Background

Phthalates are a group of heavily produced endocrine disruptors that are widely used in personal care products, food packaging, building materials, and medical device. Few epidemiological studies have examined the effect of repeated prenatal exposure to multiple phthalates on preschooler cognitive development.

Objectives

This study aimed to examine the association between prenatal phthalate exposure measured at multiple time points and the intelligent quotient (IQ) scores of preschoolers, and to further identify the critical windows and specific intelligence domains in which phthalate exposure would affect preschooler cognitive development.

Methods

The current study was based on the Ma’anshan Birth Cohort (MABC) study. Seven phthalate metabolites were measured in 2128 maternal urine samples collected during the first, second, and third trimesters of pregnancy. The IQ score of preschool-aged children were assessed with the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth edition (WPPSI-Ⅳ CN). Linear mixed models (LMMs) were used to assess the longitudinal effects of repeated prenatal phthalate exposure on children’s IQ score. Multiple linear regression models were fitted to determine whether critical window phthalate exposure would affect cognitive development of children.

Results

Overall, the repeated measures analysis indicated that the verbal comprehension index (VCI), visual space index (VSI) and full-scale intelligence quotient (FSIQ) decreased by 0.30 (95% CI: −0.60, 0; p = 0.05), 0.32 (95% CI: −0.62, −0.01; p = 0.04), and 0.31 (95% CI:-0.57, −0.04; p = 0.02) points, respectively, with each ln-transformed increase in the metabolite concentration of MBP. The fluid reasoning index (FRI) and processing speed index (PSI) increased by 0.30 (95% CI: 0.07, 0.54; p = 0.01) and 0.28 (95% CI: 0.06, 0.51; p = 0.01) points, respectively, with each ln-concentration increase in MEP. Trimester-specific regression models stratified by the sample collection time during pregnancy generated consistent results. In the first trimester, each ln-transformed MBP increase was associated with reductions in VCI, VSI and FSIQ of 0.56 (95% CI:-1.09, −0.02; p = 0.04), 0.60 (95% CI:-1.15, −0.05; p = 0.03) and 0.49 (95% CI:-0.97, −0.01; p = 0.04) points, respectively. In the third trimester, we observed that only MBzP exposure was associated with an increase in VCI (β: 0.48, 95% CI: 0.03, 0.92; p = 0.04). The gender-stratified analyses revealed that boys drove these associations.

Conclusions

Our results suggest that prenatal phthalate exposure impairs the cognitive development of preschoolers. The first trimester of pregnancy might be the most vulnerable period in terms of neurotoxicitydue to phthalate exposure. These findings warrant further confirmation.

中文翻译：

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在马鞍山出生队列（MABC）研究中，产前邻苯二甲酸酯暴露对学龄前儿童认知发展的领域和孕中期特异性影响。

背景

邻苯二甲酸盐是一组大量产生的内分泌干扰物，广泛用于个人护理产品，食品包装，建筑材料和医疗设备。很少有流行病学研究检查出生前反复接触多种邻苯二甲酸酯对学龄前儿童认知发育的影响。

目标

这项研究旨在检查在多个时间点测量的产前邻苯二甲酸酯暴露与学龄前儿童的智商（IQ）得分之间的关​​联，并进一步确定邻苯二甲酸酯暴露会影响学龄前儿童认知发展的关键窗口和特定智能领域。

方法

当前的研究基于马鞍山出生队列（MABC）研究。在怀孕的第一个，第二个和第三个三个月收集的2128个母体尿液样品中测量了7种邻苯二甲酸酯代谢物。学龄前儿童的智商得分使用中文版的《韦氏幼儿和小学智能量表》（第四版，WPPSI-ⅣCN）进行评估。线性混合模型（LMM）用于评估重复产前邻苯二甲酸酯暴露对儿童智商得分的纵向影响。拟合了多个线性回归模型，以确定临界邻苯二甲酸酯暴露量是否会影响儿童的认知发育。

结果

总体而言，重复测量分析表明，言语理解指数（VCI），视觉空间指数（VSI）和全面智能商（FSIQ）下降了0.30（95％CI：-0.60，0； p = 0.05），0.32 （95％CI：-0.62，-0.01; p = 0.04）和0.31（95％CI：-0.57，-0.04; p = 0.02）点，MBP的代谢物浓度每经过ln转换都会增加。流体推理指数（FRI）和处理速度指数（PSI）分别提高了0.30（95％CI：0.07，0.54; p = 0.01）和0.28（95％CI：0.06，0.51; p = 0.01）点，分别为MEP中每ln浓度的增加。根据怀孕期间样本收集时间分层的特定于妊娠的回归模型产生了一致的结果。在头三个月中，每个ln转换后的MBP升高都与VCI，VSI和FSIQ降低0.56（95％CI：-1）有关。09，-0.02; p = 0.04），0.60（95％CI：-1.15，-0.05; p = 0.03）和0.49（95％CI：-0.97，-0.01; p = 0.04）点。在孕晚期，我们观察到只有MBzP暴露与VCI升高有关（β：0.48，95％CI：0.03，0.92； p = 0.04）。性别分层分析显示，男孩推动了这些关联。

结论

我们的结果表明，产前邻苯二甲酸酯暴露会损害学龄前儿童的认知能力。就由于邻苯二甲酸盐暴露引起的神经毒性而言，怀孕的前三个月可能是最脆弱的时期。这些发现值得进一步确认。