有机磷酯和邻苯二甲酸盐共同暴露对学龄前儿童认知发育的孕期特异性影响：妊娠维生素D状态的调节作用

Trimester-specific effect of maternal co-exposure to organophosphate esters and phthalates on preschooler cognitive development: The moderating role of gestational vitamin D status

有机磷酯和邻苯二甲酸盐共同暴露对学龄前儿童认知发育的孕期特异性影响：妊娠维生素D状态的调节作用

Authors: Mengjuan Lu, Hong Gan, Qiong Zhou, Feifei Han, Xiaorui Wang, Fu Zhang, Juan Tong, Kun Huang, Hui Gao, Shuangqin Yan, Zhongxiu Jin, Qunan Wang, Fangbiao Tao

Source: Lu M, Gan H, Zhou Q, et al. Trimester-specific effect of maternal co-exposure to organophosphate esters and phthalates on preschooler cognitive development: The moderating role of gestational vitamin D status. Environ Res. Published online March 3, 2024. doi:10.1016/j.envres.2024.118536

Abstract

Organophosphate esters (OPEs) and phthalate acid esters (PAEs) are prevalent 26 endocrine-disrupting chemicals (EDCs). Humans are often exposed to OPEs and PAEs 27 simultaneously through multiple routes. Given that fetal stage is a critical period for 28 neurodevelopment, it is necessary to know whether gestational co-exposure to OPEs and PAEs 29 affects fetal neurodevelopment. However, accessible epidemiological studies are limited. The 30 present study included 2, 120 pregnant women from the Ma’anshan Birth Cohort (MABC) study. 31 The concentrations of tris (2-chloroethyl) phosphate (TCEP), 6 OPE metabolites and 7 PAE 32 metabolites were measured in the first, second and third trimester using ultra-performance liquid 33 chromatography-tandem mass spectrometry (LC-MS). Cognitive development of preschooler was 34 assessed based on the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition 35 (WPPSI-IV) of the Chinese version. Generalized estimating equations (GEEs), restricted cubic 36 spline (RCS) and generalized additive models (GAMs) were employed to explore the associations 37 between individual OPE exposure and preschooler cognitive development. The quantile-based 38 g-computation (QGC) method was used to estimate the joint effect of PAEs and OPEs exposure 39 on cognitive development. GEEs revealed significant adverse associations between diphenyl 40 phosphate (DPHP) (β:-0.58, 95% CI: -1.14, -0.01), bis (2-butoxyethyl) phosphate(BBOEP) (β: 41 -0.44, 95% CI: -0.85, -0.02), bis(1-chloro-2-propyl) phosphate (BCIPP) (β: -0.81, 95%CI: -1.43, 42 -0.20) and full-scale intelligence quotient (FSIQ) in the first trimester; additionally, TCEP and 43 bis(2-ethylhexyl) phosphate (BEHP) in the second trimester, as well as DPHP in the third trimester, 44 were negatively associated with cognitive development. Through the QGC analyses, mixture 45 exposure in the first trimester was negatively associated with FSIQ scores (β: -1.70, 95% CI: -3.06, 46 -0.34), mono-butyl phthalate (MBP), BCIPP, and DPHP might be the dominant contributors after 47 controlling for other OPEs and PAEs congeners. Additionally, the effect of OPEs and PAEs 48 mixtures on cognitive development might be driven by vitamin D deficiency.

有机磷酸酯（OPE）和邻苯二甲酸酯（PAE）是普遍存在的内分泌干扰化学物质（EDC）。人类经常通过多种途径同时暴露于OPE和PAE。鉴于胎儿阶段是神经发育的关键时期，有必要了解妊娠期共同暴露于OPE和PAE是否会影响胎儿神经发育。然而，可获得的流行病学研究是有限的。本研究包括来自马鞍山出生队列（MABC）研究的2，120名孕妇。采用超高效液相色谱-串联质谱（LC-MS）法测定孕早期、中期和晚期磷酸三（2-氯乙基）酯（TCEP）、6种OPE代谢物和7种PAE代谢物的浓度。学龄前儿童的认知发展是根据中文版的韦氏学前和小学智力量表-第四版（WPPSI-IV）评估的。采用广义估计方程（GEEs）、限制三次样条曲线（RCS）和广义加性模型（GAMs）来探讨个体OPE暴露与学龄前儿童认知发展之间的关联。采用基于分位数的g计算（QGC）方法估计PAEs和OPEs暴露对认知发展的联合影响。GEEs显示，磷酸二苯酯（DPHP）（β：-0.58,95%CI：-1.14，-0.01）、磷酸双（2-丁氧基乙基）酯（BBOEP）（β：-0.44,95%CI：-0.85，-0.02）、磷酸双（1-氯-2-丙基）（BCIPP）（β：-0.81,95%CI：-1.43，-0.20）与妊娠早期满量程智商（FSIQ）之间存在显著的不良关联;此外，妊娠中期的TCEP和磷酸双（2-乙基己基）酯（BEHP）以及妊娠晚期的DPHP与认知发育呈负相关。通过QGC分析，妊娠早期混合物暴露与FSIQ评分呈负相关（β：-1.70,95%CI：-3.06，-0.34），邻苯二甲酸单丁酯（MBP）、BCIPP和DPHP可能是控制其他OPEs和PAEs同系物后的主要贡献者。此外，OPEs和PAEs混合物对认知发展的影响可能是由维生素D缺乏驱动的。