Introduction

There is a growing literature on the ethical questions presented by the use of genomic sequencing tests in a prenatal setting, with a number of professional guidelines published on practical ethical issues and how to address them [1,2,3,4,5,6,7,8,9]. These practical ethical issues include the challenges of achieving valid consent, the management of patient expectations, the return of results, dealing with incidental findings, and implications of results for family members. Debates around the ethics of prenatal testing are long-standing whereby it has been positioned by some as a mechanism for reinforcing ableism [10,11,12], and others as a way to support reproductive choice [13]. There is also a discourse on the morality of prenatal testing as a way of selecting against disabling traits and avoiding the birth of children with certain conditions [14,15,16]. Thus, whilst the use of genomic technologies for prenatal diagnosis may be new, many of the ethical issues that arise from providing parents with information in the prenatal period are not.

As genomic sequencing continues to be adopted into clinical practice more widely, ethical issues will be an important consideration for optimal implementation. Reflecting on the ethical complexities of prenatal genomics is particularly timely in the English healthcare context where prenatal exome sequencing (pES) was made available in October 2020 as a national service delivered through the National Health Service (NHS) Genomic Medicine Service (GMS). The EXPRESS study is a multidisciplinary evaluation of the national implementation of the NHS prenatal exome sequencing (pES) service [17]. As part of this study here, we examine the ethical issues arising from the introduction of pES using qualitative interviews with parents offered pES and health professionals involved in delivering the service.

Interview participants in this study raised many of the practical ethical considerations outlined above that have been previously described in the literature [1,2,3,4,5,6,7,8,9]. They also highlighted structural and systemic ethical issues which, as far as we are aware, have not been explored in previous empirical work. For this reason, this manuscript focuses on these ethical issues, gathering them under two interrelated and, to some degree, interdependent sets of issues: those concerning questions of equity, and those relating to the challenges for decision making that arise out of the time constraints created by the intersection of legal, health system, and biological timelines.

Subjects and methods

Study design

This was a nationwide study investigating the ethical issues impacting the provision of pES in England. The study draws on qualitative interviews conducted with professionals involved in delivering pES, and parents who have been offered pES. Detailed methods and the findings relating to professional [18] and parent experiences [19] have been reported elsewhere. Our approach for this work specifically was to identify within the interviews key issues with an ethical focus. Using moral imagination to consider to what extent core principles of prenatal diagnostic testing are consistent (or inconsistent) with the ethical trade-offs, we focused on issues of fairness and justice with respect to moral and professional codes of ethics.

Setting

pES is offered nationally in England through the NHS GMS. pES is offered in pregnancies where structural anomalies are thought likely to have a genetic aetiology, as determined by a multidisciplinary team that includes fetal medicine and genetics experts [20]. Ideally whole exome sequencing is performed on the trio (fetus, biological mother and father), with subsequent analysis performed using a panel of more than 1300 genes known to cause structural anomalies detectable by imaging in the prenatal or early neonatal period [21]. Variants of uncertain significance (VUS) are reported in some circumstances following multidisciplinary team review. Incidental findings with implications for child or parental health, or future reproductive risks are reported. Additional findings, such as cancer susceptibility genes, are not looked for. Although the rapid testing pathway is aimed primarily at those for whom a result may influence future pregnancies, a non-urgent exome sequencing service is available for foetal testing where termination of pregnancy has already been decided or when foetal demise has occurred or is imminent. The target turnaround time for a result in the non-urgent pathway is within 84 days from receipt of all necessary samples and paperwork.

Recruitment

Professionals, including clinical geneticists, fetal medicine specialists, midwives, genetic counsellors, and laboratory scientists from across England involved in delivering pES were sent a study invitation and participant information. Parents over 18 years who had been offered pES in the NHS GMS were recruited through the parent support charity Antenatal Results and Choices (ARC) and Fetal Medicine Units (FMUs) at six NHS hospitals. A study invitation aimed at parents was posted on the ARC website or sent by mail with a follow-up phone call from the clinical team through the potential participant’s FMU. Parents who took part in an interview were offered a £10 gift voucher as reimbursement for their time. Written or audio-recorded verbal consent was obtained from each participant prior to the interview.

