NEONATAL PHYSIOLOGY

AND TRANSITION PERIOD

Dr. Muhammad Usman Hashmi

MBBS, MD. (USA)
PGT Physiology
RMU Rawalpindi
 LEARNING
OBJECTIVE

physiological changes which take place

following birth and appreciate the
unique aspects of
neonatal physiology including:

1) limited reserve capacity for temperature

control, cardiovascular and respiratory function
2)variable and individualized fluid requirements
3) implications of hepatic and renal immaturity
 INTRODUCTION

NEWBORN-first 24 hrs of life

NEONATE-from birth to under four weeks(<28 days)

TERM NEONATE-between 37 to < 42 gestational week

PRETERM NEONATE-<37 gestational week irrespective
ofBW
POST TERM NEONATE-> or egual to 42 gestational
week

LOW BIRTH WEIGHT(LBW)<2500 GRAM irrespective of birth weight

VERY LOW BIRTH WEIGHT(VLBW)<150O GRAM
EXTREMELY LOW BIRTH WEIGHT(ELBW)< 1000 GRAM
FETAL
CIRCULATION
FETAL
CIRCULATION
AIM

✓Oxygenated placental blood is preferentially delivered to the brain,myocardium and

upper torso
✓lower oxygen tension blood distributed to the lower body and placenta
✓Preferential splitting is achieved via intra- and extracardiac shunts that direct
blood into two parallel circulations (the left ventricle providing 35% and the right
65% of cardiac output. )

Fetal cardiacoutput is therefore measured as a combined ventricular output closure

of the intracardiac (foramen ovale) and extracardiac shunts (ductus venosus and
ductus arteriosus)
 FETAL CIRCULATION
(PARALLEL
CIRCULATION)
✓ Oxygenated blood via umbilical vein either through the liver or via the ductus
venosus to reach IVC

✓ blood remains on the posterior wall of the inferior vena cava, allowing it to
be directed across the foramenovale into the left atrium by the Eustachian
valve

✓ blood passes left ventricle and aorta to supply the head and upper torso.

✓ deoxygenated blood returning from the SUPERIOR vena cava and myocardium via
the coronary sinus is directed through the right ventricle and into the
pulmonary artery.

✓ Most of this blood is returned to the descending aorta via the ductus arteriosus;
( 8-10%of total cardiac output passes through the high-resistance pulmonary
circulation.)

✓ Blood in the descending aorta either supplies the umbilical artery to be

reoxygenated at the placenta or continues to supply the lower limbs.
 PHYSIOLOGICAL CHANGES AT
BIRTH
UMBILICAL VESSELS- IMMEDIATELY AFTER CLAMPING:
➢ constrict in response to stretching and increased oxygen content at delivery
➢ large low-resistance placental vascular bed removed from the circulation
➢increase SVR
➢Reduction of blood flow along ductus venosus (passive closure over the following 3-7 days),reduced
blood flow in IVC

Lung expansion
➢drops pulmonary vascular resistance
➢ increase in blood returning to the LA
These two changes reduce right atrial and increase left atrial pressures, functionally closing the
foramen ovale within the first few breaths of life
 TRANSITION AT
BIRTH
Successful transition from fetal to postnatal circulation requires

➢ clamping of umbilical cord and removal of the placenta

➢ increased pulmonary blood flow,

➢Shunt closure
RESPIRATORY CHANGES

What part do each of these factors

play in initiation of respirations in the
neonate?

Mechanical
Initiation
of
Breathing Chemical

Sensory/ Thermal
 CHANGES AT
BIRTH….MECHANICAL
Compression of fluid from the fetal lung during vaginal delivery
establishes the lung volume

As the chest passes Subsequent recoil of the

through the birth canal chest wall produces
the lungs are compressed passive inspiration of air
into the lungs

Negative inspiratory pressures of up to 70-100 cm H2O are initially

required to expand the alveoli (LaPlace’s relationships) which
facilitate lung expansion by overcoming:
airways resistance
inertia of fluid in the airways
surface tension of the air/fluid interface in the alveolus
CHEMICAL
EVENTS
1. With cutting of the cord, remove oxygen supply

2. Asphyxia occurs

3. CO2 and O2 and pH = ACIDOSIS

4. Acidotic state-- stimulates the

respiratory center in the medulla and
the chemoreceptors in carotid artery to
initiate breathing
SENSORY / THERMAL
EVENTS
Thermal-- the decrease in

environmental temperature after

delivery is a major stimulus of
breathing

Tactile-- nerve endings in the skin

are
stimulated

Visual-- change from a dark world to

one of light
 BIOPHYSICAL CHANGE
CONTINUED
1)Alveolar distension, cortisol and epinephrine further stimulate type II
pneumocytes to produce surfactant

2) Expiration
✓ initially active,
✓pressures of 18-115 cm H2O generated
✓amniotic fluid forced out from the bronchi.

