Umbilical cord blood bilirubins, gestational age, and maternal race predict neonatal hyperbilirubinemia.

Abstract

No validated biomarker at birth exists to predict which newborns will develop severe hyperbilirubinemia. This study's primary aim was to build and validate a prediction model for severe hyperbilirubinemia using umbilical cord blood bilirubins (CBB) and risk factors at birth in neonates at risk for maternal-fetal blood group incompatibility. This study's secondary aim was to compare the accuracy of CBB to the direct antigen titer. Inclusion criteria for this prospective cohort study included: ≥35 weeks gestational age, mother with blood type O and/or Rh negative or positive antibody screen, and <24 hours of age. The primary outcome was severe hyperbilirubinemia, defined as phototherapy during the initial hospital stay. Secondary outcomes were a total serum bilirubin concentration >95th and >75th percentile during the initial hospital stay. The predictive performance and accuracy of the two tests (CBB and direct antigen titer) for each outcome was assessed using area under a receiver-operating characteristic curve (AUC), sensitivity, and specificity. When compared to neonates who did not receive phototherapy (n = 463), neonates who received phototherapy (n = 36) had a greater mean CBB ± standard deviation (2.5 ± 0.7 vs. 1.6 ± 0.4 mg/dL, p<0.001). For every 0.3 mg/dL increase in CBB, a neonate was 3.20 (95% confidence interval, 2.31-4.45), 2.10 (1.63-2.70), and 3.12 (2.44-3.99) times more likely to receive phototherapy or have a total serum bilirubin concentration >95th and >75th percentile, respectively. The AUC ± standard error (95% confidence interval) for CBB for phototherapy and a total serum bilirubin concentration >95th and >75th percentile was 0.89 ± 0.03 (0.82-0.95), 0.81 ± 0.04 (0.73-0.90), and 0.84 ± 0.02 (0.80-0.89), respectively. However, the AUC for gestational age and maternal Asian race for these outcomes was only 0.55 ± 0.05 (0.45-0.66), 0.66 ± 0.05 (0.56-0.76), and 0.57 ± 0.04 (0.05-0.64), respectively. When the CBB was combined with gestational age and maternal Asian race, the AUC for a total serum bilirubin concentration >95th percentile improved to 0.87 ± 0.03 (0.81-0.92) (p = 0.034 vs. the model with CBB only and p<0.001 vs. the model with clinical risk factors only). In a sub-group of subjects (n = 189), the AUC for the direct antigen titer for phototherapy was 0.64 ± 0.06 (0.52-0.77) with a 52% sensitivity and 77% specificity. In contrast, a CBB cut-point of 1.85 mg/dL was 92% sensitive and 70% specific for phototherapy with an AUC of 0.87 ± 0.04 (0.80-0.95). CBB, in combination with gestational age and maternal race, may be a useful, non-invasive test to predict shortly after birth which neonates will develop severe hyperbilirubinemia.