Interviews

Sixty-three interviews with professionals and 42 interviews with parents (six with male partners present) were conducted. Interview topic guides explored parent experiences with pES, parent information and support needs pre- and post-pES, benefits and concerns around pES (including ethical concerns), and impact of pES results on decisions regarding pregnancy management (see Topic guides in Supplementary Materials). Professionals were asked about the structure and delivery of the pES service. Standard demographic questions were included (Table 1). Interviews were audio-recorded, transcribed verbatim, and pseudo-anonymised prior to analysis.

Table 1 Participant characteristics (adapted from McInnes-Dean et al., 2024).
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Data analysis

Analysis of interviews was facilitated by NVivo version 13 (QSR International, Pty Ltd) and followed the principles of thematic analysis [22] with findings generated using a team-based codebook approach [23] that combined inductive and deductive approaches [24]. Further details regarding our primary analysis have been published elsewhere [18, 19]. For the purpose of this paper, MParker and MPeter conducted a secondary analysis of the coded data through an ethical lens to draw out the ethical issues linked with implementing the pES service.

Results

Interviews were conducted with 48 parents (42 pregnancies). pES was accepted in 40 pregnancies and declined in two. Where pES was accepted, 16 received a diagnosis or partial diagnosis, one received a VUS, and 23 had a ‘no findings’ result. Of all pregnancies, 21 chose termination. Participant characteristics for parents and professionals are presented in Table 1.

Interview findings

Our findings are described within two overarching themes: ‘Equity of access’ and ‘Timeliness and its impact on parental decision-making in pregnancy’ (Fig. 1).

Fig. 1
figure 1

Themes and sub-themes from interviews with parents and professionals.

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Equity of access

Eligibility criteria, gene panel contents, and resource allocation

Issues around equity of access to pES were mentioned by both parents and professionals - for example in the context of the pES eligibility criteria, which had been informed by published literature and developed through consultation with clinicians. There were clear differences of opinion amongst professionals about whether these criteria were appropriate, with some considering them ‘sensible’ and ‘a good starting point’, and others viewing them as too narrow and limiting parental access to pES (Table 2, Q1). Some parents also supported wider criteria and wanted to make the service available to all who might find it useful (Table 2, Q2).

Table 2 Equity of access.
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Professionals described the ethical challenge of testing for some conditions and not others. When interviews were conducted, genomic analysis for pES was based on a panel of around 1200 genes where variants are known to cause fetal or neonatal structural anomalies. This approach to analysis was questioned by some professionals who felt the diagnostic yield for pES (33.6%, North Thames GLH and Central and South GLH, May 2024) was ‘too high’ and that the test is ‘very selective’ in the conditions it can identify (Table 2, Q3). Many professionals did, however, recognise a dilemma associated with a broader panel approach, noting that, while testing for a wider range of conditions could provide access to pES for more parents, ‘increasing the fishing net’ would also increase the risk of identifying VUSs, thus creating uncertainty for parents.

Professionals also acknowledged that difficult resource allocation decisions were an inevitable part of publicly funded health services (Table 2, Q4). Notably, balancing cost against societal value was also recognised by parents who highlighted a need for clear, equitable processes for priority setting in the face of limited resources (Table 2, Q5).

Variation in clinical decision-making and awareness

Implications for equity also arise out of the individual judgements of clinicians, with views that eligibility decisions are sometimes subject to individual interpretation (Table 2, Q6), or differences in clinicians’ awareness of pES or their understanding of the eligibility criteria and referral processes. These knowledge gaps can potentially lead to delays for parents in accessing pES through a tertiary centre (Table 2, Q7). In addition, there was evidence that local decisions about pES referrals were impacted by resource issues, highlighting the interaction between individual or institutional referral practices and financial considerations (Table 2, Q8).

