What are the risks of abnormal bilirubin levels in babies?

Dangers of Abnormal Bilirubin in Babies

Abnormal bilirubin levels in babies can lead to bilirubin encephalopathy (kernicterus), a severe form of brain damage that can cause death or permanent neurological disabilities including cerebral palsy, hearing loss, and developmental delays. 1

Risk Assessment and Identification

Hyperbilirubinemia in newborns can be classified as:

1. Physiologic jaundice: Elevated indirect bilirubin without underlying disease
2. Pathologic jaundice: Elevated direct bilirubin with underlying disease

Major Risk Factors for Severe Hyperbilirubinemia 2, 1:

• Predischarge total serum bilirubin (TSB) in high-risk zone
• Jaundice appearing in first 24 hours of life
• Blood group incompatibility with positive direct antiglobulin test
• Hemolytic diseases (e.g., G6PD deficiency)
• Gestational age 35-36 weeks
• Previous sibling who received phototherapy
• Cephalohematoma or significant bruising
• Exclusive breastfeeding with poor feeding or excessive weight loss
• East Asian, Mediterranean, or Native American ethnicity

Minor Risk Factors 2:

• Gestational age 37-38 weeks
• Jaundice observed before discharge
• Previous sibling with jaundice
• Macrosomic infant of diabetic mother
• Maternal age ≥25 years
• Male gender

Neurological Consequences of Hyperbilirubinemia

Acute Bilirubin Encephalopathy Symptoms 1:

• Lethargy and poor feeding
• High-pitched cry
• Hypertonia or hypotonia
• Retrocollis and opisthotonus (backward arching of head, neck, and spine)
• Setting-sun sign
• Seizures

Long-term Risks:

• Chronic bilirubin encephalopathy (kernicterus) occurs in approximately 0.9 per 100,000 live births in high-income countries 1, 3
• Premature infants are at significantly higher risk for bilirubin neurotoxicity even at lower bilirubin levels 4
• Permanent neurological damage can include cerebral palsy, hearing loss, visual and gaze abnormalities, dental enamel dysplasia, and intellectual impairment 1

Risk Stratification by Population

1. Term, healthy infants: Lower risk of kernicterus, with evidence suggesting it occurs at much higher bilirubin levels than previously thought 3

2. Premature infants: Significantly higher risk of kernicterus

   • Historical data showed kernicterus rates of 10.1% in babies <30 weeks, 5.5% in 31-32 weeks, and 1.2% in 33-34 weeks gestational age without treatment 4

3. Infants with hemolytic conditions: Substantially increased risk of neurotoxicity 1, 4

Mechanism of Neurotoxicity

Bilirubin is transported in plasma bound to albumin. The unbound or "free" bilirubin can cross the blood-brain barrier and cause neuronal damage 2:

• Free bilirubin levels >0.1 mg/dL strongly correlate with encephalopathy signs 5
• The bilirubin/albumin (B/A) ratio can be used as a surrogate marker for free bilirubin 2
• Albumin binding capacity is reduced in sick and premature infants, increasing risk 2

Prevention and Management

Screening and Monitoring:

• Universal screening for hyperbilirubinemia in newborns ≥35 weeks' gestational age 1, 3
• Predischarge bilirubin measurement and plotting on hour-specific nomogram 2
• Risk assessment before discharge for all newborns 2

Treatment Thresholds:

• Phototherapy should be initiated based on AAP nomograms considering:
  • Age in hours
  • Gestational age
  • Presence of risk factors 1, 3

Effective Interventions:

• Intensive phototherapy using blue-green spectrum (425-475 nm) light with irradiance >30 mW/cm² per nm 1
• Exchange transfusion for TSB ≥25 mg/dL or if TSB reaches exchange threshold per AAP guidelines 1
• IVIG (0.5-1 g/kg over 2 hours) if TSB is rising despite intensive phototherapy 1

Breastfeeding Considerations:

• Support continued breastfeeding during phototherapy 1
• Encourage frequent nursing (8-12 times daily) in the first several days 1
• Monitor adequate intake through weight gain, wet diapers, and stool patterns 1

Special Considerations

• Direct bilirubin >1.0 mg/dL when total bilirubin is ≤5 mg/dL requires evaluation for cholestasis or other pathologic causes 1
• G6PD deficiency occurs in 11-13% of African Americans and was implicated in 31.5% of kernicterus cases in one report 2
• Exchange transfusion carries risks including hypoxic-ischemic encephalopathy and complications from blood products 2

Early identification of at-risk infants, appropriate monitoring, and timely intervention remain the cornerstones of preventing the devastating neurological consequences of severe hyperbilirubinemia.