Institute of Reproductive and Child Health/National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing 100191, China; Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Institute of Reproductive and Child Health/National Health Commission Key Laboratory of Reproductive Health, Peking University, Beijing 100191, China; Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.
Environ Int. 2020 Jun;139:105688. doi: 10.1016/j.envint.2020.105688. Epub 2020 Mar 31.
This study examined the associations between concentrations of cobalt (Co), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), and zinc (Zn) in placental tissue and risks for NTDs with a case-control design consisting of 408 fetuses or newborns with neural tube defects (NTDs) and 593 non-malformed fetuses or newborns. The concentrations of Zn and Fe were determined by inductively coupled plasma-emission spectrometer and the other four elements by inductively coupled plasma-mass spectrometer. Element concentrations were presented in ng/g or µg/g dry weight of placental tissue. The associations between the levels of each of the six ETEs and risk for NTDs were evaluated using multivariable logistic regression, and the associations between overall levels of all six ETEs and risk for NTDs were examined using Bayesian kernel machine regression (BKMR). Concentrations above the median concentration of all participants for an individual element were associated with increased risk for NTDs: Mn, 3.17-fold (95% CI 2.35-4.28); Mo, 3.73-fold (95% CI 2.74-5.07); Se, 3.28-fold (95% CI 2.44-4.42); and Zn, 2.85-fold (95% CI 2.13-3.83), and a decreased risk for Co [OR, 0.18 (95% CI 0.14-0.25)]. The risk for NTDs increased with the increase in the concentrations of Mn, Mo, Se, and Zn, but decreased for Co, in the second, third, and fourth quartiles, respectively, compared to their lowest quartile (all Ps < 0.01). In BKMR model, the risk for NTDs increased constantly when the overall exposure levels were higher than the median of the six ETEs as a co-exposure mixture, and the associations between Co, Mn, Se, and Zn and NTD risk remained when the remaining five elements were taken into consideration simultaneously. Taken together, when evaluated individually, higher levels of Mn, Se, and Zn in placental tissue are associated with increased risk for NTDs, while higher levels of Co are associated with decreased risk for NTDs; when examined collectively, the risk of NTDs increases continuously when exposure levels are higher than the median of the six ETE mixture.
本研究采用病例对照设计，纳入了 408 例神经管缺陷（NTD）胎儿或新生儿及 593 例非畸形胎儿或新生儿，检测了胎盘组织中钴（Co）、铁（Fe）、锰（Mn）、钼（Mo）、硒（Se）和锌（Zn）的浓度与 NTD 风险之间的关系。采用电感耦合等离子体发射光谱仪检测 Zn 和 Fe 的浓度，电感耦合等离子体质谱仪检测其余 4 种元素的浓度。元素浓度以胎盘组织干重的 ng/g 或 µg/g 表示。采用多变量逻辑回归评估了 6 种 ETE 中每一种的水平与 NTD 风险之间的关系，采用贝叶斯核机器回归（BKMR）检验了 6 种 ETE 总体水平与 NTD 风险之间的关系。对于个体元素，高于所有参与者中位数浓度的浓度与 NTD 风险增加相关：Mn，3.17 倍（95%CI 2.35-4.28）；Mo，3.73 倍（95%CI 2.74-5.07）；Se，3.28 倍（95%CI 2.44-4.42）；Zn，2.85 倍（95%CI 2.13-3.83），而 Co 的风险降低[OR，0.18（95%CI 0.14-0.25)]。与最低四分位数相比，第二、第三和第四四分位数的 Mn、Mo、Se 和 Zn 浓度分别增加（均 P<0.01），NTD 风险分别增加，而 Co 浓度降低。在 BKMR 模型中，当六种 ETE 作为共暴露混合物的总暴露水平高于中位数时，NTD 风险持续增加，当同时考虑其余五种元素时，Co、Mn、Se 和 Zn 与 NTD 风险之间的关联仍然存在。总的来说，当单独评估时，胎盘组织中 Mn、Se 和 Zn 水平升高与 NTD 风险增加相关，而 Co 水平升高与 NTD 风险降低相关；当综合评估时，当暴露水平高于六种 ETE 混合物的中位数时，NTD 风险持续增加。
