‘Small cost to pay for peace of mind’: Women's experiences with non‐invasive prenatal testing

Background Non‐invasive prenatal testing (NIPT) has been available in Australia on a user‐pays basis since 2012. Since its introduction, it has grown in popularity as a screening method for fetal aneuploidy and may become publicly funded. Aims To assess the motivations and experiences of women who have undergone NIPT in a user‐pays system in Australia. Materials and methods One thousand women who had undergone NIPT through the Victorian Clinical Genetics Services in Melbourne, Australia were contacted and asked to complete a mixed‐methods survey. The number of eligible responses received was 235. Quantitative data analysis was performed in STATA IC 15.1, and qualitative data were examined using content analysis. Results Women reported generally positive experiences with NIPT and 95% of respondents indicated they would undergo NIPT in a future pregnancy. Most respondents received a low‐risk result, with 2.2% receiving a high‐risk result. Respondents viewed NIPT favourably compared to invasive testing and cited reassurance as a key reason they sought it. However, a small minority of women reported negative experiences with the testing process. Women were also supportive of NIPT becoming publicly funded, with 93% of respondents indicating support. Pre‐ and post‐test counselling were identified as possible areas for improvement to ensure informed consent. Conclusion In support of the existing literature, these results indicate that Australian women generally report positive experiences with NIPT. As NIPT becomes more common, with possible integration into public healthcare, further qualitative research would be valuable to examine the motivations and experiences of women undergoing NIPT.


INTRODUCTION
Prenatal tests commonly screen for chromosomal conditions such as trisomy 21 (Down syndrome). In Victoria, yearly uptake for the most common publicly funded screening method, combined first trimester screening (CFTS), is consistently more than 80% of pregnancies. 1 A newer screening method is non-invasive prenatal testing (NIPT). NIPT is based on cell-free fetal DNA (cffDNA) in the maternal bloodstream. A blood sample is taken from the mother, and cffDNA is analysed to produce a probability of the fetus having a chromosomal condition. 2 However, NIPT is not diagnostic for the trisomy disorders 2 and any high-risk result should be confirmed with invasive diagnostic testing, such as amniocentesis.
Non-invasive prenatal testing has many benefits over CFTS.
NIPT is more accurate, with a very high sensitivity and specificity for trisomy 21 (>99%). 2 NIPT outperforms CFTS in both low-and high-risk populations. 3 NIPT can also be performed earlier in the pregnancy, usually from 10 weeks gestation. 4 Non-invasive prenatal testing became available on a user-pays basis to Victorian women in 2012, and this was associated with a 22.9% reduction in invasive testing, 5 due to the much lower falsepositive rate of NIPT compared to CFTS. 1 Availability of NIPT has had similar impacts on number of referrals for diagnostic tests in other healthcare systems. 6 Non-invasive prenatal testing in Australia currently costs approximately AUD$450. 7 Although this is less expensive than many other countries, cost remains the major barrier to widespread uptake. 8 NIPT is being implemented in other public healthcare systems such as the NHS in the United Kingdom. 9 Critical questions remain for possible implementation of NIPT in Australian public healthcare, such as the criteria for access to screening. 10 Women have reported positive experiences with NIPT, emphasising accuracy, ease and safety. 11,12 These aspects of NIPT have also emerged as important motivators for women to use it; other reasons include seeking reassurance and how early in the pregnancy NIPT can be done. 13 Concerns have been raised about the impact that routinisation of NIPT may have on informed choice; however, previous research has found high levels of informed choice among women who have undergone NIPT. 14,15 There is limited literature assessing experiences with NIPT in the Australian context. 16,17 In this study, we aimed to examine the experiences and motivations of women who had undergone NIPT through the Victorian Clinical Genetics Services (VCGS) in Victoria, Australia.

MATERIALS AND METHODS
One thousand women who had undergone the percept™ NIPT through VCGS were selected using systematic sampling (every fifth name from a selected point) from a list of 14 680 referrals in 2016. They were contacted by post in two rounds of 500 (October 2017 and February 2018) and asked to complete a survey, either online in REDCap or through hard copy. Those under the age of 18 were excluded. Respondents were advised that by commencing the survey they were consenting to use of their response data.

RESULTS
The number of women who responded to the survey was 237. Two were excluded as they did not specify age, and therefore were ineligible to participate. Demographic features are seen in Table 1.

