The value of non-invasive prenatal testing: preferences of Canadian pregnant women, their partners, and health professionals regarding NIPT use and access

Non-Invasive Prenatal Testing (NIPT)¹ is an emerging technology aiming to detect fetal aneuploidies such as trisomies 21, 18 and 13 through the analysis of cell-free DNA (cfDNA) originating from the placenta and present in maternal blood. Performed as early as 9 weeks of pregnancy, NIPT holds no risk of miscarriage and offers clinical benefits over existing prenatal screening tests, such as maternal serum screening (MSS), by detecting the presence of trisomy 21 (Down syndrome, DS) with high sensitivity (99.9%) and specificity (98%) [1].

NIPT was first offered in 2011 and in the early days it was thought to have the potential to rapidly become a diagnostic test that would replace invasive testing methods posing risk to the fetus. Over time, professional societies recommended it as a second-tier screening test for women already identified as having a high-risk of trisomy based on traditional screening tests [2]. More recently, some have concluded, based on emerging data, that the technology is ready for implementation as a first-tier screening test for all pregnant women [3, 4]. The current mainstream use of NIPT in Canada remains as a second-tier screening test offered to women who have undergone first-tier traditional screening and have been identified as having a high risk of trisomy.

In 2011, the Society of Obstetricians and Gynecologists of Canada (SOGC) recommended that any prenatal screening test offered to Canadian women should have, at minimum, a detection rate of 75.0% with no more than a 3.0% false-positive rate in the first trimester and a detection rate of 75.0% with no more than a 5.0% false-positive rate in the second trimester [5]. Each province/territory devised their own screening program, so the specific screening test used varies across Canada.

In 2013, the Genetics Committee of the SOGC recommended that NIPT be offered to pregnant women who have been identified as being at increased risk of fetal aneuploidies, through the screening available in their province/territory, i.e. as a second-tier screening test [6]. In 2014, the International Society for Prenatal Diagnosis (ISPD) considered the offer of NIPT as a first-tier screening test for all pregnant women to be an “appropriate” option [7]. However, concerns regarding sensitivity, specificity and positive predictive value remain [8]. Moreover, the cost of NIPT in 2018 in Canada - C$300 to C$500 – can create a barrier to access for many prospective parents, which in turn, raises issues of equity of access and justice. Such issues may be mitigated by ensuring NIPT is publicly funded. Currently, in Canada, only the provinces of Ontario and British Columbia and the territory of Yukon [9] have decided to reimburse the test under certain conditions, i.e., only for pregnant women at high risk of fetal aneuploidies, and at the time of the study, only Ontario was reimbursing the test [10]. In the other provinces, patients need to pay for the test out of pocket or through private insurance.

The cost-effectiveness analysis of NIPT and its introduction into the public healthcare system have been subject to studies in several countries such as Italy [11], Australia [12], Sweden [13], United States [14] and Canada [15]. However, little is known about the preferences of different Canadian publics regarding NIPT implementation and coverage. Results presented here come from the first large-scale study of Canadian pregnant women, their partners and health professionals regarding their perceptions of and attitudes towards NIPT. This study was part of a pan-Canadian research project titled “Personalized Genomics for prenatal Aneuploidy Screening Using maternal blood” (or PEGASUS), aiming to “validate the performance and utility of [NIPT] for screening for major fetal chromosome imbalances”. This paper focuses specifically on the preferences of pregnant women, their partners, and health professionals regarding the implementation and coverage of NIPT by the public healthcare system.

The study consisted of three surveys aimed at three populations: pregnant women, their partners, and health professionals. It ran during a 16-month period, from March 2015 to July 2016. Recruitment occurred at 5 Canadian sites in Alberta, BC, Ontario and Québec, where the PEGASUS study ran, as well as one additional site in Newfoundland & Labrador.

All pregnant women and their partners attending a routine appointment regarding their current pregnancy at one of these sites during that period were eligible to participate. Aside from being currently pregnant, there were no other explicit inclusion criteria. No incentive for participating was provided (aside from the general incentive of furthering knowledge inherent in any study). Respondents were provided with a paper copy of the questionnaire, which included a URL for an online version. Health professionals were recruited at conferences, at the 6 sites participating in the study, and via mailing lists of 10 Canadian professional societies.

