Effects of gastroesophageal reflux disease on adverse pregnancy outcomes: a Mendelian randomization study

Abstract

Abstract Background More and more studies have shown that gastroesophageal reflux disease (GERD) is negatively associated with adverse pregnancy outcomes (APOs), including spontaneous abortion, gestational diabetes, pre-eclampsia or eclampsia, premature rupture of membranes, premature separation of the placenta, and postpartum hemorrhage. Nevertheless, the causal relationship between the two is not clear. The study aimed to evaluate the causal relationship between GERD and APOs. Methods Based on published genome-wide association studies, two-sample Mendelian randomization (MR) analysis was used to infer the causal relationship between GERD and APOs, in which the fixed-effects inverse variance weighting (IVW) method was the primary method. Various methods were conducted for sensitivity analysis. First, Cochran's Q test assessed heterogeneity among individual SNP estimates. Secondly, MR Egger addressed the pleiotropy effect. Third, a leave-one-out sensitivity analysis was performed to determine whether a single SNP was responsible for the results. Fourth, the funnel plot and forest plot are used to show the pleiotropy directly. Results GERD causally increased the risks of spontaneous abortion (odds ratio (OR) = 1.127, 95% confidence interval (CI) = 1.030–1.233, p = 0.009), gestational diabetes (OR = 1.201, 95% CI = 1.075–1.342, p = 0.001), and pre-eclampsia or eclampsia (OR = 1.183, 95% CI = 1.020–1.372, p = 0.026). No associations were observed for premature rupture of membranes, premature separation of the placenta, or postpartum hemorrhage. No evidence of heterogeneity and directional pleiotropy was detected. The leave-one-out sensitivity analysis revealed that the overall estimates were not disproportionately affected by any individual SNP. Conclusions This two-sample MR analysis found that GERD was positively associated with spontaneous abortion, gestational diabetes, and pre-eclampsia or eclampsia.