Introduction

Prenatal diagnostic testing has been available to parents since the middle of the last century, when amniocentesis became available for the detection of fetal aneuploidy.1 Initially, examination of the fetal chromosome number and microscopic structure could be offered; however, as understanding of the molecular basis of many genetic conditions has increased, so have the opportunities for prenatal diagnosis (PND) of a wide range of disorders.2 PND using samples obtained via invasive tests (amniocentesis, chorionic villus sampling (CVS) or, very rarely, cordocentesis) is still generally used to detect monogenic and chromosomal disorders in the fetus.3 In some clinical settings, amniocentesis or CVS for aneuploidy has been offered to all pregnant women of advanced maternal age.4, 5, 6 In other circumstances or countries, discussion of invasive testing may be prompted by a high-risk screening result.7 However, the opportunity to use non-invasive techniques for some conditions is now feasible8 and these are increasingly available to women in some countries.9

Advances in technology increasingly facilitate parental choice with regard to PND; however, there are many ethical,10 legal,11 and social and psychological12 issues related to the clinical offer of prenatal screening and testing that require consideration.13 As with other medical procedures, enabling the parents to make an informed choice is integral to good clinical care; however, this can be challenging because of the understandable reluctance of parents to anticipate an abnormality in the fetus and the unpredictable nature of their reaction to the results.12 Furthermore, there is evidence that parents may not be aware that such tests are optional. In a qualitative study of 38 mothers who had undergone prenatal testing, Potter et al14 found that some women believed they had not given informed consent, mainly because of their beliefs that the testing was a routine part of antenatal care. Authors of the same study found that many women made their decisions based on moral judgements related to their own values, interpreting the factual information provided through their own moral lens. Therefore, whereas health professionals emphasise the importance of providing information, exploration of the individual views of the parents may be just as important in facilitating them to make a decision compatible with their beliefs.

Beliefs and values relate to cultural norms, and women from dissimilar cultural backgrounds may show varied responses towards information and prenatal counselling. For example, Tschudin et al15 identified that Turkish women reacted differently while considering PND when compared with women of other European nationalities and found the counselling process itself more unsettling. Authors of other studies confirmed differences in the uptake of PND in women of Israeli Arab5 and African American16 ethnicity, while attitudes towards prenatal testing and subsequent pregnancy management varied depending on condition in a study comparing Pakistani and White women living in the United Kingdom.17 It therefore appears that, although guidance on the best practice in counselling for prenatal testing can be devised, it must be sufficiently flexible to take cultural norms into account.

Non-invasive techniques to test the fetus, using cell-free fetal DNA in the maternal circulation, are increasingly available for fetal sex determination (for sex-linked conditions), aneuploidy detection18 and diagnosis of single-gene disorders.19 According to a recent systematic review on the factors influencing the use of NIPT,20 users and potential users cite the advantages of the non-invasive test as including earlier diagnosis (allowing earlier reassurance or decisions about the future of the pregnancy) and removal of the risk of fetal loss owing to the test.21, 22 However, the ease with which the test can be performed has made some women, health professionals and members of the general public concerned that parents might consent to the test without sufficient consideration of the consequences.23, 24 A recent position statement on NIPT published by the National Society of Genetic Counsellors25 cited the need for both appropriate counselling to accompany the test and the need for informed consent. This is particularly pertinent to the NIPT approach, as women and health professionals seem to vary in their attitudes towards this mode of testing26, 27 and ease of testing may increase use of direct-to-consumer testing.28 It is essential therefore that pre- and post-test counselling and consent procedures should be rigorous, whether the sample was taken via an invasive or non-invasive route.

Despite the long history of PND, there have been no general guidelines issued to ensure that parents are equipped to make informed decisions about such testing. A search of the International Guidelines Library (http://www.g-i-n.net/library/international-guidelines-library) indicated that, although there were 10 guidelines related to antenatal care, none of these focussed on diagnostic testing. As part of the EuroGentest2 project, we were charged with producing a set of guidelines for those offering prenatal diagnostic tests in a clinical setting. According to local practice and the condition for which testing is offered, PND counselling may be provided by health professionals in the midwifery, obstetric or specialist genetics clinical teams, providing further challenges for ensuring good practice and equity of care. In view of the need for individual approaches to ensure that each woman or couple can make an informed choice, we developed a set of guidelines that can be adapted for use in a range of settings and according to the individual circumstances of the woman, couple or family involved.

The aim of this study was, therefore, to formulate a set of best practice guidelines for offering genetic testing in specific prenatal contexts, including NIPT.

