Enabling real-world evidence for medication safety in pregnancy: Determinants of research participation and linked EHR data use

OBJECTIVE: Real-world evidence for medication safety in pregnancy increasingly relies on linked electronic health record (EHR) data. However, the success of such systems depends on pregnant women's willingness to participate in research and to permit secondary use of their clinical data. We synthesised evidence on determinants shaping research participation and acceptability of linked EHR data use in pregnancy. METHODS: We conducted a mixed-methods systematic review in accordance with PRISMA 2020 and ENTREQ guidelines. MEDLINE, PubMed, CINAHL, and Google Scholar were searched (January 2008-August 2025). Eligible studies examined perspectives of pregnant women, women with children, healthcare professionals, researchers, or the public regarding research participation or EHR data sharing. Thematic synthesis was undertaken, and methodological quality was assessed using CASP checklists. RESULTS: Sixty-one studies (44,722 participants; 22 countries) were included. Participation and EHR data-sharing decisions reflected a balance between perceived benefit and perceived burden, mediated by trust and transparency, governance, regulatory, and health system structures, and infant-centred considerations. Facilitators included perceived maternal or societal benefit, altruistic motivation, trust and transparency, collaborative decision making, quality patient-provider communication, governance transparency, and electronic health literacy. Barriers included recruitment logistics, privacy and confidentiality concerns, biological specimen collection, culture and socioeconomic factors. Willingness to share EHR data varied widely (22-100%), with governance safeguards, trust in institutions and participant control strongly influencing acceptability. CONCLUSION: Acceptability of linked EHR use in pregnancy is shaped by socio-technical factors extending beyond technical safeguards. Real-world evidence initiatives aiming to strengthen medication safety should incorporate transparent governance, proportionate consent models, clinician-mediated engagement, and burden-reducing study designs to support equitable inclusion in learning health systems.