Fetal and Neonatal Physiology:

Amniotic fluid:

Volume varies in range of 500 – 1500ml. Vol peaks at ~34/40, then slowly decreases.

Functions: - protection @ physical impacts (“cushion”)

- route for recycling of fetal renal output
- space for “symmetric” fetal growth
- helps distribute pressure of uterine contractions evenly over fetus

Formation: Ultrafiltrate of fetal plasma in early pregnancy (~ part of fetal ECF)

Late pregn = mainly fetal urine. Swallowed by fetus, reabsorbed in
Fetal gut. Turnover ~ 1-2 days.

Respiratory changes at birth:

 loss of placental gas exchange

 initiation of ventilation of newborn’s lung
 start of pulmonary gas exchange
 establishment of FRC

 Physiology of the First few breaths:

Pre-delivery fetal lung contains ~ 20ml/kg fluid. Some expelled with thoracic
compression during vaginal delivery. Rest rapidly absorbed + replaced by air.
1st breath requires very large negative ITP’s (–60 to –70 cmH2O)  subsequent breaths
progressively less negative ITP needed because of establishment of air-liquid interface +
role of surfactant at this interface.
FRC rises rapidly after 1st breath  by 10mins FRC ~ 17ml/kg
 by 30 – 60min ~ 30 ml/kg! (adult value = for rest of life)

CVS changes at birth: (see addendum at back)

 Loss of umbilical circulation to placenta

 Closure of ductus venosus
 Functional closure of foramen ovale
 Closure of ductus arteriosus (reversible)(DA less responsive to O2 in prems)
 Large increase in pulmonary circulation secondary to large drop in PVR (reversible)

Q: Describe the sequence and relationship of these events

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 Physiological differences in neonate/infant

Classification:

Neonate: 1st 28 days

Infant: 28 days to 1 yr

A) Cardiovascular:

Term 6/12 1yr 2yr 5 yr 12yr adult

___________________________________________________

HR 130 120 120 105 90 70 75

___________________________________________________
SBP 80 90 96 100 94 113 120
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DBP 45 60 66 64 55 60 80
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SV 4.5 7.4 11.5 17 28 53 85
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VO2 6 5 5.2 6.4 6 3.3 3.3
___________________________________________________
Hb 16.5 11.5 12 12.5 12.5 13.5 14
___________________________________________________
P50 18 24 27 27

Notes:

- Rule of thumb: SBP in kids ~ 80 + (age x 2)

- Heart rate: although basal HR is higher c/f adults, vagal stim, anaes Rx OD,
and hypoxia  severe bradycardia + dramatic drop in CO (3 major
causes for bradycardia are, hypoxia , vagal stim, volatiles )
- CO : = HR-dependant because of fixed SV (non-compliant + poorly developed LV)
- SNS + baroreflexes not fully mature. CVS has blunted response to exogenous
catecholamines (ca) as well as lowered ca-stores. Less able to respond to hypovol
with vasoconstriction. Hallmark of iv vol depletion in neonates/infants = hypotension
without tachycardia.
- Blood volume: neonate =90ml/kg and infant ~ 80
- Premature babies / neonates: - rule of thumb; MAP ~ PCA in weeks.
Hb 19g/dl

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B) Respiratory system:

CL Csp MV I:E FRC VO2 CV P50 RR DS TV Shunt (A-a)O2

(ml/kg) (ml/kg) (ml/kg) (ml/kg) (mmHg)

Neonate 5 .05 220 1:1 30 6 12 18 40 2.2 7 10% 25

Adult 200 .05 100 1:2 30 3.3 7 27 13 2.2 7 2-5% 5

ABG:

Prem term 1/12 1yr

PH 7.37 7.4 7.41 7.39

PO2 60 70 95 93
PCO2 37 39 40 41
HCO3 20

Notes:

-Airway resistance: 15 fold higher ( 25 vs 1.6 cmH2O/l/s)

