Birth Asphyxia & Hypoxic-Ischaemic Encephalopathy
Paediatrics · Neonatology · lean revision notes
Birth Asphyxia & Hypoxic-Ischaemic Encephalopathy
Birth asphyxia is impaired gas exchange around the time of birth leading to hypoxaemia, hypercarbia and metabolic acidosis; when this insult injures the brain, the resulting clinical syndrome is hypoxic-ischaemic encephalopathy (HIE). HIE remains a leading cause of neonatal mortality and lifelong neurodisability (cerebral palsy), and the only proven neuroprotective therapy — therapeutic hypothermia — must be started within 6 hours of birth, making early recognition a high-yield, time-critical topic.
Definitions & diagnostic criteria
"Birth asphyxia" is a clinical-pathophysiological term, not a single number. The WHO loosely defines it as failure to initiate and sustain breathing at birth. For research and medicolegal purposes, the ACOG / AAP essential criteria for an acute intrapartum hypoxic event sufficient to cause cerebral palsy are tighter and very examinable.
High-yield: A low Apgar score alone does NOT define birth asphyxia. You also need biochemical (umbilical artery acidosis) and clinical (encephalopathy) evidence.
ACOG/AAP essential criteria (all four required)
| Criterion | Cut-off / definition |
|---|---|
| Metabolic acidosis | Umbilical arterial pH < 7.0 AND base deficit ≥ 12 mmol/L |
| Encephalopathy | Early-onset moderate-to-severe HIE in ≥ 34 weeks neonate |
| Cerebral palsy type | Spastic quadriplegic or dyskinetic CP |
| Exclusion | No other identifiable cause (trauma, infection, coagulopathy, genetic/metabolic) |
High-yield: Umbilical artery (not vein) blood is the gold-standard sample for intrapartum acid–base status. Arterial pH < 7.0 with base deficit ≥ 12 = significant metabolic acidosis.
Apgar score — what it is and is NOT
The Apgar score (devised by Virginia Apgar, an anaesthesiologist) is recorded at 1 and 5 minutes, and every 5 minutes thereafter up to 20 minutes if it remains < 7.
| Sign | 0 | 1 | 2 |
|---|---|---|---|
| Appearance (colour) | Blue/pale | Body pink, extremities blue | Completely pink |
| Pulse (heart rate) | Absent | < 100/min | > 100/min |
| Grimace (reflex irritability) | None | Grimace | Cough/cry/sneeze |
| Activity (tone) | Limp | Some flexion | Active motion |
| Respiration | Absent | Slow/irregular | Good cry |
High-yield: Apgar is for assessing response to resuscitation, NOT for guiding it — resuscitation begins immediately based on breathing, heart rate and tone, not after waiting for the 1-minute score. A persistently low Apgar at 10–20 min correlates with poor outcome, but the score is a poor stand-alone predictor.
Mnemonic for Apgar components: "How Ready Is This Child?" → Heart rate, Respiration, Irritability (reflex), Tone, Colour. (Or simply A-P-G-A-R as above.)
Etiology
Causes are best grouped by timing relative to birth.
| Timing | Examples |
|---|---|
| Antepartum (~20%) | Maternal hypotension/hypoxia, severe anaemia, pre-eclampsia, IUGR/placental insufficiency, post-term, maternal diabetes |
| Intrapartum (~70%) | Cord prolapse / true knot / nuchal cord, abruptio placentae, uterine rupture, shoulder dystocia, prolonged/obstructed labour, placenta praevia |
| Postpartum (~10%) | Severe cyanotic congenital heart disease, recurrent apnoea, severe pulmonary disease, sepsis/shock |
The common final pathway in all is interruption of placental/pulmonary gas exchange → hypoxaemia + hypercarbia + acidosis.
Pathophysiology — the two-phase injury
Understanding the biphasic energy failure explains why hypothermia works and why the 6-hour window exists.
Primary energy failure → acute hypoxia–ischaemia depletes ATP → failure of Na⁺/K⁺-ATPase → cell depolarisation, cytotoxic oedema, glutamate release → excitotoxic Ca²⁺ influx and immediate necrosis.
Then a brief latent phase (≈ 1–6 h) of partial recovery of oxidative metabolism — this is the therapeutic window.
Secondary energy failure (≈ 6–48 h) → mitochondrial dysfunction, oxidative stress, inflammatory cytokines, and apoptosis (delayed/programmed cell death). The severity of secondary failure correlates best with outcome.
