Prenatal exposure to metal(loid)s mixture and childhood lung function: Exploring sex-specific associations

The link between prenatal exposure to metal(loid)s and childhood lung function, including sex-specific effects, has not been completely elucidated. We aimed to examine sex-specific individual and joint effects of prenatal metal(loid)s exposure on children's lung function.

Analyses included 438 mother-child dyads from the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort in Mexico City. Metal(loid)s levels (As, Cd, Co, Cu, Mn, Ni, Pb, Se, and Zn) were measured in maternal blood collected during the second and third trimesters. Lung function in children was assessed once at ages 8-14 years. Multiple linear regression was performed to evaluate individual associations. Mixture effects were assessed through repeated holdout weighted quantile sum regression and hierarchical Bayesian kernel machine regression. Effect modification by sex was examined.

Second-trimester Ni was inversely associated with FEV₁/FVC ratio in the overall sample and in females, while Pb was linked to lower FEV₁ z-score in females. Third-trimester Co and Pb were also negatively associated with FVC z-score in females, with Pb also associated with lower FEV₁ z-score in females. Higher metal mixture concentrations were associated with lower FEV₁/FVC ratio (β = -0.33, 95% confidence interval: -0.48, -0.16) and FEF_25%-75% z-score (β = -0.22, 95% confidence interval: -0.39, -0.07) in females, with similar sex-specific patterns of association in weighted quantile sum and Bayesian kernel machine regression models.

Second-trimester metal mixture exposure is associated with lower childhood lung function; females are potentially more susceptible to these exposures, which underscores the need to understand critical windows of exposure and sex-specific differences.