Genetic Causal Association Between 15 Micronutrients and 12 Obstetric-Related Diseases: A Mendelian Randomization...

Micronutrients, namely vitamins and minerals, are associated with pregnancy outcomes. However, the effects reported in previous observational studies and randomized controlled trials have been inconsistent. Using publicly available genetic data, we conducted a two-sample MR analysis to estimate the causal association between 15 micronutrient levels and 12 obstetric-related diseases. Sensitivity analysis was performed to assess the robustness of the results, detect heterogeneity, and examine the potential existence of horizontal pleiotropy. Iron was protective against gestational diabetes mellitus (GDM) (OR = 0.597, 95% CI 0.438-0.814, P = 0.001), while zinc increased the risk of pregnancy hypertension (OR = 1.064, 95% CI 1.004-1.128, P = 0.035). Vitamin B6 was associated with increased risk of spontaneous abortion (OR = 1.222, 95% CI 1.001-1.490, P = 0.047), and vitamin D was linked to poor fetal growth (OR = 1.612, 95% CI 1.018-2.552, P = 0.041). Conversely, vitamin B12 showed protective effects against preterm birth (OR = 0.686, 95% CI 0.482-0.976, P = 0.036). Selenium and vitamin E were protective against polyhydramnios (OR = 0.828, 95% CI 0.698-0.981, P = 0.030; OR = 0.441, 95% CI 0.213-0.910, P = 0.026), whereas selenium increased the risk of premature rupture of membranes (OR = 1.083, 95% CI 1.007-1.164, P = 0.030).However, no causal links were found between the other micronutrients analyzed and obstetric-related diseases. Sensitivity analyses revealed no significant heterogeneity or pleiotropy. Our research has clarified the causal link between micronutrients and obstetric-related diseases, assisting clinicians in offering personalized guidance on the appropriate intake of micronutrients for women preparing for pregnancy and those who are pregnant. These findings are essential for screening and preventing pregnancy complications, and they also provide new insights and evidence for improving pregnancy outcomes through nutritional interventions.