An Investigation of the Association Between Newborn Screening Biomarkers and Total Serum Bilirubin Levels in Ontario Newborns

Abstract

The performance of biomarker-based screening tests may be improved by the identification of circumstances associated with biomarker differences aside from presence or absence of screen-targeted disease. We conducted a systematic review and database analysis investigating the association between total serum bilirubin (TSB) near the time of newborn screening for rare disease (NBS) and concentrations of NBS biomarkers, with implications for false positive (FP) results. Sixteen studies were identified reporting associations and lack thereof between NBS biomarkers and hyperbilirubinemia, evidencing a relatively unexplored subject. We conducted a cross-sectional analysis of NBS biomarkers and TSB using results from universal screening tests. Correlations revealed TSB level associated with most NBS biomarkers. Reassuringly, TSB was not significantly associated with FP risk for conditions with high FP rates such as congenital adrenal hyperplasia, congenital hypothyroidism, or phenylketonuria in regression analyses. Ascertainment of NBS specificity in neonates with common transient conditions such as hyperbilirubinemia may be a viable approach to improve the accuracy of NBS tests.