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

Authors：Wang X, Tong J, Liang C, Wang X, Ma Y, Tao S, Liu M, Wang Y, Liu J, Yan S, Gao G, Wu X, Huang K, Cao Y, Tao F.

Source：Sci Total Environ. 2023 Jun 26;895:165086.

DOI: 10.1016/j.scitotenv.2023.165086.

Abstract：

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-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and TNF-α) 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-α (β = 0.33, 95 % CI: 0.13, 0.53); Cu was positively associated with IL-8 (β = 0.23, 95 % CI: 0.07, 0.39); Ba was positively associated with IFN-γ and IL-6; As was negatively associated with IFN-γ and IL-17A; and Cd was negatively associated with IFN-γ, IL-1β, IL-12p70, IL-17A, and TNF-α. BKMR revealed that exposure to metal mixtures in the first trimester was positively associated with IL-8 and TNF-α 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 between Cd and V with IL-17A. Among males, As decreased inflammatory cytokines; among females, Cu increased inflammatory 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 differences. Further studies are warranted to support the findings and explore the mechanism of the susceptibility window and sex-specific disparity.

Keywords: BKMR; Birth cohort; Inflammatory cytokines; Metal mixtures; Prenatal exposure.

中文摘要：

背景:脐带血炎症细胞因子在生命早期编程中至关重要。越来越多的研究关注母亲在怀孕期间暴露于不同金属元素对炎症细胞因子的影响，但有限的研究探讨了母亲暴露于混合金属与脐带血炎症细胞因子水平之间的关系。

方法:对1436名马鞍山出生队列的母婴分别在妊娠1、2、3个月测定血清中钒(V)、铜(Cu)、砷(As)、镉(Cd)、钡(Ba)的浓度和8种血清炎性因子(IFN-γ、IL-1β、IL-6、IL-8、IL-10、IL-12p70、IL-17A和TNF-α)。采用广义线性模型和贝叶斯核机回归(BKMR)分别评估妊娠期间单一和混合金属暴露与脐带血清炎症细胞因子水平的关系。

结果:对于妊娠早期金属暴露，V与TNF-α呈正相关(β = 0.33, 95% CI: 0.13, 0.53);Cu与IL-8呈正相关(β = 0.23, 95% CI: 0.07, 0.39);Ba与IFN-γ、IL-6呈正相关;As与IFN-γ、IL-17A呈负相关;Cd与IFN-γ、IL-1β、IL-12p70、IL-17A、TNF-α呈负相关。BKMR显示，孕早期暴露于金属混合物与IL-8和TNF-α呈正相关，与IL-17A呈负相关。此外，V对这些关联的贡献最大。Cd与As之间、Cd与Cu与IL-8之间、Cd与V与IL-17A之间存在互作效应。在男性中，As降低了炎症细胞因子;在雌性中，Cu增加了炎症细胞因子水平，而Cd降低了炎症细胞因子浓度。

结论:孕早期母体接触金属混合物会干扰脐带血清炎症细胞因子水平。母亲暴露于砷、铜和镉与炎性细胞因子的关系存在性别差异。需要进一步的研究来支持这一发现，并探索易感窗口和性别差异的机制。

关键词:BKMR;出生队列;炎性细胞因子;金属混合物;产前暴露。