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. 2024 Mar 14:14:1343499.
doi: 10.3389/fcimb.2024.1343499. eCollection 2024.

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

Jialyu Huang #  1 , Yuxin Liu #  2 , Dingfei Xu #  1 , Mengyi Chen  1 , Qiqi Xie  1 , Jia Chen  1 , Leizhen Xia  1 , Lamei Yu  3 , Qiongfang Wu  1 , Zengming Li  4 , Jiawei Wang  5 , Lifeng Tian  1
Affiliations

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

Jialyu Huang et al. Front Cell Infect Microbiol. .

Abstract

Background: Observational 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.

Methods: A 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.

Results: IVW 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.

Conclusion: Our 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.

Keywords: Helicobacter pylori; Mendelian randomization; preeclampsia; pregnancy; premature rupture of membranes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study design. IV, instrumental variable; SNP, single nucleotide polymorphism.
Figure 2
Figure 2
Leave-one-out plots for the causal associations between anti-H. pylori IgG levels and nine pregnancy and neonatal outcomes. (A) Sporadic miscarriage. (B) Preeclampsia or eclampsia. (C) Gestational diabetes mellitus. (D) Placental abruption. (E) Premature rupture of membranes. (F) Postpartum haemorrhage. (G) Birthweight. (H) Gestational age. (I) Preterm birth. MR, mendelian randomization.
Figure 3
Figure 3
Scatter plots for the causal associations between anti-H. pylori IgG levels and nine pregnancy and neonatal outcomes. (A) Sporadic miscarriage. (B) Preeclampsia or eclampsia. (C) Gestational diabetes mellitus. (D) Placental abruption. (E) Premature rupture of membranes. (F) Postpartum haemorrhage. (G) Birthweight. (H) Gestational age. (I) Preterm birth. Five MR methods are indicated by different colors, including inverse variance weighted (light blue), MR Egger (dark blue), weighed median (dark green), weighted mode (red), and simple mode (light green). SNP, single nucleotide polymorphism; MR, mendelian randomization.
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