Some professionals highlighted differential access to ‘proper foetal medicine phenotyping’ (Professional 37 – FMU Consultant) as another way in which the realities of practice introduce inequity. Where expert foetal imaging is unavailable locally, parents may be required to travel for specialist care and must balance the feasibility and practicalities of attending their clinic appointment against their desire for information from pES. The costs of travel and childcare could also act as barriers to access (Table 2, Q9). Variation in the level of specialist input at multidisciplinary team (MDT) meetings was also felt to contribute to inequity, with MDTs in some hospitals attended by prenatal geneticists whilst others operated without regular access to this expertise.

Equity issues also include parents’ ability to access private healthcare, with some parents seeking additional opinions in the private sector which resulted in them gaining access to pES (Table 2, Q10). Navigating these situations was clearly difficult for parents, but these scenarios also present a complex moral and ethical challenge for clinicians who may feel undue pressure to offer pES when they do not feel it is necessary.

Litigation worries

Some professionals felt that referral for pES could be influenced by worries about the implications of not offering it. Many were concerned that, in our ‘increasingly litigious and entitled society’ (Professional 1 — Clinical geneticist), clinicians could be sued if pES was not offered or refused, and a genetic condition discovered after birth (Table 2, Q11). Professionals also noted that these worries could influence referral practice in ways that stretched the application of eligibility criteria (Table 2, Q12), resulting in significant variation in parental access to pES.

Managing equity of access issues on the frontline

Participants described the ethical complexities of managing parents’ expectations around access to pES, particularly when there were uncertainties around whether the case would meet the eligibility criteria. Similarly, care pathways that minimise delays by opportunistically collecting the blood samples for pES before eligibility is confirmed, require clinicians to be careful not to build false hope that the referral will be accepted (Table 2, Q13). Professionals also noted that an increased public awareness of pES places pressure on professionals to carefully manage parents’ expectations of being offered testing as the eligibility criteria may not be met (Table 2, Q14). Notably, several parents described the stress and frustration of waiting for eligibility to be confirmed when it was unclear whether their pregnancy would meet the criteria.

Reflecting existing health inequalities

Though not unique to pES, social and health inequalities were seen to impact access as parents constrained by geographic and financial boundaries were felt to be less likely to benefit. One professional described an example of pES results being delayed because the parents could not afford to travel to have a blood sample taken. Notably, the costs associated with travel had not prevented any of the parents we interviewed from attending their appointments; the need for information outweighed the financial costs incurred. However, there was acknowledgement that travel costs are not affordable to everyone (Table 2, Q15) and that families with different financial priorities may not be in a position to choose.

Whilst not confined to the pES setting, discussing nuanced and complex information with parents with learning disabilities, limited education or whose first language is not English was described by professionals as difficult and could bring about inequity. Experiences with interpreter services were mixed; it could sometimes be challenging to book an interpreter at the required time and while many individual interpreters were very good, some conveyed limited or inaccurate information (Table 2, Q16) which can lead to misunderstandings that impact informed decision-making.

Timeliness and its impact on parental decision-making in pregnancy

Termination and the law

The ethical issues that parents and professionals found most challenging were those arising out of the interrelationships between the timelines linked to pES, the requirements of the laws around termination, and the decision-making needs of parents. Timeliness of referral and return of pES results can be crucial for parents wanting to use this information to guide decisions about continuing or ending their pregnancy. It is, however, important to note that these decisions are not always contingent on pES results; in some cases, decisions can be based on scan findings that show definitively that the fetus is severely affected.

In our interviews, parents and professionals described the challenges of the time sensitive nature of pES for parental decision-making around termination of pregnancy (Table 3, Q1). These challenges arise as most referrals for pES are made following the identification of fetal structural anomalies at the routine 18–20-week fetal anomaly scan. This is close to 24 weeks where the law in England changes and termination is only permitted if there is ‘substantial risk’ of serious impairment in the child if born. In addition, the timelines for pES can be impacted by multiple factors, such as delays in obtaining parent samples, additional investigations prior pES referral or the need for further investigations to clarify a potential diagnosis following whole exome sequencing (Table 3, Q2).