Methods

We used an expert group to formulate the guidelines through a process of consensus and consultation. This approach has been utilised in other work to develop policy or recommendations in a genetic health-care context.29, 30 We aimed to invite a cohort of 13 experts with maximum variation in terms of European country of origin and clinical specialism and profession to participate in a workshop. We therefore invited specialists in the field of PND from Belgium, Czech Republic, Denmark, Finland, Greece, Italy, the Netherlands, Spain, Sweden and the United Kingdom. However, the participant from Greece was unable to attend, leaving representatives of nine European countries to contribute (see Supplementary File 1 for country, background and expertise of the participants). As the workshop was held in the United Kingdom, several additional people with relevant expertise working in the United Kingdom were also able to join the group. Prior to the workshop, the aims of the meeting and relevant peer-reviewed papers on the topic of PND were circulated (see online appendix for details) to enable the participants to become familiar with the latest existing work on the topic. Although all attendees were experts in their own areas, this established a foundation of knowledge across different disciplines.

The workshop began with an introduction and discussion to agree the aims and objectives. Representatives of clinical practice were then asked to make a short presentation on the way in which PND was offered in their own country. This enabled the participants to gain an appreciation of the areas of commonality and variations in practice, national policies and legal regulation in those European countries. A presentation on service-user views and experiences of NIPT with a focus on the psychosocial aspects of the test was also given.

The participants decided to develop guidelines under four main headings: objectives of PND, general principles, logistical considerations (process) and principles related to the content of the counselling. We first agreed the objectives and determined the scope of the guidelines. After much discussion around the boundaries between prenatal screening and testing, we decided to address the issue by focussing on defining the three main groups of women who might present for prenatal testing in practice (Table 1). Another key issue covered in the initial discussion was whether the guidelines for non-invasive PND should be different in any way than those for invasive testing: the outcome was a decision to write the guidelines for invasive testing and then review them critically to see whether and how they might have to be altered for NIPT.

Table 1 Specific considerations for each group of women
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Work to further develop the guidelines under the three remaining headings (general principles, logistics and counselling content) was conducted in three multidisciplinary groups. The groups met at the end of each session for plenary discussions to raise specific matters that had arisen during small group discussion with the entire group. In the final plenary session, all guidelines were further discussed until a consensus was obtained. Returning to fitness of the guidelines for use with NIPT, it was agreed that they were equally applicable to invasive and non-invasive prenatal testing.

Following the workshop, the draft guidelines were sent to each participant for further consideration and suggestions. The document was then circulated broadly for consultation to the following:

  1. 1

    Members of the European Society for Human Genetics (ESHG)

  2. 2

    National professional societies for human genetics in all European countries

  3. 3

    European societies for those practising obstetrics and gynaecology

  4. 4

    Participants in the EuroGentest2 project.

The document was also posted onto the websites of the ESHG and EuroGentest2 project to enable open access by any interested person. This resulted in receipt of detailed comments from a further 14 experts from 12 countries and approval from members of the Executive Board of the ESHG and other national organisations (Supplementary File 2). Finally, the guidelines were reviewed and amended slightly where necessary, in the light of the comments received.

Scope of the guidelines

These guidelines relate to PND for women whose fetus is at an increased risk of a specific condition. They, therefore, relate to testing offered with the intention of determining the presence or absence of a genetic or multifactorial condition in the fetus. Such testing may be performed using invasive or less invasive procedures (such as analysis of cffDNA or fetal imaging). Here, we suggest guidelines for the practical aspects of delivering PND to these high-risk women: discussion on more general ethical, legal, social and economic aspects is outwith the scope of this document. The guidelines do not refer to antenatal screening tests. Within the guidelines we used the terms women, parents, couples (women and their partners) or families, as appropriate; however, we did not make any assumptions about family composition when using those terms.

The guidelines are presented in three sections: general principles, logistical considerations (process) and principles related to the content of the counselling.

Results

Objective and context

The objective of PND is to provide prenatal diagnostic testing services (for genetic conditions) that enable families to make informed choices, consistent with their individual needs and values and to support them in dealing with the outcome of such testing. For the purpose of these guidelines, we are referring to prenatal diagnostic tests that may be offered to pregnant women in one of the three groups (Table 1).

General principles underpinning PND

The general principles are presented in Figure 1. In order to provide a service that ensures appropriate standards of care for women and their families, all of the principles should be adhered to, although specific content addressed during counselling may vary according to the particular family situation and the condition (see Table 1).

Figure 1
figure 1figure 1

General principles underpinning PND.

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Logistical considerations (process)

The general considerations that apply to all the three groups of women are as follows:

  1. 1

    There should be a designated professional who will act as the coordinator and facilitate communication between the multidisciplinary team(s), the local doctor/midwife and the family.

  2. 2

    Sensitive counselling by an appropriately trained professional should always be offered to support the couple in both making decisions and adjusting to the outcome, whatever their decision is.

  3. 3

    To ensure effective communication with the woman and her partner, independent interpreting services should be used where necessary.

  4. 4

    In every case, implications for other family members should be considered and appropriate family management should be discussed with the parents.

