母亲孕期有机磷酸酯暴露可能会增加学龄前儿童ADHD症状中高得分轨迹发生风险，孕期维生素D缺乏的母亲有机磷酸酯暴露与儿童ADHD症状高得分轨迹呈正相关

Associations of Prenatal Exposure to Individual and Mixed Organophosphate Esters with ADHD Symptom Trajectories in Preschool Children: The Modifying Effects of Maternal Vitamin D

产前单一和混合有机磷酸酯暴露与学龄前儿童ADHD症状轨迹的关联：母体维生素D水平的效应修饰作用

Author: Han Lia, Juan Tong, Xing Wang, Mengjuan Lu, Fengyu Yang, Hui Gao Hong Gan, Shuangqin Yan, Guopeng Gao, Kun Huang, Yunxia Cao, Fangbiao Tao

Source: Journal of Hazardous Materials

DOI：10.1016/j.jhazmat.2024.135541.

Abstract

Background: Organophosphate esters (OPEs) are a class of environmental chemicals with endocrine-disrupting properties. Epidemiologic studies have demonstrated that prenatal OPEs exposure is associated with neurodevelopmental disorders in offspring. However, studies assessing the effects of prenatal OPEs exposure on the dynamic changes in attention deficit hyperactivity disorder (ADHD) symptoms in preschoolers are scarce. Since vitamin D has been demonstrated to have a "neuroprotective" effect, the modifying effects of maternal vitamin D were estimated.

Methods: The present study included 2410 pregnant women from the Ma'anshan Birth Cohort. The levels of OPEs in the mothers' urine were examined in the three trimesters. The Chinese version of the Conners Abbreviated Symptom Questionnaire was used to examine preschoolers' ADHD symptoms at 3, 5, and 6 years of age. ADHD symptom trajectories were fitted via group-based trajectory modeling. We used multinomial logistic regression, Bayesian kernel machine regression, quantile-based g-computation, and generalized linear models to assess individual and mixed relationships between OPEs during pregnancy and preschoolers' ADHD symptoms and trajectories.

Results: Preschoolers' ADHD symptom scores were fitted to 3 trajectories, including the low-score, moderate-score, and high-score groups. First-trimester dibutyl phosphate (DBP), second-trimester bis(2-butoxyethyl) phosphate (BBOEP), and third-trimester diphenyl phosphate (DPHP) were associated with an increased risk in the high-score group (p < 0.05). BBOEP in the third trimester was associated with decreased risk in the moderate-score group (OR = 0.89, 95% CI: 0.79, 1.00). For mothers with 25(OH)D deficiency, a positive relationship was observed between OPEs during pregnancy and symptom trajectories. Our results did not reveal any mixed effects of OPEs on ADHD symptom trajectories.

Conclusion: Prenatal exposure to OPEs had heterogeneous associations with ADHD symptom trajectories in preschoolers. Additionally, the effect of individual OPEs on symptom trajectories was intensified by vitamin D deficiency.

Keywords: Organophosphate esters; Prenatal exposure; Attention deficit hyperactivity disorder; Trajectory; Prospective birth

摘要

背景：有机磷酸酯（OPEs）是一类具有内分泌干扰特性的化学物质。流行病学研究表明，产前接触OPEs与子代的神经发育障碍有关。然而，评估产前OPEs暴露对学龄前儿童注意缺陷多动障碍（ADHD）症状动态变化的影响的研究较为缺乏。维生素D已被证明具有神经保护作用，因此本研究评估了母体维生素D的效应修饰作用。

方法：本研究包括马鞍山出生队列中的2410名孕妇。检测了孕三期母亲尿液中的OPEs暴露量。本研究采用中文版Conners简明症状问卷评估了儿童在3、5和6岁时的ADHD症状情况。使用组基轨迹模型拟合了ADHD症状轨迹。 采用多项式Logistic回归、贝叶斯核机器回归、分位数g计算和广义线性模型来评估产前OPEs与学龄前儿童ADHD症状和轨迹之间的单一和混合关系。

结果：学龄前儿童的ADHD症状得分轨迹拟合为3个，包括低得分组、中得分组和高得分组。孕妇孕早期磷酸二丁酯（DBP）、孕中期磷酸二（2-丁氧基乙基）酯（BBOEP）以及孕晚期磷酸二苯酯（DPHP）暴露与ADHD症状轨迹高得分组的风险增加有关（p < 0.05）。孕晚期暴露于BBOEP与中得分组的风险降低有关（OR = 0.89，95% CI：0.79，1.00）。孕期维生素D缺乏的母亲OPEs暴露与儿童ADHD症状轨迹呈正相关。在本研究中没有发现OPEs对ADHD症状轨迹有混合效应影响。

结论：产前暴露于OPEs与学龄前儿童ADHD症状轨迹有异质性关联。此外，母体缺乏维生素D会加剧个别OPEs代谢物对症状轨迹的影响。