SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China; Center for Environment and Health, Peking University, Beijing 100871, China.
Institute of Reproductive and Child Health, Peking University/Key Laboratory of Reproductive Health, National Health Commission of the People's Republic of China, Beijing 100191, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.
Environ Int. 2022 Jan;158:106966. doi: 10.1016/j.envint.2021.106966. Epub 2021 Nov 1.
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.
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.
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.
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.
很少有研究探讨多种类型的金属/类金属对自发性早产（SPB）的影响。本研究在山西省进行了一项嵌套病例对照研究，旨在探讨孕妇妊娠早期暴露于 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。
本嵌套病例对照研究共纳入 74 例足月分娩的对照和 74 例 SPB 病例。采用 ICP-MS 和 UPLC-QqQ-MS/MS 分别检测血清中的金属/类金属和外周血单个核细胞 DNA 中的 DNA 加合物。采用非条件 logistic 回归模型估计金属浓度与 SPB 风险之间的关联，以及氧化应激/DNA 甲基化水平之间的关联。此外，还采用线性回归模型研究金属/类金属浓度与氧化应激/DNA 甲基化水平之间的关系。
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 的比值比分别增加到 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）（四分位数 4）。Fe、Pr、Eu、Er 和 Lu 暴露量增加与 8-OHdG 显著升高有关。5-MdC、5-HmdC 和 N6-MdA——DNA 甲基化的指标——与多种金属/类金属的暴露有关。然而，氧化应激或 DNA 甲基化水平与 SPB 风险之间没有观察到显著关联。
妊娠早期暴露于多种类型的金属/类金属与 SPB 风险呈正相关。氧化应激和 DNA 甲基化与多种金属/类金属的暴露显著相关。系统性氧化应激和 DNA 甲基化尚未被证明是金属增加 SPB 风险的中介机制。
