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

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 is 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. Will be provided asap This article does not contain any studies with human or animal subjects performed by any of the authors. No original data are presented. The manuscript summarizes plenary lectures from David Bick, Henrietta Hopkins, Tanja Krones and Edith Gross at the SSIEM 2022 symposium in Freiburg, Germany. Each author wrote his own part and the different contributions are clearly marked in the text. DB wrote his part together with Richard Scott. Ute Spiekerkoetter und Jim Bonham led the plenary discussion on genomic newborn screening at the SSIEM 2022 symposium, provided a frame for the different perspectives and summarized the main discussion points in the manuscript. US and JB reviewed and edited the manuscript. This article is protected by copyright. All rights reserved.