Pre-pregnancy Body Mass Index and Adverse Pregnancy Outcomes: A Cross-Sectional Analysis Followed by Mendelian Randomization Study

Background Pre-pregnancy body mass index (BMI) is closely associated with a wide range of pregnancy outcomes, yet controversies persist, and large-scale causal evidence remains limited. Methods To address this, we conducted a retrospective cohort study using U.S. National Vital Statistics System (NVSS) birth data (2015–2024). Logistic regression was used for binary outcomes (gestational diabetes mellitus [GDM], hypertensive disorders of pregnancy [HDP], eclampsia, preterm birth), and linear regression for continuous outcomes (birth weight), calculating effect estimates with 95% confidence intervals (CIs). A multivariable-adjusted restricted cubic spline model explored nonlinearity, with threshold effects analyzed by two-piecewise linear regression. Finally, two-sample Mendelian randomization (MR) was performed to infer causality. Results This study included 31,209,649 participants. Compared to the underweight group, higher pre-pregnancy BMI was associated with increased risks of most adverse outcomes. A J-shaped association was observed between pre-pregnancy BMI and preterm birth risk: the risk decreased across the lower BMI range(OR = 0.965, 95% CI: 0.956–0.974, P < 0.001) but increased beyond an inflection point(OR = 1.027, 95% CI: 1.015–1.039, P < 0.01). For other outcomes, pre-pregnancy BMI showed positive linear correlations. MR analysis provided genetic evidence supporting a causal role.Sensitivity analyses supported the robustness of these findings. Conclusion Pre-pregnancy BMI exhibited a complex, non-linear relationship with preterm birth and significant positive correlations with GDM, HDP, and birth weight. The Mendelian randomization analysis strengthens the evidence for potential causal relationships, highlighting the importance of pre-pregnancy weight management.