Perspectives on Next-Generation Newborn Screening

ABSTRACT

Newborn screening (NBS) has been effective for detecting asymptomatic newborns with inherited metabolic diseases and has facilitated early clinical intervention, which has resulted in significant decreases in the rates of morbidity and mortality caused by these diseases. The outcome of the NBS program heavily depends on technological advances. Since Dr. Robert Guthrie developed a bacterial inhibition assay to screen for metabolic diseases in the early 1960s, use of the NBS program has spread to many countries. Tandem mass spectrometry (TMS) was a second major technological breakthrough that has allowed screening to be extended to disorders of fatty acid and organic acid metabolism as well as to those of amino acid metabolism, and recently screening has also been expanded to include lysosomal storage diseases. TMS can detect multiple analytes rapidly and simultaneously and is currently applied to nearly 80% of the newborn population in Korea. Next-generation sequencing (NGS) technology could be another major breakthrough to improve the current NBS program. To integrate NGS into the NBS program, various considerations about its analytical validity, clinical validity, clinical utility, and ethical, legal, and social implications should be addressed on the basis of population screening. Here, the authors review population screening criteria, the current status of NBS, and recent advances in NGS. In addition, we discuss the practical and ethical issues, opportunities, and challenges regarding the implementation of NGS in NBS.