PHYSIOLOGICAL CHANGES LEAD TO-

▪ increasing blood flow
▪ and initiating the cardiovascular changes

.
 SHUNT
CLOSURE
physiological reverse shunt from left to right commonly occurs.

FORAMEN OVALE
✓ completely closed in 50% of children by 5 years
✓ remains probe patent in 30% of adults,
✓ can facilitate paradoxical embolus and potential stroke.

DUCTUS ARTERISUS-
✓ drop in pulmonary artery pressure and increase in SVR reverses
flow across the ductus arteriosus from L TO R
✓ affected by blood oxygen content
✓ circulating prostaglandins. E2
✓ Functional closure occurs by 60 hours in 93% of term infants.,4-8
weeks permanent structural closure occurs via endothelial destruction
and subintimal proliferation.
CARDIOVASCULAR
CHANGES
3. Ductus Arteriosus
begins to constrict
2. Blood flows
to the lungs

4.Pressure in the
1. Pressure LA increases RT
in RA decreases Flow of blood
from the lungs
5.Increase pressure
in the LA forces
the foramen ovale
to close
 SHUNT
CLOSURE
IMPORTANT-

stimulus such as hypoxia, acidaemia or structural anomaly can increase

pulmonary vascular resistance and potentially re-open the ductus arteriosus or
foramen ovale. which allows a right-to-left shunt, which worsens hypoxia
. Eg seen in persistent pulmonary hypertension of the newborn.
 NEONATAL MYOCARDIAL
FUNCTION
➢term neonatal cardiac output is approximately 200 ml/kg/minute

➢fewer myofibrils in a disordered pattern,

➢Less mature sarcoplasmic reticulum and transtubular system -nt

➢dec CA-ATP ACTIVITY,dependent on exogenous ionized calcium

➢follows the Franke Starling relationship of filling pressure to stroke volume, but
on a much flatter section of the curve compared with adults. i.e limited increase in
stroke volume for a given increase in ventricular filling volume.

➢dependent on heart rate to increase cardiac output and cardiac output can
respond to increased ventricular filling.
➢3 month parasympathetic vervous system effect more developed than
sympathetiv
➢Baroreceptors not well developed compared to chemoreceptorsfurther depressed
under anaesthesia-bradycardia
Ventricular maturation and associated
ECG changes
The fetal heart - right-side dominant, with the right ventricle
responsible for 65% of cardiac output in utero.

The neonatal ECG reflects

➢ RAD
➢R wave dominance in lead V1
➢S wave dominance in lead V6.

At 3-6 months
the classical LAD pattern established
as ventricular hypertrophy occurs in response to increased systemic
vascular resistance
 LOW CARDIAC
RESERVE-
Left ventricle has high tone has limited contractile
reserve due to;-

▪ Reduced no of alpha receptors

▪ High level of circulating cathecholamines
▪ Limited recruitable stroke volume
▪ Immature calcium transport system
▪ Dec ventricular compliance
▪effect of parasympathetic nervous system is more
predominent
▪Beta adrenergic receptors are more developed
than alpha thus respond better to dobutamine and
isiproterenol
 MYOCARDIAL
METABOLISM
neonates can tolerate hypoxia better due to
➢High concentration of glycogen
➢More effective utilisation of anaerobic metabolism
➢Hence can be resusitated easily if oxygenation and
perfusion are reestablished

Oxygen consumption increases after birth( at

neutral temperature )
Full term child
➢At birth-6ml/kg/min
➢10 days- 7 ml/kg/min
➢4 week-8 ml/kg/min
CARDIAC
VALUES
 FETAL RESPIRATORY
SYSTEM
ALVEOLAR DEVELOPMENT
✓Continues even after birth
✓At birth 24 million alveoli
✓increases fivefold in -300
million by 8 years of age
✓Initally increases in no
, further increase by inc in
size and airway development

Lungs develop from the third

week of gestation with
completion of the terminal
bronchioles by week 16
 FETAL RESPIRATORY
SYSTEM
SURFACTANT
✓type I and II pneumocytes are distinguishable only by 20-22 weeks
present only after 24 weeks,
✓the watershed time for pulmonary gas exchange and
therefore extra- uterine survival
✓production can be increased after 24 weeks by giving
betamethasone to the mother, thereby improving neonatal lung
function if premature delivery is anticipated