Stepwise summary: Asphyxia → ↓ATP & glutamate excitotoxicity (necrosis) → latent phase (window) → mitochondrial failure + apoptosis (secondary injury) → neuronal death.
High-yield: Therapeutic hypothermia works mainly by interrupting the secondary phase — it slows cerebral metabolism, reduces glutamate/free-radical release and inhibits the apoptotic cascade. Hence it must be started before secondary energy failure sets in (within 6 h).
Selective regional vulnerability
The pattern of injury depends on severity and maturity:
- Acute, profound (total) asphyxia → deep grey matter — basal ganglia, thalamus and brainstem → later dyskinetic CP.
- Prolonged, partial asphyxia → parasagittal watershed cortical/subcortical white matter → spastic quadriplegia, cognitive deficits.
- In preterm infants → periventricular leukomalacia (PVL) and germinal matrix/IVH.
The "diving reflex" redistributes blood to brain, heart and adrenals at the expense of gut, kidney, skin and muscle — explaining the multi-organ involvement below.
Clinical features & Sarnat staging
HIE is graded clinically using the Sarnat & Sarnat staging (Stage I/II/III = mild/moderate/severe). This is one of the single most-asked tables in paediatrics.
| Feature | Stage I (Mild) | Stage II (Moderate) | Stage III (Severe) |
|---|---|---|---|
| Level of consciousness | Hyperalert, irritable | Lethargic / obtunded | Stupor / coma |
| Muscle tone | Normal | Hypotonia | Flaccid |
| Posture | Mild distal flexion | Strong distal flexion | Decerebrate |
| Tendon reflexes | Increased | Increased | Depressed/absent |
| Myoclonus | Present | Present | Absent |
| Moro reflex | Strong | Weak, incomplete | Absent |
| Suck | Active | Weak | Absent |
| Pupils | Dilated, reactive | Constricted | Variable/fixed, poor light reflex |
| Seizures | Absent | Common (peak ~24 h) | Uncommon (or subtle); EEG burst-suppression |
| Autonomic | Sympathetic (tachycardia) | Parasympathetic (bradycardia, ↑secretions) | Both depressed |
| EEG | Normal | Low voltage, periodic, seizures | Burst-suppression → isoelectric |
| Duration / outcome | < 24 h, excellent prognosis | 2–14 days, variable | Hours–weeks, high mortality / severe sequelae |
High-yield: Mild (Sarnat I) HIE has a near-normal outcome and does NOT qualify for therapeutic hypothermia. Cooling is indicated only for moderate-to-severe (Sarnat II/III) encephalopathy.
High-yield: Seizures in HIE peak at ~12–24 hours of life, are commonest in moderate (Stage II) HIE, and are frequently subtle (lip-smacking, cycling, eye deviation, apnoea) rather than overt tonic-clonic.
Multi-organ dysfunction (MSOF)
Asphyxia is a multi-system disease; the brain is the most important but rarely the only organ hit. Examiners love the kidney as the most commonly affected organ.
| System | Manifestation |
|---|---|
| Renal (most common) | Acute tubular necrosis, oliguria, ↑creatinine, SIADH |
| CNS | HIE, seizures, cerebral oedema |
| Cardiac | Myocardial ischaemia, hypotension, tricuspid regurgitation, cardiogenic shock |
| Pulmonary | PPHN, meconium aspiration syndrome, RDS, pulmonary haemorrhage |
| GI | Feed intolerance, necrotising enterocolitis |
| Haematological | DIC, thrombocytopenia |
| Metabolic | Hypoglycaemia, hypocalcaemia, hyponatraemia, metabolic acidosis |
| Hepatic | Transaminitis, coagulopathy |
High-yield: The kidney (ATN) is the most frequently involved organ in perinatal asphyxia. Monitor urine output and creatinine. Hypoglycaemia worsens brain injury and must be aggressively corrected.
Diagnosis & investigations
HIE is primarily a clinical diagnosis (encephalopathy + evidence of perinatal insult). Investigations confirm, grade severity and predict outcome.
- Cord/early arterial blood gas → pH, base deficit (defines acidosis).
- Blood glucose, calcium, electrolytes, RFT, LFT, coagulation → MSOF and correctable factors.
- aEEG / continuous EEG → seizure detection + background grading (best bedside predictor; see below).
- Cranial ultrasound → bedside, detects oedema, IVH, gross lesions; poor for early cortical injury.
