Metal mixture exposure and elevated risk of hypertensive disorders in pregnancy: Insights from a case-control study in northwestern China.

Exposure to metal mixtures has been associated with increased hypertensive disorders of pregnancy (HDP) risk, but evidence in northwestern China concerning the impact of environmental metals exposure on HDP risk remains limited. Thus, this study aims to investigate the association between multi-metal exposure and HDP among pregnant women in northwestern China. We conducted a case-control study from January 2023 to May 2024 involving 94 pregnant women with newly diagnosed HDP and 188 controls. Plasma concentrations of 23 metals were measured. Single-metal models and multiple metal mixture models, including logistics regression, variable selection, weighted quantile sum (WQS), quantile g-computation (Q-gcomp), and bayesian kernel machine regression (BKMR) models, were fitted to evaluate the individual and joint effects of metal concentrations on HDP. After adjusted for potential confounders, single-metal models revealed significant associations with HDP risk: positive associations for rubidium (Rb) (odds ratio (OR)=2.34, 95 % confidence interval (CI): 1.50, 3.67), thallium (Tl) (OR=1.95, 95 % CI: 1.21, 3.14), cesium (Cs) (OR=1.87, 95 % CI: 1.19, 2.94), and manganese (Mn) (OR=2.25, 95 % CI: 1.30, 3.87), and a negative association for cobalt (Co) (OR=0.64, 95 % CI: 0.43, 0.95). In multiple-metal models, WQS, Q-gcomp, and BKMR analyses indicated a positive joint effect of the five-metal mixture on HDP, with Rb as the strongest contributor. Interaction analysis showed that high Tl with low Co significantly increased HDP risk. Our findings indicate that both individual and combined exposure to metals during pregnancy was associated with an increased risk of HDP. Potential interaction effects between Tl and Co on HDP risk were also observed.