Table 3 Timeliness and its impact on parental decision-making in pregnancy.
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From a parent perspective, the intersecting timelines of the pES testing process and England’s 24-week termination limit was described as ‘incredibly tight’ and ‘stressful’ (Table 3, Q3). Worries about timing were a source of great stress and anxiety noted by both parents and professionals, with parents feeling they have to make rapid, difficult, life-changing decisions. Ultimately the interconnectedness of legal, technological and health system timelines meant that some parents had to make decisions about their pregnancy prior to the return of pES results (Table 3, Q4).

Prioritisation of pES for parents considering termination

Some parents were made to feel that access to pES was dependent on whether or not they planned to continue their pregnancy. For example, one parent described being asked on multiple occasions whether she planned to continue her pregnancy because if so, the test would not be run. She also recalled feeling added pressure to confirm her stance on termination of her pregnancy after a clinician mentioned the cost of the test, stating, “that’s what put me under pressure, and I didn’t like it at all” (Parent 28 — mother, diagnosis from pES (termination of pregnancy)).

From a parent perspective, prioritisation of pES for those whose termination decision will be informed by the result could be experienced as distressing and unjust. However, from the perspective of a health system that needs to consider the needs of all parents, the prioritisation of those whose decision hangs on the test result makes financial sense (Table 3, Q5).

The special status of pES

It was clear that pES can be seen by parents and professionals as the most important—and sometimes overriding—component in the assessment of risk and in pregnancy management. Although pES is just one source of information amongst others, such as scan results, pES could be viewed as key for decision-making and the relevance of other results overlooked (Table 3, Q6).

The importance of training for clinicians to be able to interpret a ‘no findings’ result from pES in the context of other clinical findings and convey this information to parents was highlighted. Understanding the nuances of a ‘no findings’ result was also true for parents. Some professionals were concerned that parents could be overly reassured by a ‘no findings’ result. Careful counselling is needed to ensure that parents understand that this result does not eliminate the possibility of the baby having a genetic condition (Table 3, Q7), and that the anomalies seen on scan have implications for prognosis.

Discussion

The analysis presented here illustrates the value of undertaking an integrated ‘equity and ethics impact assessment’ as part of the evaluation of health systems interventions and its potential to inform the provision of better and more equitable services for patients and families. Here, we explored the experiences of health professionals and parents through an ethical lens and identified two clusters of structural ethical factors that are important for the successful and equitable provision of pES.

The first cluster of structural issues comprised a range of interacting practical ways in which equity of access to pES can be threatened. Decisions on eligibility criteria and gene panel content were common issues that were linked by participants to equity, as they govern access to the test and the conditions tested for. Many participants, however, also recognised that healthcare resources are limited and that difficult prioritising decisions are needed that may restrict access to pES. It was also apparent that factors including variation in clinician referral practices, lack of awareness at peripheral units of the availability of pES services, and concerns about litigation impacted on equity of access. Many of these issues can be addressed by improving awareness through education of all stakeholders.

Our second cluster of structural ethical issues were linked to the timeliness of pES and its impact on decisions to continue or terminate the pregnancy. Many of these issues hinge on the change in the legal basis for termination of pregnancy that occurs at 24 weeks gestation whereby termination is only permitted if “there is a substantial risk that if the child were born it would suffer from such physical or mental abnormality as to be seriously handicapped”. For our participants, the change in law at 24 weeks meant that timely referral and the efficient return of results to parents were essential requirements for an effective and ethical pES service. Waiting for the results of pES when close to 24 weeks was an extremely stressful experience for many parents and for the clinicians who care for them. Indeed, some parents felt they could not wait for pES results as the deadline drew near and made decisions about ending or continuing the pregnancy in the absence of the additional information from pES. The relationship between pES and termination of pregnancy is complex and multifaceted, and likely to change over time. Whilst there are some cases in which a pES finding informs a decision to terminate, there are others in which results show a less severe condition than expected allowing parents to decide to continue the pregnancy. In the future, as therapies become available it is possible that pES will come to play a role in identifying opportunities for early intervention.

