Newborn Sequencing: The Promise and Perils

Newborn screening for phenylketonuria began in the United States in the early 1960s, and it expanded one disease at a time until the development of tandem mass spectrometry. This technology allowed for screening many conditions simultaneously, but its uneven adoption led to wide disparities. A collaboration between the American College of Medical Genetics and Genomics and the US Health Resources and Services Administration resulted in a recommended uniform screening panel. Newborn sequencing (NBSeq) identifies many monogenic disorders, although to date it cannot identify all cases identified by tandem mass spectrometry. NBSeq has the potential to reduce diagnostic odysseys and increase health equity, but it could also exacerbate disparities and cause psychosocial and clinical harms due to overdiagnosis, oversurveillance, and/or overtreatment. By expanding beyond previously established public health screening principles, NBSeq also challenges the mandatory nature of current screening. In this review, we examine the promise and perils of NBSeq.