Facilitating informed choice about non-invasive prenatal testing (NIPT): a systematic review and qualitative meta-synthesis of women’s experiences

Non-invasive prenatal testing (NIPT) for chromosomal anomaly represents a significant evolution of prenatal screening technology. Commercially available to many since 2011, NIPT assesses cell-free fetal DNA present in maternal blood to screen pregnancies for common chromosomal anomalies, either through a quantitative “counting” method that uses targeted parallel sequencing, or by identifying maternal and fetal allele distributions using single-nucleotide polymorphisms (SNPs) [1]. It is most often used to detect aneuploidy in chromosomes 13, 18, 21, and the sex chromosomes. The SNP-based NIPT can also identify five clinically significant microdeletions [2], and clinical applications are expanding rapidly [3].

Testing with NIPT can be done as early as 9 to 10 weeks of pregnancy, up until the time of birth. It is more accurate than other forms of prenatal screening, with a sensitivity ranging from 90 to 99% and specificity ranging from 99 to 100% depending on the condition [4]. When compared to other prenatal screening tests, it carries a low false positive rate of 0.09 to 0.13% depending on the condition [5]. NIPT is not accurate enough to be considered a diagnostic test [6]. Since it is non-invasive, it is not associated with iatrogenic pregnancy loss [7].

NIPT has been commercially available in Hong Kong and the United States since 2011, and has quickly spread to over 60 countries [8]. The price of the test varies internationally and depends on the anomalies being tested for. In Canada, NIPT costs between CAN $550–$795 [9], while in the United States, prices range from US $600–$800 [10]. In the United Kingdom, the test costs from £375–£1500 [11]; elsewhere in Europe the price is typically between €260–€770 [12‐14].

Increasing numbers of health insurance companies and publicly funded health systems are providing coverage for NIPT, with most reimbursing women who are at high risk for chromosomal anomalies. “High risk” is variously defined, and often operationalized using maternal age, history, or positive results from other screening tests [15]. In North America, some Canadian provinces adopted this model of coverage as early as 2014, with others not providing any coverage. In the United States, the majority of insurance companies fund NIPT for high-risk pregnancies, though several have expanded their coverage to all pregnant women [10]. In some jurisdictions such as Hong Kong and Singapore, NIPT is available only through a private-pay system [16, 17]. In Europe, Denmark, France, the Netherlands, and Switzerland offer public funding for NIPT, contingent with risk [18]. In the United Kingdom, reimbursement is only provided in the context of a 2-year study that began in 2018 [18], but the National Screening Committee has recommended that screening with NIPT be done for high-risk pregnancies [19]. To date, Belgium is the only country to publicly fund NIPT as a first-tier or primary test [18].

NIPT has attracted significant attention, in part due to its rapid diffusion, but also because of the potential to disrupt traditional prenatal testing pathways and its myriad ethical implications. NIPT is not a diagnostic test, and as a result most clinical practice guidelines recommend that all positive NIPT results should be confirmed with invasive fetal diagnostic testing, as well as that no irrevocable decisions about a pregnancy should be made on the basis of NIPT alone [6, 7, 20]. However, the introduction of NIPT has been associated with a decreased uptake of diagnostic testing [21], and some clinicians have reported a decrease in the number of invasive diagnostic procedures performed since NIPT was introduced [22].

Research on women’s preferences about NIPT shows high levels of support for this technology [23‐32] as well as a strong desire that it be available to all women due to its accuracy and safety [28, 30, 33, 34]. Despite these benefits, NIPT raises several ethical issues. For instance, because NIPT is able to provide accurate information about fetal sex early in a pregnancy, one concern is that test results could be used for sex selective termination [35, 36]. In countries without universal public funding for NIPT, there may be inequity of access to the test and subsequent prenatal care opportunities [36‐38]. The accuracy and early timing of NIPT results may also have implications for the disabled community, in that the number of people born with a disability may decrease over time, leading to increased discrimination and stigmatization, as well as diminished availability of resources and supports [39].