- MRI brain (investigation of choice for prognosis) → done at day 4–7 (or up to 2 weeks). Diffusion-weighted imaging (DWI) shows restricted diffusion earliest (24 h–4 days, may pseudonormalise by day 7–10).
High-yield: MRI is the imaging investigation of choice for confirming and prognosticating HIE. Basal ganglia/thalamus and posterior limb of internal capsule (PLIC) involvement predicts the worst neuromotor outcome; an abnormal PLIC signal is a strong predictor of adverse outcome.
aEEG / EEG monitoring
Amplitude-integrated EEG (aEEG) is used both for eligibility screening and prognosis. Background patterns from best to worst:
Continuous normal voltage → discontinuous normal voltage → burst-suppression → continuous low voltage → flat (isoelectric).
High-yield: A burst-suppression, low-voltage or flat (isoelectric) aEEG that fails to recover by 24–48 h carries a poor prognosis. Early recovery of a normal background within 24–36 h is reassuring.
Management
A. Delivery-room resuscitation (NRP)
Follow the Neonatal Resuscitation Programme (NRP) algorithm:
Initial steps (warmth, position, clear airway, dry, stimulate) → if apnoeic/HR < 100 → PPV (the single most important step) → if HR < 100 despite effective ventilation → MR SOPA corrective steps → if HR < 60 after 30 s of effective PPV → chest compressions (3:1 with ventilation) + 100% O₂ → if still HR < 60 → IV adrenaline 0.01–0.03 mg/kg.
High-yield: Effective ventilation (PPV) is the cornerstone of neonatal resuscitation — most asphyxiated newborns respond to ventilation alone. Compressions and adrenaline are needed only in a minority.
High-yield: Start resuscitation of term/near-term infants with room air (21% O₂), titrating to preductal SpO₂ targets, rather than 100% oxygen (hyperoxia is harmful). Reserve higher FiO₂ for compressions or failure to improve.
B. Therapeutic (controlled) hypothermia — the only proven neuroprotectant
High-yield: Cool moderate-to-severe HIE (Sarnat II/III) infants to a core temperature of 33–34 °C for 72 hours, started within 6 hours of birth, followed by slow rewarming (~0.5 °C/hour). Either whole-body cooling or selective head cooling can be used.
Eligibility (typical) criteria — all met:
| Domain | Requirement |
|---|---|
| Gestation | ≥ 36 weeks (some units ≥ 35) and birth weight ≥ 1800–2000 g |
| Age | < 6 hours of life |
| Physiological evidence | Apgar ≤ 5 at 10 min, OR ongoing resuscitation/PPV at 10 min, OR cord/early pH < 7.0 or base deficit ≥ 16 (≥12 with other criteria) |
| Neurological | Moderate-to-severe encephalopathy clinically and/or abnormal aEEG |
Benefit: Major trials (CoolCap, NICHD, TOBY) showed cooling reduces the combined outcome of death or major neurodevelopmental disability; NNT ≈ 7–9. Most effective in moderate HIE.
Contraindications/cautions: preterm < 35–36 weeks, > 6 h of age, major congenital anomaly, severe coagulopathy/bleeding, severe IUGR. Side-effects: sinus bradycardia (expected/benign), thrombocytopenia, subcutaneous fat necrosis, mild coagulopathy, persistent pulmonary hypertension.
C. Supportive care (equally vital)
- Ventilation/oxygenation: maintain normocapnia (avoid hypocapnia → cerebral vasoconstriction worsens ischaemia) and normoxia (avoid hyperoxia).
- Circulation: maintain normal BP/perfusion; treat hypotension with volume/inotropes; avoid fluid overload.
- Glucose: maintain euglycaemia — both hypo- and hyperglycaemia worsen injury.
- Fluids: mild fluid restriction anticipating SIADH/ATN; monitor urine output, electrolytes.
- Correct hypocalcaemia, acidosis, coagulopathy.
- Seizure control (see DOC below).
- Avoid hyperthermia at all costs — even mild fever worsens outcome.
D. Seizure management — drug of choice
High-yield: Phenobarbitone (phenobarbital) is the first-line drug of choice for neonatal/HIE seizures: loading dose 20 mg/kg IV, may repeat 10 mg/kg up to 40 mg/kg total. Second line: phenytoin/fosphenytoin or levetiracetam; midazolam infusion for refractory seizures.
Correct hypoglycaemia and hypocalcaemia first, as these are reversible causes.
