Fetal and neonatal physiology

Fetal oxygenation

• Blood in the umbilical vein (the most oxygenated fetal blood, leaving the placenta) has a PO₂ of only about 30 mmHg (4 kPa) but a saturation of about 80%.
• HbF (α₂γ₂) binds 2,3-BPG poorly, so its oxygen affinity is higher (P50 about 19 mmHg against 27 for HbA; curve shifted left). It has no greater CO₂ capacity, and it does not bind oxygen less well.
• High haemoglobin (17–20 g/dL) and high cardiac output per kilogram compensate for low PO₂. The double Bohr effect at the placenta (maternal blood gains CO₂ and releases O₂; fetal blood loses CO₂ and takes up O₂) aids transfer.
• Haemoglobin sequence: embryonic Gower and Portland haemoglobins (ζ and ε chains) in the first trimester, then HbF, with switching to HbA over the first 6 months. β-thalassaemia major therefore presents at about 3–6 months, when γ-chain production falls (HbF needs no β chains), whereas α-thalassaemia major causes hydrops in utero because both HbF and HbA need α chains.
• Haematopoiesis moves from yolk sac to liver (the main site from about 6 weeks to mid-gestation; it still contributes in late fetal life) to bone marrow.

Fetal circulation and its closure

• Fetal pulmonary blood flow is only about 10% of output because the fluid-filled lungs have high pulmonary vascular resistance.
• At birth: first breaths expand the lungs, oxygen dilates pulmonary vessels, so pulmonary resistance falls; cord clamping removes the low-resistance placenta, so systemic resistance rises. Left-sided pressures now exceed right, closing the shunts.
• Indomethacin closes a patent ductus; prostaglandin E₁ keeps it open in duct-dependent heart disease. Maternal NSAIDs after 32 weeks may close it prematurely.
• Persistent pulmonary hypertension of the newborn: resistance stays high (hypoxia, meconium aspiration, sepsis) and blood shunts right to left through the duct and foramen.

Lung maturation and surfactant

• Surfactant (dipalmitoylphosphatidylcholine with proteins, from type II pneumocytes) lowers alveolar surface tension, prevents collapse of small alveoli at end-expiration, increases compliance and reduces the work of breathing. It is adequate from about 34 weeks.
• Fetal cortisol is the main stimulus for surfactant synthesis and lung maturation; this is why antenatal corticosteroids (betamethasone or dexamethasone) are given before preterm delivery. Thyroid hormone also helps; fetal hyperinsulinaemia in diabetic pregnancy delays surfactant, so infants of diabetic mothers get respiratory distress even near term.
• Respiratory distress syndrome (hyaline membrane disease) from surfactant deficiency is the commonest cause of respiratory failure and death in preterm infants.
• Labour catecholamines switch the lung epithelium from secreting to absorbing fluid; babies born by elective caesarean may develop transient tachypnoea.

Fetal adrenal, oestriol and growth

• The large fetal zone of the adrenal cortex makes DHEA-S, which the fetal liver hydroxylates and the placenta converts to oestriol. Anencephaly (no ACTH drive, adrenal hypoplasia) and fetal death cause very low oestriol; placental sulphatase deficiency is another cause.
• Symphysis–fundal height in centimetres roughly equals gestation in weeks from 24 weeks (within 2 cm). A height of 28 cm at 34 weeks suggests fetal growth restriction (or oligohydramnios).
• Amniotic fluid after mid-pregnancy is mostly fetal urine. Bilateral renal agenesis causes severe oligohydramnios and the Potter sequence: flattened face, limb deformities and fatal pulmonary hypoplasia. The commonest cause of urinary obstruction in newborn boys is posterior urethral valves.

Temperature and glucose

• Newborns have a large surface area to mass ratio, little subcutaneous fat and weak shivering.
• Brown adipose tissue (between the scapulae, around the neck and kidneys) produces heat by non-shivering thermogenesis: uncoupling protein 1 (thermogenin) lets protons leak back across the inner mitochondrial membrane, releasing energy as heat; noradrenaline on β3 receptors switches it on.
• Cold stress causes hypoglycaemia, acidosis and respiratory distress; dry the baby and keep skin-to-skin.
• After cord clamping glucose falls for a few hours, then glycogenolysis and gluconeogenesis take over. Hypoglycaemia risk: preterm and small-for-dates babies (low glycogen), infants of diabetic mothers (fetal hyperinsulinaemia), hypothermia and sepsis.
• Weight: a breastfed term baby may lose up to about 10% of birth weight in the first days (fluid loss, small early feeds) and should regain it by about 2 weeks. Larger loss with high sodium suggests dehydration from poor feeding.

Bilirubin and vitamin K

• Physiological jaundice appears after 24 hours, peaks on days 3–5 and settles by 2 weeks: high red cell mass with shorter survival, immature UDP-glucuronyl transferase, increased enterohepatic circulation.
• Jaundice in the first 24 hours is pathological (Rh or ABO haemolysis, G6PD deficiency, spherocytosis). Unconjugated bilirubin can cross the immature blood–brain barrier and cause kernicterus; phototherapy or exchange transfusion prevent it.
• Vitamin K is given at birth because stores are low, breast milk contains little and the gut is not yet colonised, preventing haemorrhagic disease of the newborn.

Immunity and maternal antibodies

• IgG is actively transported across the placenta (FcRn), mostly in the third trimester, so preterm babies receive less. Secretory IgA in colostrum protects the gut.
• Harmful maternal IgG also crosses: anti-Ro (SSA) in mothers with lupus or Sjögren syndrome damages the fetal conducting system, causing congenital complete heart block; anti-D causes haemolytic disease; TSH-receptor antibodies cause neonatal thyrotoxicosis. After anti-D prophylaxis, passively acquired anti-D may be detectable in the newborn.
• Babies of HBsAg and HBeAg positive mothers need hepatitis B vaccine plus hepatitis B immunoglobulin within 12–24 hours of birth.
• Cytomegalovirus is the commonest congenital viral infection and the leading non-genetic cause of childhood sensorineural deafness.
• DiGeorge syndrome (22q11 deletion): neonatal hypocalcaemia (absent parathyroids), cleft palate, conotruncal heart defects and recurrent infections from thymic aplasia.

Newborn screening

Heel-prick (blood spot) screening detects disorders that are silent at birth but cause irreversible damage unless treated early, notably congenital hypothyroidism (thyroxine started in the first weeks prevents intellectual disability), phenylketonuria, sickle cell disease and cystic fibrosis.

Remember At birth, pulmonary resistance falls and systemic resistance rises; oxygen and falling PGE₂ close the duct.

Exam trap HbF binds 2,3-BPG poorly, so it holds oxygen more tightly, not less.

Exam trap Jaundice in the first 24 hours is always pathological.

How FCPS asks about this

• Fetal hormone driving surfactant production: cortisol; antenatal steroids before preterm birth.
• Fetal Hb versus adult Hb: higher O₂ affinity because it binds 2,3-BPG poorly; fetal blood has lower PO₂.
• β-thalassaemia appearing at 6 months: HbF needs no β chains.
• Very low oestriol with anencephaly: fetal adrenal DHEA-S is its precursor.
• Congenital heart block with maternal dry eyes and mouth: anti-Ro (SSA) antibodies.
• Day-4 weight loss of 7%: normal up to about 10%; regained by 2 weeks.
• Why screen for congenital hypothyroidism: early treatment prevents disability.