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. 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. 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 ( < 0.05). BBOEP in the third trimester was associated with decreased risk in the moderate-score group ( = 0.89, 95: 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. 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.

中文翻译：

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产前接触单一和混合有机磷酸酯与学龄前儿童 ADHD 症状轨迹的关联：母体维生素 D 的改变作用


有机磷酸酯（OPE）是一类具有内分泌干扰特性的环境化学品。流行病学研究表明，产前 OPE 暴露与后代神经发育障碍有关。然而，评估产前 OPE 暴露对学龄前儿童注意力缺陷多动障碍 (ADHD) 症状动态变化影响的研究很少。由于维生素 D 已被证明具有“神经保护”作用，因此评估了母体维生素 D 的调节作用。本研究纳入了马鞍山出生队列的 2410 名孕妇。在妊娠的三个三个月中检查了母亲尿液中 OPE 的水平。采用中文版康纳斯简明症状问卷调查学龄前儿童3、5、6岁时的ADHD症状。通过基于组的轨迹模型拟合 ADHD 症状轨迹。我们使用多项式逻辑回归、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 OPE 与学龄前儿童 ADHD 症状和轨迹之间的个体和混合关系。学龄前儿童的 ADHD 症状评分符合 3 个轨迹，包括低分组、中分组和高分组。孕早期磷酸二丁酯 (DBP)、孕中期磷酸二(2-丁氧基乙基)酯 (BBOEP) 和孕晚期磷酸二苯酯 (DPHP) 与高分组风险增加相关 (< 0.05)。妊娠晚期的 BBOEP 与中等评分组的风险降低相关 (= 0.89, 95: 0.79, 1.00)。对于 25(OH)D 缺乏的母亲，怀孕期间的 OPE 与症状轨迹之间存在正相关关系。 我们的结果没有揭示 OPE 对 ADHD 症状轨迹的任何混合影响。产前接触 OPE 与学龄前儿童 ADHD 症状轨迹存在异质关联。此外，维生素 D 缺乏会加剧个体 OPE 对症状轨迹的影响。