孕期同时接触有机磷酸酯和邻苯二甲酸盐对学龄前儿童胰岛素作用的性别及孕期特异性影响：马鞍山出生队列研究结果
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.
作者信息
Gan Hong, Lu Mengjuan, Tong Juan, Li Huijuan, Zhou Qiong, Han Feifei, Wang Xiaorui, Yan Shuangqin, Huang Kun, Wang Qunan, Wu Xiaoyan, Zhu Beibei, Gao Hui, Tao Fangbiao
机构信息
Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei 230032 Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032,Anhui, China; Anhui Provincial Key Laboratory of Environment and Population Health across the Life Course, Anhui Medical University, No 81 Meishan Road, Hefei 230032 Anhui, China.
Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032,Anhui, China; Anhui Provincial Key Laboratory of Environment and Population Health across the Life Course, Anhui Medical University, No 81 Meishan Road, Hefei 230032 Anhui, China.
出版信息
Environ Int. 2025 Feb;196:109287. doi: 10.1016/j.envint.2025.109287. Epub 2025 Jan 18.
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 BayesianKernel 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.
引言
孕妇产前接触有机磷酸酯（OPEs）和邻苯二甲酸酯（PAEs）的情况普遍存在。然而，关于产前同时接触OPEs和PAEs与儿童胰岛素功能之间关系的研究仍然有限。
方法
在本研究中，利用马鞍山出生队列中2246对母婴的数据，分析了同时接触OPEs和PAEs与胰岛素作用之间的关联。从孕妇尿液中收集了磷酸三（2-氯乙基）酯、六种OPE代谢物和七种PAE代谢物的重复测量数据。胰岛素抵抗的稳态模型评估（HOMA-IR）和胰岛素作用指数（IAI）作为结果指标。在调整潜在混杂因素后，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
研究时儿童的平均年龄为5.33岁。重复测量分析显示，产前接触2-甲氧基乙酸乙酯与HOMA-IR升高呈正相关（β，0.027；95%CI：0.002，0.053），而IAI与2-甲氧基乙酸乙酯水平升高呈负相关（β，0.025；95%CI：-0.046，-0.004）以及与2-乙基-5-羟基己基邻苯二甲酸酯暴露呈负相关（β，-0.128；95%CI：-0.218，-0.037）。混合暴露模型进一步表明，同时接触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），在孕中期观察到更强的影响。值得注意的是，与男性儿童相比，这种关联在女性儿童中更为明显。
结论
本研究提供了首个流行病学证据，突出了产前同时接触OPEs和PAEs与儿童胰岛素作用之间特定于妊娠和性别的联系。
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