Fractionated Bilirubin Among 252 892 Utah Newborns with and Without Biliary Atresia: A 15-year Historical Birth Cohort Study

Abstract

To determine whether neonatal conjugated or direct bilirubin levels were elevated in infants with biliary atresia, and to estimate the number of newborns that would have positive screens in the nursery necessitating repeat testing following discharge. We used administrative data from a large integrated healthcare network in Utah to identify newborns who had a fractionated bilirubin recorded during birth admission from 2005 through 2019. Elevated conjugated bilirubin was defined as greater than 0.2 mg/dL and direct bilirubin was defined as greater than 0.5 mg/dL (>97.5th percentile for the assays). We performed simulations to estimate the anticipated number of false positive screens. There were 32 cases of biliary atresia and 468,161 live births during the study period (1/14,700). 252,892 newborns had fractionated bilirubin assessed including 26 of those subsequently confirmed to have biliary atresia. Conjugated or direct bilirubin was elevated in all 26 infants with biliary atresia and an additional 3,246 (1.3%) newborns without biliary atresia. Simulated data suggest nine to 21 per 1,000 screened newborns will have an elevated conjugated or direct bilirubin using laboratory-based thresholds for a positive screen. Screening characteristics improved with higher thresholds without increasing false negative tests. This study validates the previous findings that conjugated or direct bilirubin are elevated in the newborn period in patients with biliary atresia. A higher threshold for conjugated bilirubin improved screening performance. Future studies are warranted to determine the optimal screening test for biliary atresia and to assess the effectiveness and cost-effectiveness of implementing such a program.