Perinatal Asphyxia and Hypoxic-Ischaemic Encephalopathy — Criteria, Sarnat Staging and Therapeutic Hypothermia

Perinatal asphyxia occurs when blood flow or gas exchange to or from the fetus is disrupted immediately before, during or after birth. Partial (hypoxia) or complete (anoxia) oxygen deprivation causes progressive hypoxaemia and hypercapnia; if severe, the tissues switch to anaerobic metabolism and lactic acidosis follows. The brain injury that results is called hypoxic-ischaemic encephalopathy (HIE), but the heart, kidneys, liver, lungs and gut are hurt as well.

WHO's working definition of birth asphyxia is simpler and clinical: failure to initiate and sustain breathing at birth. Many studies in low-resource settings also use an Apgar score below 7 at 5 minutes despite resuscitation. These field definitions overcall asphyxia, which is why stricter criteria (below) exist for research, cooling and medicolegal purposes. See Apgar score for how the score is built.

• Maternal — haemodynamic compromise: amniotic fluid embolism, sepsis, shock.
• Uterine — uterine rupture.
• Placenta and cord — placental abruption, cord knot, cord compression or prolapse.
• Fetal / neonatal — infection; failure to breathe after birth in a compromised baby needing resuscitation.

Most cases arise intrapartum; about 20% are antepartum, and some occur in the early postnatal period. Only a minority of babies with HIE have a documented sentinel event. StatPearls gives an incidence of about 2 per 1000 term births in high-resource countries and ten times higher where maternal and newborn care is limited; 15–20% of affected infants die in the neonatal period and up to 25% of survivors have permanent neurological deficits.

Exams still quote the older American Academy of Pediatrics (AAP) and ACOG essential criteria, in which all four had to be present before an event was called asphyxia. In 2014, the ACOG Task Force on Neonatal Encephalopathy replaced this checklist with a set of neonatal signs and associated factors that make an acute peripartum hypoxic-ischaemic cause more likely.

Cord blood gas is the most objective marker. In uncomplicated term births the mean umbilical arterial pH is 7.24–7.27 and the venous pH 7.32–7.34; arterial blood is more acidotic because it carries the fetus's CO₂. An isolated pH below 7.00 poorly predicts brain injury — most such babies do well — but combined with an abnormal fetal heart tracing, a 5-minute Apgar of 5 or less or the need for intubation it strongly predicts seizures and adverse outcome. About 80% of infants with a cord pH below 6.70 develop neonatal encephalopathy.

1. Primary energy failure — oxygen and glucose delivery stop, ATP falls, the Na⁺/K⁺-ATPase pump fails, sodium and water enter the cell, causing swelling, depolarisation and death.
2. Excitotoxicity — dying cells release glutamate, which opens NMDA receptor channels and floods neurons with calcium, killing more cells.
3. Latent phase (about 6 hours) — reperfusion occurs, some cells recover, inflammation begins. This is the therapeutic window for cooling.
4. Secondary energy failure (next 24–48 hours) — reperfusion spreads toxic neurotransmitters into damaged areas and widens the injury; clinical deterioration and seizures often appear.
5. Tertiary phase (months) — remodelling and late cell death.

The pattern depends on the insult. With a partial, prolonged insult the brain redirects blood to the brainstem and cerebellum, so injury falls on the watershed areas. An acute, profound insult hits the basal ganglia and thalami hardest. Preterm babies show more white matter injury and intraventricular haemorrhage and fewer obvious seizures.

Sarnat and Sarnat (1976) described three clinical stages of postanoxic encephalopathy in 21 infants above 36 weeks. The modified Sarnat examination is now used to grade encephalopathy and decide eligibility for cooling in babies of 36 weeks or more: abnormality in at least 3 of 6 categories defines the stage, with level of consciousness as the tie-breaker.

• Stage I — lasts less than 24 hours; sympathetic overdrive (mydriasis, brisk reflexes); EEG normal; good prognosis.
• Stage II — obtundation, hypotonia, strong distal flexion, parasympathetic signs (miosis, bradycardia, secretions); seizures are common.
• Stage III — stupor, flaccidity, suppressed brainstem and autonomic function; EEG isopotential or with infrequent periodic discharges; clinical seizures are less common because the injured cortex cannot propagate them.

• Avoid hyperoxia during and after resuscitation — it increases free-radical injury.
• Avoid hypocapnia — babies compensate for metabolic acidosis by blowing off CO₂, and low CO₂ worsens brain perfusion.
• Keep euglycaemia — the brain is the main glucose consumer.
• Keep blood pressure steady — avoid both hypo- and hypertension.
• Treat seizures with anticonvulsants and EEG monitoring.

Therapeutic hypothermia is the standard treatment for moderate to severe HIE in term and near-term babies. It lowers cerebral metabolic rate and reduces inflammation, apoptosis and excitotoxic receptor activity during the latent phase. There is no specific treatment for mild HIE or for preterm babies, who receive supportive care with normothermia.

• Exclusions: under 36 weeks, under 1800 g, older than 6 hours, major congenital anomaly, inevitable death; life-threatening coagulopathy with active bleeding may exclude; significant head trauma with major intracranial haemorrhage.
• Imperforate anus excludes selective head cooling (no rectal probe) but not whole-body cooling with an oesophageal probe.
• Adverse effects: sinus bradycardia (heart rate falls about 15/min per 1 °C; 80–100/min at 33.5 °C is expected), hypotension, prolonged QT, pulmonary hypertension, hypokalaemia and other electrolyte changes, platelet dysfunction and coagulopathy, sepsis risk, feed intolerance and altered drug handling. Rewarming can trigger seizures, apnoea and hypotension.

Evidence: the NICHD trial cooled 208 term infants to 33.5 °C for 72 hours and reduced death or disability at 18 months (RR 0.72). A systematic review of 11 randomised trials (1505 infants) confirmed that cooling lowers mortality without increasing disability in survivors.

Outcome tracks the severity of encephalopathy. Mild (stage I) HIE usually recovers, although some children later show lower cognitive scores. Severe HIE carries high mortality, mostly in the first days. Survivors may develop cerebral palsy (classically spastic quadriplegic or dyskinetic after an acute intrapartum insult), intellectual disability, epilepsy, blindness and hearing loss. MRI soon after birth predicts death or disability well in severe injury but less well in mild or moderate patterns.

• Prevention starts in labour: recognise abnormal fetal heart patterns, manage abruption, cord prolapse and uterine rupture promptly.
• Skilled newborn resuscitation — effective ventilation in the first minute; see CPR and basic life support.
• Early referral of encephalopathic babies to a unit that can cool within 6 hours.

• Criteria — cord pH < 7.0, base deficit ≥ 12, Apgar 0–3 beyond 5 minutes (old) or < 5 at 5 and 10 minutes (2014), encephalopathy, multi-organ dysfunction.
• Sarnat stage from a vignette — hyperalert with dilated pupils = I; lethargic, miosis, seizures = II; flaccid, coma, apnoea = III.
• Cooling details — ≥ 36 weeks, ≥ 1800 g, within 6 hours, 33.5 °C, 72 hours, rewarm 0.5 °C/hour.
• Commonest cooling side effect — sinus bradycardia.
• Brain injury pattern — watershed (prolonged partial) vs basal ganglia–thalamus (acute profound).
• Multi-organ effects — oliguria, raised transaminases, coagulopathy, hypoglycaemia, PPHN.