School of Mathematics, University of Edinburgh, Peter Guthrie Tait Road, EH9 3FD Edinburgh, United Kingdom.
Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Av. Catalunya 21, 46020 Valencia, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Av. Monforte de Lemos, 3-5. Pabellón 11, 28029 Madrid, Spain.
Int J Hyg Environ Health. 2019 Apr;222(3):503-512. doi: 10.1016/j.ijheh.2019.01.007. Epub 2019 Feb 1.
Copper (Cu) is an essential element involved in biological processes; however, excessive Cu could be harmful because of its reactive nature. Very few studies have evaluated its potential neurotoxic effects. We aimed to evaluate the association between maternal Cu levels and children's neuropsychological development.
Study subjects were mother-child pairs from the Spanish INMA (i.e. Childhood and Environment) Project. Cu was measured by inductively coupled plasma mass spectrometry in serum samples taken at the first trimester of pregnancy (2003-2005). Neuropsychological development was assessed using the Bayley Scales of Infant Development (BSID) at 12 months (n = 651) and the McCarthy Scales of Children's Abilities (MSCA) at 5 years of age (n = 490). Covariates were obtained by questionnaires during pregnancy and childhood. Multivariate linear and non-linear models were built in order to study the association between maternal Cu and child neuropsychological development.
The mean ± standard deviation of maternal Cu concentrations was 1606 ± 272 μg/L. In the multivariate analysis, a negative linear association was found between maternal Cu concentrations and both the BSID mental scale (beta = -0.051; 95% confidence intervals [CI]: -0.102, -0.001) and the MSCA verbal scale (beta = -0.044; 95%CI:-0.094, 0.006). Boys obtained poorer scores than girls, with increasing Cu at 12 months (interaction p-value = 0.040 for the mental scale and 0.074 for the psychomotor scale). This effect modification disappeared at 5 years of age. The association between Cu and the MSCA scores (verbal, perceptive performance, global memory and motor, general cognitive, and executive function scales) was negative for those children with lowest maternal iron concentrations (<938μg/L).
The Cu concentrations observed in our study were within the reference range established for healthy pregnant women in previous studies. The results of this study contribute to the body of scientific knowledge with important information on the possible neurotoxic capability of Cu during pregnancy.
铜（Cu）是一种参与生物过程的必需元素；然而，由于其反应性，过多的铜可能是有害的。很少有研究评估其潜在的神经毒性作用。我们旨在评估母体铜水平与儿童神经心理发育之间的关系。
研究对象为西班牙 INMA（即儿童与环境）项目中的母婴对子。在妊娠早期（2003-2005 年）采集血清样本，用电感耦合等离子体质谱法（ICP-MS）测定 Cu 含量。12 个月时使用贝利婴幼儿发展量表（BSID）评估神经心理发育（n=651），5 岁时使用麦卡锡儿童能力量表（MSCA）评估神经心理发育（n=490）。怀孕期间和儿童期通过问卷调查获取协变量。建立了多元线性和非线性模型，以研究母体 Cu 与儿童神经心理发育之间的关系。
母体 Cu 浓度的平均值±标准差为 1606±272μg/L。在多变量分析中，母体 Cu 浓度与 BSID 心理量表（β=-0.051；95%置信区间[CI]：-0.102，-0.001）和 MSCA 言语量表（β=-0.044；95%CI：-0.094，0.006）呈负线性关系。男孩的得分低于女孩，12 个月时 Cu 浓度增加（心理量表的交互 p 值=0.040，精神运动量表的交互 p 值=0.074）。这种效应修饰在 5 岁时消失。对于母体铁浓度最低的儿童（<938μg/L），Cu 与 MSCA 评分（言语、知觉表现、整体记忆和运动、一般认知和执行功能评分）之间的关系为负相关。
我们研究中观察到的 Cu 浓度在以前研究中为健康孕妇建立的参考范围内。本研究的结果为 Cu 在怀孕期间可能具有神经毒性能力的这一科学知识提供了重要信息。
