# Multiplexable, High-Throughput DNA-Based Technologies in Screening and Confirmatory Testing of Newborn Conditions: A Scoping Review

## TL;DR

This scoping review explores DNA-based technologies for newborn screening and confirms that targeted gene sequencing is most commonly used, with a combined approach showing promise.

## Contribution

The study identifies and evaluates the use of multiplexable, high-throughput DNA technologies in newborn screening and confirmatory testing.

## Key findings

- Targeted gene sequencing was the most commonly used technology in the reviewed studies.
- A combined approach using NGS and biochemical tests is suggested as optimal for newborn screening.
- Ethical and economic evidence related to these technologies is limited in the literature.

## Abstract

Newborn screening (NBS) is evolving as novel technologies offer the opportunities to include a broader range of treatable disorders in its programs. Multiplexable, high-throughput DNA-based technologies such as next-generation sequencing (NGS) are being explored to improve and expand disease detection, although several issues have been raised with its use. This scoping review aimed to identify multiplexable, high-throughput, DNA-based technologies that were used for screening or confirmatory testing of newborn disorders in published studies. Available evidence on the appropriateness of technologies in the NBS context was extracted. A literature search (Medline, Embase, and Web of Science) was performed from inception up to April 2024 in collaboration with a medical information specialist. After selection, 26 journal articles were included that used these technologies for either screening (n = 12) or confirmatory testing (n = 14). Five technologies were identified: whole-genome sequencing, whole-exome sequencing, targeted gene sequencing (TGS), quantitative polymerase chain reaction, and MassARRAY. The majority used TGS (n = 19, 73.08%). The data extracted concern mainly technical aspects, and these suggest that a combined approach, i.e., testing via NGS plus a biochemical test, in parallel or reflex, emerges as the optimal option. Ethical and economic evidence is limited and rarely reported in the reviewed articles.