Abstract 054: Prospective associations of pregnancy heavy metals and essential elements with women’s mid-life obesity risk: implications of folate supplementation as a possible intervention strategy to mitigate metal-related health effects

Background: Pregnancy is a critical period for women’s long-term cardiometabolic health, with women being particularly sensitive to environmental exposures. The effects of heavy metals and essential elements during pregnancy on long-term obesity risk are understudied. Cohort studies and trials suggest that folate may mitigate metal toxicity—a recent AHA Scientific Statement on metals identified this area of research as a critical gap and priority. Objective: 1) To investigate the associations of pregnancy levels of metals and elements with women’s mid-life obesity risk; and 2) to explore whether adequate pregnancy folate mitigates the obesogenic effects of metals. Methods: Project Viva is a pregnancy cohort enrolled in Eastern MA between 1999-2002 (median age: 32.9y). We measured (As, Ba, Cd, Cs, Hg, Pb) and elements (Cu, Mg, Mn, Se, Zn) in red blood cells and folate in plasma collected during the first trimester. At the Mid-Life visit (2017-2021; median age: 51.2y), we measured weight and height and defined obesity as BMI >30 kg/m 2 (reference: ≤30 kg/m 2 ). We examined associations of metals and elements with obesity using modified Poisson regression, adjusting for confounders ( Figure 1 footnote ). We used Bayesian kernel machine regression (BKMR) to assess the mixture effects of all metals, elements, and folate. Results: We followed 500 women (72% White, 11% Black) for a median of 18.1y (range: 17.5-20.8y). Cs and Cu were associated with a lower risk of obesity: per doubling, Cs and Cu were associated with 0.78 (95% CI: 0.63-0.97) and 0.71 (95% CI: 0.50-0.99) times the obesity risk, respectively. Mg, Se, and Zn were also associated with >10% lower obesity risk, though the 95% CIs crossed the null ( Figure 1 ). BKMR results confirmed consistent dose-response associations ( Figure 2 ). Although neither As nor folate was individually associated with obesity, they showed an interaction in association with obesity ( Figure 3 ): at lower folate levels, As was associated with a higher obesity risk, but as folate levels increased, the As-obesity association was attenuated and eventually became inverse. Conclusion: Optimal pregnancy levels of essential elements (e.g., Cu, Se, Mg, Zn) were associated with a lower risk of mid-life obesity, while adequate folate levels may counteract the obesogenic effects of As. Our study advances a research priority in the AHA Scientific Statement, suggesting folate as a potential intervention strategy to mitigate metal-related health effects.