BackgroundNumerous observational studies have revealed a correlation between telomere length (TL) and adverse pregnancy outcomes (APOs). However, the impacts of TL on APOs are still unclear.MethodsMendelian randomization (MR) was carried out using summary data from genome-wide association studies (GWAS). Inverse variance weighted (IVW) was employed as the primary analysis to explore the causal relationship between TL and APOs. The exposure data came from a GWAS dataset of IEU analysis of the United Kingdom Biobank phenotypes consisting of 472,174 European participants. Summary-level data for five APOs were obtained from the GWAS datasets of the FinnGen consortium. We also performed multivariate MR (MVMR), adjusting for smoking, alcohol intake, body mass index (BMI), and number of live births. In addition, we conducted a series of rigorous analyses to further examine the validity of our MR findings.ResultsAfter Bonferroni correction and rigorous quality control, univariable MR (UVMR) demonstrated that a shorter TL was significantly associated with an increased risk of spontaneous abortion (SA) (odds ratio [OR]: 0.815; 95% confidence interval [CI]: 0.714–0.930; P = 0.002) and preterm birth (PTB) (OR: 0.758; 95% CI: 0.632-0.908; P = 0.003) in the IVW model. There was a nominally significant relationship between TL and preeclampsia (PE) in the IVW model (OR: 0.799; 95% CI: 0.651-0.979; P = 0.031). However, no significant association was found between TL and gestational diabetes mellitus (GDM) (OR: 0.950; 95% CI: 0.804-1.122; P = 0.543) or fetal growth restriction (FGR) (OR: 1.187; 95% CI: 0.901-1.565; P = 0.223) among the five statistical models. Furthermore, we did not find a significant causal effect of APOs on TL in the reverse MR analysis. MVMR analysis showed that the causal effects of TL on SA remained significant after accounting for smoking, alcohol intake, BMI, and number of live births.ConclusionOur MR study provides robust evidence that shorter telomeres were associated with an increased risk of SA. Further work is necessary to investigate the potential mechanisms. UVMR and MVMR findings showed limited evidence that TL affects the risk of PTB, PE, GDM, and FGR, illustrating that the outcomes of previous observational studies may have been confounded.

Background There is a growing body of evidence showing an association between women's reproductive behavior (RB) and socio-economic status (SES) with the incidence of postpartum depression (PPD). However, the causal relationship between these factors and PPD remains unclear. To facilitate timely screening and effective prevention of maternal emotional disorders, we conducted a Mendelian randomization (MR) study to assess causality between RB/SES and PPD. This study aims to provide new insights into the etiology of PPD and inform public health strategies for its prevention and management. Methods A two-sample Mendelian randomization (MR) study was conducted to investigate the causal effects of reproductive behavior (RB) and socio-economic status (SES) on postpartum depression (PPD). Strongly associated genetic variants for each phenotype were selected as instrumental variables using a predetermined threshold. The primary analysis was conducted using inverse variance weighted method, with additional MR methods including MR-Egger, weighted median, and weighted mode estimate. Potential pleiotropy of instrumental variables (IVs) was evaluated using the MR pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression methods, and outliers were identified by MR-PRESSO. Heterogeneity among IVs was assessed using Cochran's Q statistic. Leave-one-out sensitivity analysis was performed to identify SNPs that significantly impacted the results. This study aims to provide a better understanding of the causal relationship between RB/SES and PPD and inform future prevention and intervention strategies. Result We found a statistically significant association between age of first sexual intercourse , age at first birth, lifetime number of sexual partners, age completed full-time education, Townsend deprivation index at recruitment, and PPD. However, after Bonferroni correction, only earlier age of first sexual intercourse and age completed full-time education remained significantly associated with an increased risk of PPD. These results were reliable and stable and sensitivity analysis showed no violation of the MR assumptions. This study provides important insights into the causal relationship between RB and SES on PPD and highlights the need for targeted interventions to address risk factors for PPD. Conclusions. MR study provides robust evidence that SES/RB play broad impacts on PPD.