Optimising Exome Prenatal Sequencing Services (EXPRESS): a study protocol to evaluate rapid prenatal exome sequencing in the NHS Genomic Medicine Service

Melissa Hill^{1

2}, Sian Ellard^{3

4}, Jane Fisher⁵, Naomi Fulop⁶, Marian Knight⁷, Mark Kroese⁸, Jean Ledger⁶, Kerry Leeson-Beevers⁹, Alec McEwan¹⁰, Dominic McMullan¹¹, Rhiannon Mellis^{1

2}, Stephen Morris¹², Michael Parker¹³, Dagmar Tapon¹⁴, Emma Baple^{3

15}, Laura Blackburn⁸, Asya Choudry¹⁶, Caroline Lafarge¹⁷, Hannah McInnes-Dean^{1

2

5}, Michelle Peter^{1

2}, Rema Ramakrishnan⁷, Lauren Roberts¹⁸, Beverly Searle¹⁹, Emma Smith¹, Holly Walton⁶, Sarah L Wynn¹⁹, Wing Han Wu^{1

2}, Lyn S Chitty^{1

2}

Affiliations

¹ NHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children, London, UK.
² Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, UK.
³ Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, UK.
⁴ Exeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
⁵ Antenatal Results and Choices, London, UK.
⁶ Department of Applied Health Research, University College London, London, UK.
⁷ National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK.
⁸ PHG Foundation, University of Cambridge, Cambridge, UK.
⁹ Alström Syndrome UK, Torquay, UK.
¹⁰ Department of Obstetrics and Gynaecology,, Nottingham University Hospitals NHS Trust, Nottingham, UK.
¹¹ West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
¹² Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹³ The Ethox Centre, Nuffield Department of Population Health and Wellcome Centre for Ethics and Humanities, University of Oxford, Oxford, UK.
¹⁴ Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London, UK.
¹⁵ Peninsula Clinical Genetics Service, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
¹⁶ Manchester University NHS Foundation Trust, Manchester, UK.
¹⁷ School of Human and Social Sciences, University of West London, London, UK.
¹⁸ Genetic Alliance UK, London, UK.
¹⁹ Unique - Rare Chromosome Disorder Support Group, Oxted, UK.

PMID: 35935673
PMCID: PMC7613246
DOI: 10.3310/nihropenres.13247.2

Optimising Exome Prenatal Sequencing Services (EXPRESS): a study protocol to evaluate rapid prenatal exome sequencing in the NHS Genomic Medicine Service

Melissa Hill et al. NIHR Open Res. 2022.

. 2022 Jul 18:2:10.

doi: 10.3310/nihropenres.13247.2. eCollection 2022.

Authors

Affiliations

¹ NHS North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children, London, UK.
² Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, UK.
³ Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, UK.
⁴ Exeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
⁵ Antenatal Results and Choices, London, UK.
⁶ Department of Applied Health Research, University College London, London, UK.
⁷ National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK.
⁸ PHG Foundation, University of Cambridge, Cambridge, UK.
⁹ Alström Syndrome UK, Torquay, UK.
¹⁰ Department of Obstetrics and Gynaecology,, Nottingham University Hospitals NHS Trust, Nottingham, UK.
¹¹ West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.
¹² Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹³ The Ethox Centre, Nuffield Department of Population Health and Wellcome Centre for Ethics and Humanities, University of Oxford, Oxford, UK.
¹⁴ Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London, UK.
¹⁵ Peninsula Clinical Genetics Service, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
¹⁶ Manchester University NHS Foundation Trust, Manchester, UK.
¹⁷ School of Human and Social Sciences, University of West London, London, UK.
¹⁸ Genetic Alliance UK, London, UK.
¹⁹ Unique - Rare Chromosome Disorder Support Group, Oxted, UK.

PMID: 35935673
PMCID: PMC7613246
DOI: 10.3310/nihropenres.13247.2

Abstract

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). is 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.

Keywords: counselling; ethics; genomic medicine service; mixed methods; prenatal exome sequencing; study protocol.

Plain language summary

Background: Prenatal exome sequencing is a new test that is offered through the NHS Genomic Medicine Service. Prenatal exome sequencing is offered to pregnant women when ultrasound scans suggest that their baby may have a genetic condition that cannot be diagnosed using standard tests. If a genetic condition is diagnosed this can give parents important information about the outlook for their baby. It can also help with their decisions about whether to continue or end the pregnancy, pregnancy management, post-birth care and future pregnancies.

Study methods: The aim of this study is to evaluate the prenatal exome sequencing service. To do this we will; 1. Study how prenatal exome sequencing is delivered across England using surveys and interviews with professionals.2. Interview parents to ask what they think of prenatal exome sequencing and how support and information could be improved3. Look at how many parents have prenatal exome sequencing and the test results. We will look carefully at who has access to the test and whether any particular groups are less likely to be offered testing.4. Conduct workshops with health professionals and parents to identify any practical or ethical problems that arise when prenatal exome sequencing is offered.5. Look at the cost of prenatal exome sequencing and compare it to the cost of other tests that are offered to diagnose genetic conditions in pregnancy.6. Gather our findings together to make recommendations for best practice. Patient and Public Involvement: A patient and public Involvement, engagement and participation (PPIEP) advisory group will work closely with the research team to design the study and develop study materials. They will also help us understand our findings to make sure the information and recommendations that come out of our research will be helpful to parents and the NHS.

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Conflict of interest statement

No competing interests were disclosed.

Figures

**Figure 1.. Conceptual framework underpinning our evaluation of the prenatal ES service.**
Adapted from Fulop *et al.* ^,.

See this image and copyright information in PMC

References

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1. Petrovski S, Aggarwal V, Giordano JL, et al. : Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study. Lancet. 2019;393(10173):758–767. 10.1016/S0140-6736(18)32042-7 - DOI - PubMed
1. Best S, Wou K, Vora N, et al. : Promises, pitfalls and practicalities of prenatal whole exome sequencing. Prenat Diagn. 2018;38(1):10–19. 10.1002/pd.5102 - DOI - PMC - PubMed

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Optimising Exome Prenatal Sequencing Services (EXPRESS): a study protocol to evaluate rapid prenatal exome sequencing in the NHS Genomic Medicine Service

Affiliations

Optimising Exome Prenatal Sequencing Services (EXPRESS): a study protocol to evaluate rapid prenatal exome sequencing in the NHS Genomic Medicine Service

Authors

Affiliations

Abstract

Plain language summary

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources