产前共暴露于有机磷酸酯和邻苯二甲酸酯会增加学龄前儿童胰岛素抵抗降低胰岛素敏感性

Sex- and trimester-specific impact of gestational co-exposure to organophosphate esters and phthalates on insulin action among preschoolers: Findings from the Ma’anshan Birth Cohort

妊娠期共暴露于有机磷酸酯和邻苯二甲酸酯对学龄前儿童胰岛素作用的性别和孕期特异性影响:来自马鞍山优生优育队列的发现

Authors: Hong Gan^#, Mengjuan Lu^#, Juan Tong, Huijuan Li, Qiong Zhou, Feifei Han, Xiaorui Wang, Shuangqin Yan, Kun Huang, Qunan Wang, Xiaoyan Wu, Beibei Zhu^*, Hui Gao^*, Fangbiao Tao^*

Source: Environment International

DOI: 10.1016/j.envint.2025.109287

PMID: 39848094

Abstract

Introduction: Prenatal exposure to organophosphate esters (OPEs) and phthalic acid esters (PAEs) is ubiquitous among pregnant individuals. However, research exploring the relationship between prenatal co-exposure to OPEs and PAEs and childhood insulin function remains limited.

Methods: In this study, utilizing data from 2,246 maternal-fetal dyads in the Ma’anshan Birth Cohort, associations between co-exposure to OPEs and PAEs and insulin action were analyzed. Repeated measures of tris (2-chloroethyl) phosphate, six OPE metabolites, and seven PAE metabolites were collected from maternal urine. Homeostasis model assessment of insulin resistance (HOMA-IR) and the insulin action index (IAI) served as outcome measures. After adjusting for potential confounders, the effects of repeated exposure on insulin action were evaluated using generalized estimating equations, while mixture effects were assessed through Bayesian kernel machine regression and Quantile-Based G-Computation.

Results: The average age of the children at the time of the study was 5.33 years. Repeated measures analysis revealed that prenatal exposure to MEP was positively associated with increased HOMA-IR (β, 0.027; 95% CI: 0.002, 0.053), while IAI was inversely correlated with rising MEP levels (β, 0.025; 95% CI: －0.046, －0.004) and MEHHP exposure (β, －0.128; 95% CI: -0.218, －0.037). Mixed exposure modeling further indicated that co-exposure to OPEs and PAEs was positively linked to HOMA-IR (β, 0.058; 95% CI: 0.001, 0.114) and negatively correlated with IAI (β, －0.054; 95% CI: －0.097, －0.010), with stronger effects observed during the second trimester. Notably, the association was more pronounced in female children compared to males.

Conclusions: This study provides the first epidemiological evidence highlighting the pregnancy- and sex-specific links between prenatal co-exposure to OPEs and PAEs and childhood insulin action.

Keywords: Endocrine disrupting chemicals; Homeostatic model assessment of insulin resistance; Insulin action index; Quantile g-computation; Bayesian kernel machine regression; Birth cohort.

摘要

背景：产前暴露于有机磷酸酯（organophosphate esters，OPEs）和邻苯二甲酸酯（phthalic acid esters，PAEs）在孕妇中普遍存在。然而，探索产前共暴露于OPEs和PAEs和儿童期胰岛素功能之间关系的研究仍有限。

方法：在本研究中，利用马鞍山优生优育队列中2 246对母子对数据，分析共暴露于OPEs和PAEs与胰岛素作用之间的关系。从收集的孕三期母体尿液中检测三（2-氯乙基）磷酸酯（tris (2-chloroethyl) phosphate，TPHP）、6种OPE代谢物和7种PAE代谢物的浓度。胰岛素抵抗稳态模型评估（Homeostasis model assessment of insulin resistance，HOMA-IR）和胰岛素作用指数（insulin action index，IAI）作为结果指标。调整潜在的混杂因素后，使用广义估计方程评估重复暴露对胰岛素作用的影响，同时通过贝叶斯核机器回归和基于分位数的G-计算评估混合效应。

结果：本研究中儿童的平均年龄为5.33岁。重复测量分析显示，产前暴露于MEP与HOMA－IR增加呈正相关（β，0.027；95% CI：0.002，0.053），而IAI与MEP（β，0.025；95%CI：－0.046，－0.004）和MEHHP暴露水平升高呈负相关（β，－0.128；95%CI：－0.218，－ 0.037）。混合暴露模型进一步表明，同时孕中期暴露于OPEs和PAEs与HOMA－IR呈正相关（β，0.058；95% CI： 0.001，0.114）与IAI呈负相关（β，－0.054；95%CI：－0.097，－0.010）。值得注意的是，与男孩相比，这种联系在女孩中更显著。

结论：这项研究提供了第一个流行病学证据，强调了产前共暴露于OPEs和PAEs与儿童期胰岛素作用之间的妊娠和性别特异性关系。

关键词：内分泌干扰化学物质；胰岛素抵抗稳态模型评估；胰岛素作用指数；分位数g-计算；贝叶斯核机器回归；出生队列