Iron as a Modifiable Factor for Adverse Pregnancy Outcomes: Refining and Understanding Causal Estimates Using...

Many observational studies have explored the correlation between iron and adverse pregnancy outcomes (APOs). However, existing findings yield inconsistent conclusions, and the causal relationship is unclear. This study is aimed at determining the causal connection between iron status and APOs. A two-sample Mendelian randomization study was conducted utilizing summary data of genome-wide association studies (GWAS). Data for iron status were collected from a GWAS meta-analysis, and data for APOs were obtained from the FinnGen database. The exposure-outcome relationship was explored by employing inverse variance weighting (IVW) with a range of supplementary methods. Additional sensitivity analyses were performed to verify the robustness of the results. The results suggested that increased serum iron was significantly associated with an increased risk of pregnancy hypertension (odds ratio (OR) 1.20, 95% confidence intervals (CI) 1.05-1.38), pre-eclampsia (OR 1.23, 95% CI 1.03-1.47), and pre-eclampsia or eclampsia (OR 1.29, 95% CI 1.08-1.53). The level of transferrin saturation was inversely linked with gestational diabetes (OR 0.91, 95% CI 0.83-0.99) and placenta praevia (OR 0.78, 95% CI 0.61-0.99). Furthermore, genetically predicted total iron binding capacity may augment the risk of spontaneous abortion (OR 1.14, 95% CI 1.06-1.23), ectopic pregnancy (OR 1.17, 95% CI 1.01-1.35), and intrahepatic cholestasis of pregnancy (OR 1.39, 95% CI 1.02-1.90). The study identified the causal link between iron status and APOs, offering new insights to the clinical research on iron status-related pregnancy outcomes. Further studies are required to elucidate the role of iron status in the underlying mechanisms of APOs.