  5. 5

    Where sharing of information is required, national practice should be followed, and consent sought to share the relevant case details with other professionals – for example, the referring doctor.

  6. 6

    Where the diagnosis is uncertain and parents decide to terminate the pregnancy, they should be made aware that having a termination using medical methods could enable other investigations to take place, even if this means delaying termination following an early pregnancy diagnosis. This may facilitate diagnosis and identification of the underlying cause of fetal abnormality, which will be beneficial for risk assessment in future pregnancies and for other family members.

  7. 7

    If informed consent is given for PND, the procedure should be undertaken by a trained professional with appropriate skills. The sample should be tested in an appropriate laboratory (see Table 1, section 1d).

  8. 8

    Test results should only be conveyed by an appropriately trained professional. Post-test counselling should be offered and all options for management of the current pregnancy should be discussed within the local ethical and legal framework.

  9. 9

    If PND is declined or not appropriate, as it is too late in pregnancy for intervention, (and the fetus is therefore still considered to be at risk) or the pregnancy continues with an affected fetus, there may be a need for referral for specialist ongoing pregnancy management and postnatal support.

  10. 10

    Additional counselling should be offered after pregnancy to discuss future reproductive options and consequences, if they exist, for other family members.

  11. 11

    Consent should be obtained for relevant DNA, tissue or other biological materials to be taken, stored and analysed.

Counselling topics when offering a diagnostic test for a specific genetic condition

The key counselling topics should be discussed, and ideally a written summary of the discussion should be provided. Table 2 gives an indication of the main topics; however, the discussion should be tailored to individual circumstances. Although many topics will be discussed prior to the test, appropriate post-test counselling to discuss the outcomes and support parental decision-making should always be available.

Table 2 Topics to be covered during counselling for prenatal diagnostic tests
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Discussion

Although new technologies may change the way in which samples for PND are obtained and tested, the underpinning principle of informed consent remains unchanged. These guidelines include the need for pre- and post-test counselling by an appropriate health professional to ensure that the woman (and her partner, if relevant) is able to access the information required to enable her to make an autonomous decision, and to use the results as she wishes, within the context of the local ethical and legal guidelines. However, despite a relatively long history of such testing, there is evidence that health professionals still find counselling in such situations challenging. Eldahdah et al,31 for example, reported that some experienced obstetricians used a directive approach and reported discomfort with giving results of prenatal testing for chromosomal abnormalities, whereas Williams et al32 highlighted the challenges faced by both obstetricians and midwives in facilitating choice regarding prenatal testing. Adequate training for health professionals is essential to facilitate effective prenatal diagnostic counselling, and for that reason we have specified that the person providing counselling should be appropriately trained.

Information should be provided to women in both verbal and written forms. Kuppermann et al33 undertook a study using a computerised decision tool to support information provision in a cohort of pregnant women and found that women preferred these to standard written information. However, other studies have shown that women value the opportunity to discuss their screening decisions in a personalised way with an appropriately trained health professional,34 and there is no indication that this would be different in a diagnostic testing scenario.35, 36 In addition to this point, providing only written information assumes a level of literacy in the patient. We therefore recommend that individual discussion is undertaken to enable the woman to place the information into the context of her own life and that of her family. Of further relevance to this point is the need to employ trained interpreters for discussion when indicated, as women who are not fluent in the language routinely used in the clinic are disadvantaged in terms of their ability to discuss and consider their options, make autonomous decisions and provide consent.37

In writing these guidelines, we have made an attempt to address not only current clinical issues but also those that may arise in the near future.38 For example, the use of microarray testing in place of conventional karyotyping for fetal chromosomal analysis is increasing the potential for unexpected findings.39 Although the empirical data available to inform the management of such findings are limited, albeit growing rapidly, it is claimed that the respect for patients’ autonomy and the avoidance of paternalism necessitate disclosure.36 We therefore suggest that the potential nature of unexpected findings, as well as whether and how they will be disclosed to the parents should be discussed before the sample is taken.

Strengths and limitations

These guidelines have been based on in-depth discussions between acknowledged experts across the specialities involved in PND. In addition, they have been open for consultation among a much wider group of health professionals. Although the expert group took into account the current scientific evidence available through peer-reviewed literature, there are few empirical studies that involve a comparison of different models of care. This inevitably limits the objective scientific basis of this work.

Conclusions

These guidelines are offered to health professionals working in a range of contexts. Owing to the need for an individualised approach that takes into account individual values and beliefs, cultural norms and ethnicity,38 we have developed general guidelines that can be adapted to the individual setting and family. However, they will require modification for local, regional and national conditions. In the light of the rapidly changing situation in genetic healthcare, the guidelines should be reviewed every 3 years. This should be undertaken by relevant organisations working together to ensure that women and their partners are offered prenatal testing in a way that ensures that they have adequate information, are able to make an appropriate decision for their own family and are supported throughout the process.