Optimising rapid prenatal exome sequencing in the NHS genomic medicine service: the EXPRESS Synopsis

Prenatal exome sequencing for the diagnosis of fetal anomalies was implemented nationally in England in October 2020 by the National Health Service Genomic Medicine Service.

To evaluate the new prenatal exome sequencing service to provide evidence that will inform improvements to quality of care and equity of access for parents having prenatal tests.

Our theoretically driven, multi-site, convergent parallel mixed-methods study design combined qualitative analyses of the service, stakeholder perspectives and ethical considerations with quantitative analyses of staff experiences, clinical outcomes and cost-effectiveness. Our final data set included interviews with parents offered prenatal exome sequencing (n = 48) and professionals (n = 63), surveys with professionals (n = 159) and data from prenatal exome sequencing testing referrals between October 2021 and June 2022 (413 referrals and 241 prenatal exome sequencing tests) linked to National Congenital Anomaly and Rare Disease Registration Service data and the Maternity Services Data Set. The study had oversight from a Steering Group and a Patient and Public Involvement Advisory Group. The Patient and Public Involvement Advisory Group contributed to study design, developing study materials and interpreting findings.

Parents and professionals welcomed the introduction of a national prenatal exome sequencing service. Parents need emotional support across the testing journey, including follow-up care. A newly developed prenatal sequencing animation increased self-reported and objective knowledge of prenatal exome sequencing. Good communication and close working between genetics, fetal medicine and laboratory teams has supported successful implementation. Challenges for service delivery included increased administrative time and gaps in genomics education, particularly for midwives and fetal medicine clinicians. Local implementation varied in leadership, staffing and approaches to multidisciplinary team working. Ethical issues centred on barriers for equity of access and the intersecting timelines of prenatal exome sequencing testing and termination of pregnancy laws. Between October 2021 and June 2022, the diagnostic yield for prenatal exome sequencing was 35% (85/241) with a median turnaround time of 15 days to the final report. For 85 women who had a diagnosis, 40% had a termination of pregnancy, 18% had a stillbirth and 42% had a live birth. For women with a no findings result, 18% had a termination of pregnancy, 5% had a stillbirth and 78% had a live birth. The median gestational age at termination was 26 weeks. Total National Health Service costs for the 413 cases in the study period, with the most common staffing model, was £962,727 (£775,454 to £1,204,027, 95% credibility interval), or £2331 per case referred and £3592 per case that proceeded with testing.

Our parent interview sample lacked diversity, with most being White/White British and educated to degree level or above. Details on prenatal exome sequencing service pathways from smaller units have not been captured. Assessment of variation in outcomes was restricted by the relatively small sample size of prenatal exome sequencing tests in the study period.

This is the first study to explore the implementation of the national prenatal exome sequencing service in England. Our findings will inform the evolving prenatal exome sequencing service to ensure equity of access, high standards of care and benefits for all parents.

Future research should include gathering the views and experiences from parents from diverse backgrounds, evaluating the prenatal sequencing animation in clinical practice and building on EXPRESS to identify and agree optimal care pathways that will ensure equity of access for all parents.

This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR127829.