产前接触有机磷酸酯可能会对学龄前儿童行为产生影响，并可能是由妊娠相关焦虑驱动

Pregnancy-related anxiety modifies the effects of maternal exposure to organophosphate esters on preschoolers' behavioral development

与妊娠有关的焦虑会改变母体接触有机磷酸酯对学龄前儿童行为发育的影响

Authors：Mengjuan Lu, Feifei Han, Yuan Liu, Hong Gan, Xiaorui Wang, Fu Zhang, Juan Tong, Kun Huang, Shuangqin Yan, Shuman Tao, Fangbiao Tao

Source：Environmental Research

PMID: 39923820

DOI: 10.1016/j.envres.2025.121081

Abstract

Longitudinal associations with psychological factors modifying the effects of chemicals have not been sufficiently explored in epidemiologic studies. Our birth cohort study is the first to assess the associations between prenatal organophosphate ester (OPE) exposure and child behavior and to determine whether these associations change with pregnancy-related anxiety (PRA). Ultra-performance liquid chromatography‒tandem mass spectrometry (LC‒MS) was used to measure the tris(2-chloroethyl) phosphate (TCEP) and OPE metabolites in the 1st, 2nd and 3rd trimester urine samples. The evaluation of the behavioral development of children aged 4 years was based on the Chinese version of the Child Behavior Checklist (CBCL 1.5-5) from the main caregivers' reports. Two PRA groups (anxiety vs. nonanxiety) were identified using growth mixture models (GMMs). Generalized linear models (GLMs) and quantile-based g-computation (QGC) models were established to assess the effects of individual OPEs and a mixture of OPEs on preschoolers' behaviors stratified by PRA. Among the 1148 mother‒child pairs, GLMs revealed that, in the 1st trimester, children in the highest tertile of dibutyl phosphate (DBP) concentration presented remarkably greater behavioral problem scores than did those in the lowest tertile. First-trimester diphenyl phosphate (DPHP) was positively associated with internalizing problem scores, whereas bis(2-ethylhexyl) phosphate (BEHP) was negatively associated with behavioral problem scores. Third-trimester bis(1-chloro-2-propyl) phosphate (BCIPP) was associated with increased internalizing problem scores. Notably, positive associations between 1st trimester DBP, 2nd trimester DPHP and 3rd trimester BCIPP and behavioral problem scores were stronger among children of mothers with PRA. Using the QGC model, when the analysis was performed separately in the anxiety group, significant associations were found between the mixture of OPEs during the 3rd trimester and internalizing (β = 4.25, 95% CI: 0.24, 8.26) and total problem scores (β = 3.97, 95% CI: 0.64, 7.30). Prenatal OPE exposure may impair preschoolers' behavior, and this effect is potentially driven by PRA.

Keywords: Anxiety; Behavior; Birth cohort; Neurodevelopment; Organophosphate flame retardants.

摘要：

流行病学研究尚未充分探讨心理因素对化学品影响的纵向关联。我们的出生队列研究首次评估了产前有机磷酸酯（OPE）暴露与儿童行为之间的关联，并确定了这些关联是否会随着妊娠相关焦虑（PRA）而发生变化。研究采用超高效液相色谱-串联质谱法（LC-MS）测量了第一、第二和第三孕期尿液样本中的磷酸三（2-氯乙基）酯（TCEP）和 OPE 代谢物。对 4 岁儿童行为发育的评估基于主要照顾者报告的中文版儿童行为检查表（CBCL 1.5-5）。利用生长混合模型（GMM）确定了两个 PRA 组（焦虑组和非焦虑组）。建立了广义线性模型（GLMs）和基于量级的 g 计算（QGC）模型，以评估按 PRA 分层的单个 OPE 和混合 OPE 对学龄前儿童行为的影响。在 1148 对母子中，GLM 显示，在妊娠头三个月，磷酸二丁酯 (DBP) 浓度最高三等分的儿童的行为问题得分明显高于最低三等分的儿童。第一孕期的磷酸二苯酯（DPHP）与内化问题得分呈正相关，而磷酸二（2-乙基己基）酯（BEHP）与行为问题得分呈负相关。第三孕期双（1-氯-2-丙基）磷酸酯（BCIPP）与内化问题得分增加有关。值得注意的是，在患有 PRA 的母亲的子女中，怀孕三个月前的 DBP、怀孕三个月后的 DPHP 和怀孕三个月后的 BCIPP 与行为问题得分之间的正相关性更强。使用 QGC 模型，在焦虑组中单独进行分析时，发现怀孕三个月期间的 OPE 混合与内化（β = 4.25，95% CI：0.24，8.26）和问题总分（β = 3.97，95% CI：0.64，7.30）之间存在显著关联。产前接触 OPE 可能会损害学龄前儿童的行为，而这种影响可能是由 PRA 驱动的。

关键词：焦虑；行为；出生队列；神经发育；有机磷阻燃剂