University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of Environmental Epidemiology Applied to Development and Respiratory Health, Institute for Advanced Biosciences, Grenoble, France.
Pediatric Department, Grenoble Alpes University Hospital, La Tronche, France.
Environ Health Perspect. 2023 Aug;131(8):87006. doi: 10.1289/EHP11798. Epub 2023 Aug 9.
Previous studies aiming at relating exposure to phenols and phthalates with child social behavior characterized exposure using one or a few spot urine samples, resulting in substantial exposure misclassification. Moreover, early infancy exposure was rarely studied.
We aimed to examine the associations of phthalates and phenols with child social behavior in a cohort with improved exposure assessment and to identify the chemicals supported by a higher weight of evidence.
Among 406 mother-child pairs from the French Assessment of Air Pollution exposure during Pregnancy and Effect on Health (SEPAGES) cohort, 25 phenols/phthalate metabolites were measured in within-subject pools of repeated urine samples collected at the second and third pregnancy trimesters ( samples/trimester) and at 2 months and 1-year of age ( samples/period). Social behavior was parent-reported at 3 years of age of the child using the Social Responsiveness Scale (SRS). A structured literature review of the animal and human evidence was performed to prioritize the measured phthalates/phenols based on their likelihood to affect social behavior. Both adjusted linear regression and Bayesian Weighted Quantile Sum (BWQS) regression models were fitted. False discovery rate (FDR) correction was applied only to nonprioritized chemicals.
Prioritized compounds included bisphenol A, bisphenol S, triclosan (TCS), diethyl-hexyl phthalate (), mono-ethyl phthalate (MEP), mono--butyl phthalate (MnBP), and mono-benzyl phthalate (MBzP). With the exception of bisphenols, which showed a mixed pattern of positive and negative associations in pregnant mothers and neonates, few prenatal associations were observed. Most associations were observed with prioritized chemicals measured in 1-y-old infants: Each doubling in urinary TCS (; 95% CI: 0.00, 1.55) and MEP (; 95% CI: , 1.96) concentrations were associated with worse total SRS scores, whereas MnBP and were associated with worse Social Awareness (; 95% CI: 0.01, 0.50) and Social Communication (; 95% CI: , 0.89) scores, respectively. BWQS also suggested worse total SRS [; 95% credible interval (CrI): , 2.97], Social Awareness (; 95% CrI: 0.06, 0.70), and Social Communication (; 95% CrI: 0.31, 1.53) scores per quartile increase in the mixture of prioritized compounds assessed in 1-y-old infants. The few associations observed with nonprioritized chemicals did not remain after FDR correction, with the exception of benzophenone-3 exposure in 1-y-old infants, which was suggestively associated with worse Social Communication scores (corrected ).
The literature search allowed us to adapt our statistical analysis according to the weight of evidence and create a corpus of experimental and epidemiological knowledge to better interpret our findings. Early infancy appears to be a sensitive exposure window that should be further investigated. https://doi.org/10.1289/EHP11798.
之前的研究旨在将酚类和邻苯二甲酸酯类暴露与儿童社会行为相关联，这些研究使用一个或几个点尿样来描述暴露情况，这导致了大量的暴露分类错误。此外，很少有研究关注婴儿早期的暴露情况。
我们旨在通过一项改善暴露评估的队列研究，检查邻苯二甲酸酯和酚类与儿童社会行为之间的关系，并确定有更多证据支持的化学物质。
在法国空气污染暴露评估及其对健康影响（SEPAGES）队列的 406 对母婴中，在妊娠第二个和第三个三个月（每个妊娠周期采集的样本数）和 2 个月及 1 岁时，对重复尿液样本进行了 25 种酚类/邻苯二甲酸酯代谢物的亚个体池检测（每个时期采集的样本数）。在孩子 3 岁时，通过社会反应量表（SRS）由家长报告其社会行为。对动物和人类证据进行了结构化文献综述，根据其对社会行为产生影响的可能性，对测量的邻苯二甲酸酯/酚类进行了优先级排序。分别采用调整后的线性回归和贝叶斯加权和（BWQS）回归模型进行拟合。仅对非优先级排序的化学物质进行了错误发现率（FDR）校正。
被优先考虑的化合物包括双酚 A、双酚 S、三氯生（TCS）、邻苯二甲酸二乙基己酯（）、邻苯二甲酸单乙酯（MEP）、邻苯二甲酸单--丁酯（MnBP）和邻苯二甲酸单苄酯（MBzP）。除双酚类物质外，这些物质在孕妇和新生儿中表现出正相关和负相关的混合模式，很少有产前关联。大多数关联与在 1 岁婴儿中测量的优先考虑的化学物质有关：TCS 尿液浓度每增加一倍（ ；95%可信区间：0.00，1.55）和 MEP （ ；95%可信区间： ，1.96）与 SRS 总分较差相关，而 MnBP 和 与社会意识（ ；95%可信区间：0.01，0.50）和社会沟通（ ；95%可信区间： ，0.89）得分较差有关。BWQS 还表明，总 SRS [ ；95%可信区间（CrI）： ，2.97]、社会意识（ ；95%CrI：0.06，0.70）和社会沟通（ ；95%CrI：0.31，1.53）的得分在 1 岁婴儿中优先考虑的化合物混合物每增加一个四分位数都有所下降。在经过 FDR 校正后，除了 1 岁婴儿中苯甲酮-3 的暴露外，非优先级排序的化学物质与几个关联不再显著，苯甲酮-3 与社会沟通评分较差有关（校正后 ）。
文献检索使我们能够根据证据权重调整我们的统计分析，并创建一个实验和流行病学知识的语料库，以更好地解释我们的发现。婴儿早期似乎是一个敏感的暴露窗口，应该进一步研究。https://doi.org/10.1289/EHP11798.
