Birth Asphyxia and Stage 3 Hypoxic-Ischemic Encephalopathy in Neonates
Birth asphyxia (BA) with stage 3 (severe) hypoxic-ischemic encephalopathy (HIE) represents a life-threatening neonatal emergency characterized by profound perinatal oxygen deprivation leading to severe brain injury, with mortality rates of 27% and permanent neurological disability in 48% of survivors even with optimal treatment. 1
Definition and Pathophysiology
Birth asphyxia is defined by failure to initiate or sustain spontaneous breathing at birth due to interruption of placental blood flow, resulting in impaired gas exchange. 2 The diagnosis requires:
- Apgar score <5 at 5 and 10 minutes 1, 3
- Severe acidemia with umbilical arterial pH ≤7.0 and/or base deficit ≥12 mmol/L 1, 2
- Need for assisted ventilation in the delivery room 1
- Inability to cry or breathe at birth despite stimulation 1
Stage 3 (severe) HIE represents the most severe form of brain injury following birth asphyxia, characterized by: 1, 4
- Stupor or coma 1
- Absent Moro, grasping, and sucking reflexes 1
- Severe alterations in muscle tone (flaccidity or rigidity) 1
- Seizures (often refractory) 4
- Cardiorespiratory instability requiring intensive support 4
Common Etiologies
The most frequent causes of birth asphyxia leading to HIE include: 1, 5
- Placental abruption (20-fold increased risk of severe HIE) 5
- Umbilical cord prolapse 1
- Uterine rupture 1
- Velamentous or marginal cord insertion (39% of HIE cases vs 7% of controls; 5.6-fold increased risk) 5
Clinical Presentation and Diagnosis
Immediate assessment must document: 1, 3
- Sequential Apgar scores at 1,5, and 10 minutes (significantly lower in HIE) 3
- Umbilical cord blood gas (pH, base deficit, bicarbonate) 3
- Initial hemoglobin level (low hemoglobin increases HIE risk) 3
- Normoblast count (elevated in severe asphyxia) 3
Neurological examination in stage 3 HIE reveals: 1, 4
- Profound depression of consciousness (stupor/coma)
- Absent primitive reflexes
- Severe hypotonia or decerebrate posturing
- Absent or minimal spontaneous movement
- Seizures (generalized, often status epilepticus)
Diagnostic Studies with Prognostic Value
Amplitude-integrated EEG (aEEG) performed within 24-96 hours has high diagnostic and prognostic value for predicting neurodevelopmental outcomes. 1
MRI brain with spectroscopy should be obtained between 7-21 days after birth for definitive prognostic assessment. 1
Critical Management: Therapeutic Hypothermia
Induced hypothermia to 33.5°C for 72 hours must be initiated before 6 hours of age in infants with evolving moderate-to-severe HIE. 6, 1 This intervention:
- Reduces mortality from 35% to 27% 1
- Reduces permanent neurological disability from 48% to 27% 1
- Requires strict temperature control and rewarming over at least 4 hours 6
Eligibility criteria for therapeutic hypothermia: 6
- Term or near-term (≥35 weeks gestation)
- Evidence of perinatal hypoxia-ischemia
- Moderate-to-severe encephalopathy on examination
- Treatment in NICU with multidisciplinary capabilities
- Access to IV therapy, respiratory support, pulse oximetry, anticonvulsants, and laboratory testing
Oxygen Management During Resuscitation
For neonates requiring resuscitation, begin with room air rather than 100% oxygen. 6 The rationale:
- Healthy term newborns start with oxygen saturation of 60% and take 10 minutes to reach 90% 6
- Hyperoxia is toxic, particularly to preterm infants 6
- 100% oxygen confers no advantage over air and may increase time to first breath 6
Once chest compressions are needed (indicating failure of ventilation with low-concentration oxygen), increase supplementary oxygen concentration, then wean as soon as heart rate recovers. 6
Target oxygen saturations: Use pulse oximetry on the right upper extremity to guide titration, avoiding both hypoxemia and hyperoxemia. 6
Prognosis and Outcomes
Stage 3 HIE carries grave prognosis: 1, 4
- 27% mortality even with therapeutic hypothermia 1
- 48% develop permanent neurological deficits (cerebral palsy, developmental delay, epilepsy) without cooling 1
- 27% develop permanent neurological deficits with therapeutic hypothermia 1
Mild HIE (stage 1) typically shows complete recovery within 3 days with minimal or no neurodevelopmental alterations. 1
Critical Pitfall to Avoid
Never assume sudden unexpected postnatal collapse (SUPC) is the primary diagnosis without excluding birth asphyxia. SUPC can develop grade 2 HIE, but requires normal 5-minute Apgar and initial wellness, whereas birth asphyxia presents with low Apgar scores from birth. 6 Other conditions to exclude before diagnosing BA/HIE include sepsis and congenital cardiac disease. 6