Experiences of pregnant women with genome-wide non-invasive prenatal testing in a national screening program

Non-invasive prenatal testing (NIPT) has rapidly disseminated due to high sensitivity and low false-positive rates for common aneuploidies. Although many platforms are whole-genome based, clinical use often targets trisomies 21, 18, and 13. Genome-wide (GW) NIPT can also report additional findings (e.g., rare autosomal trisomies, structural aberrations, sex chromosome anomalies), but professional consensus on its routine use is limited due to uncertainties regarding clinical validity and utility. Commercial panels vary and have raised concerns about accuracy (e.g., microdeletions). Technological advances may soon broaden NIPT’s scope to include monogenic disorders and maternal-fetal risk factors, increasing decision-making complexity. In the Netherlands, as part of TRIDENT-2, NIPT is offered as a first-tier test with a choice between targeted and GW analysis. The study’s aim was to evaluate pregnant women’s experiences with the offer of first-tier GW-NIPT in this national screening program, focusing on satisfaction, choices and reasons, anxiety, and views on the future scope of screening.

Design and setting: Nationwide prospective survey within the Dutch TRIDENT-2 first-tier prenatal screening program. Participants choosing NIPT could select either targeted NIPT (trisomies 21, 18, 13) or genome-wide (GW) NIPT (reporting additional findings such as structural aberrations and rare autosomal trisomies). Data were collected via two questionnaires: pre-test (Q1) and post-test (Q2) after receiving NIPT results. Participants: Initial invitations were sent to pregnant women opting for first-tier NIPT. After exclusions (e.g., women who chose fetal aneuploidy screening other than NIPT), the final analytic sample comprised 474 pregnant women who completed both Q1 and Q2 and had NIPT. At Q1, mean maternal age was 32.2 years (SD 3.9); most were highly educated and of Dutch origin. Measures: - Choice and reasons: Participants indicated their chosen analysis (GW-NIPT or targeted NIPT). Reasons for or against GW-NIPT were captured via open-ended responses, allowing multiple reasons per participant. - Anxiety: Measured at Q1 and Q2 with the 6-item short-form Spielberger State-Trait Anxiety Inventory (STAI). Items scored 1–4; total multiplied by 20/6 to yield 20–80; dichotomized into normal (<43) vs high (≥43). Cronbach’s alpha = 0.84. - Pregnancy-related anxiety: 4-item PRAQ-R subscale on worries about bearing a physically or mentally handicapped child, scored 1–5; total 4–20. As no validated cut-offs exist, the fourth percentile (score ≥13) was used to denote elevated pregnancy-related anxiety. Cronbach’s alpha = 0.86. - Satisfaction and decision evaluation: Post-test items assessed satisfaction with having been offered NIPT and the choice between targeted vs GW-NIPT, perceived difficulty of choosing, reassurance after results, and regret. - Future scope of screening: Agreement with offering first-tier screening for categories of conditions (e.g., severe untreatable life-threatening disorders, disorders with mental disability, treatable conditions during pregnancy, severe physical disabilities), stratified by choice of GW vs targeted NIPT. Analysis: Descriptive statistics summarized participant characteristics and outcomes. Group differences were tested with t-tests; Wilcoxon signed-rank tests compared pre- vs post-test STAI and PRAQ-R scores. Mann–Whitney U tests compared anxiety between GW vs targeted NIPT choosers. Logistic regression examined predictors of choosing GW vs targeted NIPT. Open-text reasons were analyzed with inductive content analysis by one researcher and checked by another. Significance threshold p < 0.05. Analyses conducted in IBM SPSS Statistics 26. Respondents who mismatched Q1/Q2 samples (n=16) or completed Q2 after birth (n=2) were excluded from anxiety analyses. Anxiety outcomes were stratified by low-risk vs high-risk NIPT result.

