Changes in Fetal Circulation After Birth

Fetal Circulation - Background

The Two Primary Vascular Resistance Changes at Birth

Why PVR falls so dramatically:

• In utero, compressed, unexpanded lung vessels have high resistance
• Hypoxia of fetal lungs causes tonic vasoconstriction
• At birth: lung expansion physically decompresses pulmonary vessels
• Increased alveolar O2 eliminates hypoxic vasoconstriction
• Oxygen acts as a pulmonary vasodilator via nitric oxide (NO) production
• Bradykinin, released from lungs during initial inflation, also contributes to pulmonary vasodilation
• PVR falls to less than 20% of in-utero values after the first few breaths

"The pulmonary vascular resistance falls to less than 20% of the value in utero after the lungs are expanded by the first few breaths." - Ganong's Review of Medical Physiology, 26th Ed., p.616

Closure of the Three Fetal Shunts

1. Closure of the Foramen Ovale

• In fetal life: Right atrial pressure > Left atrial pressure → blood flows R→L through foramen ovale
• At birth:
  • SVR rises → left atrial pressure rises
  • PVR falls → increased pulmonary venous return → left atrial pressure rises further
  • Right atrial pressure falls (less venous return from placenta, lower PVR)
• Result: Left atrial pressure exceeds right atrial pressure by 2-4 mmHg → the valve-like flap (septum primum) on the left side of the interatrial septum is pushed against the opening and functionally closes the foramen ovale

• Functional closure: within minutes of birth
• Anatomical (adhesive) closure: within a few months to years in ~2/3 of people
• In ~20% of adults, structural fusion never completes (patent foramen ovale, PFO), but left atrial pressure keeps the valve sealed and it remains functionally closed

2. Closure of the Ductus Arteriosus

• Fetal ductus blood: PO2 only 15-20 mmHg
• After birth: PO2 rises to ~100 mmHg within hours
• High O2 directly contracts ductal smooth muscle

• High concentrations of PGE2 (vasodilator) keep the ductus open in fetal life
• After birth, PGE2 synthesis is blocked (cyclooxygenase inhibition at birth), removing this vasodilatory stimulus
• Bradykinin (released from lungs on first inflation) also acts as a vasoconstrictor on the ductus

• In fetal life: pulmonary artery pressure > aortic pressure → flow goes PA → Aorta (R→L)
• After birth: aortic pressure rises, pulmonary artery pressure falls → flow reverses to Aorta → PA (L→R) briefly before the ductus constricts

3. Closure of the Ductus Venosus

• In fetal life: oxygenated umbilical venous blood bypasses the liver via the ductus venosus, flowing directly into the IVC
• After birth: umbilical cord clamping stops flow through the umbilical vein → ductus venosus pressure falls
• Within 1-3 hours: smooth muscle in ductus venosus wall contracts strongly → active closure
• Portal venous pressure rises from ~0 to 6-10 mmHg, now sufficient to drive portal blood through the liver sinuses (full hepatic circulation established)

Umbilical Vessels - Closure

• Umbilical arteries: After birth, rising blood O2 (via pulmonary respiration) reaches the umbilical arteries → vasoconstriction. Cold and handling of the cord augment this. Completely constricted within 3-5 minutes.
• Umbilical vein: Flow continues briefly after arterial constriction due to increased placental pressure within the contracting uterus and the baby's negative intrathoracic pressure during breathing efforts (-30 to -50 mmHg). This redistribution is called the "placental transfusion." Flow ceases within ~5 minutes.

Stimulus for First Breath

• Sudden exposure to cold air
• Light, sound, and tactile stimuli

Net Circulatory Result: Parallel → Series Transition

Summary of Closure Timeline

• Guyton and Hall Textbook of Medical Physiology, pp. 1051-1053
• Ganong's Review of Medical Physiology, 26th Ed., p. 616
• Bailey and Love's Short Practice of Surgery, 28th Ed., p. 985
• Mulholland and Greenfield's Surgery: Scientific Principles and Practice, 7th Ed., pp. 5283-5284

Changes in Other Systems at Birth (Neonatal Physiology)

1. Respiratory System

• The stimulus is not primarily hypoxia - main triggers are sudden exposure to cold air, light, sound, and tactile stimuli
• The first breath requires a very large negative inspiratory force to overcome fluid surface tension in the airways
• Pulmonary fluid in alveoli is absorbed into the interstitial space and fetal circulation during and after the first breaths
• Delay in this process causes Transient Tachypnea of the Newborn (TTN) - usually resolves within 2-48 hours

