The effects of proton pump inhibitors during pregnancy on treatment of preeclampsia and related outcomes: a systematic review and meta-analysis

Objective: This systematic review evaluated the available evidence on the effects of proton pump inhibitors during pregnancy on preeclampsia and related maternal, fetal, and neonatal outcomes.

Data sources: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and Global Medicus Index) were searched on November 17, 2023.

Study eligibility criteria: Randomized controlled trials of pregnant women who used any class or dose of proton pump inhibitor were eligible.

Methods: A meta-analysis was conducted for all outcomes of interest using random-effects models. Results were presented as risk ratios or mean difference. Quality assessment was performed using the Risk of Bias 2 tool, and Grading of Recommendations, Assessment, Development, and Evaluations assessment was completed to evaluate the certainty of the evidence. The study was registered in the International Prospective Register of Systematic Reviews under identifier CRD42023423673.

Results: Our search identified 3879 records that were screened independently by 2 authors. Nine reports (describing 8 trials) met our eligibility criteria, however, 6 trials were ultimately excluded from our analysis because women were only given proton pump inhibitors immediately before cesarean delivery for acid aspiration prevention. The 2 trials that were included in the meta-analysis evaluated the treatment of 177 women with diagnosed preeclampsia. For the primary outcomes, moderate-certainty evidence showed that the use of proton pump inhibitors likely has no effect on the risk for hemolysis, elevated liver enzymes, and low platelet count syndrome (risk ratio, 1.21; 95% confidence interval, 0.37-3.99; I²=0%) or perinatal mortality (risk ratio, 0.81; 95% confidence interval, 0.36-1.79; I²=0%), and there were insufficient data to conduct a meta-analysis on all other primary outcomes, including eclampsia and neonatal mortality. No trials investigated the use of proton pump inhibitors for the prevention of preeclampsia.

Conclusion: Given the limited outcome data, we are uncertain about the effect of proton pump inhibitors on women with preeclampsia. Further trials are required to determine what (if any) effects proton pump inhibitors might have for preeclampsia prevention or treatment.