Site: Neonate – nose 28%, upper airway 46% , LRT 26%
Adult - nose 62% , URT 34% , LRT 4%
- Resp system fully developed @ 8yrs (SA 8  70 sq m)
- CC > FRC and CC only equals FRC @ ~ 6yrs  atelectases + V/Q mismatch
MR’s + diaphragm splinting with GA’s further decreases FRC.
- Diaphragm: = most important muscle for resp in neonates/inf’s. Until 1yr , diaphr has
only 30% type 1 fibres (slow contr/high oxidative) easily fatigued by e.g. incr
Rairway or impaired fx. Also, diaphr inserts horizontally, thus mechanically inefficient.
- Because of above factors, controlled ventilation should be used in all
neonates/infants (unless very short procedures)
- Breathing pattern = sinusoidal with no expiratory pause
- TV = limited by horizontal rib-cage  only way to incr VA is by incr RR.
- Respir response to O2 and CO2 = N in term, but decr in prems.
- I:E ratio of 1:1 + expiratory grunting (relatively high upper airway resistance) =
ways to provide “auto-peep”
- Less bronchial SM – less bronchospasm and less responsive to bronchodilators

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C) Airway :

- Large head + occiput incr flex of neck + pot obs (pharyngeal

buckling)
- Tongue relatively large for oropharynx. Genioglossus m is very
sensitive to anaes  obs/diff airway.
- Epiglottis: large + floppy+ U-shaped (use straight blade)
- Larynx;- higher(C3/4 vs C5/6) + anteriorly tilted
funnel shaped. The cricoid = narrowest part of URT
- Trachea: diam 6mm vs 14 mm
Length = proportional to weight = ave 5cm

D) Renal :

Esp re Prems: - decr creat clearance (s-cr ~ 70 umol/l and 20 -70 umol/l at 1 month old)
- 1-9yr old (s- creat 10-60 umol/l)
- decr Na retention (oblig salt losers)
- However, also poor capability of handling high salt loads
- decr diluting + concentrating ability
- decr glucose excretion + decr HCO3 reabsorption, -former is offset by
tendency towards hypoglycaemia in neonates/prems/SGA/diabetic
mother

E) GIT :

- Several studies show decr pH + incr gastric vol, but prolonged fasting
may incr gastric vol  so, receiving clear fluids up to +/- 2hrs pre-op
may result in lower gastric vol+ incr pH

F) Fluid requirements:
- Note: TBWater = 80% of TBWeight (c/f 60% in adults)
- Water: D1 = 2ml/kg/hr (50-60ml/kg/d). D2 = 3ml/kg/hr.
D3 and beyond = 4,2,1 rule.(note: D = day of life)
- Electrolytes: Na = 3-5mmol/kg/d
K = 2-3mmol/kg/d Cl= 1-3mmol/kg/d
- peri-op Glucose: 120mg/kg/hr (=enough to prevent hypoglycaemia)
- note: lower N limit for BSL . In infants > 3d = 2.2mmol/l

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G) CNS:

- decr central control of respiration (esp prems ++ prone to apnoea)

- decr ventil response to CO2 in prems ( N in term babies)
- MAC: Halothane : -neonate = .87 1-6months = 1.08
Isoflurane : - neonate = 1.6% 1-6m = 1.87
- prem <32w =1.28 32-37w = 1.4
Sevo : - neonate – 6 month = 3.2 –3.3 6m-12 yr = 2.5%

H) Thermoregulation and metabolism:

- “Poikilotherms” – large BSA:Wt  more susc to T changes 2o to radiation,

convection and evaporation.

- Thermoneutral zone: = range of ambient T’s where VO2 =minimum

Prem=34-36 C, Term =32-34 C, adult = 25-30 C

- Neutral T (NT) : = ambient T where VO2 minimum

Prem=34C, Term= 32C, adult = 28C
- Critical T (CT): Ambient T where naked, non-anaesthetised cannot maintain N core T.
Prem = 28C, Term = 23C, Adult = 1C

- Interthreshold range: = range of core T’s between which no autonomic

responses triggered.

- Problems specific to neonates/prems: - large BSA, - little insulating fat,

-open/flaccid posture, - rel large head with prop large blood flow, - decr central control of T-
regulation, - less able to compensate with behavioral mech’s e.g. clothe/fan etc, - large MV.

- Response to COLD : -behavioral (crying)  skin vasoconstriction 

Non-shivering-thermogenesis (NST)   muscle activity /movement
  contin cold stress  bradycardia /apnoea / hypoglycaemia/ m acid
NB : prems and newborns (< 3 months) cannot shiver!

