Associations of maternal exposure to 41 metals/metalloids during early pregnancy with the risk of spontaneous preterm birth: Does oxidative stress or DNA methylation play a crucial role?,Environment International

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Associations of maternal exposure to 41 metals/metalloids during early pregnancy with the risk of spontaneous preterm birth: Does oxidative stress or DNA methylation play a crucial role?
Environment International ( IF 10.3 ) Pub Date : 2021-11-01 , DOI: 10.1016/j.envint.2021.106966
Ruiwei Xu ₁ , Xin Meng ₁ , Yiming Pang ₂ , Hang An ₂ , Bin Wang ₂ , Le Zhang ₂ , Rongwei Ye ₂ , Aiguo Ren ₂ , Zhiwen Li ₂ , Jicheng Gong ₁

Affiliation

Background

Few studies have explored the effects of multiple types of metals/metalloids on spontaneous preterm birth (SPB). A nested case–control study was conducted in Shanxi Province to investigate the associations between maternal exposure to 41 metals/metalloids during early pregnancy and the risk of SPB, and to clarify the underlying mechanisms of oxidative stress and DNA methylation.

Methods

A total of 74 controls with full-term delivery and 74 cases with SPB were included in the nested case–control study. The metals/metalloids in serum and the DNA adducts in peripheral blood cell DNA were determined using ICP-MS and UPLC-QqQ-MS/MS, respectively. Unconditional logistic regression models were employed to estimate the associations of the risk of SPB with the metal concentrations, as well as with the levels of oxidative stress/DNA methylation. In addition, linear regression models were used to investigate the associations between the metal/metalloid concentrations and the levels of oxidative stress/DNA methylation.

Results

After adjusting for potential confounders, the concentrations of Mn, Fe, Cu, Nd, Hg, and Pb in maternal serum during early pregnancy were positively associated with the risk of SPB. Compared with the lowest levels (Quartile 1) of Mn, Fe, Cu, Nd, Hg, and Pb, the odds ratios of SPB increased to 5.21 (95% CI: 1.63, 16.68), 3.47 (95% CI: 1.07, 11.21), 16.23 (95% CI: 3.86, 68.18), 10.54 (95% CI: 2.79, 39.86), 5.88 (95% CI: 1.72, 20.11), and 4.09 (95% CI: 1.31, 12.77) in the highest levels (Quartile 4), respectively. A significant increase in 8-OHdG was associated with the increased exposure to Fe, Pr, Eu, Er, and Lu. The levels of 5-MdC, 5-HmdC, and N6-MdA—the indicators of DNA methylation—were associated with exposure to multiple metals/metalloids. However, no significant associations were observed between the levels of oxidative stress or DNA methylation and the risk of SPB.

Conclusions

Exposure to multiple types of metals/metalloids during early pregnancy is positively associated with the risk of SPB. Oxidative stress and DNA methylation are significantly associated with exposure to multiple metals/metalloids. Systemic oxidative stress and DNA methylation have not been proven to be the mediating mechanisms of metals increasing the risk of SPB.

中文翻译：

孕早期母亲暴露于 41 种金属/类金属与自发早产风险的关联：氧化应激或 DNA 甲基化是否起关键作用？

背景

很少有研究探讨多种金属/准金属对自发性早产 (SPB) 的影响。在山西省进行了一项巢式病例对照研究，以调查母亲在妊娠早期接触 41 种金属/类金属与 SPB 风险之间的关系，并阐明氧化应激和 DNA 甲基化的潜在机制。

方法

巢式病例对照研究共纳入 74 名足月分娩对照和 74 名 SPB 病例。分别使用 ICP-MS 和 UPLC-QqQ-MS/MS 测定血清中的金属/准金属和外周血细胞 DNA 中的 DNA 加合物。采用无条件逻辑回归模型来估计 SPB 风险与金属浓度以及氧化应激/DNA 甲基化水平的关联。此外，线性回归模型用于研究金属/准金属浓度与氧化应激/DNA甲基化水平之间的关联。

结果

调整潜在混杂因素后，妊娠早期母体血清中 Mn、Fe、Cu、Nd、Hg 和 Pb 的浓度与 SPB 风险呈正相关。与 Mn、Fe、Cu、Nd、Hg 和 Pb 的最低水平（四分位数 1）相比，SPB 的优势比增加到 5.21（95% CI：1.63、16.68）、3.47（95% CI：1.07、11.21） )、16.23 (95% CI: 3.86, 68.18)、10.54 (95% CI: 2.79, 39.86)、5.88 (95% CI: 1.72, 20.11) 和 4.09 (95% CI: 1.31, 12.77) 处于最高水平（四分位数 4），分别。8-OHdG 的显着增加与对 Fe、Pr、Eu、Er 和 Lu 的暴露增加有关。5-MdC、5-HmdC 和 N6-MdA（DNA 甲基化的指标）的水平与接触多种金属/准金属有关。然而，