The present study, to the best of our knowledge, is the first large-scale survey on NIPT that takes into consideration the attitudes of pregnant women, their partners as well as healthcare professionals. It offers evidence of some main stakeholders’ opinions regarding how the test should be used and whether it should be covered by public insurance. While policy decisions regarding the implementation of NIPT (e.g. as second versus first tier screening test) should be based on scientific evidence regarding its performance in various populations (e.g. high versus low risk pregnancies), it is also important to consider the attitudes and preferences of stakeholders regarding the various uses of this technology, as these reflect values underlying its use.

This study is particularly timely given the rapid evolution of the performance of the test and given that the political debate on the topic in Canada is gearing up. Two provinces and a territory have so far decided to offer public coverage of NIPT to women with pregnancies considered at high risk and discussions are ongoing in others. At the time that the survey ran, Ontario was the only province covering NIPT for women with high risk pregnancies. Thus, comparing attitudes in Ontario with the other provinces may be informative of how views regarding a medical technology are affected by shifting barriers to access.

A significant result of this study is the notable difference between the way in which pregnant women and couples prefer to see NIPT funded and the way healthcare professionals do. Namely, a majority of healthcare professionals thought that only high-risk pregnancies should be eligible for funding, while the majority of pregnant women and partners thought that all pregnancies should be eligible. It is important to remember that both women and partners, and healthcare professionals, received the same information regarding the performance and the limitations of NIPT (see Fig. 1 = informational sheet).

Furthermore, women and partners thought that their decision to test would be highly impacted by NIPT being accessible free of charge. Simultaneously, when asked whether they are concerned that NIPT being covered as part of routine prenatal care could lead to increased pressure on women to use it, the majority of pregnant women reported ‘no concern’ whatsoever and only a very small percentage (1.8%) reported being ‘very concerned’. These results may mean that the impact of public funding for NIPT on women’s decision-making would be rather autonomy-enhancing.

Nevertheless, it is important to consider the minority of Canadian women and couples who prefer not to screen for DS, and the concern that routinization of NIPT (i.e. the test being covered and offered routinely) may exacerbate current pressures to screen and/or terminate following a diagnosis, thereby restricting their reproductive autonomy [24‐26]. Pregnant women from Ontario, the only province covering NIPT for high-risk pregnancies at the time of the study, were willing to pay significantly less than women from all other provinces. This was the only question where attitudes held by pregnant women in Ontario differed from the rest of Canada.

Healthcare professionals thought financial cost is an important barrier to accessing NIPT in Canada, and while they were more concerned than pregnant women about the potential for NIPT routinization to pressure women into screening, they were still largely unconcerned. Even so, although the groups seem to largely agree regarding how cost affects patients’ decision-making, healthcare professionals did not see the issue of barrier to access as justifying coverage of NIPT for all Canadian women. This may be due to healthcare professionals being more sensitive to issues of justice and prioritization, and their awareness that publicly funding a certain intervention means foregoing another. Or, it may be due to the fact that healthcare professionals have a deeper and more nuanced understanding of the limitations of NIPT as an emerging technology and its reliability as depending on the population in which it is performed (high versus low risk pregnancies). Given that views on public coverage are divided, it seems imperative to ensure transparency in how all available evidence regarding stakeholders’ preferences is taken into account in policy-making.

Another notable difference in the preferences of healthcare professionals and pregnant women and their partners related to how NIPT should be used. At the time of the survey, recommended practice was to offer NIPT as second-tier screening, i.e. to pregnant women at high risk for trisomy, and confirming any positive NIPT result with a diagnostic test. Half of surveyed healthcare professionals’ preferences were aligned with these professional guidelines, but a sizeable minority believed that NIPT ought to replace MSS as a first-tier screening technology. However, couples were unequivocally more interested in a broader use of NIPT than health professionals or than current policies recommend. While the performance of NIPT in low risk pregnancies has been the focus of much scientific debate [27, 28], the strong preference of women and partners for its use as a first-tier screen means that it may be of great value to them even at a time that its reliability in this population is still debated, so long as women are fully and clearly informed regarding the limitations of the test and the exact meaning of its results in their case.

