Objective: To determine associations of calcium-based antacid and PPI use during pregnancy with late-onset preeclampsia (≥34 weeks of gestation), taking into account dosage and timing of use. Design: Prospective cohort study. Setting: This study used data from the PRIDE Study (2012-2019) and Dutch Pregnancy Drug Register (2014-2019). Sample: A total of 9,058 pregnant Dutch women aged ≥18 years. Methods: Data were collected through web-based questionnaires and obstetric records. We estimated risk ratios (RRs) for late-onset preeclampsia for any use and trajectories of calcium-based antacid and PPI use before gestational day 238, and hazard ratios for time-varying exposures after gestational day 237. Main outcome measure: Late-onset preeclampsia. Results: Late-onset preeclampsia was diagnosed in 2.6% of pregnancies. Any use of calcium-based antacids (RR 1.2 [95% CI 0.9-1.6]) or PPIs (RR 1.4 [95% CI 0.8-2.4]) before gestational day 238 was not associated with late-onset preeclampsia. Use of low-dose calcium-based antacids in gestational weeks 0-16 (<1g/day; RR 1.8 [95% CI 1.1-2.9]) and any use of PPIs in gestational weeks 17-33 (RR 1.6 [95% CI 1.0-2.8]) seemed to increase risks of late-onset preeclampsia. We did not observe associations between late-onset preeclampsia and use of calcium-based antacids and PPIs after gestational day 237. Conclusions: In this prospective cohort study, use of calcium-based antacids and PPIs during pregnancy was not found to reduce the risk of late-onset preeclampsia. Funding: Netherlands Organisation for Health Research and Development [ZonMw; grant number 848018010].

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