Association between newborn screening analyte profiles and infant mortality.

Objective: To assess whether newborn screening analytes could be utilized beyond their traditional application to identify infants at high risk of mortality within the first 6 months of life.Methods: We linked a province-wide newborn screening registry with health administrative databases to identify infant deaths within 6 months in a source population of live-born infants between 2010 and 2014. We used a nested case-control study design, in which all infant deaths between 7 days and 6 months of age were included as cases, and a random sample of infants from the source population were selected as controls and were matched to cases at a ratio of 10:1. We examined the association between mortality and screening analytes (acylcarnitines, amino acids, fetal-to-adult hemoglobin ratio, endocrine markers, and enzymes) using lasso regression to fit multivariable models.Results: Among 350 infant deaths between 7 days and 6 months of age, and 3498 matched controls with complete data, our multivariable model demonstrated only modest ability to identify infant deaths (optimism-corrected c-statistic: 0.61, 95% confidence interval: 0.50-0.71).Conclusion: We did not find newborn screening analytes to be strongly predictive of infant mortality between 7 days and 6 months of age in the general population of newborns. Future studies should investigate whether predictive modeling within more homogeneous cause-of-death categories could lead to improved predictive ability for infant mortality.