International experiences of genomic newborn screening

Abstract

Genomic sequencing has the potential to transform newborn screening (NBS) for rare diseases but raises significant pragmatic, clinical, psychosocial, ethical, and policy issues. Evidence is urgently needed to guide policy as healthcare systems around the world contemplate implementation. In 2025, four major genomic NBS (gNBS) studies, totaling over 10,800 newborns from the US, Belgium, and Australia, published initial results. The adoption of different approaches to key implementation issues in diverse healthcare systems by these studies allows us to draw comparisons and enable collective learning. All studies reported successful use of dried blood spots for DNA extraction, which supports integration with existing NBS infrastructure. Experience with automation of genomic data analysis and reporting was variable, with valuable insights gained about balancing sensitivity, specificity, scalability, and resource utilization going forward. The screen-positive rate ranged from 1.6% to 3.7%, with G6PD deficiency by far the most common condition identified. Further comparison of results was limited by wide variation in the number and type of conditions included and by inconsistencies in how outcomes were defined and reported, highlighting the need for greater harmonization of study designs and data collection. The ability to deliver gNBS at the scale and pace that would be required for a public screening program remains untested, and data on long-term outcomes and costs are still needed. Concerns also remain about inequitable access and outcomes, particularly for families at socioeconomic, linguistic, and geographical disadvantage, and these key questions need to be addressed next as the field continues to evolve.