The simplicity and ease of the test also raises concerns about informed decision making and the potential for routinization. Informed decisions are those that are founded upon relevant knowledge and are concordant with a person’s values [40]. They enable a person to exercise autonomy, which is regarded in the ethical literature as intrinsically valuable [40]. Promoting reproductive autonomy is recognized as one of the core principles of prenatal testing [41]. While NIPT can facilitate a woman’s reproductive autonomy by providing her with accurate information risk-free and early in her pregnancy, these same elements of the test could also lead to an erosion of informed choice and a reduced ability to exercise autonomy [40, 41]. Because NIPT is a simple procedure that poses no risk to the fetus, there is the danger that women may view it as just “another blood test” [42, 43] and therefore opt-in without fully understanding its importance or implications [41]. The rapid diffusion and widespread implementation of NIPT also raises concerns that health care providers may not yet be fully prepared to counsel women appropriately due to a lack of time and a lack of confidence in counselling about this new technology [34, 41]. An additional challenge to informed decision making exacerbated by NIPT is that it could lead to greater societal pressure for women to undergo prenatal testing [40, 42, 43]. Because of the accuracy of results, and the lack of physical risk creating the perception that there is no disadvantage to testing, women may feel that they are expected to have NIPT [43]. For these reasons, it is important to understand how to facilitate informed, autonomous decisions about NIPT. This includes understanding women’s values as they consider their prenatal care, how they make decisions around their pregnancy, and what their preferences are for education, resources, and support during this time.

This review answers the following research questions: How do women experience informed decision making about NIPT? How do they use information and negotiate between different aspects of the test to make a decision? What are their preferences for the facilitation of informed choice? There is a burgeoning amount of empirical literature [44‐48] about the challenges of informed decision making about NIPT. The purpose of this review is to bring together this collection of primary research to comment on women’s perspectives, experiences, and preferences for informed decision making about NIPT.

We performed a systematic review of primary qualitative research about NIPT as part of a Health Quality Ontario (HQO) health technology assessment (HTA) on NIPT. Detailed methods are available in that report (Vanstone M, Cernat A, Majid U, De Freitas C, Trivedi F. Women’s and clinician perspectives on non-invasive prenatal testing (NIPT): a systematic review and qualitative meta-synthesis, forthcoming). The systematic review and meta-synthesis conducted for HQO described the experiences of women, clinicians, and others with rich lived experience of the test (e.g. parents of children with conditions detected by NIPT). For the current paper, we focus on the literature about women’s and their partners’ experiences, preferences, and values pertaining to making informed decisions about NIPT.

Our systematic search yielded 948 studies (with duplicates removed). We also conducted a hand-search of reference lists of all included articles and continued to retrieve relevant hits from monthly search updates. In total, 30 studies were eligible for inclusion. These included studies involved 1237 patients and family members with experience with NIPT. Figure 1 illustrates the search process, while Tables 1, 2, 3 and 4 describe the included studies, including the study design, geographic location, and number and type of participants.

Through our staged coding process, we identified a wide variety of themes related to informed decision making, such as pre-test counselling and availability of information, test accuracy, procedural ease, safety of NIPT, and test timing and return of results. These themes are interconnected and we synthesize them by discussing two main elements of informed choice: first, women’s access to information on NIPT, and second, women’s understanding and use of that information. We then outline potential threats to informed choice such as routinization and a pressure to test, and present some of women’s preferences that may help safeguard and facilitate informed choice.

Of those studies that specified their number and type of participants, six included both patients and their partners or family members [26, 29, 32, 58‐60]. We report on women’s access, information, and preferences because these studies amalgamated their findings into participant views, rather than distinguishing the source – patient or family member – of each perspective or experience [26, 29, 32, 60], or they focused predominantly on women’s perspectives [59]. These studies did not report tension between women and their partners or relatives regarding NIPT. One paper included only male partners [61]; their views were consistent with those of women in other studies, but where applicable we have indicated that the given views are shared by both women and their partners.

In order for a woman to make an informed decision around NIPT, she first requires access to high quality, accurate information about the technology. Across the studies included in our review, the majority of women preferred that this information come from their clinicians. However, most were disappointed by the counselling they received, particularly from family physicians, general practitioners, and obstetricians. In order to fill gaps in the information they desired, women sought information from a variety of other sources including the media, discussion groups, forums, and websites. Although many women were satisfied with their understanding of NIPT, several misconceptions still persisted, raising questions as to whether they were adequately informed about the test.

