Association between newborn screening analyte profiles and infant mortality

Abstract

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-ofdeath categories could lead to improved predictive ability for infant mortality.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…Several other publications in 2021 dealt with NBS issues: a study of the predictive value of NBS analytes found a lack of association with infant mortality between 7 days and 6 months of age [ 387 ]; a study of sickle cell carrier status, which is not reported in Ontario NBS, identified statistically significant differences in health services use among sickle carriers relative to controls, with small effect sizes and inconsistent association directions across age groups and health service types indicating that carrier status is likely benign in early childhood [ 119 ]; a report recommending testing and follow-up protocols for implementation of NBS for SMA in Ontario included a standardized path to early diagnosis and treatment for optimal screening outcome [ 388 ]; a report estimating a minimum prevalence for 22q11.2 deletion of 1:2148 making it one of the more common rare genetic conditions and supporting the importance of NBS for early diagnosis and disorder management [ 389 ]; and a report of low TREC copy numbers when screening for SCID likely caused by neonatal abstinence syndrome [ 66 ].…”