Associations Between Late-Onset Preeclampsia and the Use of Calcium-Based Antacids and Proton Pump Inhibitors During Pregnancy: A Prospective Cohort Study

Abstract

Marleen MHJ van Gelder,1 Pim Beekers,1,2 Yrea RJ van Rijt-Weetink,3 Joris van Drongelen,4 Nel Roeleveld,1 Luc JM Smits5 1Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands; 2National Health Care Institute, Diemen, the Netherlands; 3Netherlands Pharmacovigilance Centre Lareb,‘s-Hertogenbosch, the Netherlands; 4Department of Obstetrics & Gynecology, Radboud University Medical Center, Nijmegen, the Netherlands; 5Department of Epidemiology, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the NetherlandsCorrespondence: Marleen MHJ van Gelder, Department for Health Evidence (HP 133), Radboud University Medical Center, P.O. Box 9101, Nijmegen, 6500 HB, the Netherlands, Tel [phone], Fax [phone], Email [email protected]: Preeclampsia is a leading cause of maternal morbidity and mortality. Calcium-based antacids and proton pump inhibitors (PPIs) are commonly used during pregnancy to treat symptoms of gastroesophageal reflux disease. Both have been hypothesized to reduce the risk of preeclampsia. We determined 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.Patients and Methods: We included 9058 pregnant women participating in the PRIDE Study (2012– 2019) or The Dutch Pregnancy Drug Register (2014– 2019), two prospective cohorts in The Netherlands. 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 (HRs) for time-varying exposures after gestational day 237.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 (< 1 g/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 (HR 1.0 [95% CI 0.6– 1.5]) and PPIs (HR 1.4 [95% CI 0.7– 2.9]) after gestational day 237.Conclusion: 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.Keywords: extended Cox models, gestational hypertension, gastroesophageal reflux disease, longitudinal clustering methods, PRIDE study, The Dutch Pregnancy Drug Register

Keywords

• extended cox models
• gestational hypertension
• gastroesophageal reflux disease
• longitudinal clustering methods
• pride study
• the dutch pregnancy drug register