APPLIED
➢seen preterm babies
➢ decreases the compliance
– risk for respiratory distress syndrome
, bronchopulmonary dysplasia
and pulmonary hypertension
RESPIRATORY
SYSTEM
Diaphragm-two types of fibres

Type 1-slow twitch, highly

oxidative ,sustained contraction
,less fatigue
Type 2-fast twitch, low oxidative
,quick contraction and easily
fatigued

New born have 25% TYPE-1,

(PRETERM 10%),BY AGE OF TWO
YRS 55%
APPLIED-risk of diaphragmatic
NEONATAL
AIRWAY
 NEONATAL
AIRWAY

✓ Larynx is funnel shaped

✓ narrowest portion is cricoid – uncuffed
tube preferred(micro cuff useful ,costly)
✓ Large size of the tongue-increases chances of
obstruction and difficult laryngoscopy
✓ Higher level of larynx( c3 in preterm,c4 in term
and c5-c6 in adults)-straight blade more useful
✓ Epiglottids- short,stubby,omega shaped,
angled over laryngeal inlet-control with
laryngeal blade more difficult
✓ Tip of epiglottids lies at c1, with close
apposition with soft palate-allows
simultaneously sucking and breathing
✓ Vocal cords angled-blind intubation ,tube
may lodge at anterior commisure
✓ Large occiput- more flexion may lead to
DEVELOPMENTAL CHANGES OF
RIB CAGE

Chest wall development

▪ Ribs oriented parallel and

unable to increase the
thoracic volume during
inspiration

▪ At 2 yrs old associated

with standing and walking,
ribs are oriented oblique

Cartilaginous structure with

inward movement during
inspiration
 NEONATAL LUNG
MECHANICS
imbalance exists between chest wall rigidity and elastic recoil of
neonatal lungs. ( CONTAIN IMMATURE ELASTIC FIBRES, thus
tendency to recoil)

➢increase closing capacity to the point of exceeding

functional residual capacity ( FRC) until the age of 6.
➢To counteract this, neonates produce positive end expiratory
pressure( PEEP) via high resistance nasal airways and partial
closure of the vocal cords
➢Limited Inspiratory reserve volume
➢Minute volume is maintained by high respiratory rate
➢Respiratory fatigue common
Neonatal lung mechanics-gas exchange

❑ immature in neonates,
❑total shunt estimate of 24% of the cardiac output at birth, reducing to 10% of
cardiac output at 1 week.
❑rapid reduction in shunt fraction improves arterial oxygenation and reduces the
effort of breathing.

implications during anaesthesia.

➢ effective FRC is reduced( physiological PEEP and intercostal muscle tone is lost)
➢ along with an increased shunt fraction and
➢High metabolic rate (6-8ml ofO2/kg/minute),
➢These factors contribute to a potential rapid desaturation in neonates under
anaesthesia.
Control of ventilation
Peripheral chemoreceptors
✓functional at birth but are initially silent because of high post delivery
blood oxygen content.
✓Receptor adaptation occurs over 48 hours,

APNOEA OF PREMATURITY
neonates exhibit periodic breathing pattern defined as an apnoea of less than
5 seconds often followed by tachypnoea.,

Premature neonates exhibit apnoeic episodes of more than 15 seconds or

a shorter period a/w fall in heart rate
➢ due to loss of central respiratory drive
➢ improves with maturity
➢ may persist up to 60 weeks postconceptual age
➢Anaemia i.e. haematocrit<30% is any independent risk factor
RESPONSE TO
HYPOXIA

characterized by
1)an initial increase in ventilation followed by a decrease in ventilation;
2).much rapid than adults due to low resting carbon dioxide

Response Varies with

➢ temperature,
➢level of arousal
➢and maturity

.
 PERSISTENT PULMONARY HYPERTENSION
OF THE NEW BORN/PERSISTENT FETAL
CIRCULATION
PATHOPHYSIOLOGY
hypoxia, acidosis and inflammatory mediators
l/t persistent increase in pulmonary artery
pressure
persistent fetal circulation
Ppt condition-
➢birth asphyxia,
➢meconium aspiration
➢sepsis,
➢CDH,
➢maternal use of nsaids,
➢GDM,, casearen delivery
Leads to R TO L shunt resulting in
profound hypoxia,with elevated PCO 2
 PERSISTENT FETAL
CIRCULATION

