Next-Generation Sequencing in Newborn Screening: A Review of Current State

Abstract

Newborn screening was first introduced at the beginning of the 1960s with the successful implementation of the first phenylketonuria screening programs. Early expansion of the included disorders was slow because each additional disorder screened required a separate test. Subsequently, the technological advancements of biochemical methodology enabled the scaling-up of newborn screening, most notably with the implementation of tandem mass spectrometry. In recent years, we have witnessed a remarkable progression of high-throughput sequencing technologies, which has resulted in a continuous decrease of both cost and time required for genetic analysis. This has enabled more widespread use of the massive multiparallel sequencing. Genomic sequencing is now frequently used in clinical applications, and its implementation in newborn screening has been intensively advocated. The expansion of newborn screening has raised many clinical, ethical, legal, psychological, sociological, and technological concerns over time. This review provides an overview of the current state of next-generation sequencing regarding newborn screening including current recommendations and potential challenges for the use of such technologies in newborn screening.

Keywords: DNA sequencing; NBS; NGS; expanded NBS program; high-throughput sequencing; neonatal screening; newborn screening; next generation sequencing.

FIGURE 1

A brief outline of topics covered in this review. The first section covers concerns regarding the basic technical feasibility of the use of next-generation sequencing (NGS) technology in newborn screening (NBS). The second section reveals the main factors impacting the cost of the use of such technology in NBS. The third section deals with medical problems the use of NGS would raise in NBS. The final sections engage in discussing legal, ethical, and psychological problems concerning NGS in the setting of NBS.