NST: =includes (not restricted to) metabolism of brown fat (uncoupling of oxidative
Phosphorylation) incr heat prod/gram fat. Brown fat found in abdomen (perinephric),
around large blood vessels, interscapular area and base of neck. Contrib to 2-6% of neonates’
TBWt.
Heat is generated by signaling the mitochondria to allow protons to run back along the
gradient without producing ATP (proton leak). This can occur since an alternative return
route for the protons exists through an uncoupling protein in the inner membrane. This
protein, known as uncoupling protein 1 (thermogenin), facilitates the return of the protons
after they have been actively pumped out of the mitochondria by the electron transport chain.
This alternative route for protons uncouples oxidative phosphorylation and the energy in the
PMF is instead released as heat. (PMF = proton motive force)
NB: Oxygen needed for met of brown fat,  combination of cold +hypoxia=BAD
Incr brown fat met also redirects CO to brown fat (up to ~25%)  direct heating of blood as
well.
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- Response to HEAT: - behavior (crying/remove coverings) skin vasodilation 
sweating.
NB: prems cannot sweat at all. Ability to sweat is limited in neonates, but
evaporative heat loss much more effective c/f adults because of large BSA.

- Due to large BSA, metabolism and its associated parameters (VO2, VA, CO) correlate
better with BSA than with weight.
- Some rules of thumb:
- Weight (50th centile) = ~ (age x 2) + 9
- Calculation of drug doses: < 30kg = BWTx2 = % of adult dose
> 30kg = BWT+30 =% of adult dose
(this correlates very well with BSA).

Specific problems related to prematurity:

 Respiratory:

- Respiratory distress syndrome (  surfactant )

- Bronchopulmonary dysplasia  chronic lung disease
- Apnoea / periodic breathing
- Persistent pulmonary HTN

 CVS:

- PDA: premature ductus = less responsive to oxygen (may remain

patent)

 CNS:

- Intraventricular haemorrhages
- Reduced cerebral autoregulation
- Retinopathy of prematurity (worse with ↑ FiO2)

 GIT:

- GORD
- NEC ( associated with hypoxia)

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 Metabolic:

- Prone to hypoglycaemia ( low glycogen stores)

- Hypocalcaemia (immature parathyroid fx + low vit D stores)
- Jaundice (poor hepatic conjugation +  bilirubin load)

 Skin:

- Fluid losses (thin epidermis, large SA   insensible losses)

- Infection: immature immune system

Old SAQ's:

Compare and contrast lung function in the neonate with that in an adult. (2013a)

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 Above diagram = approximated from animal studies, % O2 saturation
 R & L systems are in parallel (vs series once ex-utero)
 Umbilical vein (from placenta) SO2 = 80%
 UV + PV blood flow – 50% to liver, 50% to IVC via ductus venosus
 Bloods from IVC – 40% through foramen ovale, 60% through to RV
 Blood from PA – 90% through ductus arteriosus (patency maintained by relative
hypoxaemia), 10% through to lungs (high PVR due to HPV)

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Circulatory changes at birth

 Umbilical vessels have thick, muscular walls – extremely reactive to trauma, tension,
catecholamines, bradykinin, angiotensin and changes in PaO 2.
 Closure of these vessels -> increase in fetal TPR + BP
 When flow through the umbilical vein ceases, the ductus venosus closes by an
unknown mechanism.
 Asphyxia from cessation of placenta circulation and cooling of the body -> activation
of the respiratory centre of the newborn.
 With inflation of lungs, PVR falls to about 1/10 of its intrauterine value. This is not
caused by the presence of O2 as inflation of lungs with N2 produces the same
decrease in resistance.

 The LA pressure rises above that of RA + IVC due to:

o Decrease PVR – increased LA filling.
o Decrease in RA filling due to cessation of umbilical vein flow.
o Increased LV afterload due to closure of umbilical arteries
 Increase in LA pressure abruptly “closes” the foramen ovale + fusion in several days.

 Pulmonary artery pressure falls to ½ of intrauterine value -> 35 mmHg.

 This change, plus the increase in aortic pressure, reverse flow through the ductus
arteriosus.
 However, within minutes, the DA begins to close, producing turbulent flow =
“murmur of the newborn”.
 Closure of the DA is usually complete 1-2 days after birth, and appears to be initiated
by the raised PaO2. Possible mediators being prostaglandins, bradykinin or
adenosine.

 At birth, the two ventricles are of similar weights, having been pumping in parallel in
the fetal circuit.
 The arterioles of the pulmonary circuit are thick and muscular, maintaining the high
PVR during feta life.
 After birth, the RV fails to grow to the same extent as the LV, the latter becoming
dominant and the muscular layer of the pulmonary vessels is lost.
 These changes take several weeks.

In summary
 At birth, inflation of lungs and closure of umbilical vessels lead to
o Decrease in DV flow -> close
o Reversal of FO flow -> close
o Reversal of DA flow -> close
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