Facilitating informed decisions about NIPT is challenged by issues beyond obtaining high quality information. Given that NIPT is procedurally simple, consisting of a single blood test which may be experientially similar to the other blood tests required in pregnancy, there is a risk that informed choice may be challenged by routinization [76]. Routinization has been raised as a challenge to informed decisions about prenatal tests for decades; it refers to the potential for a prenatal screening test to become a normalized part of the prenatal care pathway, and correspondingly for women’s acceptance of that test to be highly correlated to institutional and provider support, suggesting that individual women are not making autonomous decisions about whether or not to accept the test [77]. Routinizing the offer and uptake of prenatal testing is problematic, since people’s desire for genomic information in the prenatal context has been shown to vary [78]. One study found that pregnant women who used an interactive decision-support guide were better informed of the benefits and risks of various prenatal testing modalities and were less likely to choose diagnostic testing, compared to women who received the standard of care [79]. Another study in which chromosome microarray was used to provide pregnant women with fetal genomic information found that, while women were initially enthusiastic about testing, many who received uncertain test results felt “blindsided,” described the results as “toxic knowledge,” and expressed regret at having undergone testing [80]. This was attributed at least in part to a lack of opportunity to weigh the benefits, risks, and consequences of testing [80]. The potential for routinization of NIPT is high, given its similarity to existing normalized prenatal tests and especially because of the simplicity of the procedure. If NIPT is routinized, women may not be provided with adequate opportunity to decline testing, or may not receive sufficient information to make an informed decision [76, 81], and may ultimately feel disempowered, rather than empowered, by their choice.

The worry around erosion of informed choice is a legitimate one: a previous study in the United Kingdom found that a small minority of clinicians believe the non-invasive, risk-free nature of NIPT means there is a less stringent requirement for informed choice [82]. Notwithstanding routinization, the current quality and quantity of information available raises concerns about informed decision making. We found that although women were satisfied with their understanding of NIPT [24, 25, 27], they demonstrated misunderstanding about certain aspects of the test, especially regarding the accuracy of NIPT [25, 27, 70], which conditions NIPT tests for [27], and the waiting period for return of results [27]. We also found that women were sometimes disappointed with the information their health care providers were able to provide [25, 34]. This is unsurprising given the range of sources from which clinicians learn about NIPT. A survey of 258 American obstetricians found that 36% of respondents first learned about NIPT from peer-reviewed publications, 36% from publications produced by professional organizations, and 28% from commercial laboratories [83]. More than that, 48% used commercial laboratories as their primary source of continued education about NIPT [83]. In some cases, the lack of standardized education on NIPT has led physicians to make errors when discussing it with patients, such as presenting NIPT as a diagnostic test rather than a screening test [84]. A recent study exploring the role of Dutch midwives as counsellors on NIPT found that only 59% were able to correctly answer seven or more questions out of eight standard knowledge questions about NIPT [85].

These discrepancies in clinician knowledge are an issue that needs to be remedied, however, there have been few suggestions for ameliorating this challenge. In a 2017 study, Oxenford and colleagues developed a training resource for health professionals offering NIPT in the United Kingdom, and evaluated the change in participants’ knowledge and confidence after a 40-min training session. [86]. Following the training session, there was a statistically significant increase in the number of participants who said they would feel confident discussing NIPT with patients, as well as a statistically significant increase in both perceived and actual knowledge about NIPT [86]. However, even after the training session, over 65% of participants still had some misconceptions, such as test turnaround time, false positive rates, whether the cell free fetal DNA originates from the placenta, and whether the concentration of fetal DNA in the bloodstream increases as the pregnancy progresses Martin and colleagues [85] also found significant knowledge discrepancies about NIPT among Dutch midwives, although noted that continuing education was positively correlated with an increase in participants’ knowledge about NIPT. It is clear that non-biased education resources in a variety of formats are needed to increase the confidence and comfort of health care providers counselling about NIPT.

