Abstract

Newborn screening is a cornerstone of preventive public health, enabling the early identification of congenital and 
metabolic disorders for which timely intervention can substantially reduce morbidity and mortality. Advances in 
metabolomics now present an opportunity to expand newborn screening beyond current targeted assays, allowing 
the simultaneous measurement of hundreds of metabolites from dried blood spots and thereby broadening disease 
coverage and improving diagnostic accuracy. This paper critically evaluates the expansion of newborn screening 
through metabolomics, examining its scientific rationale, methodological foundations, anticipated public health 
benefits, and potential harms. We assess analytical and biostatistical considerations, including assay validation, 
data interpretation, false-positive rates, incidental findings, and long-term outcome uncertainty. Particular 
attention is given to health equity, resource use, sustainability, and the ethical, legal, and governance challenges 
associated with large-scale population screening. Drawing on established benefit–harm assessment models and 
public health decision frameworks, the paper outlines criteria for policy adoption and responsible implementation. 
We conclude that metabolomics-based expansion of newborn screening holds significant promise for improving 
population health outcomes, but its adoption must be guided by rigorous evidence, transparent governance, 
stakeholder engagement, and equity-focused implementation strategies to ensure that benefits clearly outweigh 
harms at the population level.