Prenatal exome sequencing (pES) has shown promise as a powerful tool for prenatal diagnosis of fetuses with anomalies. With the potential to improve the diagnostic yield of monogenic conditions (Lord et al., 2019; Petrovski et al., 2019), pES provides parents with clinically useful information for pregnancy, early neonatal management, and longer-term prognosis (Skirton et al., 2014; Chandler et al., 2018).

Recent decisions to mainstream pES in England have been guided by evidence on its feasibility and clinical utility (Chandler et al., 2018; Lord et al., 2019; Petrovski et al., 2019). Introduced into antenatal care by England’s National Health Service’s (NHS) Genomic Medicine Service (GMS) in October 2020 (NHS England and NHS Improvement, 2020), pES is now offered routinely when abnormalities detected on fetal imaging are suspected to have monogenic aetiology following multidisciplinary review that includes a clinical geneticist, and molecular diagnosis may influence parental decision-making or pregnancy or neonatal management (Figure 1 illustrates the general pES pathway). Testing ideally involves trio sequencing, and analysis uses a panel of more than 1200 genes (Genomics England, 2021) associated with congenital structural anomalies presenting prenatally or in the newborn period.

The eligibility criteria and panel approach used for analysis is designed to maximise the identification of monogenetic conditions whilst minimising incidental findings. Parents receive pre-test counselling during which the possibility of the identification of incidental findings and variants of uncertain significance (VUS) is discussed. Parents are not able to opt out of receiving incidental findings since they are detected through the process of trio sequencing to identify an underlying cause for the fetal abnormalities. However, current national guidelines advise that both VUS and incidental findings are only reported to parents after multidisciplinary team (MDT) discussion determines the variant is relevant to the fetal phenotype or will impact on parental health or future reproductive risks (Supplementary Material).

Currently offered via referral through clinical genetics, England’s pES service relies on coordination between specialist genetics and fetal medicine (FM) professionals and clinical scientists. Considerations around professional education, the need for expert counselling, and the type of results returned to families have been highlighted as key issues when introducing pES into mainstream care (Quinlan-Jones et al., 2016; Brew et al., 2019; Chandler et al., 2022; Mellis et al., 2022). Understanding the impact of delivering pES as a national service from the perspective of healthcare professionals is necessary for recognising areas of success and efficiency, highlighting areas for improvement, and identifying support needs. Optimising EXome PREnatal Sequencing Services (EXPRESS) (NIHR127829) is a national study examining the delivery of pES across England through the NHS GMS (Hill et al., 2022). In the mixed methods study described here, we have used surveys and interviews with professionals to address the research question: What does delivery of a national pES service look like from the perspective of healthcare professionals, and what should it look like in the future?

To build a picture of pES service delivery from implementation through the first 2 years of service in the NHS, we focused on four areas: 1) views on the pES service), 2) capacity and resources, 3) awareness, knowledge, and educational needs and 4) ambitions and goals for the future.

Of 280 surveys distributed, 179 were started. Surveys where participants had started but entered no data (n = 4) or completed demographic information only (n = 15) were excluded. The final dataset comprises 159 surveys (response rate: 57%). Of 134 professionals invited to participate, 63 were interviewed, 70 did not respond, and one actively declined (recruitment rate: 47%). Interviews were conducted by video call (n = 53), face-to-face (n = 6) and telephone (n = 2) and lasted between 23 and 80 min (median duration 44 min). Participant characteristics are presented in Table 1.

This study is the first to offer insight into professionals’ experiences of delivering a national pES service at the outset of implementation, and their views on what it should look like in the future. We found that both FM and genetics professionals were positive about England’s pES service. In line with other research (Quinlan-Jones et al., 2016; Narayanan et al., 2018; Mellis et al., 2022) professionals were enthusiastic about the clinical benefits of pES and described how the increased opportunity to receive actionable results during a critical period for parental decision-making had helped them to improve support for parents. Furthermore, and in keeping with NHS England’s vision to provide equity of access to genomic medicine (NHS England, 2022) embedding pES into mainstream care was seen as fundamental for ensuring that all parents eligible for pES will be offered it.

In recent work exploring stakeholder views of moving pES from research into a clinical setting in the NHS, professionals anticipated that effective service delivery would need FM and genetics professionals to work together (Mellis et al., 2022). The benefits of collaborative working for variant interpretation when offering pES have also been reported. Our findings indicate that implementing the pES service has fostered close relationships between FM and genetics teams and provided opportunities for learning and knowledge exchange across specialisms that supports successful service delivery.

However, offering pES routinely in a clinical setting has brought several challenges. Additional administrative processes and extra clinic time needed to counsel parents were experienced by professionals from all disciplines, with genetic professionals impacted to a greater extent. Although many professionals welcomed the reassurance of discussing cases with specialists, others reported a perceived lack of autonomy in decision-making that left them frustrated at having to seek approval for referrals despite their own expertise. System-level changes to the referral process may come with time, however, improvements to existing resources, streamlining of care pathways and the inclusion of additional staff groups to support pES delivery could be addressed immediately. For example, expanding the genomics workforce to include staff such as “genomics associates” who can support the consent process and administrative tasks could provide professionals with more time for specialist tasks and allow the pES service to be delivered more efficiently. Improvements to IT systems could also facilitate the various processes involved in sharing documentation with the labs and monitoring test status. Similar approaches to improve efficiency have been suggested in recent research looking at offering whole genome sequencing in the NHS GMS (Friedrich et al., 2023).

