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Publications
Publications (109)
Introduction In October 2020, a national rapid prenatal exome sequencing (pES) service was rolled out across the English National Health Service (NHS). This service is delivered by multiple clinical and two laboratory teams. Whilst there was high level national guidance to support implementation, it was unclear how the service has been delivered in...
Objective
Prenatal exome sequencing (pES) for diagnosing fetal structural anomalies commenced in the English National Health Service (NHS) in 2020. We evaluated cost‐effectiveness to the healthcare system, and costs to families, of pES in addition to standard testing, compared to standard testing alone.
Design
A cost‐effectiveness analysis combini...
Introduction:
The National Health Service (NHS) in England is the first to offer whole genome sequencing (WGS) as part of standard care. As a high-income country with a universal healthcare system, England contributes a valuable perspective to global developments in WGS.
Methods:
We used an implementation science approach with mixed methods to c...
Introduction
Prenatal exome sequencing (pES) can enhance genetic diagnosis of fetuses with structural anomalies and has recently been introduced as a national service in England. We aimed to examine service outcomes such as diagnostic yield (definite final diagnosis), referral rate, and sources of referral, and explore variation in outcomes of pES...
Participants in the 100,000 Genomes Project (100kGP) could consent to receive additional finding (AF) results, individual variants relating to genes associated with susceptibility to cancer and familial hypercholesterolemia (FH). In the study reported here, qualitative interviews were used to explore the experiences of National Health Service (NHS)...
Genome sequencing (GS) has the potential to reduce the “diagnostic odyssey” that many parents of children with rare undiagnosed conditions experience. While much research has considered the impact of receiving a diagnostic result, research has rarely focused solely on the impact of receiving a “no primary finding” (NPF) result. This study aimed to...
Prenatal sequencing tests are being introduced into clinical practice in many developed countries. In part due to its greater ability to detect genetic variation, offering prenatal sequencing can present ethical challenges. Here we review ethical issues arising following the implementation of prenatal sequencing in the English National Health Servi...
Background
With the potential to identify a vast number of rare diseases soon after birth, genomic newborn screening (gNBS) could facilitate earlier interventions and improve health outcomes. Designing a gNBS programme will involve balancing stakeholders’ opinions and addressing concerns. The views of medical students—future clinicians who would de...
Introduction
In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES ser...
In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during t...
Introduction
Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester feta...
The role of genomics in healthcare is expanding rapidly and many countries are set to explore the possibility of using genomic sequencing to expand current newborn screening programmes. Offering routine genomic newborn screening (gNBS) would allow newborn screening to include a much broader range of rare conditions, but there are many technical, pr...
Objectives
In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England. This study aimed to explore parent experiences and their information and support needs from the perspective of parents offered pES and of health professionals involved in its delivery.
Methods
In this qualita...
We used cross-sectional surveys to compare the knowledge, attitudes, and decision regret of participants who had consented for genome sequencing (GS) for rare disease diagnosis in the 100,000 Genomes Project (100kGP) across two timepoints (at the time of consenting for GS (T1) and 12–18 months later (T2)). At T1, participants ( n = 504) completed a...
Although there are numerous benefits to diagnostic prenatal testing, such as fetal exome sequencing, there are also consequences, including the possibility of receiving variants of uncertain significance or identifying secondary findings. In this study, we utilized a survey-based discrete choice experiment to elicit the preferences of pregnant peop...
Public and patient involvement (PPI) - the collaboration in research with members of the public and patients with relevant experience - is becoming well established in health service research in the UK. It is supported by funders and academic institutions. Published principles and guidelines for researchers, developed through consultation and conse...
Objectives:
Prenatal exome sequencing (pES) for the diagnosis of fetal abnormalities is being introduced more widely in clinical practice. Here we explore parents' and professionals' views and experiences of pES, to identify perceived benefits, concerns, and support needs.
Methods:
Semi-structured interviews were conducted with 11 parents and 20...
Objective:
We conducted a survey-based discrete-choice experiment (DCE) to understand the test features that drive women's preferences for prenatal genomic testing, and explore variation across countries.
Methods:
Five test attributes were identified as being important for decision-making through a literature review, qualitative interviews and q...
In this mixed methods study, a survey and in-depth interviews were used to explore whether decision regret and the psychological impact of receiving genome sequencing (GS) results differed between parents and patients, and between those who received a genetic diagnosis and those who did not. Participants (n = 77) completed a survey that included th...