- Sample and choices: Of 474 women completing both surveys and NIPT, 76.5% chose GW-NIPT; approximately 21–22% chose targeted NIPT. Nearly all (98.7%) received a low-risk result; six received a high-risk result (3 trisomy 21, 1 trisomy 18, 2 structural aberrations reported through GW-NIPT). - Reasons for choices: • For GW-NIPT (376 reasons from 336 women): most frequent were wanting as much information as possible about the child’s health (38.6%), being prepared for everything (23.8%), making optimal use of the test’s abilities (13.9%), reassurance (7.1%), ability to make informed reproductive decisions (6.3%), general interest (5.7%), receiving information about maternal health (4.8%), gaining certainty (3.6%), intuitive right decision (3.3%), and family history/risk factors (2.4%). • Against GW-NIPT (108 reasons from 86 women): avoiding uncertain results/outcomes (33.7%), not wanting to unnecessarily worry (32.6%), not wanting/needing this information (12.8%), concerns about reliability (11.6%), only wanting information on trisomies 21, 18, 13 (10.5%), belief that it’s impossible to know everything (9.3%), other reasons (7.0%), not wanting to know about mild conditions (5.8%), would not terminate for additional findings (2.3%). - Anxiety outcomes: • Low-risk result subgroup: STAI decreased from mean 32.7 (SD 9.6) pre-test to 28.2 (SD 8.0) post-test (p < 0.001). PRAQ-R decreased from 9.2 (SD 3.1) to 8.2 (SD 2.9) (p < 0.001). No significant differences in pre-/post-test anxiety between women choosing GW vs targeted NIPT. • High-risk result subgroup (n=6): Mean STAI increased from 35.6 (SD 12.1) pre-test to 57.3 (SD 22.0) post-test; PRAQ-R increased from 8.5 (SD 2.9) to 14.8 (SD 6.3). - Satisfaction and decision evaluation: 99.2% were glad to have been offered NIPT; 99.6% would make the same choice in retrospect. 90.4% appreciated having a choice between targeted and GW-NIPT. Among GW choosers, 3.3% would have preferred not having the choice option versus 31.6% among targeted choosers (p < 0.001). Choosing between targeted and GW was (somewhat) difficult for 18.2% of GW choosers versus 40.2% of targeted choosers (p < 0.001). After a low-risk result, 95.4% felt reassured and 96.8% did not regret testing; among high-risk results, 1/6 (16.7%) reported regret. Nearly all GW choosers (98.9%) were glad NIPT could detect findings beyond trisomies 21, 18, 13, compared with 39.4% of targeted choosers. - Future scope of screening: High levels of agreement for offering first-tier screening for severe untreatable life-threatening disorders (about 93.0% GW vs 91.2% targeted), disorders characterized by mental disability (about 90.5% vs 81.4%), disorders treatable during pregnancy (about 88.2% vs 78.4%), and severe physical disabilities (about 86.1% vs 76.5%). Support was generally higher among GW choosers but substantial in both groups.

Offering first-tier GW-NIPT alongside targeted NIPT was well-received, with most women valuing the option to choose. The preference for GW-NIPT was driven by a desire for more comprehensive information and preparation for potential outcomes, aligning with prior evidence that pregnant women often prioritize information breadth even at the expense of test simplicity. Those choosing targeted NIPT typically aimed to avoid uncertainty and potential worry, reflecting current uncertainties around the clinical validity and utility of additional GW findings rather than a lack of interest in fetal health information. Anxiety significantly decreased after low-risk results regardless of test scope, suggesting that expanding scope did not increase anxiety overall. High-risk results were associated with increased anxiety, highlighting the need for robust post-test counseling and support. Women broadly supported expanding the scope of prenatal screening to severe and, where possible, treatable conditions, though expansion increases counseling complexity and the risk of information overload. Ensuring high-quality, value-based counseling to support informed choices is critical as NIPT’s scope broadens and as policies consider equity, access, and the child’s future interests when contemplating inclusion of late-onset or less actionable findings.

Most women undergoing first-tier NIPT appreciated having a choice between GW and targeted analyses and favored a broader future scope of prenatal screening, irrespective of their own test choice. Findings support offering choice within national programs, coupled with high-quality counseling to facilitate informed decision-making. Results can inform policy, professional guidelines on GW-NIPT, and patient information materials. Future research should evaluate counseling models that balance information breadth with value-based decision support and further examine psychological impacts, particularly following high-risk GW findings.

The sample was predominantly highly educated Dutch women, and questionnaires were only available in Dutch, which limits generalizability. Most participants received low-risk results, potentially influencing satisfaction and anxiety outcomes. Respondents’ understanding of condition categories for future screening may have varied; examples provided for some categories could have shaped responses. The study relied on self-reported reasons and perceptions, and there were few high-risk results, limiting inferences about psychological impact following high-risk GW findings. Ongoing TRIDENT-2 research will address impacts of high-risk additional findings; qualitative studies are needed for deeper exploration of women’s perspectives on scope.