Reasons for undergoing NIPT
Many respondents (n = 200, 85.8%) indicated that detecting chromosomal abnormalities was a reason they underwent NIPT ( Fig. 1). A minority of 31.3% (n = 73) wanted to determine fetal sex ( Fig. 1). Advice from a medical professional was also a prevalent response, with 38.2% (n = 89) indicating this was a reason for undergoing testing (Fig. 1).
Seeking reassurance and 'peace of mind' emerged as important motivators for undergoing NIPT, with 56% (n = 131) of respondents selecting it (Fig. 1 Twenty-three percent of women (n = 54) were motivated to undergo NIPT to avoid invasive testing (Fig. 1

Attitudes toward funding
Respondents were favourable toward NIPT being integrated into public healthcare (Fig. 3). Respondents indicated an interest in ensuring public funding was directed to where it was perceived as 'necessary', excluding non-medical traits.
More important that the testing is available and government subsidised than to have an expensive fancy test that provides results that really are inconsequential.

Test results
The majority of women received a low-risk result (97.8%, n = 227).
Three women (1.3%) received a high-risk result for a trisomy disorder, one woman (0.4%) received a high-risk result for a sex chromosome aneuploidy (false positive), and one woman (0.4%) indicated a highrisk result of 'other'. Therefore, the proportion of women who received any high-risk result was 2.2%, comparable to the overall number of high-risk results from the percept test (2.1%, internal VCGS data).
The three women who received a high-risk result for a trisomy disorder confirmed the diagnosis with invasive testing, and all three opted for termination of pregnancy.

Experience with the NIPT process
Women's experiences with NIPT were generally positive ( Table 2).
Most respondents (n = 218, 94%) felt they were provided with adequate information on the nature of the test and possible results.
Most respondents (n = 219, 95%) also indicated they would probably or definitely undergo NIPT again.  The respondents in our study were generally highly educated, wealthy and in a stable relationship (see Table 1), indicating high socioeconomic status. This is consistent with a previous study that showed women receiving NIPT-indicated diagnoses in Victoria are more advantaged than those receiving diagnoses from other methods such as CFTS. 19 This is unsurprising considering NIPT's cost. These results suggest NIPT is less accessible to women of low socioeconomic status, which would change if the test becomes publicly funded.
The most common primary treating professional was a private obstetrician (69%, Fig. 2

). A 2015 study of Australian and New
Zealand medical professionals found there was no significant difference between those working in public and private care offering NIPT to high-risk women, with cost remaining the main access barrier. 16 It is plausible private professionals may offer NIPT more frequently to low-risk women (a category covering most respondents) than public healthcare professionals. However, it is equally possible low-risk women most likely to be interested in NIPT seek out private care. Further research into the understanding of health professionals about NIPT and screening options may shed further light on these results.
The mean gestational age at blood draw for the VCGS cohort capturing the respondents in this sample was 11.0 ± 1.9 weeks, with approximately 80% of the total cohort using NIPT as their primary screening test. 20 Approximately half the respondents were under the age of 35 at the time of completing the survey.
Therefore, demand from a low-to average-risk population appears to be high. In addition to the VCGS data, an audit of Australian women who had undergone NIPT up until the end of 2013 found that 21% had no specific risk factor indicating need for a referral (eg advanced age or high-risk CFTS result). 21 A 2016 study of 5267 Australian women found nearly two-thirds had used NIPT as a first-line screen, usually under 11 weeks gestation. 22 Analysis of over 900 000 worldwide Harmony NIPT tests (Ariosa Diagnostics, San Jose, CA, USA) suggest the demand from the low-risk population for NIPT is increasing, 23 which is supported by our results.
Most respondents were not supportive of the current userpays system and would prefer some form of government funding. NIPT is becoming integrated into several public healthcare systems, such as the NHS. 24 It is possible that NIPT will become subsidised through the Australian Medicare system, with applications having been made. 25 Our results suggest women who have  The findings of this study suggest that overall, women have positive experiences with NIPT and support implementation into the Australian public healthcare system. Additional development of pre-and post-test counselling was identified as an area of importance to ensure informed consent. The data from this study support further in-depth qualitative research into the motivations and experiences of women who have undergone NIPT, particularly important as it becomes more common as a prenatal screening option.