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 diagnose...
Objectives:
We conducted a systematic review and meta-analysis to determine the diagnostic yield of ES for prenatal diagnosis of fetal structural anomalies, where karyotype/chromosomal microarray (CMA) is normal.
Methods:
Following electronic searches of four databases, we included studies with ≥10 structurally abnormal fetuses undergoing ES or...
Prenatal DNA tests, such as chromosomal microarray analysis or exome sequencing, increase the likelihood of receiving a diagnosis when fetal structural anomalies are identified. However, some parents will receive uncertain results such as variants of uncertain significance and secondary findings. We aimed to develop a set of attributes and associat...
Background: A new nationally commissioned NHS England Genomic Medicine Service (GMS) was recently established to deliver genomic testing with equity of access for patients affected by rare diseases and cancer. The overarching aim of this research is to evaluate the implementation of the GMS during its early years, identify barriers and enablers to...
Background: A new nationally commissioned NHS England Genomic Medicine Service (GMS) was recently established to deliver genomic testing with equity of access for patients affected by rare diseases and cancer. The overarching aim of this research is to evaluate the implementation of the GMS during its early years, identify barriers and enablers to...
Objective:
To identify what online patient information (presented in English) is available to parents about prenatal microarray (CMA) and exome sequencing (ES), and evaluate its content, quality, and readability.
Method:
Systematic searches (Google and Bing) were conducted, and websites were categorised according to their purpose. Websites categ...
Purpose
The purpose of this study was to assess decisions, attitudes, and understanding of participants (patients, parents, relatives) having genome sequencing for rare disease diagnosis.
Methods
This study involved a cross-sectional observational survey with participants in the 100,000 Genomes Project.
Results
Survey response rate was 51% (504/9...
Background
Osteogenesis Imperfecta (OI) is a rare genetic condition characterised by increased bone fragility. Recurrent fractures, pain and fatigue have a considerable impact on many aspects of the life of a person affected with OI and their families.
Objective
To improve our understanding of the impact of OI on the daily lives of individuals and...
Exome sequencing (ES) enhanced the diagnostic yield of genetic testing, but has also increased the possibility of uncertain findings. Prenatal ES is increasingly being offered after a fetal abnormality is detected through ultrasound. It is important to know how to handle uncertainty in this particularly stressful period. This systematic review aime...
Objectives
To conduct qualitative interviews with healthcare providers working in different countries to understand their experiences of dealing with uncertain results from prenatal chromosome microarray analysis (CMA) and exome sequencing (ES).
Methods
Semi‐structured interviews with 31 healthcare providers who report or return prenatal CMA and/o...
Objective
To compare the effectiveness of an animation against two leaflets with and without images, in educating young people about genome sequencing (GS).
Methods
An experimental survey with three assessment points (pre- intervention [T1], post – intervention [T2], 6-week follow-up [T3]). Participants (N = 606) were randomly assigned to receiv...
Genome sequencing (GS) will have a profound impact on the diagnosis of rare and inherited diseases in children and young people. We conducted 27 semi-structured interviews with young people aged 11–19 having GS through the UK 100,000 Genomes Project. Participants demonstrated an understanding of the role and function of genes and DNA, however the t...
For a number of prospective parents, uncertainty during pregnancy starts when an anomaly is found during a routine fetal anomaly scan. This may be followed by numerous tests to determine the etiology and nature of the anomaly. In this study, we aimed to understand how prospective parents perceive and manage uncertainty after being confronted with a...
Rapid genomic sequencing (RGS) is increasingly being used in the care of critically ill children. Here we describe a qualitative study exploring parent and professional perspectives around the usefulness of this test, the potential for unintended harms and the challenges for delivering a wider clinical service. The Rapid Paediatric Sequencing (RaPS...
Background:
Tests in pregnancy such as chromosomal microarray analysis (CMA) and exome sequencing (ES) are increasing diagnostic yield for fetal structural anomalies, but havegreater potential to result in uncertain findings. This systematic review investigated the experiences of prospective parents about receiving uncertain results from these tes...
The 100,000 Genomes Project is a hybrid clinical and research project in which patients and parents are offered genome sequencing for cancer and rare and inherited disease diagnosis; all participants receive their main findings and contribute their data for research, and are offered optional secondary findings. Our aim was to explore participating...