• The low functional residual capacity means blood gas concentrations fluctuate more widely if breathing slows - the residual air in adult lungs buffers gas changes
• Respiratory rate of ~40 breaths/min and minute respiratory volume ~twice that of an adult per unit body weight

2. Hematological System

Red Blood Cells

• At birth: RBC count averages ~4 million/mm³
• If umbilical cord blood is stripped into the infant, RBC count rises by 0.5-0.75 million → peak ~4.75 million/mm³ in the first few hours
• In the following weeks: very few new RBCs are formed - the hypoxic stimulus of fetal life (which drove erythropoiesis) is gone
• The old fetal RBCs (which have a shorter lifespan) break down faster than new ones are made
• Result: Physiological Anaemia - RBC count falls to less than 4 million/mm³ by 6-12 weeks of life, then recovers

Haemoglobin Transition

• Fetal haemoglobin (HbF, α₂γ₂) has higher O₂ affinity than adult HbA (α₂β₂) - essential in the low-PO₂ fetal environment
• After birth, O₂ demand increases but HbF's high affinity impairs O₂ delivery to tissues
• During the 1-2 month transition period: rising levels of 2,3-DPG and mild acidosis reduce O₂ affinity and improve tissue delivery

Neonatal Jaundice (Physiological Hyperbilirubinaemia)

• In fetal life, bilirubin crosses the placenta and is excreted by the mother's liver
• After birth, the neonate must rely on its own liver - which is immature and cannot conjugate bilirubin with glucuronic acid adequately for the first week or so
• Result: Plasma bilirubin rises from <1 mg/dL to an average of 5 mg/dL in the first 3 days, causing mild jaundice of skin and sclerae, then falls as liver matures
• Treatment: Phototherapy with blue-green light (peak 478 nm) converts unconjugated bilirubin in skin microcirculation to water-soluble isomers excreted in urine and faeces

3. Circulatory Parameters (Post-transition)

• BP gradually rises over months toward ~90/60 mmHg, then slowly to adult values at adolescence
• Cord stripping: the extra 75 mL of blood redistributes - fluid shifts to tissues, raises haematocrit, blood volume returns to ~300 mL. Some risk of mild pulmonary oedema

4. Liver Function

1. Poor bilirubin conjugation - cannot conjugate bilirubin with glucuronic acid adequately → physiological jaundice (described above)
2. Low plasma protein synthesis - plasma protein concentration falls 15-20% below normal in first weeks → risk of hypoproteinaemic oedema
3. Deficient gluconeogenesis - blood glucose falls to 30-40 mg/dL (~40% of normal) in the unfed neonate; the infant depends on stored fat for energy until feeding is established
4. Deficient coagulation factor synthesis - liver produces insufficient clotting factors → risk of neonatal bleeding (Vitamin K-dependent factors II, VII, IX, X particularly affected)

5. Renal Function

• Renal functional development is not complete until the end of the first month of life
• Urine concentrating ability: Neonate can concentrate urine to only 1.5× plasma osmolality vs. adult capacity of 3-4× plasma osmolality
• Fluid turnover: Rate of fluid intake and excretion is 7× greater per unit weight than in adults
• Metabolic rate is 2× greater per kg → 2× more acid produced → tendency toward metabolic acidosis
• Consequences: Neonates are highly vulnerable to:
  • Acidosis
  • Dehydration
  • (Less commonly) Overhydration

6. Thermoregulation

• Metabolic rate is ~twice that of adults per kg - generates more heat
• BUT body surface area is disproportionately large relative to body mass → heat is rapidly lost
• At birth: Body temperature often falls several degrees in the first few hours
• Recovery: Returns to normal in 7-10 hours
• Temperature regulation remains immature for the early days of life → marked fluctuations continue for days

• Premature infants are especially vulnerable - less subcutaneous fat, even larger surface-to-mass ratio, poorer thermoregulatory mechanisms

7. Gastrointestinal System

1. Pancreatic amylase deficiency - starches are poorly digested; not significant if diet is breast milk/formula (low starch)
2. Reduced fat absorption - cow's milk (high fat) is less well absorbed; breast milk has lipases that compensate
3. Unstable blood glucose - liver dysfunction means glucose cannot be reliably maintained

8. Nutritional Requirements - Key Deficiency Risks

9. Hormonal / Neurogenic Control Systems

• All hormonal and neurogenic control systems show instability in the neonate
• Due to: (a) immature organ development AND (b) control systems not yet calibrated to extrauterine life
• Examples: poor blood glucose regulation, poor temperature regulation, immature autonomic reflexes

10. Haemoglobin / Oxygen Delivery - Transition Summary