Potential Uses and Inherent Challenges of Using Genome-Scale Sequencing to Augment Current Newborn Screening

Abstract

Since newborn screening (NBS) began in the 1960s, technological advances have enabled its expansion to include an increasing number of disorders. Recent developments now make it possible to sequence an infant's genome relatively quickly and economically. Clinical application of whole-exome and whole-genome sequencing is expanding at a rapid pace but presents many challenges. Its utility in NBS has yet to be demonstrated and its application in the pediatric population requires examination, not only for potential clinical benefits, but also for the unique ethical challenges it presents.

Figure 1.

Milestones in newborn screening are depicted in the lower portion of the figure, with approximate dates on the horizontal axis. The number of conditions screened for (or potentially screened for) is depicted chronologically with asterisks on the vertical axis, plotted on a logarithmic scale. Screening programs have historically differed between states, most dramatically observed after development of tandem mass-spectrometry technology in the 1990s. Adoption of a recommended uniform screening panel in 2005–2006 has gradually led to greater consistency. Development of next-generation sequencing technology in the early 2000s, with subsequent reduction in the cost of genome-scale sequencing, makes it possible to analyze thousands of disease genes. The number of conditions potentially screened for is indicated with a question mark to emphasize the substantial concerns regarding the application of such technology in healthy newborns.