Children and young people with rare and inherited diseases will be significant beneficiaries of genome sequencing. However, most educational resources are developed for adults. To address this gap in informational resources, we have co-designed, developed and evaluated an educational resource about genome sequencing for young people. The first anim...
Background:
Consent rates for postmortem (PM) examination in the perinatal and paediatric setting have dropped significantly in the United Kingdom, the United States, and the Western Europe. We explored the factors that act as facilitators or barriers to consent and identified processes and practices that support parental decision-making.
Methods...
Objectives
Genome sequencing is poised to be incorporated into clinical care for diagnoses of rare diseases and some cancers in many parts of the world. Healthcare professionals are key stakeholders in the clinical delivery of genome sequencing-based services. Our aim was to explore views of healthcare professionals with experience of offering geno...
The Rapid Paediatric Sequencing (RaPS) study at GOSH offers trio genome sequencing (GS) for rapid diagnosis of critically ill children with a likely monogenic disorder. Main findings and medically actionable secondary findings are reported. Here we describe a qualitative study exploring parental and professional perceptions of RaPS, the psychosocia...
Background
Fetal exome sequencing (ES) for the diagnosis of fetal abnormalities will soon be implemented in the UK National Health Service. Current guidance for offering fetal ES is limited so research is needed to guide implementation in a manner that maximises benefit for patients. Here we explore health professionals’ views and experiences of fe...
Background:
Noninvasive prenatal diagnosis (NIPD) for monogenic disorders has a high uptake by families. Since 2013, our accredited public health service laboratory has offered NIPD for monogenic disorders, predominantly for de novo or paternally dominantly inherited mutations. Here we describe the extension of this service to include definitive N...
Background
Less invasive perinatal and paediatric autopsy methods, such as imaging alongside targeted endoscopy and organ biopsy, may address declining consent rates for traditional autopsy, but their acceptability and accuracy are not known.
Objectives
The aims of this study were to provide empirical data on the acceptability and likely uptake fo...
The Boost Brittle Bones Before Birth (BOOSTB4) clinical trial is investigating the safety and efficacy of transplanting fetal derived mesenchymal stromal cells (MSCs) prenatally and/or in early postnatal life to treat severe Osteogenesis Imperfecta (OI). This study aimed to explore stakeholder views to understand perceived benefits or concerns, ide...
Objective
To investigate whether less invasive methods of autopsy would be acceptable to bereaved parents and likely to increase uptake.
Design
Mixed methods study.
Setting
Bereaved parents recruited prospectively across seven hospitals in England and retrospectively through four parent support organisations.
Sample
Eight hundred and fifty‐nine...
Background:
Osteogenesis Imperfecta (OI) is a rare genetic condition whose key characteristic is increased bone fragility. OI has the potential to impact upon all family members, making it important to consider the challenges families face, how they cope and their support needs as the affected individual moves from childhood through to adult life....
Purpose:
Little is known about how health-care professionals communicate with patients about consenting to genome sequencing. We therefore examined what topics health-care professionals covered and what questions patients asked during consent conversations.
Methods:
Twenty-one genome sequencing consent appointments were audio recorded and analyz...
Background
Perinatal and paediatric autopsy rates are at historically low levels with declining uptake due to dislike of the invasiveness of the procedure, and religious objections particularly amongst Muslim and Jewish parents. Less invasive methods of autopsy including imaging with and without tissue sampling have been shown to be feasible altern...
Key informant interview questions.
(DOCX)
Parent interview questions.
(DOCX)
Description of NIA and MIA given to participants.
(DOCX)
(Abstracted from Prenat Diagn 2017;37:1281–1290)
Noninvasive prenatal testing (NIPT) for aneuploidy using cell-free DNA (cfDNA) has become widely available and popular for detection of Down syndrome (DS) because of its high sensitivity (99%) and specificity (99.5%). The acceptance of NIPT as an alternative to the first-trimester combined test has g...
Objective
To assess health professionals’ and coroners’ attitudes towards non-minimally and minimally invasive autopsy in the perinatal and paediatric setting.
Methods
A qualitative study using semistructured interviews. Data were analysed thematically.
Results
Twenty-five health professionals (including perinatal/paediatric pathologists and anat...
Background:
Implementation of non-invasive prenatal testing (NIPT) as a highly accurate aneuploidy screening test has raised questions around whether the high uptake may result in more terminations of pregnancies and fewer births of children with Down Syndrome (DS).
