Genomics to enhance newborn screening?

Abstract

Newborn screening is a major public health achievement, enabling early detection and treatment of serious medical conditions before the onset of irreversible damage to health. The scope of newborn screening has continuously expanded with the addition of and innovations in screening platforms, including tandem mass spectrometry. Genomic newborn screening (gNBS) provides another platform that uses genomic DNA sequencing as a first-tier test to improve and expand screening for actionable genetic conditions. Genome coverage affords flexibility to incorporate new diseases rapidly as new effective therapies become available. Several pilot studies around the world have demonstrated the feasibility and high parental uptake of gNBS and highlighted challenges that need to be addressed, including accurate and efficient variant interpretation across all ancestral groups, effective methods to physiologically assess DNA screening results, accurate penetrance estimates with population-based screening to inform which genes and variants within genes to include on screening panels and how to manage individuals with positive screening results, meeting rapid turnaround time requirements, increasing scale, decreasing cost, and providing evidence and health economic data about value to inform policy. Successful implementation will likely evolve over time and would be facilitated by a dedicated national infrastructure to support DNA sequencing, variant interpretation, and follow-up, allowing for feedback to improve and optimize the screening system. International sharing of gNBS experience could maximize the efficiency of improvement, especially in these early stages, and will need to balance data sharing with data privacy. By dramatically expanding the scope of conditions screened and identified shortly after birth, gNBS has the potential to improve public health for future generations of children, especially if and when platforms for gene-based therapies are safe, effective, and affordable for large numbers of conditions.