Prenatal placental metal accumulation and its association with child attention deficit/hyperactivity disorder and autism spectrum disorder symptom at 3 years of age: The role of psychosocial-environmental support in infancy

产前胎盘金属蓄积及其与 3 岁儿童注意缺陷/多动障碍和自闭症谱系障碍症状的关联：婴儿期社会心理环境支持的作用

Authors：Jixing Zhou, Juan Tong, Chunmei Liang, Penggui Wu, Jiajun Ouyang, Wenjin Cai, Jie Sheng, Guopeng Gao, Shuangqin Yan, Fangbiao Tao, Kun Huang

Source：Environmental Research

PMID: 40058545

DOI: 10.1016/j.envres.2025.121294

Abstract

The placenta is recognized as a barrier to the passage of harmful substances and is an ideal biomonitoring sample for assessing cumulative prenatal exposure to metals. However, scientific knowledge is insufficient regarding the effects of cumulative prenatal exposure to metal mixtures on behavioral development in early life. This study included 2154 mother-infant pairs from the Ma'anshan Birth Cohort study. Concentrations of eleven metals in the placenta were quantified, and attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) symptom were assessed in 3-year-old children. Thrive factor (T-factor) scores, derived from factors such as breastfeeding, sleep, parenting style, secondhand smoke exposure, family income, and parental absence, were calculated during infancy. It was found that elevated concentrations of cadmium (Cd) (OR: 1.36, 95% CI: 1.06, 1.75), manganese (Mn) (OR: 1.34, 95% CI: 1.02, 1.77), and copper (Cu) (OR: 1.53, 95% CI: 1.05, 2.23) in the placenta were associated with increased ADHD risk in children. Additionally, arsenic (As) showed a moderate association with ADHD risk (OR: 1.34, 95% CI: 0.99, 1.83). Results from the Bayesian Kernel Machine Regression (BKMR) model indicated significant positive associations between the mixture of placental metals and ADHD symptom risk when all eleven metal concentrations were elevated. The quantile-based g-computation (Qgcomp) approach also suggested a nearly significant association between the total mixture of eleven metals/elements and ADHD symptom risk (OR: 1.27, 95% CI: 0.97, 1.65). Among the metals, Cd was the largest contributor to the positive association, followed closely by Cu, cobalt (Co), Mn, mercury (Hg), As, and chromium (Cr). Conversely, zinc (Zn) was the largest contributor to the negative association, followed by selenium (Se) and lead (Pb). Further analysis revealed that a simultaneous increase in metal concentrations (Cd, Cu, Co, Mn, Hg, As, and Cr) by one quartile was significantly associated with ADHD symptom risk (OR: 1.31, 95% CI: 1.03, 1.69). Moreover, higher T-factor scores, composed of breastfeeding, sleep, parenting style, secondhand smoke exposure, household income, and parental absence, were significantly associated with decreased ADHD and ASD symptom risk at age 3. We observed a gradual attenuation or even disappearance of the associations of placental Cu and Mn with ADHD symptom as T-factor scores increased. Our findings suggest that Cd, Cu, and Mn are key metals associated with ADHD risk in early life, and that psychosocial environmental factors in infancy are potential modifiers of these associations.

Keywords: ADHD; ASD; Cohort; Metal; Placenta.

摘要：

胎盘被公认为是阻止有害物质通过的屏障，也是评估产前金属累积暴露情况的理想生物监测样本。然而，关于产前累积暴露于金属混合物对儿童早期行为发育的影响，科学认知尚显不足。本研究纳入了来自马鞍山出生队列研究的2154对母婴。对胎盘中11种金属的浓度进行了定量检测，并对3岁儿童的注意缺陷/多动障碍（ADHD）和自闭症谱系障碍（ASD）症状进行了评估。在婴儿期计算了由母乳喂养、睡眠、养育方式、二手烟暴露、家庭收入和父母缺位等因素得出的茁壮成长因子（T因子）得分。研究发现，胎盘中镉（Cd）浓度升高（优势比（OR）：1.36，95%置信区间（CI）：1.06 - 1.75）、锰（Mn）浓度升高（OR：1.34，95% CI：1.02 - 1.77）和铜（Cu）浓度升高（OR：1.53，95% CI：1.05 - 2.23）与儿童患ADHD的风险增加有关。此外，砷（As）与ADHD风险存在适度关联（OR：1.34，95% CI：0.99 - 1.83）。贝叶斯核机器回归（BKMR）模型的结果显示，当11种金属的浓度均升高时，胎盘金属混合物与ADHD症状风险之间存在显著的正相关。基于分位数的g计算（Qgcomp）方法也表明，11种金属/元素的总混合物与ADHD症状风险之间几乎存在显著关联（OR：1.27，95% CI：0.97 - 1.65）。在这些金属中，Cd对这种正相关的贡献最大，紧随其后的是Cu、钴（Co）、Mn、汞（Hg）、As和铬（Cr）。相反，锌（Zn）对负相关的贡献最大，其次是硒（Se）和铅（Pb）。进一步分析显示，金属（Cd、Cu、Co、Mn、Hg、As和Cr）浓度同时升高一个四分位数与ADHD症状风险显著相关（OR：1.31，95% CI：1.03 - 1.69）。此外，由母乳喂养、睡眠、养育方式、二手烟暴露、家庭收入和父母缺位等因素构成的T因子得分越高，3岁时儿童患ADHD和ASD症状的风险显著降低。我们观察到，随着T因子得分的增加，胎盘Cu和Mn与ADHD症状之间的关联逐渐减弱甚至消失。我们的研究结果表明，Cd、Cu和Mn是与儿童早期ADHD风险相关的关键金属，婴儿期的社会心理环境因素可能会改变这些关联。

关键词：注意缺陷/多动障碍；自闭症谱系障碍；队列研究；金属；胎盘。