Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA; Division of Epidemiology and Biostatistics, School of Public Health, College of Health and Human Services, San Diego State University, San Diego, CA, USA.
Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
Int J Hyg Environ Health. 2024 Jul;260:114407. doi: 10.1016/j.ijheh.2024.114407. Epub 2024 Jun 15.
Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited.
We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture.
The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident.
We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.
执行功能在儿童期迅速发展，使他们能够解决问题、集中注意力和规划。孕妇接触环境中的有毒物质可能会损害儿童健康的执行功能发育。鉴于多环芳烃 (PAH) 能够穿过胎盘和胎儿的血脑屏障，人们越来越关注它们，但来自流行病学研究的证据有限。
我们在 ECHO-PATHWAYS 联盟的两个美国队列中，检查了 814 名不吸烟母亲的孩子在怀孕期间接触多环芳烃与执行功能之间的关系。在妊娠中期尿液中测量了七种单羟基化 PAH 代谢物，并分别和混合分析。在 8-9 岁时测量了三个执行功能领域：认知灵活性、工作记忆和抑制控制。进一步计算了量化整体表现的综合评分。我们拟合了线性回归模型，调整了社会人口统计学、孕产妇健康行为和心理测量因素，并检查了儿童性别和妊娠期间的生活压力事件的修饰作用。进行了贝叶斯核机器回归以估计 PAH 混合物的交互和总体效应。
线性回归的主要分析结果通常为零，并且没有表明儿童性别或母亲压力有任何修饰作用。混合物分析表明，在工作记忆方面，个别 PAH 代谢物之间存在几种相互作用，方向各不相同，特别是 2/3/9-FLUO 和其他 PAH 代谢物之间的相互作用，但没有明显的整体或个体效应。
我们在两个队列的大型合并样本中对 PAH-执行功能的关联进行了新颖的探索。尽管发现主要为零，但该研究对未来的研究具有重要意义，并为发育起源疾病的不断发展的科学做出了贡献。