Goal-
Pa CO2-50 TO 55mmhg and Pao2-50-70 mmhg
MANAGEMENT:-
1) treat precipitating condition eg hypoxia,hypoglycemia
2) Inhaled nitric oxide
3) Mechanical ventilation
4)high frequency ventilation
5) exogenous steroids
6) inhaled steroid
7) ECMO
8) experimental-
slidnafil
 MECONIUM
ASPIRATION

➢ Marker for chronic hypoxia in utero in third trimester due to

interferance in maternal circulation
➢ passage of meconium in utero-fetus breathes in meconium
mixed amniotic fluid enters in pulmonary circulation
➢ Leads to varying degree of respiratory distress
➢ Increase in amount of amount of musle in blood
vessels of distal respiratory units
 GUIDELINES FOR MANAGEMENT
FOR MECONIUM ASPIRATION

“If the baby is not vigorous (Apgar 1-3 ): Suction the

trachea soon after delivery (before many
respirations have occurred) for ≤ 5 seconds. If
no meconium
retrieved, do not repeat intubation and suction.
If meconium is retrieved and no bradycardia
present, reintubate and suction. If the
heart rate is low,
administer PPV and consider repeat suctioning.
“

“ If the baby is vigorous (Apgar >5): Clear secretions

and meconium from the mouth/ nose with a
 Thermogregulation

✓2.5-3.0 times higher surface area BW

✓limited insulating capacity from subcutaneous fat and
✓the inability of neonates to generate heat by shivering until 3 months of
age.

Heat loss
1) radiation(39%)
2)convection (34%)
3)evaporation (24%) and
4)conduction(3%).

THERMOGENESIS
1) by limb movement and
2) by stimulationof
brown fat (non-
shivering
thermogenesis).
 B
a
b
Rad Cond Conv Evap
iati ucti
y ecti orati
on on on on
Co l d R o Cold Be d N e Wet
om Te Sc a r A ir V D ia p
mp. a le ent er
C o ld Cold X- Oxyge B
W ray pl n le f at
a l ls ates t on h
Co l d I Cold P a s s in Tac
BROWN FAT

➢6% of term bodyweight (dec in preterm)

➢found in the interscapular region, mediastinum, axillae, vessels of the neck and
perinephric fat
➢highly vascular with sympathetic innervation
➢high mitochondrial content to facilitate heat generation

Non-shivering thermogenesis

. 1 . Skin receptors perceiv e a drop

in environmental temperataure
2. Transmit impulses to the central
nervous system
3. Which stimulates the sympathetic
nervous system
4. Norepinephrine is released at local
nerve endings in the brown
5.Metabolism of brown fat
6. Release of fatty acids
 HEAT
CONSERVATION

heat loss minimized by

➢ increasing the temperature of the surrounding environment.

CAREFUL;- the environmental temperature exceeds neonatal

temperature then heat will be gained, which can be harmful as the
ability to sweat is present only after 36 weeks postconceptual age.)

➢by warming surrounding air and minimizing air speed across the
baby’s skin,

➢increasing ambient humidity and reducing air speed across the

neonate.

➢Insensible water loss through the skin can be minimized by putting

the preterm neonate in a plastic bag or covering the body,and
especially the head
Haematology

contains both adult (HbA) and fetal haemoglobin

HbF
➢70-80% upto 90% in preterm
➢four globin chains alpha2delta2
➢greater affinity for oxygen and helps maintain
the molecular structure and
function in a more acidic environment
➢facilitates oxygen transfer across the placenta
from maternal HbA.
➢replaced with HbA at approximately 6 month of
age.

Postdelivery,

increase in 2,3-diphosphoglycerate levels, shifting

the oxygen dissociation curve to the right,
 HAEMATOPOIESI
S
occurs in the liver in utero
but is restricted to bone marrow from 6 weeks post delivery,
thus limiting potential sites for haemoglobin synthesis.

PHYSIOLOGICAL ANAEMIA OF INFANCY

❑Occcurs around 8-10 week of age
❑HbF is lost faster than HbA is synthesized.
❑ low levels of erythropoietin due to improved tissue
oxygenation after birth
❑decreased lifespan of HbF-laden red blood cells
❑ relative increase in the blood volume,
These factors contributes to the shrinking cellmass
 Hepatic

➢Most enzymatic pathways are present

➢inactive at birth
➢become fully active at 3 months
➢Albumin level low-more free drug in circulation
➢Risk of hypoglycemia-low glycogen stores and dec synthetic function

