Trimester-specific effects of maternal exposure to single and mixed metals on cord serum inflammatory cytokines levels: A prospective birth cohort study

Background: Cord blood inflammatory cytokines are vital in early-life programming. An increasing number of studies concern the effect of maternal exposure to different metal elements during pregnancy on inflammatory cytokines, but limited studies have explored the association between maternal exposure to mixed metals and cord blood inflammatory cytokine levels. Methods: We measured serum concentrations of vanadium (V), copper (Cu), arsenic (As), cadmium (Cd), and barium (Ba) in the first, second, and third trimesters and eight cord serum inflammatory cytokines (IFN-& gamma;, IL-1f3, IL-6, IL-8, IL10, IL-12p70, IL-17A, and TNF-& alpha;) in 1436 mother-child dyads from the Ma'anshan Birth Cohort. Generalized linear models and Bayesian kernel machine regression (BKMR) were performed to assess the association of single and mixed metal exposure during each trimester with cord serum inflammatory cytokine levels, respectively. Results: Regarding metal exposure in the first trimester, V was positively associated with TNF-& alpha; (& beta; = 0.33, 95 % CI: 0.13, 0.53); Cu was positively associated with IL-8 (& beta; = 0.23, 95 % CI: 0.07, 0.39); Ba was positively associated with IFN-& gamma; and IL-6; As was negatively associated with IFN-& gamma; and IL-17A; and Cd was negatively associated with IFN-& gamma;, IL-1f3, IL-12p70, IL-17A, and TNF-& alpha;. BKMR revealed that exposure to metal mixtures in the first trimester was positively associated with IL-8 and TNF-& alpha; but negatively associated with IL-17A. Moreover, V contributed the most to these associations. Interaction effects were observed between Cd and As and between Cd and Cu with IL-8, and be- tween Cd and V with IL-17A. Among males, As decreased inflammatory cytokines; among females, Cu increased in- flammatory cytokine levels, whereas Cd decreased inflammatory cytokine concentrations. Conclusions: Maternal exposure to metal mixtures in the first trimester interfered with cord serum inflammatory cytokine levels. The associations of maternal exposure to As, Cu and Cd with inflammatory cytokines showed sex dif- ferences. Further studies are warranted to support the findings and explore the mechanism of the susceptibility win- dow and sex-specific disparity.

Automated summary

This study explored the impact of maternal exposure to multiple metal elements during pregnancy on cord blood inflammatory cytokine levels. The results showed positive associations between exposure to metal mixtures and levels of IL-8 and TNF-α, and negative associations with IL-17A. V contributed the most to these associations. Sex differences were observed, with maternal exposure to As reducing inflammatory cytokine levels, while exposure to Cu increased levels and exposure to Cd decreased concentrations.