DNA Sequencing in Newborn Screening: Opportunities, Challenges, and Future Directions

Abstract Background Newborn screening is a public health system designed to identify infants at risk for conditions early in life to facilitate timely intervention and treatment to prevent or mitigate adverse health outcomes. Newborn screening programs use tandem mass spectrometry as a platform to detect several treatable inborn errors of metabolism, and the T-cell receptor excision circle assay to detect some inborn errors of the immune system. Recent advancements in DNA sequencing have decreased the cost of sequencing and allow us to consider DNA sequencing as an additional platform to complement other newborn screening methods. Content This review provides an overview of DNA-based newborn screening, including its applications, opportunities, challenges, and future directions. We discuss the potential benefits of expanded DNA sequencing in newborn screening, such as expanding conditions screened and improved specificity and sensitivity of currently screened conditions. Additionally, we examine the ethical, legal, and social implications of implementing genomic sequencing in newborn screening programs, including issues related to consent, privacy, equity, data interpretation, scalability, and psychosocial impact on families. Additionally, we explore emerging strategies for addressing current limitations and advancing the field of newborn screening. Summary DNA sequencing in newborn screening has the potential to improve the diagnosis and management of rare diseases but also presents significant challenges that need to be addressed before implementation at the population level.