It was surprising that 2.2% of healthcare professionals surveyed thought NIPT’s current performance justifies using it as a diagnostic test to replace amniocentesis, considering that some women may choose to terminate a pregnancy based on a positive result. Health professionals’ most preferred testing pathway, i.e. adding NIPT as a second-tier test, has been criticized as unnecessarily medicalizing pregnancy, although some have argued that the additional anxiety induced by adding another test may be alleviated by “the woman’s knowledge that she had followed a testing pathway designed to minimize risk to the pregnancy” [29]. To alleviate some of the additional anxiety, the ethically controversial solution of ‘reflex testing’ has been proposed [30], where two blood samples are taken during conventional serum screening, and if the first-tier screening result is “high risk”, the second blood sample is sent for NIPT in order to inform the woman of the result only once more reliable NIPT results are available. However, if this process is not reliably explained beforehand, this could result in decreased autonomy in reproductive decision-making in at least some cases, due to women receiving their NIPT results without appropriate consent [30].

Nearly 4/5 of the pregnant women, on the other hand, reported preferring replacing current screening with NIPT (NIPT as first-tier test), citing increased accuracy and earlier availability of results as the main reasons. Moreover, over 2/3 of pregnant women preferred NIPT to amniocentesis as a diagnostic test after current screening, disregarding the possibility of false positives and negatives, stating that avoiding the risk of miscarriage associated with amniocentesis is prospective parents’ most important consideration, corroborating the literature indicating the importance of avoiding risk to the fetus in women’s decision-making regarding their prenatal care [31‐33].

Interestingly, reporting having been informed about NIPT by a genetic counsellor correlated with more frequent preference on the part of pregnant women for amniocentesis, a preference more aligned with current recommendations. Further research is warranted into possible causality behind this correlation. In particular, reporting having been informed by a genetic counsellor in this study also correlated with other demographic variables (namely having a child with DS, having a child with a disability, being low or high-risk for the current pregnancy, and having had a prenatal diagnosis in the past (p < 0.001); and to lesser extents, the age of the respondent, their province of residence, the way the current pregnancy was conceived, and having undergone prenatal screening in the past, as well as the kind of result of the said screen (p < 0.05)). However, could genetic counsellors be more cautious regarding the use of NIPT over current diagnostic tests due to their possibly more nuanced understanding of its limits? Could communicating with a genetic counsellor thus enhance reproductive autonomy? Depending on what future research concludes, important policy decisions might have to be made in Canada in relation to the fact that only 7.9% of the pregnant women in this survey were informed about current screening, NIPT or amniocentesis by genetic counsellors.

While 52.9% of pregnant women reported being interested in knowing whether their fetus has DS in order to “consider terminating the pregnancy if the baby was diagnosed with DS”, that leaves a sizable portion of the population testing for other reasons, medical or not [34]. Only 2.3% claim they do not want to know at all. As remarked by Nowotny, “worrying about risks is another way of coping with uncertainty. Unable to face the complexity that surrounds them, people take refuge in what is familiar. These are the risks they know. Worrying about them provides some comfort” [35]. It thus makes sense that so few people preferred amniocentesis. Why risk miscarriage if they might want to know “for knowing’s sake” only? In this context, NIPT can provide a measure of psychological tranquility, even if the result is positive.

Even though the respondents were chosen from a population that can most easily imagine themselves faced with the choices this study examines, i.e., pregnant women, their partners and health professionals dealing with pregnant women, it bears noting that stated hypothetical preferences do not always accurately predict what decisions the respondents would actually make in real-life situations. Our response rate is 47.1%, which is not that different from other similar studies [36]. It is possible that participants self-selected based on specific preferences that are not necessarily representative of the pregnant population in Canada as a whole. The choice of p < 0.001 as a threshold of statistical significance could have led to overlooking potentially valuable insights; however, in the interest of not overstating the findings, this more conservative choice was made by the research team. Additionally, although the aggregated results presented herein may be interpreted as if there is a monolithic group of Canadian pregnant women, it is important to note that Canadian pregnant women’s decision-making regarding NIPT can be differently affected by relevant policies and contexts that vary between regions.

The key contributions of this study are three-fold. First, it reveals Canadian stakeholders’ preferences regarding public coverage of NIPT and their expected repercussions of universal coverage on women’s decision regarding testing, and draws attention to evidence of shifting attitudes towards coverage as policy evolves. Second, it reveals the contrasting testing preferences of expecting parents and health professionals. Third, it examines the factors that could potentially influence Canadians’ preferences.