Objective: Cell-free DNA (cfDNA) screening test has been reimbursed in France since 2019 as part of the national trisomy 21 (T21) screening program. The expansion of cfDNA sequencing in September 2024 to include additional chromosomal anomalies raises new challenges for information delivery and informed consent. This study aimed to assess pregnant women’s understanding of trisomy 21 prenatal screening information, distinct from satisfaction with or access to information, in light of these developments.

Study design: A cross-sectional online survey was conducted in August–September 2024 among women aged ≥18 years who had experienced at least one pregnancy since January 2019. Participants were recruited via Instagram and targeted mailing. The questionnaire assessed participants perceptions of the clarity, completeness, and sufficiency of T21 screening information, and included five open-ended questions to assess objective understanding. A comprehension score (0–10) was calculated using semantic analysis (BERT model) and predefined criteria. Associations between comprehension and sociodemographic factors were examined.

Results: Among 2,146 respondents, 94.5% received information from a healthcare professional. Within this group, 35.6% sought additional sources. Only 43.8% judged the information as very clear, and less than 30% considered it sufficient or complete. The median comprehension score was 2.6 out of10. Misconceptions were common, notably the confusion between screening and diagnosis. Higher comprehension was significantly associated with full-time employment (p = .001), higher education level (p < .001), and multiparity (p = .003).

Conclusion: Although most women received information from a healthcare professional, both their perceived and actual comprehension of trisomy 21 screening, especially regarding cfDNA screening test, remained limited. These findings highlight the need for improved communication tools and tailored support to ensure informed decision-making across diverse populations.