of pregnancy.
Our case is a first time report of a Kabuki syndrome diagnosed antenatally.

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