Proton Pump Inhibitors and Preeclampsia Risk Among 157 720 Women

Preeclampsia is a hypertensive disorder of pregnancy with a high rate of maternal and neonatal morbidity and mortality. The only definite treatment is delivery. Preclinical investigations have identified proton pump inhibitors (PPIs), which are commonly used to treat reflux during pregnancy, as a potential treatment for preeclampsia. The aim of this study was to determine the association between PPI use during pregnancy and preeclampsia risk in a population-based register cohort. Using the Swedish Pregnancy Register, we conducted a cohort study of nulliparous pregnant women delivering from January 2013 to July 2017. Associations between PPI use and preeclampsia were investigated using logistic regression analyses with risk estimates presented as crude and adjusted odds ratios (aOR) with 95% CI. Of 157 720 nulliparous pregnant women, 6051 (3.8%) reported PPI use during pregnancy. PPI use during any point of pregnancy was associated with an increased risk of overall preeclampsia (aOR of 1.17; 95% CI, 1.04-1.32) and preeclampsia at term (aOR of 1.20; 95% CI, 1.04-1.39). However, PPI use recorded after 28 gestational weeks was associated with a reduced risk of preterm (delivery <37 weeks) preeclampsia (aOR of 0.63; 95% CI, 0.41-0.96) and early (delivery <34 weeks) preeclampsia (aOR of 0.41; 95% CI, 0.20-0.82). These findings highlight the heterogeneity of this disease, with a potential role PPIs for preventing preterm preeclampsia when used in close proximity to disease onset. Targeting PPI use to women at greatest risk of preterm preeclampsia may help prevent this severe form of disease.