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Magnifico et al. Rare Dis Orphan Drugs J 2023;2:16 Rare Disease and
DOI: 10.20517/rdodj.2023.17
Orphan Drugs Journal

Systematic Review Open Access

A systematic review of real-world applications of
genome sequencing for newborn screening

Giuditta Magnifico, Irene Artuso, Stefano Benvenuti

Fondazione Telethon ETS, Milan IT 20129, Italy.
Correspondence to: Dr. Stefano Benvenuti, Fondazione Telethon ETS, via Carlo Poerio 14, Milan IT20129, Italy. E-mail:
sbenvenuti@telethon.it

How to cite this article: Magnifico G, Artuso I, Benvenuti S. A systematic review of real-world applications of genome
sequencing for newborn screening. Rare Dis Orphan Drugs J 2023;2:16. https://dx.doi.org/10.20517/rdodj.2023.17

Received: 21 Jun 2023 Revised: 9 Aug 2023 Accepted: 22 Aug 2023 Published: 29 Aug 2023

Academic Editors: Daniel Scherman, Virginie Bros-Facer Copy Editor: Yanbing Bai Production Editor: Yanbing Bai

Abstract
Aim: With the costs of genomic sequencing falling quickly and an ever-increasing number of clinical laboratories
equipped with new-generation sequencing machines, healthcare systems around the world are getting ready to
enter the era of genomic newborn screening (NBS). However, the adoption of Genomic Sequencing (GS),
encompassing whole-exome sequencing (WES) and whole-genome sequencing (WGS), in NBS programs raises a
number of clinical, ethical, and legal questions as well as organizational and economic challenges. This systematic
review is part of a feasibility study to assess the introduction of WGS for NBS in Lombardy region with the specific
aim of gathering evidence from existing pilots in the field whose results have been published.

Methods: Three different sources were identified for the selection of articles in order to obtain a various and
unbiased set of publications. 33 articles were retained for analysis to answer the following questions:
1. Clinical: Does genomic sequencing demonstrate clinical utility in the context of NBS? What are the limitations of
these kind of programs?
2. Societal: What are the social, ethical and psychological implications of using GS for NBS?

3. Governance: What are the legal, economic, and organizational challenges for GS-based NBS programs?

Results: There is a general consensus in the literature on the key principles that should guide the adoption of GS in
NBS, such as the inclusion of actionable genes only, the need for informed consent from the parents, the right of the
newborn to an open future, which means the exclusion of late-onset diseases even when those are considered
treatable. However, there are still several differences in how these principles are detailed and applied.

Conclusion: Real-world evidence from a handful of pilot projects (namely BabySeq and NC-Nexus, both carried out
© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
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