The state of prospective genomic newborn screening: implications for a national implementation strategy

Abstract

Newborn screening (NBS) enables early detection of inherited diseases but is largely limited to conditions with reliable biomarkers. Advances in genomics have therefore prompted pilot studies evaluating DNA sequencing as an expansion of NBS, termed genomic NBS (gNBS). This review summarizes evidence from international gNBS studies, focusing on methodological frameworks, screen-positive rates, and early clinical and psychosocial outcomes. Major initiatives demonstrate technical feasibility and actionable findings in up to 4 % of newborns in the reviewed studies, with even higher estimates reported in individual studies in the broader literature. Parental acceptance depends on high test validity, clinical actionability, and high-quality counseling. Key challenges include variant interpretation, management of uncertainty, infrastructure demands, and cost-benefit considerations. International experience highlights implications for Germany, including evidence-based disease selection, integration of sequencing into existing NBS infrastructures, robust consent models, and harmonized national pathways for reporting, follow-up, and data governance.