Table_2_Causal associations between Helicobacter pylori infection and pregnancy and neonatal outcomes: a two-sample Mendelian randomization study.xlsx

BackgroundObservational studies have reported that Helicobacter pylori (H. pylori) infection is associated with a series of pregnancy and neonatal outcomes. However, the results have been inconsistent, and the causal effect is unknown.
MethodsA two-sample Mendelian randomization (MR) study was performed using summary-level statistics for anti-H. pylori IgG levels from the Avon Longitudinal Study of Parents and Children Cohort. Outcome data for pregnancy (miscarriage, preeclampsia-eclampsia, gestational diabetes mellitus, placental abruption, premature rupture of membranes, postpartum hemorrhage) and neonates (birthweight, gestational age, and preterm birth) were sourced from genome-wide association meta-analysis as well as the FinnGen and Early Growth Genetics Consortium. Causal estimates were calculated by five methods including inverse variance weighted (IVW). The heterogeneity of instrumental variables was quantified by Cochran’s Q test, while sensitivity analyses were performed via MR-Egger, MR-PRESSO, and leave-one-out tests.
ResultsIVW estimates suggested that genetically predicted anti-H. pylori IgG levels were significantly associated with increased risks of preeclampsia-eclampsia (odds ratio [OR] = 1.12, 95% confidence interval [CI] 1.01–1.24, P = 0.026) and premature rupture of membranes (OR = 1.17, 95% CI 1.05–1.30, P = 0.004). Similar results were obtained for preeclampsia-eclampsia from the MR-Egger method (OR = 1.32, 95% CI 1.06–1.64, P = 0.027) and for premature rupture of membranes from the weighted median method (OR = 1.22, 95% CI 1.06–1.41, P = 0.006). No significant causal effects were found for other outcomes. There was no obvious heterogeneity and horizontal pleiotropy across the MR analysis.
ConclusionOur two-sample MR study demonstrated a causal relationship of H. pylori infection with preeclampsia-eclampsia and premature rupture of membranes. The findings confirm the epidemiological evidence on the adverse impact of H. pylori in pregnancy. Further studies are needed to elucidate the pathophysiological mechanisms and assess the effectiveness of pre-pregnancy screening and preventive eradication.

背景 观察性研究表明，幽门螺杆菌（Helicobacter pylori，H. pylori）感染与一系列妊娠及新生儿结局相关。但现有研究结果并不一致，且其因果效应尚未明确。

方法 本研究采用两样本孟德尔随机化（Mendelian randomization, MR）设计，使用来自雅芳父母与儿童纵向研究队列（Avon Longitudinal Study of Parents and Children Cohort）的抗幽门螺杆菌IgG水平汇总统计数据。妊娠结局（包括流产、子痫前期-子痫、妊娠期糖尿病、胎盘早剥、胎膜早破、产后出血）及新生儿结局（包括出生体重、胎龄、早产）的数据来源于全基因组关联研究荟萃分析、FinnGen数据库以及早期生长遗传学联盟（Early Growth Genetics Consortium）。本研究采用包括逆方差加权法（inverse variance weighted, IVW）在内的五种方法计算因果效应估计值。采用Cochran Q检验量化工具变量的异质性，并通过MR-Egger、MR-PRESSO以及留一法（leave-one-out test）进行敏感性分析。

结果 逆方差加权法分析显示，遗传预测的抗幽门螺杆菌IgG水平与子痫前期-子痫（比值比[OR]=1.12，95%置信区间[CI] 1.01~1.24，P=0.026）及胎膜早破（OR=1.17，95%CI 1.05~1.30，P=0.004）的发病风险升高显著相关。MR-Egger法分析子痫前期-子痫（OR=1.32，95%CI 1.06~1.64，P=0.027）、加权中位数法分析胎膜早破（OR=1.22，95%CI 1.06~1.41，P=0.006）也得到了相似结果。其余结局未发现显著因果效应。本次孟德尔随机化分析未发现明显异质性及水平多效性。

结论 本两样本孟德尔随机化研究证实，幽门螺杆菌感染与子痫前期-子痫及胎膜早破存在因果关联。本研究结果为幽门螺杆菌对妊娠的不良影响提供了流行病学证据支持。未来仍需进一步研究阐明其病理生理机制，并评估孕前筛查及预防性根除治疗的有效性。