Background

Lead (Pb), manganese (Mn), selenium (Se) and methylmercury (MeHg) can be neurotoxic individually, despite Mn and Se also being essential elements. Little is known about the joint effects of essential and non-essential elements on neurobehavior, particularly for prenatal exposures.

Objectives

To evaluate associations of prenatal exposure to multiple elements with executive function and neurobehavior in children.

Methods

Participants included 1009 mother-child pairs from the Project Viva pre-birth cohort. We estimated maternal erythrocyte Pb, Mn, Se, and Hg concentrations prenatally. In 6-11-year old children (median 7.6 years), parents and teachers rated children's executive function-related behaviors using the Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite score and behavioral difficulties using the Strengths and Difficulties Questionnaire (SDQ) total difficulties score. We evaluated associations of element mixtures with neurobehavior using Bayesian kernel machine regression (BKMR), multivariable linear regression, and quantile g-computation.

Results

Median erythrocyte Pb, Mn, Se, and Hg concentrations were 1.1 μg/dL, 33.1 μg/L, 204.5 ng/mL, and 3.1 ng/g, respectively. Findings from BKMR and quantile g-computation models both showed worse (higher) parent-rated BRIEF and SDQ z-scores with higher concentrations of the mixture, although estimates were imprecise. When remaining elements were set at their median within BKMR models, increases in Pb and Se from the 25th to 75th percentile of exposure distributions were associated with 0.08 (95% CI: 0.02, 0.19) and 0.07 (95% CI: 0.03, 0.16) standard deviation increases in parent-rated BRIEF scores, and 0.08 (95% CI: 0.02, 0.17) and 0.05 (95% CI: 0.03, 0.13) standard deviation increases in SDQ scores, respectively. There was no evidence of element interactions.

Discussion

Although associations were small in magnitude, we found a trend of worsening neurobehavioral ratings with increasing prenatal exposure to an element mixture. However, we may be observing a limited range of dose-dependent impacts given the levels of exposure within our population.

中文翻译：

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产前暴露于儿童中期混合元素和神经行为结果：Project Viva 的结果

背景

尽管 Mn 和 Se 也是必不可少的元素，但铅 (Pb)、锰 (Mn)、硒 (Se) 和甲基汞 (MeHg) 可能分别具有神经毒性。关于必需元素和非必需元素对神经行为的联合影响知之甚少，特别是对于产前暴露。

目标

评估产前接触多种元素与儿童执行功能和神经行为的关系。

方法

参与者包括来自 Project Viva 出生前队列的 1009 对母子。我们在产前估计了母体红细胞 Pb、Mn、Se 和 Hg 浓度。在 6-11 岁儿童（中位数 7.6 岁）中，家长和教师使用执行功能行为评级清单 (BRIEF) 全球执行功能综合评分和使用优势和困难问卷 (SDQ) 的行为困难对儿童的执行功能相关行为进行评级) 总难度分数。我们使用贝叶斯核机器回归 (BKMR)、多变量线性回归和分位数 g 计算评估了元素混合物与神经行为的关联。

结果

红细胞中 Pb、Mn、Se 和 Hg 浓度分别为 1.1 μg/dL、33.1 μg/L、204.5 ng/mL 和 3.1 ng/g。BKMR 和分位数 g 计算模型的结果都显示出更差（更高）的父级评价的 BRIEF 和 SDQ z 分数与更高浓度的混合物，尽管估计是不精确的。当其余元素在 BKMR 模型中设置为中位数时，Pb 和 Se 从暴露分布的第 25 个百分位到第 75 个百分位的增加与 0.08（95% CI：0.02，0.19）和 0.07（95% CI：0.03，0.16）相关父母评定的BRIEF分数的标准差增加，SDQ分数的标准差分别增加0.08（95% CI：0.02、0.17）和0.05（95% CI：0.03、0.13）。没有元素相互作用的证据。

讨论

尽管关联的幅度很小，但我们发现随着产前接触元素混合物的增加，神经行为评级恶化的趋势。然而，鉴于我们人口中的暴露水平，我们可能会观察到有限范围的剂量依赖性影响。