Kernicterus: Definition and Clinical Significance
Kernicterus is the chronic form of bilirubin encephalopathy characterized by permanent neurological damage from bilirubin toxicity to the brain, specifically affecting the basal ganglia and brainstem nuclei, resulting in severe neurological sequelae including athetoid cerebral palsy, auditory dysfunction, dental-enamel dysplasia, and paralysis of upward gaze. 1, 2
Pathophysiology
Kernicterus develops when:
- Unconjugated bilirubin, especially the unbound or loosely bound portion, crosses the blood-brain barrier
- Bilirubin deposits in brain tissue, particularly targeting the basal ganglia, cerebellum, and auditory system
- Irreversible damage occurs to vulnerable neurons 1, 2, 3
The risk of bilirubin encephalopathy depends on:
- Total serum bilirubin (TSB) level
- Unbound bilirubin concentration
- Susceptibility of central nervous system cells to damage 1
Progression from Acute Bilirubin Encephalopathy to Kernicterus
Acute bilirubin encephalopathy progresses through three distinct phases:
Early phase:
- Lethargy
- Hypotonia
- Poor feeding/sucking
Intermediate phase:
- Moderate stupor
- Irritability
- Hypertonia
- Fever
- High-pitched cry
- Alternating drowsiness and hypotonia
- Retrocollis (backward arching of neck)
- Opisthotonos (arching of trunk)
Advanced phase:
If the infant survives acute bilirubin encephalopathy, kernicterus may develop as the chronic manifestation with permanent neurological sequelae.
Clinical Manifestations of Kernicterus
Kernicterus spectrum disorder includes:
- Motor-predominant kernicterus: Severe athetoid cerebral palsy
- Auditory neural sensory dysfunction: Hearing impairment ranging from high-frequency hearing loss to complete deafness
- Dental-enamel dysplasia
- Paralysis of upward gaze (setting-sun sign)
- Intellectual disabilities (less common)
- Subtle kernicterus: Milder manifestations with less obvious neurological findings
- Kernicterus plus: Additional neurological complications 1, 2, 3
Epidemiology and Risk Factors
Kernicterus is rare but devastating, affecting:
- Primarily full-term and near-term infants
- Disproportionately affecting Black infants (>25% of kernicterus cases in the US despite comprising only ~14% of births) 4
Risk factors include:
- Severe hyperbilirubinemia (TSB >25 mg/dL)
- Blood group incompatibility
- Hemolytic diseases
- G6PD deficiency
- Exclusive breastfeeding with poor intake
- Early discharge without proper follow-up
- Delayed recognition of jaundice
- Genetic factors affecting bilirubin metabolism 2, 5
Prevention and Monitoring
Prevention strategies include:
- Universal risk assessment before hospital discharge
- Pre-discharge measurement of TSB or transcutaneous bilirubin (TcB)
- Close follow-up after discharge
- Screening for G6PD deficiency in at-risk populations
- Promoting successful breastfeeding
- Parent education about jaundice monitoring 2, 6
Key Clinical Implications
- Kernicterus should be largely preventable with proper monitoring and timely intervention
- Early identification and treatment of severe hyperbilirubinemia is essential
- Exchange transfusion may reverse central nervous system changes if performed during the intermediate phase
- Once advanced phase is reached, neurological damage is likely irreversible 1, 6
- Some infants develop kernicterus despite minimal or no signs of acute bilirubin encephalopathy 1
Common Pitfalls in Management
- Dismissing parental concerns about jaundice
- Assuming jaundice is physiologic without proper assessment
- 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 2
Kernicterus remains a significant public health concern that requires vigilance and prompt intervention to prevent its devastating neurological consequences.