Delivering diagnosis for prenatal medicine – lessons from implementation of a national service

National implementation of a new service can be a complex and challenging process. Addressing change in the NHS requires an understanding of what service is being delivered, how it is being delivered, and what this means for patients in terms of their experiences and clinical outcomes. 

This is exactly what the Optimising Exome PREnatal Sequencing Services (EXPRESS) study sought to achieve for a new prenatal medicine service. Ultrasound scans through pregnancy are emotional, offering the opportunity to see your baby and discover the gender. However, for some, this screening comes with unwelcome findings and enormous uncertainty for parents. Advances in diagnostics have sought to provide timely answers and, if possible, provide key information to support parents when making life changing decisions.

EXPRESS and rapid prenatal sequencing

The EXPRESS study, coordinated by Great Ormond Street Hospital (GOSH) and with input from the PHG Foundation, has been evaluating the implementation of the national rapid prenatal exome sequencing (pES) service. 

Prenatal exome sequencing for the diagnosis of fetal anomalies was implemented nationally in England in October 2020 by the NHS Genomic Medicine Service. Fetal anomalies are typically identified during the 20-week scan and parents are referred to fetal medicine units. Prenatal exome sequencing is one of a number of tests offered to parents, depending on criteria which suggest a genetic disease may underlie phenotypes – visible features – identified on the scan. The urgent nature of referral requires close working between the fetal medicine team, clinical genetics and the testing laboratory. 

Evaluating a service

The EXPRESS study team found that parents and healthcare professionals welcomed the introduction of this new test, especially for the potential to identify a diagnosis. The rapid pES service is running effectively with parents referred across England for this test. Unsurprisingly, a diagnosis is often informative for parents, particularly when making decisions on continuation of pregnancy. A no finding result was also valued by parents and overall rapid pES testing informed clinical management for 56% of referred parents. The EXPRESS study did identify key areas for improvement, captured in the policy report co-authored by the PHG Foundation.

Delivery of pES testing requires a network of healthcare professionals to coordinate this complex test pathway with tight timescales. However, as is the case across the NHS, services are stretched and this is a challenge for delivery of a national and equitable service. 

Areas for action include greater support and better education needs of parents and healthcare professionals. Development of guidelines on use of prenatal exome sequencing is needed, including essential pathway components and pathway audit to inform optimal service delivery. The EXPRESS team has developed an animation, in partnership with Antenatal Reproductive Choices (ARC), their PPI group and healthcare professionals, to educate parents on genetic sequencing. This animation has been evaluated with parents and will be released in multiple languages as a resource, particularly to support consent. There are outstanding questions and key research questions to be answered, which are contributing to an ongoing conversation about the role of rapid pES in the management of pregnancy.

So, what next?

Across England, clinical teams delivering rapid pES referrals and testing are thinking about how to improve the agility of this service to best support parents with timely information. Clinicians shared their experiences at a recent end of project conference and identified opportunities that could address key barriers:

• Expertise is limited. A national network multidisciplinary team – a group of experts who meet regularly to discuss clinical cases – accessible to all clinicians would enable them to access expert fetal medicine phenotyping and prenatal clinical genetics expertise, if this is not available locally, or could ensure a more timely result for parents.
• Midwives and sonographers are the face of the service. Current guidelines and discussions often focus on the role of clinicians, but these healthcare professionals are responsible for informing parents of scan results and provide essential pastoral support. They need to be better equipped and informed to support parents in these vital roles.
• Bringing clarity to the gaps. There are areas where current data collection and integration is insufficient to address outstanding clinical questions. One important question is the need to understand the entire test pathway, in terms of what happens when, and why, from 20-week scan through to clinical outcomes of post-natal care. The types of information required include when and how samples are collected from parents, when these samples are sent to the laboratory, when results are returned and what happens to the pregnancy and the parents after testing. This data is the foundation to inform best practice and changes to improve service delivery for all parents, particularly since it could identify where delays are occurring.
• Interrelated clinical network. The care of parents who are undergoing pES takes place in a wider context of prenatal, perinatal and postnatal care. The interactions between these different forms of care are not without challenges. For example, should a baby not survive pregnancy or birth, many parents understandably want to know why. The quest for answers is not without limits and resource constraints of clinicians needs to be balanced against the likelihood of identifying answers. The interrelated roles of prenatal medicine, perinatal pathology and fetal imaging need to be considered to provide a complete service while recognising resource requirements for these services. One innovation being explored is the use of different imaging technologies to carry out non-invasive autopsies. 
• Addressing uncertainty in consent. Parents who may benefit from rapid pES testing do not always perfectly match eligibility criteria. Clinicians described the challenge of balancing taking consent and samples opportunistically against best timing the process when supporting parents in the context of wider testing. Guidance could support clinicians as to best practice, taking into account different needs of parents.

The EXPRESS study has provided insight into implementation of this novel service and, yet, gaps remain to be addressed in what is an evolving field. The EXPRESS study team is now considering next steps, including targeted research to explore the views and experiences of parents from diverse backgrounds, that were not captured in this study. This study has also better articulated where there are data gaps and what data is needed if we are to fully understand how the service is performing. Addressing these data gaps in NHS digital infrastructure will enable better insights into these services – ultimately, to optimise delivery of timely results to support parental decision making.