What is kernicterus?

Kernicterus: A Preventable Neurological Disorder

Kernicterus is a severe neurological disorder caused by bilirubin toxicity to the brain, specifically affecting the basal ganglia and brainstem nuclei, resulting from untreated severe hyperbilirubinemia in newborns. 1 It represents the chronic and permanent sequelae of bilirubin-induced neurological damage, which should be largely preventable with proper monitoring and timely intervention.

Definition and Pathophysiology

Kernicterus was originally a pathologic diagnosis characterized by bilirubin staining of the brainstem nuclei and cerebellum. However, to improve consistency in medical literature, the American Academy of Pediatrics recommends using:

• Acute bilirubin encephalopathy: The acute manifestations of bilirubin toxicity
• Kernicterus: The chronic and permanent clinical sequelae of bilirubin toxicity 1

The condition occurs when excessive unconjugated bilirubin crosses the blood-brain barrier and irreversibly damages vulnerable brain cells, particularly in:

• Basal ganglia
• Cerebellum
• Auditory system 2

Clinical Manifestations

Acute Bilirubin Encephalopathy

Progresses through three phases:

1. Early phase:

   • Lethargy
   • Hypotonia
   • Poor feeding/sucking 1

2. Intermediate phase:

   • Moderate stupor
   • Irritability
   • Hypertonia
   • Fever
   • High-pitched cry
   • Alternating drowsiness and hypotonia
   • Retrocollis (backward arching of neck)
   • Opisthotonos (backward arching of trunk) 1

3. Advanced phase (likely irreversible):

   • Pronounced retrocollis-opisthotonos
   • Shrill crying
   • Setting-sun sign
   • Seizures
   • Coma 1

Kernicterus Spectrum Disorder

Several subtypes have been identified:

• Motor-predominant kernicterus
• Auditory neural sensory dysfunction
• Subtle kernicterus
• Kernicterus plus 2

Risk Factors

Several factors increase the risk of developing kernicterus:

• Severe hyperbilirubinemia
• G6PD deficiency (present in 11-13% of African Americans)
• Hemolytic conditions
• Prematurity (especially 35-37 weeks gestation)
• Early hospital discharge without proper follow-up
• Inadequate breastfeeding
• Genetic factors 1, 3

Epidemiology and Health Disparities

Despite being rare, kernicterus continues to occur in both developed and developing countries. A significant health disparity exists:

• Black neonates account for over 25% of kernicterus cases in the US despite representing only 14% of births
• This disparity exists despite a lower overall incidence of significant hyperbilirubinemia in Black neonates 4

Prevention Strategies

The American Academy of Pediatrics emphasizes that kernicterus should be largely preventable through:

1. Universal systematic assessment for risk of severe hyperbilirubinemia
2. Close follow-up based on risk assessment
3. Prompt intervention when necessary 1

Specific Prevention Approaches:

• Promote and support successful breastfeeding with 8-12 feedings per day
• Avoid routine supplementation with water or dextrose water in non-dehydrated breastfed infants
• Perform pre-discharge measurement of serum or transcutaneous bilirubin in all infants
• Screen for G6PD deficiency in infants with significant hyperbilirubinemia
• Plot TSB levels on hour-specific nomograms to assess risk
• Intervene at lower TSB levels for high-risk infants (including those with G6PD deficiency)
• Provide written and verbal information to parents about jaundice monitoring 1, 3, 5

Treatment

When severe hyperbilirubinemia is identified, prompt treatment is essential:

• Phototherapy: First-line treatment, can be enhanced by combining traditional phototherapy from above with fiberoptic blanket from below 6
• Exchange transfusion: Reserved for cases not responding to phototherapy or with extremely high bilirubin levels 1
• Pharmacologic therapy: Tin-mesoporphyrin (not FDA approved) may help prevent exchange transfusions by inhibiting heme oxygenase 1

Monitoring

• Brain stem auditory evoked responses and MRI can effectively monitor the effects of severe hyperbilirubinemia 6
• End-tidal carbon monoxide (ETCOc) measurements can confirm the presence of hemolysis and provide direct measurement of heme catabolism rate 1

Key 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 (e.g., methylene blue, dapsone)
• Dismissing parental concerns about jaundice
• Assuming jaundice is physiologic without proper assessment

Conclusion

Kernicterus represents a devastating but largely preventable condition. Through systematic risk assessment, appropriate monitoring, parent education, and prompt intervention, healthcare providers can significantly reduce its incidence and the associated long-term neurological sequelae.