Complications
Acute: refractory seizures, cerebral oedema/raised ICP, SIADH, ATN/renal failure, PPHN, NEC, DIC, cardiogenic shock, death.
Long-term neurodevelopmental:
- Cerebral palsy — spastic quadriplegic (watershed pattern) or dyskinetic/athetoid (basal ganglia pattern).
- Cognitive impairment / learning disability.
- Epilepsy.
- Sensorineural hearing loss and visual (cortical) impairment.
- Microcephaly, feeding difficulties.
Predictors of poor neurodevelopmental outcome
| Strong adverse predictor | Note |
|---|---|
| Severe (Sarnat III) encephalopathy | Highest risk of death/CP |
| Apgar 0–3 beyond 5–10 min (esp. persisting at 20 min) | |
| Persistent burst-suppression / low-voltage aEEG > 24–48 h | |
| MRI: basal ganglia/thalamus + abnormal PLIC | Worst motor outcome |
| Seizures, especially early and refractory | |
| Failure to establish spontaneous respiration by 20–30 min | |
| Multi-organ failure |
Key differentials
HIE is a diagnosis that requires excluding mimics of neonatal encephalopathy:
- Sepsis / meningitis (GBS, E. coli, HSV) — always rule out; treat empirically if in doubt.
- Inborn errors of metabolism — urea cycle defects, maple syrup urine disease, non-ketotic hyperglycinaemia (encephalopathy ± acidosis ± hypoglycaemia, often with a symptom-free interval).
- Metabolic disturbances — hypoglycaemia, hypocalcaemia, hyponatraemia, kernicterus.
- Intracranial haemorrhage / traumatic birth injury — subdural, IVH.
- Neonatal stroke (arterial ischaemic) — often presents only with focal seizures in an otherwise well baby.
- Neuromuscular disorders / congenital myopathies — hypotonia without encephalopathy.
- Drug effects — maternal opioids/magnesium, neonatal sedatives.
High-yield: A baby with focal seizures but a normal inter-ictal state and no asphyxial history suggests neonatal arterial ischaemic stroke, not global HIE.
Recently asked / exam angle
- Sarnat staging matched to a clinical vignette (consciousness + tone + reflexes + seizures) — the single most repeated question. Know which stage is eligible for cooling (II/III only).
- Therapeutic hypothermia numbers: 33–34 °C, 72 hours, within 6 hours, ≥ 36 weeks — direct one-liner MCQs.
- ACOG criteria / umbilical artery pH < 7.0, base deficit ≥ 12 as the definition of significant intrapartum acidosis.
- "Most common organ affected in birth asphyxia" → kidney (ATN).
- MRI (with DWI) as investigation of choice for prognosis; basal ganglia/PLIC = worst outcome.
- Phenobarbitone 20 mg/kg as first-line anticonvulsant.
- "Apgar is for assessing response, not for initiating resuscitation"; resuscitation is driven by HR, breathing, tone.
- Effective PPV as the most important step in neonatal resuscitation; room air for term babies.
- Trial names: CoolCap, NICHD, TOBY (hypothermia evidence).
- Seizures peak at 12–24 h and are often subtle.
Rapid revision
- Birth asphyxia = hypoxaemia + hypercarbia + metabolic acidosis; HIE = the brain injury that follows.
- ACOG significant acidosis = umbilical artery pH < 7.0 + base deficit ≥ 12 mmol/L.
- Apgar scored at 1 and 5 min; assesses response, does not guide resuscitation.
- Injury is biphasic — primary necrosis → latent window → secondary apoptotic energy failure; hypothermia targets the secondary phase.
- Acute total asphyxia → basal ganglia/thalamus (dyskinetic CP); prolonged partial → watershed cortex (spastic quadriplegia); preterm → PVL.
- Sarnat I = excellent prognosis & not cooled; II/III = candidates for hypothermia.
- Cool to 33–34 °C for 72 h within 6 h of birth in ≥ 36-week infants with moderate-severe HIE.
- Most common organ involved = kidney (ATN); watch for SIADH and hypoglycaemia.
- Investigation of choice for prognosis = MRI (DWI); abnormal PLIC / basal ganglia = worst motor outcome.
- aEEG burst-suppression/flat not recovering by 24–48 h = poor prognosis.
- Phenobarbitone 20 mg/kg IV = first-line anticonvulsant; correct glucose & calcium first.
- Avoid hyperthermia, hyperoxia, hypocapnia and hypoglycaemia — all worsen the brain injury.