UNCONJUGATED HYPERBILIRUBINEMIA

Unconjugated bilirubin levels rise during the first 48 hours

❑ rapid breakdown of HbF
❑poor conjugating abilities of the immature liver.
❑exacerbated in presence of haemolysis, sepsis, dehydration or excessive bruising;
❑ can cross the blood brain barrier
❑kernicterus and subsequent developmental delay.
❑Bilirubin levels gradually fall over the first 2weeks,
❑ jaundice in term infants being rare beyond this period
Clotting factors
1) do not cross the placenta;
2)factors V, VIII and XIII are at adult concentrations before birth.
3)vitaminK-dependent clotting factors (II, VII, IX, X, protein C and S) are
initially low

# because of a lack of vitamin K stores and

# immaturehepatocyte function causing a prolongation in prothrombin time

.4)Platelet function diminished due to low levels of serotonin and adenine

nucleotides, despite platelet counts in the adult range

VITAMIN K PROPHYLAXIS

#Breast milk is a poor source of vitamin K

#Endogenous synthesis by the gut flora is not established for the first few weeks
after birth.
#protect against haemorrhagic disease of thenewborn
 Renal

EXCRETORY FUNCTION
➢1 million nephrons is present by 34 weeks ’gestation.
➢The glomeruli and nephrons are immature at birth
➢Low GFR and limited concentrating ability.
➢ Suseptible to both dehydration and volume overload
➢Lack of renal medulla osmotic gradient and absence of medullary tubules limit
urinary concentrating ability,half that of the adult (1200-1400 mOsm/kg)
➢Glycosuria and aminoaciduria are commonly detected because of immature active
transport pumps in the proximal tubule.

ENDOCRINOLOGY
Renal immaturity affects vitamin D formation and calcium homeostasis.
The fetus and neonate have a high calcium and phosphate requirement for bone
formation and growth.
 BODY FLUID
COMPOSITION
✓75% of TBW,80-85% IN PRETERM
✓Reduced to 60-65% BY one year
✓ECF:ICF IS 2:1,
✓The diuresis reduces the extracellular water
(30% of TBW) and ICF increases due to growth
of cellls-
✓reaches adult value by 1 yr

✓Blood volume
Full term-85 ml /kg
Preterm90-100 ml /kg(50 ml/kg is plasma)

✓important postnatal adaptation to facilitate

lung function and reduces the risks of
symptomatic patent ductus arteriosus,
necrotizing enterocolitis and bronchopulmonary
dysplasia
 FLUID
THERAPY
MAINTAINENCE FLUID-
70,80 ,90,120 ml/kg on day 1/3
/5/7 Rest period-150 ml/ kg/ 24hr

Fluid choice
FIRST 48 hrs-10 %
glucose Higher in pre
term
Na and k 2-3 meq/100 ml
Beyond that- 5% glucose(preterm higher
glucose requirement)
IMPORTANT-newborn of diabetic mother, small for
gestational age, glucose monitoring must
 NERVOUS
SYSTEM

➢ precocious in development ,

➢continues to develop to achieve a full complement of cortical and brainstem cells

by 1 year.

➢neonatal cerebral circulation receiving one-third of cardiac output compared with

one-sixth of cardiac output in adults

➢The blood brain barrier is immature in the neonatal period

➢ increased permeability to fat-soluble molecules

➢potentially increasing the sensitivity to certain anaesthetic drugs(

 NERVOUS
SYSTEM
➢ Cerebral autoregulation is fully developed at term, maintaining cerebral perfusion
down to a mean arterial pressure of 30 mmHg, reflecting the lower blood pressures
found in neonates.

➢ ANS better developed to protect against hypertension than hypotension because

the parasympathetic system predominates., reflected in the propensity of
neonates to bradycardia and relative vasodilation.
➢ Delayed myelination-easier intraneural penetration of LA,short time of onset
and diluted conc as effective as concentrated
 NOCICEPTION

➢ pathways are developed by 24-28 weeks’ gestation,

➢The concept of neonatal nociception is now widely accepted, with adultlike

physiological stress and behavioural responses to a noxious Stimulus

➢ Neonates undergoing awake nasal intubation increase mean arterial

pressure by 57% and intracranial pressure by a similar amount.

➢ Noxious stimulus exposure in the neonatal period can also affect behavioural
patterns in later childhood, suggesting adaptive behaviour and memory for
previous experience
 IMMUNOLOGIC
ADAPTATION

Active acquired immunity

▪ Pregnant woman forms antibodies herself

Passive acquired immunity

▪ Mom passes antibodies to the fetus
▪ Lasts for 4-8 months

▪ Newborn begins to produce own immunity about 4 weeks of

age
KEY
POINTS
KEY
POINTS
THANK
YOU