What is Hypoxic-Ischemic Encephalopathy (HIE) in newborn babies?

What is Hypoxic-Ischemic Encephalopathy (HIE) in Newborn Babies?

HIE is a brain injury syndrome in newborns caused by insufficient oxygen and blood flow to the brain during the peripartum period, resulting in neurological dysfunction that ranges from mild and fully reversible to severe with permanent disability or death. 1, 2

Definition and Core Pathophysiology

HIE occurs when impaired cerebral blood flow and oxygen delivery during or around the time of birth leads to brain cell damage and dysfunction. 2, 3 The condition specifically affects term and near-term infants (≥36 weeks gestational age) who experience perinatal asphyxia. 4, 5

The brain injury evolves through distinct phases:

• Primary phase: Immediate energy failure and cell metabolism collapse at the time of the hypoxic-ischemic insult 2
• Latent phase: Brief recovery period lasting approximately 6 hours after the initial insult 2
• Secondary phase: Delayed energy failure occurring 6-48 hours after birth, characterized by increased cytotoxicity, apoptosis, activated microglia, and inflammation 2, 6
• Tertiary phase: If injury persists, ongoing neuronal loss and reduced neural plasticity continuing for months 2

Clinical Presentation and Severity Grading

HIE presents as a clearly recognizable clinical syndrome with specific diagnostic criteria:

Required diagnostic criteria include:

• Inability to cry or breathe at birth despite stimulation, requiring assisted ventilation in the delivery room 5
• Apgar score <5 at 5 and 10 minutes 5
• Severe acidemia with pH ≤7.0 and/or base deficit ≥12 mmol/L 5
• Altered consciousness and abnormal reflexes (Moro, grasping, sucking) 5
• Abnormal muscle tone and stretching 5

HIE is classified into three severity grades:

• Mild HIE: Complete recovery within 3 days with minimal or no neurodevelopmental alterations 5
• Moderate HIE: Significant risk of permanent neurological deficits 4, 5
• Severe HIE: High mortality (27%) and permanent neurological disability (48%) in survivors 5

Epidemiology and Causes

HIE affects 1.5 per 1000 live births in developed countries (range 1-8 per 1000) but rises dramatically to 25 per 1000 in developing countries. 5, 7 It represents the dominant cause of neonatal seizures, accounting for 46-65% of all cases. 1, 8

Common precipitating events include:

• Placental abruption 5
• Umbilical cord prolapse 5
• Uterine rupture 5
• Maternal hypotension or cardiac arrest 2

Approximately 90% of seizures in HIE occur within the first 2 days of life, making early timing a key diagnostic clue. 1, 8

Diagnostic Approach

MRI with diffusion-weighted imaging is the gold standard for diagnosing HIE and should be performed between 24-96 hours after birth for optimal detection of injury patterns. 1, 5 This timing captures the evolving injury during the secondary phase and has high diagnostic and prognostic value. 5

Head ultrasound serves as initial bedside screening if the infant is unstable or MRI is unavailable, though it has limited sensitivity for detecting hypoxic-ischemic injury. 1

Amplitude-integrated EEG or conventional EEG performed within the first 24-96 hours provides additional diagnostic and prognostic information. 5

Treatment

Therapeutic hypothermia (cooling to 33-34°C for 72 hours) is the only evidence-based treatment for moderate-to-severe HIE and must be initiated within 6 hours of birth. 4, 2 This intervention reduces mortality from 35% to 27% and permanent neurological disability from 48% to 27%. 5

The treatment protocol requires:

• Initiation within 6 hours of birth 4
• Strict temperature control to 33-34°C 4
• Duration of 72 hours 4
• Slow rewarming over at least 4 hours 4
• Multidisciplinary neonatal intensive care with capabilities for respiratory support, pulse oximetry, IV therapy, antibiotics, antiseizure medications, and comprehensive monitoring 4

Common adverse effects of therapeutic hypothermia include thrombocytopenia and increased need for inotropic support. 4

Prognosis and Long-term Outcomes

Without treatment, 15-20% of infants with HIE die in the early neonatal period. 7 Survivors face significant risks of:

• Cerebral palsy 4, 7
• Epilepsy 7
• Visual and hearing impairment 7
• Cognitive and intellectual disabilities 7
• Behavioral and social disorders 7

The absence of major cerebral lesions on MRI is highly predictive of normal neurological outcome, making neuroimaging valuable for prognostication. 1

Critical Pitfall

Do not delay hypothermia initiation while awaiting confirmatory testing—the 6-hour window is critical for neuroprotection. 4 Treatment should be implemented under clearly defined protocols in facilities with comprehensive neonatal intensive care capabilities, as adoption without proper monitoring and support may lead to harm. 4