Ethical implications of the use of genome-wide sequencing for rare diseases in newborn screening

Research Question: What are the ethical issues associated with genome-wide sequencing for rare diseases in newborn screening? Are there any ethical issues specific to the use of genome-wide sequencing to screen for rare diseases in newborns? Background: With the advent of affordable sequencing technologies, genome-wide sequencing (GWS) is playing an increasingly prominent role in the diagnosis of rare genetic disorders in the context of screening, GWS for rare diseases in newborns has been linked to earlier diagnoses and treatment that can improve outcomes for babies and their families. However, it is also associated with a range of harms including uncertain results, overdiagnosis and concerns about the way that genomic data are stored, accessed and used following screening. Studies across the globe are exploring the impact of GWS in newborn screening. In England, the ‘Generation Study’ aims to sequence the genomes of 100,000 newborn babies to evaluate GWS as a screening test for over 200 conditions. The ethical acceptability of screening programmes is considered as a key part of the UK NSC (UK National Screening Committee) criteria for the evaluation of screening programmes. Moreover, the ethical principles of health screening are encompassed within the ethical framework for health screening. However, for GWS in newborns, the full range of ethical issues have not been ascertained. Moreover, it’s not clear whether and how GWS in newborns will introduce new, or modify existing ethical issues already considered as part of other health screening programmes. Aims: The aim is to identify the range of ethical issues related to the use of GWS in newborn screening for rare diseases and to consider where these may differ, or not, from those associated with other health screening programmes. Methods: The review will be undertaken using a rapid review and qualitative metasynthesis methodology. Systematic literature searches will be adapted from previous reviews of the ethical literature and data extraction conducted by two lead reviewers with joint second reviewers independently assessing a random sample of 20%. Open thematic coding will be used to iteratively group ethical issues into parent codes/ ethical clusters. Meta-synthesis techniques will be used to develop the clusters and identify cross-cutting sub-themes within and across the ethical clusters, allowing comparison and characterisation of ethical issues and comparison to the UK NSC ethical framework for screening. To guide the review, we will work with a patient/ public involvement and engagement group comprising individuals with a range of lived experiences including genetic conditions and newborn screening. Additional input will be sought from an international expert review committee made up of experts in bioethics, genomics and/or newborn screening. Timelines for Delivery: The draft report will be submitted to the UK NSC in spring 2026. It will then undergo various forms of consideration, including committee discussion and public consultation before the final revised report is delivered in December 2026. Anticipated Impact and Dissemination: The report will be adapted for publication in a relevant high impact journal. The findings will also be considered, along with data from the Generation Study (including its Process and Impact evaluation) and elsewhere, when the UK NSC considers the role of GWS in newborn screening and gives its recommendations to the four UK governments.