Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Karlstad University, Karlstad, Sweden.
Environ Int. 2020 Jan;134:105185. doi: 10.1016/j.envint.2019.105185. Epub 2019 Oct 24.
Endocrine disrupting chemicals (EDCs) are xenobiotics with the ability to interfere with hormone action, even at low levels. Prior environmental epidemiology studies link numerous suspected EDCs, including phthalates and bisphenol A (BPA), to adverse neurodevelopmental outcomes. However, results for some chemicals were inconsistent and most assessed one chemical at a time.
To evaluate the overall impact of prenatal exposure to an EDC mixture on neurodevelopment in school-aged children, and identify chemicals of concern while accounting for co-exposures.
Among 718 mother-child pairs from the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA) study, we used Weighted Quantile Sum (WQS) regression to assess the association between 26 EDCs measured in 1st trimester urine or blood, with Wechsler Intelligence Scale for Children (IV) Intelligence Quotient (IQ) scores at age 7 years. Models were adjusted for child sex, gestational age, mother's education, mother's IQ (RAVEN), weight, and smoking status. To evaluate generalizability, we conducted repeated holdout validation, a machine learning technique.
Using repeated holdout validation, IQ scores were 1.9-points (CI = -3.6, -0.2) lower among boys for an inter-quartile-range (IQR) change in the WQS index. BPF made the largest contribution to the index with a weight of 14%. Other chemicals of concern and their weights included PBA (9%), TCP (9%), MEP (6%), MBzP (4%), PFOA (6%), PFOS (5%), PFHxS (4%), Triclosan (5%), and BPA (4%). While we did observe an inverse association between EDCs and IQ among all children when training and testing the WQS index estimate on the full dataset, these results were not robust to repeated holdout validation.
Among boys, early prenatal exposure to EDCs was associated with lower intellectual functioning at age 7. We identified bisphenol F as the primary chemical of concern, suggesting that the BPA replacement compound may not be any safer for children. Future studies are needed to confirm the potential neurotoxicity of replacement analogues.
内分泌干扰化学物质(EDCs)是具有干扰激素作用能力的外源性化学物质,即使在低水平下也是如此。先前的环境流行病学研究将许多疑似 EDCs(包括邻苯二甲酸酯和双酚 A(BPA))与不良神经发育结局联系起来。然而,对于某些化学物质的研究结果并不一致,而且大多数研究一次只评估一种化学物质。
评估产前暴露于 EDC 混合物对学龄儿童神经发育的总体影响,并在考虑共同暴露的情况下确定关注的化学物质。
在瑞典环境纵向、母婴、哮喘和过敏研究(SELMA)研究的 718 对母婴中,我们使用加权分位数总和(WQS)回归来评估在妊娠早期尿液或血液中测量的 26 种 EDC 与 7 岁时韦氏儿童智力量表(第四版)智商(IQ)得分之间的关系。模型调整了儿童性别、胎龄、母亲教育程度、母亲智商(RAVEN)、体重和吸烟状况。为了评估通用性,我们进行了重复预留验证,这是一种机器学习技术。
使用重复预留验证,男孩的 IQ 得分比 WQS 指数的 IQR 变化低 1.9 分(CI=-3.6,-0.2)。BPF 对指数的贡献最大,权重为 14%。其他关注的化学物质及其权重包括 PBA(9%)、TCP(9%)、MEP(6%)、MBzP(4%)、PFOA(6%)、PFOS(5%)、PFHxS(4%)、三氯生(5%)和 BPA(4%)。虽然我们在整个数据集上训练和测试 WQS 指数估计值时观察到 EDCs 与 IQ 之间存在反比关系,但这些结果在重复预留验证中并不稳健。
在男孩中,早期产前暴露于 EDCs 与 7 岁时的智力功能较低有关。我们确定双酚 F 是主要关注的化学物质,这表明 BPA 的替代化合物对儿童可能并不更安全。需要进一步的研究来确认替代类似物的潜在神经毒性。