Wang Hui, Fu Dezheng, Liu Xiaoning, Chang Xiaochen, Guo Siyu, Cheng Xiaomeng, Tian Ying, Ran Jinjun, Zhang Jun, Yin Shengju
Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Department of Maternal and Child Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Ecotoxicol Environ Saf. 2025 Jan 15;290:117618. doi: 10.1016/j.ecoenv.2024.117618. Epub 2024 Dec 31.
Neurotoxicity of organophosphate esters (OPEs) and organophosphorus pesticides (OPPs) has been documented in toxicological studies, though epidemiological evidence remains inconsistent. The developing fetal brain is susceptible to environmental exposures. Thus, we aim to investigate how prenatal exposure to OPEs and OPPs as mixture affects offspring neurodevelopment in preschool-aged children. In a study involving 530 mother-child dyads from the Shanghai Birth Cohort (SBC) with enrollment occurring between 2013 and 2016, 14 OPEs/OPPs metabolites were evaluated using high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) in maternal urine collected during both the first and second trimester. Child neurodevelopment was evaluated using the parent-reported Behavior Rating Inventory of Executive Function-Preschool version (BRIEF-P) and the Strengths and Difficulties Questionnaire (SDQ). We utilized multivariable linear regression and Bayesian kernel machine regression (BKMR) to estimate associations with individual and mixture component, respectively. We also investigated whether these associations varied by child sex. Of the 14 OPEs/OPPs metabolites, 6 were quantifiable in over 75 % of the samples. Higher prenatal O,O-dimethyl phosphate (DMP) concentrations in the first and second trimesters, as well as O,O-dimethyl thiophosphate (DMTP) in the second trimester, were associated with more behavioral difficulties. When stratified by child sex, the statistically significant inverse associations were observed exclusively in girls. Results from BKMR showed that the overall effect of prenatal exposure to OPEs and OPPs mixtures was associated with some neurodevelopmental domains in girls. For example, holding the mixture at the 75th percentile compared to the 50th percentile during the first trimester was associated with a 0.65 increase in SDQ total scores (95 % confidence interval: 0.03-1.26). DMP and DMTP may be the dominant contributors. Our findings add to the literature on the effect of prenatal exposure to OPEs and OPPs on offspring neurodevelopment and suggest that the effect seems to be sex-specific. Additional research is required to validate our findings and elucidate the underlying mechanisms.
有机磷酸酯（OPEs）和有机磷农药（OPPs）的神经毒性已在毒理学研究中得到证实，尽管流行病学证据仍不一致。发育中的胎儿大脑易受环境暴露的影响。因此，我们旨在研究产前暴露于OPEs和OPPs混合物如何影响学龄前儿童的后代神经发育。在一项涉及2013年至2016年间来自上海出生队列（SBC）的530对母婴的研究中，使用高效液相色谱/串联质谱（HPLC/MS-MS）对孕早期和孕中期收集的母体尿液中的14种OPEs/OPPs代谢物进行了评估。使用家长报告的执行功能学前版行为评定量表（BRIEF-P）和优势与困难问卷（SDQ）对儿童神经发育进行评估。我们分别利用多变量线性回归和贝叶斯核机器回归（BKMR）来估计与个体成分和混合成分的关联。我们还研究了这些关联是否因儿童性别而异。在14种OPEs/OPPs代谢物中，6种在超过75%的样本中可定量。孕早期和孕中期较高的产前O,O-二甲基磷酸酯（DMP）浓度，以及孕中期的O,O-二甲基硫代磷酸酯（DMTP），与更多的行为困难相关。按儿童性别分层时，仅在女孩中观察到具有统计学意义的负相关。BKMR的结果表明，产前暴露于OPEs和OPPs混合物的总体效应与女孩的一些神经发育领域相关。例如，在孕早期将混合物保持在第75百分位数而不是第50百分位数与SDQ总分增加0.65相关（95%置信区间：0.03-1.26）。DMP和DMTP可能是主要贡献者。我们的研究结果增加了关于产前暴露于OPEs和OPPs对后代神经发育影响的文献，并表明这种影响似乎具有性别特异性。需要进一步的研究来验证我们的发现并阐明潜在机制。
