At what age can bilirubin encephalopathy occur in newborns?

Bilirubin Encephalopathy in Newborns: Age of Occurrence

Bilirubin encephalopathy can occur as early as the first 24 hours of life in newborns with severe hyperbilirubinemia, with the highest risk during the first week of life when bilirubin levels typically peak. 1, 2

Timing and Risk Periods

• First 24 hours: Jaundice appearing within the first 24 hours is considered pathological and requires immediate investigation 2
• Peak risk period: Days 2-5 of life when physiologic hyperbilirubinemia typically reaches its maximum
• Extended risk: Can occur beyond the first week in infants with persistent hyperbilirubinemia

Clinical Presentation by Phase

Acute bilirubin encephalopathy presents in distinct phases:

1. Early phase (first 1-2 days):

   • Lethargy
   • Poor feeding
   • Hypotonia
   • High-pitched cry 2

2. Intermediate phase:

   • Moderate stupor
   • Irritability
   • Hypertonia
   • Retrocollis and opisthotonus (backward arching of head, neck, and spine)
   • Setting-sun sign 2

3. Advanced phase:

   • Deep stupor to coma
   • Pronounced retrocollis-opisthotonus
   • Shrill cry
   • Apnea
   • Seizures
   • Death 2, 3

Risk Factors for Bilirubin Encephalopathy

The American Academy of Pediatrics identifies several factors that increase the risk of developing bilirubin encephalopathy:

• Gestational age <38 weeks
• Exclusive breastfeeding, especially if feeding is not well established
• Jaundice in the first 24 hours of life
• Hemolytic conditions (ABO or Rh incompatibility, G6PD deficiency)
• Previous sibling with severe jaundice
• Cephalohematoma or significant bruising
• East Asian, Mediterranean, or Native American ethnicity 1, 2

Threshold Bilirubin Levels and Age

The risk of bilirubin encephalopathy correlates with both total serum bilirubin (TSB) levels and the infant's age:

• 25-48 hours old: Risk increases when TSB ≥15 mg/dL (257 μmol/L)
• 49-72 hours old: Risk increases when TSB ≥18 mg/dL (308 μmol/L)
• >72 hours old: Risk increases when TSB ≥20 mg/dL (342 μmol/L) 4

Notably, preterm infants are at risk for "low bilirubin kernicterus" where encephalopathy can occur at lower bilirubin levels than in term infants 3.

Long-term Outcomes

If not promptly treated, acute bilirubin encephalopathy can progress to chronic bilirubin encephalopathy (kernicterus) with permanent neurological sequelae:

• Choreoathetoid cerebral palsy
• Sensorineural hearing loss
• Gaze abnormalities (particularly upward gaze palsy)
• Dental enamel dysplasia
• Intellectual impairment 3, 5

Prevention and Management

Early identification and treatment are critical:

• Systematic assessment for hyperbilirubinemia risk before discharge
• Support for successful breastfeeding (8-12 feedings per day)
• Early follow-up based on risk assessment
• Prompt initiation of phototherapy when indicated
• Exchange transfusion for severe cases 1, 2

Clinical Pitfalls to Avoid

1. Delayed recognition: Failing to identify jaundice in the first 24 hours as pathological
2. Underestimating risk in breastfed infants: Inadequate establishment of breastfeeding coupled with early discharge can contribute to severe hyperbilirubinemia 6
3. Missing associated conditions: Sepsis, anoxia, and acidosis may increase bilirubin neurotoxicity 5
4. Overlooking preterm vulnerability: Preterm infants can develop kernicterus at lower bilirubin levels 3
5. Inadequate follow-up: The incidence of chronic bilirubin encephalopathy is estimated at 0.9 per 100,000 live births, highlighting the importance of appropriate monitoring 2