Every year, millions of newborns undergo heel-prick screening for a handful of metabolic and genetic conditions — a protocol largely unchanged for decades. The emergence of affordable whole-genome and exome sequencing now threatens to make that paradigm obsolete, with early global data suggesting genomic newborn screening can detect a substantially broader range of treatable conditions while also improving the diagnostic accuracy of existing biochemical screens.
This review in Pediatric Research synthesizes findings from genomic newborn screening (gNBS) programs conducted worldwide, assessing recruitment strategies, consent frameworks, sequencing technologies, gene panel selection, variant interpretation pipelines, and turnaround times. Across diverse study designs, early evidence consistently supports the feasibility of gNBS at scale. Crucially, gNBS both extends the number of detectable conditions beyond standard newborn screening (stdNBS) and corrects some false-positive and false-negative results that biochemical testing generates. The review also highlights significant heterogeneity — in which genes are included, how variants are classified, and how results are returned to families — that currently limits direct cross-study comparison.
Positioning this within the broader genomics landscape, the review arrives at an inflection point: sequencing costs have fallen below the threshold where per-infant genomic analysis is economically comparable to some existing specialty diagnostics, and machine-learning-assisted variant interpretation is reducing the analytic bottleneck. Yet the field faces non-trivial challenges that pure technical progress cannot resolve. Which conditions justify inclusion on a population-level screen? How should variants of uncertain significance be handled when parents receive results? What longitudinal health systems infrastructure is required to manage children whose diagnoses may not manifest for years? These questions are ethical and organizational as much as scientific. This review is best characterized as a well-structured consolidation of an evolving evidence base — confirmatory rather than paradigm-shifting — but its global scope makes it a valuable reference as health systems begin translating pilot data into policy decisions.