Some professionals questioned the use of a restricted panel of genes for pES analysis, preferring a more agnostic approach to testing that would optimise the clinical potential of pES. It was, however, acknowledged that widening the gene panel for pES would increase the chance of detecting VUS which, given the limitations in the systems used to classify variants (Lord et al., 2019), could place unmanageable demand on the service. Detection of VUS is not unique to pES: uncertain findings also arise through use of chromosomal microarray (CMA) (Wapner et al., 2012; Hillman et al., 2013) and our findings echo long-standing worries about the anxiety caused to parents by the return of uncertain results from prenatal testing (Westerfield et al., 2014; Jez et al., 2015; Harding et al., 2020; Lewis et al., 2021). In this regard, a future ambition for many professionals was the sharing of data on public genetic repositories. The use of databases such as DECIPHER, will be key as new gene variants are discovered and better understanding of existing variants evolves (Lord et al., 2019). An important consideration already highlighted will be determining responsibility for re-contacting parents when new knowledge emerges (Horn and Parker, 2018).

Previous work has shown the value of clinicians with a good understanding of pES providing detailed counselling that makes clear the limitations and potential implications of the test (Best et al., 2018; Mellis et al., 2022). The importance of accurate fetal phenotyping when offering pES has also been discussed (Aarabi et al., 2018; Monaghan et al., 2020). The current study identified gaps in genomics knowledge amongst FM professionals and a need for more genetics professionals with an understanding of prenatally diagnosed conditions. Worries about returning results from pES were also noted. As such, a key ambition for the pES service, highlighted by many professionals, will be improved access to education. This could help FM doctors and midwives improve their genomics knowledge and confidence in counselling for pES, for instance how to support parents when VUS results and incidental findings have been identified. Training would also help improve knowledge of prenatally identified conditions amongst genetics specialists new to working in the prenatal setting.

The multiple benefits of upskilling midwives to support the pES service was highlighted by many participants in our study. As has been observed elsewhere in the NHS nursing and midwifery workforce (Carpenter-Clawson et al., 2023), midwives feel limited by their knowledge and confidence about genomics despite recognising its importance in patient care. Further, and in line with recent work (Seed et al., 2022) professionals in this study highlighted a need for the teaching of genomics to begin at undergraduate level in order to better equip the medical professionals of the future. Educational opportunities are available to support the mainstreaming of genomics. For instance, the Genomics Education Programme (Genomics Education Programme, 2022), delivered by Health Education England, offers online access to short courses and clinical resources. Training materials that integrate case examples could also be effective; this approach has been shown to increase understanding of genetic concepts (Hajek et al., 2022) and aligns with the experiences of the professionals in this study who valued the national MDTs where pES cases were discussed. In addition, training facilitated by a mentor could be an effective way of establishing meaningful engagement (Bishop et al., 2019), and secondment to specialist teams for experiential learning might help to better embed knowledge and support clinical practice (McClaren et al., 2020). A common concern highlighted in this study was that professionals lack the time for further education. It is vital that protected time for additional learning is given to all professionals involved in the pES pathway. Moreover, for professionals working in local, non-specialist maternity units where awareness of the pES service may be limited, further education must be considered a priority to ensure an equitable service.

An important caveat is that whilst the introduction of the national pES service is new, the questions raised by the professionals in this study regarding implementation of a new healthcare service are not. Similar issues have been encountered elsewhere. For instance, the impact of limited knowledge of prenatal phenotypes on variant interpretation, reservations about the preparedness of clinicians, and concerns about how to counsel parents about uncertain results have been reported in studies exploring professional views on the introduction of CMA into prenatal settings (Robson et al., 2017; Lewis et al., 2021). Our findings should, therefore, be interpreted in light of these broader issues associated with the implementation of large-scale services that require adaptation within a local context.

A strength of this study is that the views of professionals from a range of backgrounds and across all regions of England were included. In addition, both quantitative and qualitative information has guided our understanding of pES service delivery. Our study commenced at the same time as the pES service was launched, allowing us the unique opportunity to capture experiences during the first years of implementation. A limitation of the study is that interviews were conducted over a 2-year period, thus individual experiences may have differed over time as the service became more established, particularly as the service was first implemented when COVID restrictions were in place. A further limitation is that respondents were self-selecting and there may be bias towards those with strong views about the pES service.

Professionals working in FM and genetics settings are enthusiastic about the benefits of pES for parents and welcome the introduction of a national pES service in England. Collaborative working between FM and genetics teams has been central to the successful delivery of pES. Our findings highlight that further education and training is needed and that constraints on time and resources can impact the ability to deliver the pES service efficiently. Improvements to IT and staffing along with a sustained effort to upskill both FM and genetics professionals could optimise the benefits of pES and lead to improved experiences for both parents and professionals.