Deficient or excessive quantities of essential trace elements (ETEs)¹ in the fetal environment can compromise developmental processes. We investigated whether concentrations of zinc (Zn), manganese (Mn), selenium (Se), cobalt (Co), molybdenum (Mo), and nickel (Ni) in umbilical cord tissue are associated with risk for neural tube defects (NTDs). Umbilical cord tissues from 166 cases of NTD cases and 166 matched controls were collected and element concentrations were measured using inductively coupled plasma-mass spectrometry. Associations between ETE concentrations and the risk for NTDs were estimated using multivariate logistic regression while adjusting for potential confounders. Bayesian kernel machine regression (BKMR) was used to examine the joint effects of these ETEs. We found that median concentrations of Ni were higher but those of Mo and Co were lower in the NTD group than in the control group. Co was the only element that was associated with NTD risk after adjusting for confounders (OR 0.31, 95% CI 0.12–0.79 for the second and OR 0.37, 95% CI 0.15–0.91 for the top tertile relative to the lowest tertile). The association between Co and NTD risk was confirmed with the BKMR model. In addition, a joint effect of the six ETE mixture on NTD risk was observed: the risk decreased with the levels of the mixture from 25^th percentile through 75^th percentile. In conclusion, higher levels of Co were associated with lower risk for NTDs, and NTD risk decreased with the levels of the six ETEs as a co-exposure mixture, suggesting a protective effect.

必需微量元素 (ETE) 不足或过量¹在胎儿环境中会损害发育过程。我们调查了脐带组织中锌 (Zn)、锰 (Mn)、硒 (Se)、钴 (Co)、钼 (Mo) 和镍 (Ni) 的浓度是否与神经管缺陷 (NTD) 的风险相关. 收集来自 166 例 NTD 病例和 166 例匹配对照的脐带组织，并使用电感耦合等离子体质谱法测量元素浓度。ETE 浓度与 NTD 风险之间的关联使用多变量逻辑回归估计，同时调整潜在的混杂因素。贝叶斯核机器回归 (BKMR) 用于检查这些 ETE 的联合效应。我们发现 NTD 组中 Ni 的中位数浓度较高，但 Mo 和 Co 的浓度低于对照组。在调整混杂因素后，Co 是唯一与 NTD 风险相关的因素（第二个 OR 0.31，95% CI 0.12–0.79，最高三分位相对于最低三分位的 OR 0.37，95% CI 0.15–0.91）。BKMR 模型证实了 Co 和 NTD 风险之间的关联。此外，还观察到 6 种 ETE 混合物对 NTD 风险的联合影响：风险随着混合物水平从 25^第75^个百分位数。总之，较高水平的 Co 与较低的 NTD 风险相关，并且 NTD 风险随着六种 ETE 作为共同暴露混合物的水平而降低，表明具有保护作用。