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Abstract Metal(loid) exposure can exert immunotoxic effects, including changes in white blood cell proportions. The impact from metal exposure mixtures during pregnancy has not been examined in relation to cell-type composition at birth. Our aim was to evaluate the associations between a prenatal metal(loid) exposure mixture and cord blood DNA methylation-derived cell-type composition. We leveraged the PROGRESS birth cohort with measured prenatal immunotoxic metal(loid)s in blood (manganese, lead) and urine (arsenic, cadmium) and DNA methylation-derived cell-type composition from cord blood (n = 428). We used the novel Dirichlet Bayesian Weighted Quantile Sum regression to elucidate the association of metal mixtures on a compositional outcome with several DNA methylation-derived cell types: granulocytes (GR), CD4+ and CD8+ T-cells, B-cells, monocytes, natural killer (NK) cells, and nucleated red blood cells (nRBCs). We also conducted stratified analyses by fetal sex. We observed no associations in the overall population. In sex-stratified models, a one-quartile increase in metal mixture among the pregnant women carrying a female was associated with a 4.85% 95% credible intervals (CrI): 1.11%, 8.81% increase in GR proportion, driven by arsenic. Conversely, a one-quartile increase in metal mixture in women carrying a male was marginally associated with a 3.44% (95% CrI: −7.08%, 0.37%; 80%CrI: −5.83%, −1.01%) decrease in GR proportion, driven by cadmium. We also observed marginal metal mixture associations with higher proportions of CD8+ T-cells in women carrying a male and lower proportion of NK cells and nRBCs in women carrying a female. Our findings suggest a potential differential metal mixture-cell composition associations given by fetal sex.
Aldana et al. (Tue,) studied this question.