Background: Prenatal exome sequencing (ES) for the diagnosis of fetal anomalies was implemented nationally in England in October 2020 by the NHS Genomic Medicine Service (GMS). The GMS is based around seven regional Genomic Laboratory Hubs (GLHs). Prenatal ES has the potential to significantly improve NHS prenatal diagnostic services by increasing genetic diagnoses and informing prenatal decision-making. Prenatal ES has not previously been offered routinely in a national healthcare system and there are gaps in knowledge and guidance. Methods: Our mixed-methods evaluation commenced in October 2020, aligning with the start date of the NHS prenatal ES service. Study design draws on a framework developed in previous studies of major system innovation. There are five interrelated workstreams. Workstream-1 will use interviews and surveys with professionals, non-participant observations and documentary analysis to produce in-depth case studies across all GLHs. Data collection at multiple time points will track changes over time. In Workstream-2 qualitative interviews with parents offered prenatal ES will explore experiences and establish information and support needs. Workstream-3 will analyse data from all prenatal ES tests for nine-months to establish service outcomes (e.g. diagnostic yield, referral rates, referral sources). Comparisons between GLHs will identify factors (individual or service-related) associated with any variation in outcomes. Workstream-4 will identify and analyse practical ethical problems. Requirements for an effective ethics framework for an optimal and equitable service will be determined. Workstream-5 will assess costs and cost-effectiveness of prenatal ES versus standard tests and evaluate costs of implementing an optimal prenatal ES care pathway. Integration of findings will determine key features of an optimal care pathway from a service delivery, parent and professional perspective. Discussion: The proposed formative and summative evaluation will inform the evolving prenatal ES service to ensure equity of access, high standards of care and benefits for parents across England.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality globally. Early detection and personalised prevention strategies are crucial for reducing the burden of CVD. The use of biomarkers plays a pivotal role in identifying individuals at risk and facilitating timely interventions. This rapid scoping review aims to identify and evaluate current research on biomarkers used for primary and secondary personalised prevention of CVD, highlighting evidence gaps and the integration of digital technologies. A comprehensive search was conducted in Medline and Embase databases from January 2020 to February 2023. Joanna Briggs Institute (JBI) Manual for Evidence Synthesis and PRISMA-ScR guidelines were followed. A total of 775 studies were included, with ischemic heart disease (IHD) and stroke being the most investigated CVDs. Molecular, cellular, imaging, physiological, and anthropometric biomarkers were included. Molecular biomarkers, particularly genetic and biochemical, were the most researched. For secondary prevention, there was considerable research using imaging biomarkers. Genetic biomarker research was the most frequent category of biomarker identified, particularly using variant analysis and polygenic scores, followed by biochemical, imaging, and physiological biomarkers. There was also evidence of the integration of artificial intelligence to enhance the predictive capabilities of these biomarkers. Despite progress, research gaps were identified for less common CVDs, such as aortic aneurysm and nonrheumatic valvular heart disease, and limited research investigating other molecular biomarker types, such as epigenetics and transcriptomics.

Background: Prenatal exome sequencing (ES) for the diagnosis of fetal anomalies has been implemented nationally in England through the NHS Genomic Medicine Service that is based around seven regional Genomic Laboratory Hubs (GLHs). Prenatal ES has the potential to significantly improve NHS prenatal diagnostic services by increasing genetic diagnoses and informing prenatal decision-making. Prenatal ES has not previously been offered routinely in a national healthcare system and there are gaps in knowledge and guidance. Methods: We are conducting a mixed-methods evaluation of the NHS prenatal ES service. Study design draws on a framework developed in previous studies of major system innovation and Normalisation Process Theory. There are five interrelated workstreams. Workstream-1 will use interviews and surveys with professionals, non-participant observations and documentary analysis to produce in-depth case studies at all GLHs. Data collection at multiple time points will track changes over time. In Workstream-2 qualitative interviews with parents offered prenatal ES or with previous experience of fetal anomalies will explore experiences and establish information and support needs. Workstream-3 will analyse data from all prenatal ES tests for nine-months to establish service outcomes (e.g. diagnostic yield, referral rates, referral sources). Comparisons between GLHs will identify factors (individual or service-related) associated with any variation in outcomes. Workstream-4 will identify and analyse practical ethical problems. Requirements for an effective ethics framework for an optimal and equitable service will be determined. Workstream-5 will assess costs and cost-effectiveness of prenatal ES versus standard tests and evaluate costs of implementing an optimal prenatal ES care pathway. Integration of findings will determine key features of an optimal care pathway from a service delivery, parent and professional perspective. Discussion: The proposed formative and summative evaluation will inform the evolving prenatal ES service to ensure equity of access, high standards of care and benefits for parents across England.

The optimising EXome PREnatal Sequencing Services (EXPRESS) policy report outlines actions to strengthen clinical implementation of, and further research on, prenatal exome sequencing services in the NHS.

Recommendations on the opportunities and challenges to deliver better precision-based approaches for infectious disease management.