Kernicterus: Comprehensive Overview
Kernicterus is the chronic, irreversible form of bilirubin encephalopathy characterized by severe neurological sequelae including athetoid cerebral palsy, auditory dysfunction, dental-enamel dysplasia, and paralysis of upward gaze, resulting from bilirubin toxicity to the basal ganglia and brainstem nuclei. 1
Definition and Pathophysiology
Kernicterus originally referred to a pathologic diagnosis characterized by bilirubin staining of the brainstem nuclei and cerebellum, but the term has evolved to describe both acute and chronic manifestations of bilirubin toxicity. 1 The American Academy of Pediatrics recommends using "acute bilirubin encephalopathy" for acute manifestations and reserving "kernicterus" for the chronic form to avoid confusion in the literature. 1, 2
Bilirubin encephalopathy describes the clinical central nervous system findings caused by bilirubin toxicity specifically to the basal ganglia and various brainstem nuclei. 1, 2
Clinical Presentation: Acute Bilirubin Encephalopathy
The acute phase progresses through three distinct stages before potentially evolving into chronic kernicterus:
Early Phase
- Lethargy and hypotonia 1
- Poor sucking 1
- These signs indicate the initial stage where intervention may still prevent permanent damage 1
Intermediate Phase
- Moderate stupor 1
- Irritability and hypertonia 1
- Fever and high-pitched cry alternating with drowsiness and hypotonia 1
- Backward arching of the neck (retrocollis) and trunk (opisthotonos) 1
- Emergent exchange transfusion at this stage may, in some cases, reverse the central nervous system changes 1
Advanced Phase
- Pronounced retrocollis-opisthotonos 1
- Shrill cry 1
- No feeding 1
- Apnea 1
- Fever 1
- Deep stupor to coma 1
- Seizures and death 1
- Central nervous system damage is probably irreversible at this stage 1
Chronic Kernicterus: Long-Term Sequelae
Surviving infants develop devastating and permanent neurological disabilities:
- Severe athetoid cerebral palsy (the hallmark finding) 1
- Auditory dysfunction (hearing impairment) 1
- Dental-enamel dysplasia 1
- Paralysis of upward gaze 1
- Intellectual and other handicaps (less common) 1
Critical Clinical Caveat
Most infants who develop kernicterus manifest signs of acute bilirubin encephalopathy, but occasionally infants develop very high bilirubin levels and subsequently show signs of kernicterus with few or no antecedent clinical signs of acute encephalopathy. 1 This underscores the importance of systematic bilirubin monitoring rather than relying solely on clinical observation.
Epidemiology and Risk Factors
Kernicterus can occur in apparently healthy, full-term, breast-fed newborns without hemolytic disease or any other discernible cause for jaundice. 3 Peak bilirubin levels in documented cases have ranged from 39.0 to 49.7 mg/dL, occurring 4 to 10 days after birth. 3
Risk is increased in:
- Countries where glucose-6-phosphate dehydrogenase deficiency is common 4
- Late preterm infants (35-37 weeks gestation) 2
- Infants with inadequate breastfeeding and dehydration 1
- Early hospital discharge with inadequate follow-up 5
Prevention Strategies
Primary Prevention
Promote successful breastfeeding with 8-12 feedings per day for the first several days to prevent poor caloric intake and dehydration that contribute to hyperbilirubinemia. 1, 2
Do not routinely supplement nondehydrated breastfed infants with water or dextrose water, as supplementation will not prevent hyperbilirubinemia or decrease total serum bilirubin levels. 1, 2
Systematic Risk Assessment
Perform prenatal testing of all pregnant women for ABO and Rh(D) blood types and screen for unusual isoimmune antibodies. 2 If the mother has not had prenatal blood grouping or is Rh-negative, obtain direct antibody test (Coombs' test), blood type, and Rh(D) type on the infant's cord blood. 2
Monitor all infants routinely for jaundice whenever vital signs are measured, but no less than every 8-12 hours. 2 Visual estimation of bilirubin levels from the degree of jaundice can lead to errors, so maintain a low threshold for measuring total serum bilirubin. 1
Screening and Monitoring
Perform transcutaneous bilirubin (TcB) and/or total serum bilirubin (TSB) measurement on every infant jaundiced in the first 24 hours after birth, as early onset jaundice suggests hemolytic disease and is a risk factor for severe hyperbilirubinemia. 2
Plot bilirubin measurements on hour-specific nomograms to assess risk and response to treatment. 2 Transcutaneous instruments generally provide measurements within 2 to 3 mg/dL of the TSB and can replace serum bilirubin measurement in many circumstances, particularly for TSB levels less than 15 mg/dL. 1
Important limitation: Phototherapy "bleaches" the skin, making both visual assessment of jaundice and TcB measurements unreliable in infants undergoing phototherapy. 1
Treatment to Prevent Kernicterus
Phototherapy
Initiate phototherapy based on TSB levels, gestational age, and risk factors using appropriate nomograms. 2 Use special blue fluorescent tubes or LED lights that deliver irradiance of >30 μW/cm²/nm for intensive phototherapy. 2
Expect a decrease of more than 2 mg/dL (34 μmol/L) in serum bilirubin concentration within 4-6 hours of initiating effective phototherapy. 2 Change the infant's posture every 2-3 hours to maximize the area exposed to light, and avoid physical obstruction of light by equipment, large diapers, head covers, or electrode patches. 2
Exchange Transfusion
Consider exchange transfusion if TSB is in the intensive phototherapy range and phototherapy does not promptly lower the TSB. 2 Do not subtract direct serum bilirubin from the TSB concentration when making decisions about exchange transfusions. 2
In the intermediate phase of acute bilirubin encephalopathy, emergent exchange transfusion may, in some cases, reverse the central nervous system changes, though this is based on anecdotal evidence. 1
Follow-Up
Provide early and focused follow-up based on risk assessment. 1, 2 After discharge, follow-up within 24-48 hours to reassess bilirubin levels and monitor for signs of worsening jaundice. 2
Assess adequacy of intake in breastfed infants: Evidence of adequate intake includes 4 to 6 thoroughly wet diapers in 24 hours and passage of 3 to 4 stools per day by the fourth day. 1 If weight loss exceeds 10% by day 3, evaluate adequacy of intake and monitor the infant closely. 1
Clinical Pitfalls
Kernicterus should almost always be preventable, yet cases continue to occur. 1 The re-emergence of kernicterus in developed countries results from:
- Early hospital discharge before the extent of jaundice is known 5
- Lack of adequate concern for risks of severe jaundice in healthy term and near-term newborns 5
- Medical care cost constraints 5
- Limitations within healthcare systems to monitor outpatient progression of jaundice 5
Any jaundiced infant who shows signs of possible neurotoxicity should receive intensive phototherapy as an emergency procedure while further evaluation continues. 4 Signs of possible neurotoxicity must never be disregarded or neglected. 4