School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, No. 130 Dong'an Road, Shanghai 200032, China.
School of Public Health/Key Laboratory of Public Health Safety of Ministry of Education/Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, No. 130 Dong'an Road, Shanghai 200032, China.
Environ Int. 2020 Jun;139:105692. doi: 10.1016/j.envint.2020.105692. Epub 2020 Apr 3.
OBJECTIVE: Prenatal exposure to heavy metals, pesticides and phenols has been suggested to interfere with neurodevelopment, but the neurotoxicity of their mixtures is still unclear. We aimed to elucidate the associations of maternal urinary concentrations of selected chemical mixtures with intelligence quotient (IQ) in children. METHODS: Maternal urinary concentrations of selected heavy metals, pesticide metabolites, and phenols were quantified in pregnant women who participated in the Sheyang Mini Birth Cohort Study (SMBCS) from June 2009 to January 2010. At age 7 years, child's IQ score was assessed using the Chinese version of Wechsler Intelligence Scale for Children (C-WISC) by trained pediatricians. Generalized linear regression models (GLM), Bayesian kernel machine regression (BKMR) models and elastic net regression (ENR) models were used to assess the associations of urinary concentrations individual chemicals and their mixtures with IQ scores of the 7-year-old children. RESULTS: Of 326 mother-child pairs, single-chemical models indicated that prenatal urinary concentrations of lead (Pb) and bisphenol A (BPA) were significantly negatively associated with full intelligence quotient (FIQ) among children aged 7 years [β = -2.31, 95% confidence interval (CI): -4.13, -0.48; p = 0.013, sex interaction p-value = 0.076; β = -1.18, 95% CI: -2.21, -0.15; p = 0.025; sex interaction p-value = 0.296, for Pb and BPA, respectively]. Stratified analysis by sex indicated that the associations were only statistically significant in boys. In multi-chemical BKMR and ENR models, statistically significant inverse association was found between prenatal urinary Pb level and boy's FIQ scores at 7 years. Furthermore, BKMR analysis indicated that the overall mixture was associated with decreases in boy's IQ when all the chemicals' concentrations were at their 75th percentiles or higher, compared to at their 50th percentiles. ENR models revealed that maternal urinary Pb levels were statistically significantly associated with lower FIQ scores (β = -2.20, 95% CI: -4.20, -0.20; p = 0.031). CONCLUSIONS: Prenatal exposure to selected chemical mixtures may affect intellectual performance at 7 years of age, particularly in boys. Pb and BPA were suspected as primary chemicals associated with child neurodevelopment.
目的：有研究表明，产前暴露于重金属、农药和酚类物质会干扰神经发育，但它们混合物的神经毒性仍不清楚。本研究旨在阐明母体尿液中选定化学混合物浓度与儿童智商（IQ）的相关性。
方法：2009 年 6 月至 2010 年 1 月，参加射阳母婴队列研究（SMBCS）的孕妇采集尿液，检测其中选定的重金属、农药代谢物和酚类物质的浓度。7 岁时，由经过培训的儿科医生使用中国韦氏儿童智力量表（C-WISC）评估儿童的 IQ 得分。使用广义线性回归模型（GLM）、贝叶斯核机器回归（BKMR）模型和弹性网络回归（ENR）模型评估个体化学物质及其混合物的尿液浓度与 7 岁儿童 IQ 得分之间的相关性。
结果：在 326 对母子中，单化学物质模型表明，7 岁儿童的产前尿液中铅（Pb）和双酚 A（BPA）浓度与全智商（FIQ）呈显著负相关[β=-2.31，95%置信区间（CI）：-4.13，-0.48；p=0.013，性别交互作用 p 值=0.076；β=-1.18，95%CI：-2.21，-0.15；p=0.025；性别交互作用 p 值=0.296，分别为 Pb 和 BPA]。按性别分层分析表明，这种相关性仅在男孩中具有统计学意义。在多化学物质 BKMR 和 ENR 模型中，产前尿液中 Pb 水平与 7 岁男孩的 FIQ 分数呈显著负相关。此外，BKMR 分析表明，当所有化学物质浓度处于第 75 百分位数或更高水平时，与处于第 50 百分位数相比，母体尿液中 Pb 水平与男孩的 IQ 下降有关。ENR 模型显示，母体尿液中 Pb 水平与较低的 FIQ 得分呈统计学显著相关（β=-2.20，95%CI：-4.20，-0.20；p=0.031）。
结论：产前暴露于选定的化学混合物可能会影响 7 岁时的智力表现，特别是在男孩中。Pb 和 BPA 被怀疑是与儿童神经发育相关的主要化学物质。
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