Causal link between maternal PCOS and fetal/neonatal hemorrhagic and hematological disorders: A 2-sample MR study

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age, affecting approximately 5 to 13% of this population. Beyond its reproductive implications, PCOS is frequently accompanied by metabolic and psychological disturbances, including obesity, insulin resistance, diabetes, and depressive symptoms. Increasing evidence suggests that genetic liability to PCOS may be associated with adverse pregnancy and neonatal outcomes; however, whether these associations reflect causal relationships remains uncertain. In this study, we conducted a 2-sample Mendelian randomization (MR) analysis to evaluate the potential association between genetically predicted PCOS liability and fetal or neonatal hemorrhagic and hematologic disorders. Genetic instruments for PCOS were obtained from large-scale genome-wide association studies, and outcome data were derived from the FinnGen consortium. The inverse variance weighted method served as the primary estimator, complemented by MR-Egger regression and weighted median approaches, along with multiple sensitivity analyses to assess heterogeneity and horizontal pleiotropy. The inverse variance weighted analysis indicated a statistically significant association between genetically predicted PCOS and an increased risk of fetal or neonatal hemorrhagic and hematologic disorders (odds ratio = 1.80; 95% confidence interval, 1.11-2.91). Although complementary MR methods did not reach statistical significance, the direction of effect was consistent across estimators, and no evidence of heterogeneity or directional pleiotropy was detected. Taken together, these findings provide genetic epidemiological evidence supporting a potential causal effect between genetic liability to PCOS and adverse fetal or neonatal hemorrhagic and hematologic disorders, warranting further validation through prospective clinical and mechanistic studies.