Non-invasive prenatal testing (NIPT), using cell-free DNA in maternal plasma, screens for fetal aneuploidies. Its advantages led to rapid global dissemination, but implementation policies vary widely. While many NIPT technologies are based on whole-genome sequencing, it's primarily used for trisomy 21, 18, and 13. Genome-wide (GW) NIPT can detect additional findings (rare autosomal trisomies, structural aberrations, sex chromosomal disorders), but its clinical validity and utility are debated. Commercial NIPT panels screen for specific conditions beyond common trisomies, often criticized for false positives. As NIPT technology advances, its potential scope is expanding to include monogenic disorders, fetal-maternal risk factors, etc., increasing complexity. In the Netherlands, NIPT is offered as a first-tier test within the national screening program (TRIDENT-2 study), allowing women to choose between targeted and GW-NIPT. This study investigates women's experiences with this choice, considering the expanding possibilities of NIPT and its implications for decision-making.

Existing literature highlights the varying perspectives on the expansion of NIPT. Some advocate for offering expanded NIPT to provide comprehensive information, while others express concerns about the clinical validity and potential psychological impact of additional findings, particularly those with uncertain clinical significance. Studies have shown that pregnant women often prioritize obtaining more information, even if the accuracy is lower, compared to healthcare professionals. This creates a challenge in providing informed choice and managing patient expectations around the limitations and uncertainties associated with GW-NIPT. The use of commercial NIPT panels screening for numerous conditions has sparked debate, due to the potential for increased false-positive rates and added anxiety. There's a need to balance the desire for comprehensive information with the risk of creating undue worry and challenging the counseling process. The study aims to fill the gap in understanding the experiences of women offered first-tier GW-NIPT within a national screening program.

A nationwide pre- and post-test questionnaire was administered to 423 pregnant women participating in the Dutch TRIDENT-2 study. Women chose between targeted NIPT and GW-NIPT. The questionnaire assessed satisfaction, reasons for choosing either option, anxiety levels (using the Spielberger State-Trait Anxiety Inventory (STAI) and the Pregnancy-Related Anxiety Questionnaire Revised (PRAQ-R)), and opinions on the future scope of NIPT. Descriptive analyses, t-tests, Wilcoxon paired ranks tests, Mann-Whitney U tests, and logistic regression were used to analyze the data. Inductive content analysis was employed to analyze open-ended responses regarding reasons for choosing GW-NIPT or targeted NIPT. Anxiety scores were dichotomized into normal and high anxiety levels. Women who chose Fetal Aneuploidy Screening were excluded (n = 135), leaving a final sample of 474 women.

Most respondents (90.4%) were glad to have been offered the choice between GW-NIPT and targeted NIPT. A substantial majority (76.5%) chose GW-NIPT. The primary reasons for choosing GW-NIPT were 'wanting as much information as possible regarding the child’s health' (36.8%) and 'to be prepared for everything' (23.8%). Conversely, the main reasons for choosing targeted NIPT were 'uncertain results/outcomes' (33.7%) and 'not wanting to unnecessarily worry' (32.6%). Nearly all (98.7%) respondents received a low-risk NIPT result. There were no significant differences in anxiety levels between women who chose GW-NIPT and those who chose targeted NIPT, both pre- and post-test. A small number of participants (1.7%) had high post-test anxiety scores. Following a high-risk result, anxiety levels significantly increased. Most respondents (across both GW-NIPT and targeted NIPT choices) favored a broader future scope of prenatal screening, including screening for a range of conditions, such as life-threatening disorders, mental disabilities, treatable disorders, and severe physical disabilities. Women choosing GW-NIPT expressed slightly higher agreement for a broader screening scope.

The study findings indicate a strong preference among pregnant women for comprehensive information regarding their child's health, even if it involves facing uncertainty. This aligns with previous research showing a willingness to accept less accurate tests to gain more information. The desire to be well-prepared for any potential outcome appears as a significant driver for choosing GW-NIPT. The choice against GW-NIPT is more driven by the avoidance of uncertain results and unnecessary worry. The lack of difference in anxiety levels between groups suggests that the decision itself doesn't necessarily increase anxiety. The high level of satisfaction with the availability of choice underscores the importance of offering women options tailored to their individual preferences and risk tolerance. The widespread support for expanding the scope of prenatal screening demonstrates the potential for future advancements in the field, provided that robust counselling and management of potential psychological impacts are in place.

This study highlights the importance of offering women a choice between targeted and GW-NIPT. The preference for comprehensive information and the desire for preparedness were key drivers for GW-NIPT selection. Most women favored expanding the scope of future prenatal screening. These findings can inform the development of governmental and professional guidelines, enhance pre-test counseling, and promote informed decision-making in prenatal care. Future research should explore the long-term psychological impact of GW-NIPT, particularly among women receiving high-risk results, and assess the effectiveness of different counseling models to manage information overload and promote equitable access to care.

The study sample was primarily composed of highly educated Dutch women, limiting the generalizability of the findings. The questionnaire was only available in Dutch. The study mainly included women who received low-risk NIPT results, which could affect the overall conclusions. A focus on women with high-risk results is needed for a complete understanding of the impact of GW-NIPT. The specific wording and examples used in the questionnaire regarding the future scope of NIPT may have influenced responses. Qualitative research could provide a more in-depth exploration of women’s perspectives.