产前暴露于单个和混合有机磷酸酯与学龄前儿童ADHD症状轨迹的关系：母体维生素D的调节作用

Associations of prenatal exposure to individual and mixed organophosphate esters with ADHD symptom trajectories in preschool children: The modifying effects of maternal Vitamin D

产前暴露于单个和混合有机磷酸酯与学龄前儿童ADHD症状轨迹的关系：母体维生素D的调节作用

Authors: Li H, Tong J, Wang X, Lu M, Yang F, Gao H, Gan H, Yan S, Gao G, Huang K, Cao Y, Tao F.

Source：J Hazard Mater. 2024 Aug 15;478:135541. 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: Attention deficit hyperactivity disorder; Organophosphate esters; Prenatal exposure; Prospective birth cohort; Trajectory.

摘要

背景：有机磷酸酯（OPEs）是一类具有内分泌干扰作用的环境化学品。流行病学研究表明，产前暴露于OPEs与后代的神经发育障碍有关。然而，研究评估的影响，产前OPEs暴露的注意缺陷多动障碍（ADHD）症状在学龄前儿童的动态变化是罕见的。由于维生素D已被证明具有“神经保护”作用，因此对母体维生素D的修饰作用进行了估计。

方法：对马鞍山市2410例孕妇进行了产前筛查。在妊娠三个月检查母亲尿液中的OPEs水平。采用Conners简明症状问卷中文版对3、5、6岁学龄前儿童ADHD症状进行了调查。通过基于组的轨迹建模拟合ADHD症状轨迹。我们使用多项逻辑回归，贝叶斯核机器回归，基于分位数的g计算和广义线性模型来评估怀孕期间OPEs与学龄前儿童ADHD症状和轨迹之间的个体和混合关系。

结果：学龄前儿童的ADHD症状评分符合低、中、高分三组轨迹。在高分组中，孕早期使用磷酸二氢钾（DBP）、孕中期使用双（2-丁氧基乙基）磷酸盐（BBOEP）和孕晚期使用磷酸二苯酯（DPHP）与风险增加相关（p 0.05）。在中评分组中，孕晚期BBOEP与风险降低相关（OR = 0.89，95%CI：0.79，1.00）。对于25（OH）D缺乏的母亲，观察到妊娠期OPEs与症状轨迹之间存在正相关。我们的研究结果没有显示出OPEs对ADHD症状轨迹的任何混合效应。

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，维生素D缺乏会加剧个体OPEs对症状轨迹的影响。

关键词：注意缺陷多动障碍;有机磷酸酯;产前暴露;前瞻性出生队列;轨迹。