Genomic newborn screening: Are we entering a new era of screening?

Abstract

Population newborn screening (NBS) for phenylketonuria began in the United States in 1963. In the 1990s electrospray ionization mass spectrometry permitted an array of pathognomonic metabolites to be identified simultaneously, enabling up to 60 disorders to be recognized with a single test. In response, differing approaches to the assessment of the harms and benefits of screening have resulted in variable screening panels worldwide. Thirty years on and another screening revolution has emerged with the potential for first line genomic testing extending the range of screening conditions recognized after birth to many hundreds. At the annual SSIEM conference in 2022 in Freiburg, Germany, an interactive plenary discussion on genomic screening strategies and their challenges and opportunities was conducted. The Genomics England Research project proposes the use of Whole Genome Sequencing to offer extended NBS to 100 000 babies for defined conditions with a clear benefit for the child. The European Organization for Rare Diseases seeks to include “actionable” conditions considering also other types of benefits. Hopkins Van Mil, a private UK research institute, determined the views of citizens and revealed as a precondition that families are provided with adequate information, qualified support, and that autonomy and data are protected. From an ethical standpoint, the benefits ascribed to screening and early treatment need to be considered in relation to asymptomatic, phenotypically mild or late‐onset presentations, where presymptomatic treatment may not be required. The different perspectives and arguments demonstrate the unique burden of responsibility on those proposing new and far‐reaching developments in NBS programs and the need to carefully consider both harms and benefits.

Prospective cohort study of genomic newborn screening: BabyScreen+ pilot study protocol

“…Most have focused on the clinical, legal, insurance and social contexts in the USA,1 10 11 13 19 20 which have limited applicability to the Australian and other public healthcare systems. Several large-scale newborn genomic screening studies are currently launching worldwide to address these gaps in knowledge 3 21 22…”

Future of Dutch NGS-Based Newborn Screening: Exploring the Technical Possibilities and Assessment of a Variant Classification Strategy

“…However, while the advantages of NGS-based genetic testing are widely recognized, many challenges remain [ 14 , 15 ]. One of these is selection of the most suitable NGS approach.…”

A Non-targeted Proteomics Newborn Screening Platform for Genetic Disorders

“…Although NBS for IEMs can be achieved by assessing metabolic function through monitoring activity of metabolites or metabolic enzymes, direct measurement of molecular function is frequently too complex and infeasible in the context of NBS for other inherited conditions. As recent advances in DNA sequencing technology have dramatically improved cost-performance and throughput, the use of genome-wide sequencing has been proposed as a new alternative modality for NBS (Berg et al, 2017); however, there remain many technical, clinical, ethical, and social issues to be addressed before implementation of genome sequencing for NBS (Spiekerkoetter et al, 2023; Ulph and Bennett, 2023). In addition, concerns regarding the use of genome sequencing persist, due to an inability to predict gene product functionality from structural genetic information with high accuracy; in the absence of accumulated in-depth genotype-phenotype data, gene structure information cannot be linked with clinical phenotypes.…”