Risk factors for neurotoxicity in newborns with severe neonatal hyperbilirubinemia

Abstract

Objective: To evaluate the importance of total serum bilirubin (TSB) and neurotoxicity risk factors in predicting acute bilirubin encephalopathy (ABE) at admission or posttreatment bilirubin encephalopathy (BE) in infants with severe hyperbilirubinemia.

Methods: We analyzed the interaction of TSB and risk factors as determinants of ABE and BE in 249 newborns admitted with a TSB level of ≥ 25 mg/dL (427 μmol/L) to Cairo University Children's Hospital during a 12-month period.

Results: Admission TSB values ranged from 25 to 76.4 mg/dL. Forty-four newborns had moderate or severe ABE at admission; 35 of 249 infants (14%) had evidence of BE at the time of discharge or death. Rh incompatibility (odds ratio [OR]: 48.6) and sepsis (OR: 20.6) greatly increased the risk for ABE/BE, but TSB levels correlated poorly with the presence or absence of ABE or BE in these patients. The OR for ABO incompatibility with anemia (1.8) was not statistically significant. Low admission weight (OR: 0.83 per 100 g) increased the risk for BE, especially when other risk factors were present. The threshold TSB level that identified 90% of infants with ABE/BE was 25.4 mg/dL when neurotoxicity risk factors were present. In contrast, neurotoxicity was first observed at a TSB level of >31.5 mg/dL in 111 infants without risk factors.

Conclusions: Newborns without risk factors for neurotoxicity have a higher tolerance for hyperbilirubinemia than recognized in management guidelines. The risk for BE in hemolytic disease varies with etiology. The great variation in response to TSB indicates that biological factors other than TSB values are important in the pathogenesis of BE.

FIGURE 1

A, ROC analysis of risk for ABE or BE (BIND score 4–9) in 138 infants with recognized risk factors; threshold TSB and FPRs at 90% sensitivity and TSB at 10% sensitivity are indicated. The subcohort excludes infants charted in B and includes infants with Rh and ABO incompatibility with evidence of hemolysis, sepsis, and/or an admission weight of ≤2700 g. Many patients had >1 risk factor. The area under the curve was 0.595 (0.533 when ABO incompatibility was excluded). B, ROC analysis of risk for ABE or BE (BIND score 4–9) in 111 infants with no recognized risk factors; threshold TSB and FPRs at 90% sensitivity and TSB at 10% sensitivity are indicated. The subcohort excludes patients with ABO incompatibility with hematocrit at ≤35%, Rh incompatibility, weight of ≤2700 g, and evidence of sepsis. Only 3 of 111 infants developed ABE (TSB: 31.8–34.5 mg/dL). Two patients had severe BE (TSB: 41.8 and 43.2 mg/dL). The area under the curve was 0.857.