Abstract
Background
Pregnancy complications are influenced by a complex interplay of socioeconomic and reproductive factors. Observational studies have suggested associations with socioeconomic traits-such as educational attainment (EDU), household income (INC), and physically demanding work (PDW)-as well as reproductive traits including age at first sexual intercourse (AFS) and age at first birth (AFB). However, observational findings are prone to confounding and reverse causation, making it difficult to establish causality. Therefore, this study applies Mendelian randomization (MR) to investigate the causal relationships between reproductive and socioeconomic traits and the risk of pregnancy complications.Methods
We conducted univariable and multivariable MR analyses to assess the causal effects of reproductive traits and socioeconomic traits on pregnancy complications. Genetic instruments reaching genome-wide significance (P 8) were selected from large-scale genome-wide association studies (GWAS) involving 263,615 to 766,345 participants for socioeconomic traits (EDU, INC, PDW) and 214,547 to 418,758 participants for reproductive traits (AFS, AFB). Outcome data were derived from GWAS based on biobank datasets for eight pregnancy complications: spontaneous abortion (SA), postpartum depression (PD), gestational diabetes (GD), Pre-eclampsia or eclampsia (PE), premature rupture of membranes (PRM), premature separation of placenta (PSP), intrahepatic cholestasis of pregnancy (ICP), and hyperemesis gravidarum (HG). Sample sizes ranged from 294 to 9,113 cases and 59,610 to 117,892 controls.Results
Univariable MR analysis identified significant associations, including AFB-PD(OR = 0.90, 95% CI: 0.81-0.98, P = 0.024 ), AFS-SA(OR = 0.77, 95% CI: 0.62-0.96, P = 0.020 ), AFS-PD(OR = 0.46, 95% CI: 0.36-0.59, P Conclusion
Lower EDU is causally associated with increased risks of PD, PE, and PRM. Educational level may influence reproductive timing, such as AFS, which in turn affects the likelihood of pregnancy complications. These findings highlight the potential benefits of targeted educational and social interventions in mitigating adverse pregnancy outcomes.