In addition to increased education for providers, allocating more time to counselling may improve informed choice. Studies of women and clinicians identified strong consensus that consultations did not provide sufficient time for thorough counselling [30, 48, 87]. Some women found that their counselling session was too short for the volume of information they were presented with, and as a result felt overwhelmed [67]. A study among Dutch midwives has found that an appointment longer than 20 min – in some cases as long as 50 min – is sometimes required to provide adequate counselling [88]. However, the amount of time officially allocated for counselling may not correspond with the amount of time a clinician spends facilitating this discussion. One study in the Netherlands demonstrated that despite having 30 min of time allocated in the fee for counselling about prenatal testing, midwives spent on average 9 min conducting this discussion [85].

Women’s understanding has been shown to improve in a research setting, or a clinical setting with dedicated time and resources for counselling [89]. Outside of these settings, group prenatal counselling by expert clinicians has been suggested as a way to alleviate the barriers of time and provider confidence [90‐92]. In the format proposed by Gammon and colleagues [90], several patients would receive education on prenatal screening and testing options at the same time, followed by a confidential, one-on-one session for individual questions and familial risk assessment. Gammon and colleagues [90] found that receiving counselling in this format increased participants’ acceptance of prenatal testing, their confidence in that decision, and their knowledge of the relevant technologies. This study provides us with an indication that group prenatal or genetic counselling sessions may be a viable option as we consider expanding access to NIPT. We are cautioned by the finding that group counselling increases uptake of prenatal testing, as this may indicate that the information provided or the social interaction of the group might make women feel pressured to test.

A small number of studies have indicated that the ease of access to NIPT, facilitated by the procedural simplicity may make women feel pressured to accept NIPT [93]. Public perception of NIPT as easy and risk-free was one source of pressure [24, 30, 93], but women also felt pressure from their family members and partners [30, 59]. Health care providers may also contribute to this pressure, as some approach NIPT with an attitude of “there is no downside” [94]. An additional worry associated with the procedurally simple, low-risk nature of NIPT, coupled with its high accuracy and early availability, is that it may be used for sex-selective termination [35, 36]. However, it is possible that ensuring women are well-informed about NIPT and other prenatal screening modalities may help to safeguard against such a use of the test. For example, Gammon and colleagues [90] found that participants who received group counselling were less likely to opt for screening for fetal sex.

A long standing concern about prenatal testing, exacerbated by the nature of NIPT is the potential for negative implications for the disabled community, as fewer people are born with conditions such as Down syndrome [39, 93, 95]. This is an enduring challenge that has been well described in the ethics literature [38, 77, 96, 97]. Many ethicists argue that the right of an individual woman to control her body and shape her family through informed autonomous choices takes priority over the more diffuse harm done to society when fewer people with particular conditions are born [98]. In this argument, the importance of informed autonomous choices is paramount. It is important that women have the opportunity to make decisions about reproduction based on their personal preferences, attitudes, and beliefs [72]. These decisions will differ – the availability of NIPT does not necessarily mean that more women will choose to terminate affected pregnancies. Some may decline all testing because they would never consider termination [68, 69]; others may decline NIPT and opt directly for invasive testing [27]; some choose to participate in NIPT in order to feel better prepared for the birth of an affected child [59]. Many mothers of children with Down syndrome would consider using NIPT if they become pregnant in the future, or would recommend NIPT to a pregnant friend [95]. Most (67%) also believe that NIPT should be available to all women [95]. When counselling women about NIPT, it is important that health care professionals provide patients with all of the information necessary to make an informed decision, in a non-biased manner, including the fact that declining prenatal testing is a valid option.

This synthesis of qualitative research builds a robust understanding of women’s preferences and experiences with making informed decisions about NIPT. While qualitative research findings are not intended to generalize directly to populations, the breadth of evidence synthesized here suggests insights which may be relevant to planning services in similar settings. Notably, all studies were conducted in high income jurisdictions, with highly-educated patient populations. Insights should be adapted accordingly when applied in other contexts.

We examined 30 empirical primary qualitative research studies that describe women’s or their partner’s perspectives, experiences, and preferences about NIPT. From this body of evidence, we identified that women access a variety of sources to educate themselves about this technology, and that a women’s unique circumstances modulate the information that they value and require most in the context of making an informed decision. Although women are quite enthusiastic about NIPT, their discussions around ease of testing highlight threats to informed decision making such as routinization and or a pressure to test. Widened availability to trustworthy information about NIPT as well as careful attention to the facilitation of counselling may help safeguard informed decision-making.