Perspectives on genomic newborn screening studies: design, implementation, and outcomes.

Abstract

With decreasing sequencing costs and increasingly accurate and scalable methods to interpret genetic variation, genomic newborn screening (gNBS) is being assessed for feasibility, acceptability, and impact worldwide. The field is evolving to determine the genes and variants to report, how to communicate with parents and pediatricians, and confirm results, and how to medically manage children with confirmed diagnoses. This review summarizes global gNBS studies, including recruitment methods, consent models, sample types, participant characteristics, sequencing methods, gene selection criteria, test performance, variant interpretation, automated reporting, turnaround time, methods to return results, confirmatory diagnostic testing, and comparisons with standard NBS (stdNBS) results. Early experience supports the feasibility and positive clinical impact of gNBS. Variability in study design, gene selection, and reporting limits direct comparability across studies but increasing and diverse experience will optimize parameters prior to broad implementation. Genomic newborn screening is feasible and expands the screening of treatable genetic conditions beyond standard newborn screening, and improves the diagnostic accuracy of standard newborn screening. Comparison of genomic newborn screening studies around the world, highlighting key differences in study design, technical approaches, clinical implementation, and current challenges. Key evidence supporting the implementation of genomic newborn screening is summarized to guide future policy and clinical practice.