A review of the literature demonstrates that severe total hyperbilirubinemia (total serum bilirubin ≥ 20 mg/dL [340 µmol/L]) in some cholestatic term (≥37 weeks) and late-preterm (≥34-36 weeks) gestation neonates poses a risk for bilirubin-induced brain damage. When the direct bilirubin fraction is <50% of the total serum bilirubin this risk is associated with the total serum bilirubin alone and treatment decisions should be based on the total serum bilirubin. On the other hand, there are limited data on the risk of bilirubin-induced brain damage in the neonate with severe total hyperbilirubinemia and a direct bilirubin fraction that is equal to or exceeds 50% of the total serum bilirubin. When this rare combination occurs, efforts to keep the indirect bilirubin fraction from reaching severe levels might, nevertheless, be prudent.
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