Assessment and Management of Hyperbilirubinemia in Infants

Clinical Significance and Risk Assessment

A total bilirubin level of 15.4 mg/dL in a 25-day-old infant is abnormal and requires urgent evaluation for pathologic causes of hyperbilirubinemia, as this level is concerning at this age and warrants immediate investigation 1, 2
Jaundice persisting beyond 3 weeks of age with elevated bilirubin levels requires measurement of both total and direct/conjugated bilirubin to identify potential cholestasis 3
The American Academy of Pediatrics guidelines indicate that sick infants and those jaundiced at or beyond 3 weeks should have measurements of total and direct/conjugated bilirubin to identify cholestasis 3
In healthy term newborns, physiologic jaundice typically resolves by 1-2 weeks of age, so persistent elevation at 25 days is concerning for pathologic causes 2

Obtain total and direct/conjugated bilirubin levels to differentiate between unconjugated and conjugated hyperbilirubinemia 3
If the direct or conjugated bilirubin is more than 1.0 mg/dL when the total bilirubin is ≤5 mg/dL, this is considered abnormal 4
Check results of newborn thyroid and galactosemia screening tests 3
Evaluate for signs of acute bilirubin encephalopathy, which may include lethargy, hypotonia, poor feeding, hypertonia, and high-pitched cry 2

Hemolytic disorders including G6PD deficiency, which can cause sudden increases in bilirubin levels 5
Biliary obstruction or liver disease, particularly if direct/conjugated fraction is elevated 6
Metabolic disorders such as galactosemia 3
Endocrine disorders such as hypothyroidism 3

If unconjugated hyperbilirubinemia predominates and no serious underlying cause is found, phototherapy may be indicated based on the level and clinical assessment 7
If conjugated hyperbilirubinemia is present, phototherapy is less effective and addressing the underlying cause is the priority 1
Exchange transfusion is reserved for extreme hyperbilirubinemia with signs of acute bilirubin encephalopathy 8

Elevated unbound bilirubin can cross the blood-brain barrier and cause neurotoxicity 5
The bilirubin/albumin (B/A) ratio correlates with measured unbound bilirubin and can be used as an approximate surrogate for assessing risk 8
Long-term adverse neurodevelopmental effects may occur with prolonged hyperbilirubinemia, even if subtle and not manifesting as classic kernicterus 1
Chronic bilirubin encephalopathy (kernicterus) can lead to athetoid cerebral palsy, auditory dysfunction, dental-enamel dysplasia, and other neurological sequelae 2

Close monitoring of bilirubin levels until resolution 3
Neurological assessment for any signs of bilirubin-induced neurological dysfunction 2
Auditory brainstem response testing may be indicated, as elevated unbound bilirubin concentrations are associated with transient abnormalities in audiometric brainstem response 5

Visual estimation of jaundice is unreliable, especially in darkly pigmented infants; laboratory measurement is essential 3
Capillary versus venous sampling: almost all published data relating bilirubin levels to outcomes are based on capillary blood measurements 4
Phototherapy may interfere with maternal-infant bonding and breastfeeding, so the benefits must outweigh these potential harms 9
The risks of exchange transfusion include significant morbidity in up to 5% of procedures 9