What are the dangers of hyperbilirubinemia?

Dangers of Hyperbilirubinemia

The primary danger of hyperbilirubinemia is the development of kernicterus, a severe and permanent form of brain damage that occurs when bilirubin crosses the blood-brain barrier and deposits in brain tissue, particularly affecting the basal ganglia and brainstem nuclei. 1, 2

Acute Bilirubin Encephalopathy Progression

Hyperbilirubinemia can lead to acute bilirubin encephalopathy, which progresses through three phases:

1. Early Phase:

   • Lethargy
   • Hypotonia
   • Poor feeding/sucking

2. Intermediate Phase:

   • Moderate stupor
   • Irritability
   • Hypertonia
   • Fever
   • High-pitched cry
   • Alternating drowsiness and hypotonia

3. Advanced Phase (likely irreversible):

   • Pronounced retrocollis-opisthotonos
   • Shrill crying
   • Setting-sun sign
   • Seizures
   • Coma 2

Neurological Consequences

Even at levels below those causing kernicterus, hyperbilirubinemia can cause:

• Transient changes in brainstem-evoked potentials
• Abnormal behavioral patterns
• Altered infant cry characteristics
• Subtle long-term neurodevelopmental effects 1

Risk Factors for Severe Hyperbilirubinemia and Kernicterus

Major Risk Factors:

• High predischarge total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) levels
• Jaundice observed in the first 24 hours of life
• Blood group incompatibility with positive direct antiglobulin test
• Hemolytic diseases (especially G6PD deficiency)
• Gestational age 35-36 weeks
• Previous sibling requiring phototherapy
• Cephalohematoma or significant bruising
• Exclusive breastfeeding with poor intake and excessive weight loss
• East Asian race 1

Minor Risk Factors:

• Predischarge TSB or TcB in high intermediate-risk zone
• Gestational age 37-38 weeks
• Jaundice observed before discharge
• Previous sibling with jaundice
• Macrosomic infant of a diabetic mother
• Maternal age >25 years
• Male gender 1

Physiological Mechanisms of Toxicity

Bilirubin is transported in plasma tightly bound to albumin. The unbound or loosely bound portion can more readily:

• Leave the intravascular space
• Cross the intact blood-brain barrier
• Enter brain tissue causing damage 1

The risk of bilirubin encephalopathy is likely a combination of:

• Total amount of bilirubin available (the miscible pool)
• Tendency of bilirubin to enter tissues (the unbound bilirubin concentration)
• Susceptibility of central nervous system cells to bilirubin damage 1, 3

Complications of Treatment

Exchange Transfusion Risks:

• Death (approximately 3 in 1000 procedures)
• Significant morbidity (5% of procedures) including:
  • Apnea
  • Bradycardia
  • Cyanosis
  • Vasospasm
  • Thrombosis
  • Necrotizing enterocolitis
  • Hypoxic-ischemic encephalopathy
  • Risks associated with blood products 1

Phototherapy Considerations:

• May disrupt mother-infant bonding
• Can cause diarrhea
• May increase risk of seizures
• May lead to unnecessary discontinuation of breastfeeding 4

Prevention and Monitoring

To prevent severe hyperbilirubinemia and its complications:

1. Universal risk assessment before discharge for all newborns
2. Predischarge measurement of TSB or TcB levels and plotting on hour-specific nomograms
3. Close follow-up based on risk assessment
4. Screening for G6PD deficiency in infants with significant hyperbilirubinemia
5. Promoting successful breastfeeding while monitoring for adequate intake
6. Providing education to parents about jaundice monitoring 1, 2

Common Pitfalls to Avoid

• Delayed recognition of jaundice or risk factors
• Inadequate follow-up after early discharge
• Failure to screen for G6PD deficiency in at-risk populations
• Using medications contraindicated in G6PD deficiency
• Dismissing parental concerns about jaundice
• Assuming jaundice is physiologic without proper assessment 2
• Relying solely on visual assessment of jaundice, particularly in darkly pigmented infants 1

Remember that while hyperbilirubinemia is common (affecting 60% of term newborns and nearly all preterm infants), severe complications are rare but devastating when they occur 5, 4. Close cooperation between the clinical laboratory and the medical team is essential for proper management 6.