Aim:
Investigate the impact of NIPT on termination and live birth rates for DS....
Figure S1. Questionnaire T1: An evaluation of NIPT for aneuploidy in an NHS setting
Objectives:
To assess rates of informed choice among women offered NIPT for aneuploidy as part of routine clinical care.
Methods:
A cross-sectional survey was conducted across six antenatal clinics in England. Women with a high risk (≥1/150) Down syndrome screening result were offered NIPT, invasive testing or no further testing. Pre-test counse...
Aims
To validate an evidence-based patient information leaflet (PIL) to support women considering non-invasive prenatal testing (NIPT) for Down's syndrome.
Methods
A PIL was developed based on qualitative interviews and expert review. The PIL was evaluated by women offered NIPT for Down's syndrome as part of a research study. Questionnaires assess...
Background:
Non-invasive prenatal diagnosis (NIPD) for sickle-cell disorder (SCD) is moving closer to implementation and studies considering stakeholder preferences are required to underpin strategies for offering NIPD in clinical practice.
Objective:
Determine service user and provider preferences for key attributes of prenatal diagnostic tests...
Background
The availability of non-invasive prenatal testing (NIPT) for aneuploidies is expanding rapidly throughout the world. Training health professionals to offer NIPT in a way that supports informed choice is essential for implementation. The aim of this study was to develop and evaluate a training package for health professionals to support t...
Background:
Postmortem examination is the single most useful investigation in providing information to parents about why their baby or child died. Despite this, uptake remains well below the recommended 75%.
Objective:
To address the question 'what are the barriers and motivators to perinatal, prenatal and paediatric PM examination?'
Search str...
(Abstracted from BMJ 2016;354:i3426)
Noninvasive prenatal testing, also known as cell-free DNA (cfDNA) screening, is an efficient screening test for Down syndrome with roughly 99% sensitivity and false-positive rates of less than 0.1% in both high-risk and general populations. This study aimed to examine the potential costs and consequences of intr...
Objective:
To explore womens attidues to NIPT and determine factors influencing their decisions around uptake of NIPT.
Method:
We conducted qualitative interviews to assess knowledge, attitude and deliberation amongst women offered NIPT in a public health service. In total, 45 women took part in telephone interviews (79% participation rate).
Re...
Objective:
To investigate the benefits and costs of implementing non-invasive prenatal testing (NIPT) for Down's syndrome into the NHS maternity care pathway.
Design:
Prospective cohort study.
Setting:
Eight maternity units across the United Kingdom between 1 November 2013 and 28 February 2015.
Participants:
All pregnant women with a current...
The ability to obtain fetal material that could be used for prenatal genetic diagnosis without requirement for an invasive test was a watershed moment in antenatal care. Cell-free fetal DNA (cffDNA) was identified in the maternal plasma by Lo and colleagues in 1997
1
and despite being technically challenging, non-invasive tests for fetal sex determ...
Non-invasive prenatal testing (NIPT) for aneuploidy is currently only available in the UK through the private sector outside of the research arena. As part of an implementation study in the UK National Health Service we conducted a mixed methods study to assess women's experience of being offered NIPT using validated measures of decisional conflict...
NIPT for Down Syndrome patient information leaflet.
(DOCX)
Objective:
Evaluate the costs of offering non-invasive prenatal diagnosis (NIPD) for single gene disorders compared to traditional invasive testing to inform NIPD implementation into clinical practice.
Method:
Total costs of diagnosis using NIPD or invasive testing pathways were compared for a representative set of single gene disorders.
Result...
Purpose of review:
To explore stakeholder views on cell-free DNA testing and highlight findings important for successful implementation and the provision of best practice in counseling.
Recent findings:
Noninvasive tests based on the analysis of cell-free fetal DNA are now widely available in clinical practice and applications are expanding rapi...
Objectives We aim to develop non-invasive prenatal diagnosis (NIPD) for cystic fibrosis (CF) and determine costs and implications for implementation. Methods A next-generation sequencing assay was developed to detect ten common CF mutations for exclusion of the paternal mutation in maternal plasma. Using uptake data from a study exploring views on...
The use of massively parallel sequencing of maternal cfDNA for non-invasive prenatal testing (NIPT) of aneuploidy is widely available. Recently, the scope of testing has increased to include selected subchromosomal abnormalities, but the number of samples reported has been small. We developed a calling pipeline based on a segmentation algorithm for...
