Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ 08854, USA; Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, NJ 08854, USA.
Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA 98101, USA.
Environ Int. 2024 Jan;183:108425. doi: 10.1016/j.envint.2024.108425. Epub 2024 Jan 4.
Prenatal exposures to chemical and psychosocial stressors can impact the developing brain, but few studies have examined their joint effects. We examined associations between prenatal phthalate exposures and child behavior, hypothesizing that prenatal stressful life events (PSLEs) may exacerbate risks. To do so, we harmonized data from three U.S. pregnancy cohorts comprising the ECHO-PATHWAYS consortium. Phthalate metabolites were measured in single mid-pregnancy urine samples. When children were ages 4-6 years, mothers completed the Child Behavior Checklist (CBCL), from which a Total Problems score was calculated. Mothers additionally provided recall on their exposure to 14 PSLEs during pregnancy. Primary models examined problem behaviors in relation to: (1) phthalate mixtures calculated through weighted quantile sums regression with permutation test-derived p-values; and (2) joint exposure to phthalate mixtures and PSLEs (counts) using interaction terms. We subsequently refitted models stratified by child sex. Secondarily, we fit linear and logistic regression models examining individual phthalate metabolites. In our main, fully adjusted models (n = 1536 mother-child dyads), we observed some evidence of weak main effects of phthalate mixtures on problem behaviors in the full cohort and stratified by child sex. Interaction models revealed unexpected relationships whereby greater gestational exposure to PSLEs predicted reduced associations between some phthalates (e.g., the metabolites of di-2-ethylhexyl phthalate, di-n-octyl phthalate, di-iso-nonyl phthalate) and problem behaviors, particularly in males. Few associations were observed in females. Additional research is needed to replicate results and examine potential mechanisms.
产前暴露于化学和心理社会应激源会影响发育中的大脑，但很少有研究检查它们的联合效应。我们研究了产前邻苯二甲酸酯暴露与儿童行为之间的关联，假设产前应激性生活事件（PSLE）可能会加剧风险。为此，我们协调了来自美国三个妊娠队列的数据，这些队列构成了 ECHO-PATHWAYS 联盟。在妊娠中期的单次尿液样本中测量了邻苯二甲酸酯代谢物。当孩子 4-6 岁时，母亲完成了儿童行为检查表（CBCL），从中计算出总问题分数。母亲还提供了怀孕期间接触 14 种 PSLE 的回忆。主要模型研究了问题行为与以下方面的关系：（1）通过加权分位数总和回归与置换检验衍生的 p 值计算的邻苯二甲酸酯混合物；（2）通过交互项联合暴露于邻苯二甲酸酯混合物和 PSLE（计数）。随后，我们根据孩子的性别分层重新拟合模型。其次，我们拟合了线性和逻辑回归模型，以检查个别邻苯二甲酸酯代谢物。在我们的主要、完全调整的模型（n=1536 对母子对）中，我们观察到一些证据表明，邻苯二甲酸酯混合物对全队列和按性别分层的问题行为有较弱的主要影响。交互模型显示出意想不到的关系，即 PSLE 的更大妊娠暴露预测了一些邻苯二甲酸酯（例如，邻苯二甲酸二（2-乙基己基）酯、邻苯二甲酸二正辛酯、邻苯二甲酸二异壬酯的代谢物）与问题行为之间的关联减少，尤其是在男性中。在女性中观察到的关联很少。需要进一步的研究来复制结果并检查潜在的机制。
