Unbound Bilirubin and Auditory Neuropathy Spectrum Disorder in Late Preterm and Term Infants with Severe Jaundice

Abstract

Objective: This study evaluates whether unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin:albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥20 mg/dL or TSB that met exchange transfusion criteria).

Study design: Infants ≥34 weeks' gestation with severe jaundice during the first 2 weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80-decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively.

Results: Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (OR, 4.6; 95% CI, 1.6-13.5; P = .002). On comparing receiver operating characteristic curves, the area under the curve for unbound bilirubin (0.92) was significantly greater (P = .04) compared with the area under the curve for TSB (0.50) or BAMR (0.62).

Conclusions: Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice.

Keywords: Total serum bilirubin; bilirubin-induced neurotoxicity; bilirubin:albumin molar ratio; sensitivity; specificity.

Figure

Receiver operating characteristics (ROC) curves of the peak TSB, peak unbound bilirubin, and peak BAMR as predictors of Auditory Neuropathy Spectrum Disorder are shown. The straight line is the expected curve (unity) if the variable has no predictive value (area under unity curve 0.5). The areas under the curves are unbound bilirubin 0.92, TSB 0.50, and BAMR 0.62. The area under the unbound bilirubin curve is significantly greater than the area under the TSB and BAMR curves.