Our analysis identified that the two clusters of ethically relevant problems—issues around equity of access and those relating to timeliness – have the potential to be mutually reinforcing. That is, problems arising out of inequity of access to services and the nature of referrals for pES based on findings from the 20-week fetal anomaly scan (or later if additional tests such as MRI are required) could make it harder to achieve timely return of results. This has the inevitable consequence that some parents’ decisions about termination of pregnancy will be made later in pregnancy or potentially without information from pES. It also seems likely that the resulting time constraints on decision-making will in turn impact those who are already disadvantaged in other ways. This suggests that there are strong equity-based reasons for paying close attention to addressing both the structural drivers of inequity and looking for ways to improve the timeliness of both referral processes and the processes of pES themselves. However, it is important to acknowledge that improving timelines is challenging as many anomalies are not detected until the routine fetal anomaly scan at 18–20 weeks. It has been suggested that the number of late terminations following pES testing could be reduced by the introduction of an earlier assessment of fetal anatomy since this would allow earlier identification of some of the cases eligible for pES [25], but this would not address the issue entirely as some fetal anomalies do not present until late in pregnancy. Fetal anomaly screening is, however, continuing to evolve with new technologies becoming available that may improve detection and impact timelines, at least in some cases [26].

A key finding from this analysis was that some parents and professionals placed special and sometimes overriding importance on pES, despite the availability of other relevant information such as a prenatal ultrasound scan or MRI findings. For example, a fetus with a very small chest and short limbs has a high chance of an underlying lethal abnormality regardless of the pES result, while a fetus with severe brain anomalies is likely to have significant developmental delay. In these circumstances counselling can be based on imaging findings, and although genetic results can influence later reproductive decision making, these are not crucial for managing the current pregnancy. Information from scans and other sources is important when interpreting a ‘no findings’ pES result, especially as professionals raised concerns that parents could be overly reassured by this result. Furthermore, other studies have shown that parents can adopt both pessimistic and optimistic interpretations to no informative findings from pES [27].

Whilst our interpretation is specific to the offer of pES in England, we anticipate that the ethical challenges we have described will be experienced in other contexts as pES is adopted more widely. Regardless of the health system in which pES is offered, clinicians must be aware of the limitations of pES and the need to interpret results in the context of other available information in order to deliver personalised post-test counselling and support for parents. Furthermore, all health systems in which pES is offered should prioritise education and training for clinicians on the clinical indications for pES. This is fundamental for supporting clinician confidence and avoiding defensive medical practice. Finally, issues around equitable access are relevant to all healthcare systems, but are especially pronounced for those in which pES is available only via out of pocket costs or specific insurance coverage. Careful attention must be paid to avoid exacerbating health inequities and to ensure that all parents who may benefit from pES are able to access it.

Limitations

A key limitation of our study is that the majority of our parent participants reported being White/White British and were educated to degree level or above. The majority had also opted to have pES. As a result, our participants do not represent the views and experiences of all parents offered pES. Further, there is a risk of responder bias since participants were self-selected.

Conclusion

In this paper, we have identified several ways in which the identification and analysis of ethical questions can be useful in the evaluation of a new clinical service. Addressing the practical ethical questions arising for health professionals and parents such as those relating to consent, feedback of findings, implications for family members, and the scope of health professionals’ responsibilities is vital for its success and can, to some extent, be mitigated by improving stakeholder education. However, identification and addressing of structural and systematic ethical concerns also require careful attention. In our analysis presented here, these structural ethical issues are experienced by both health professionals and parents particularly in relation to questions of equity and of timeliness.