Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China; MOE Key Laboratory of Population Health Across Life Cycle, No 81 Meishan Road, Hefei 230032, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei 230032, Anhui, China; Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China.
Ma'anshan Maternal and Child Healthcare (MCH) Center, Ma'anshan 243011, China.
Environ Int. 2020 Sep;142:105882. doi: 10.1016/j.envint.2020.105882. Epub 2020 Jun 25.
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.
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.
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.
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.
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.
邻苯二甲酸酯是一组大量生产的内分泌干扰物，广泛应用于个人护理产品、食品包装、建筑材料和医疗器械。少数流行病学研究检查了多次产前暴露于多种邻苯二甲酸酯对学龄前儿童认知发展的影响。
本研究旨在检验多次产前邻苯二甲酸酯暴露与学龄前儿童智商（IQ）分数之间的关系，并进一步确定邻苯二甲酸酯暴露影响学龄前儿童认知发展的关键窗口和特定智力领域。
本研究基于马鞍山出生队列（MABC）研究。在妊娠第 1、2 和 3 个三个月期间，收集了 2128 名孕妇尿液样本，测量了 7 种邻苯二甲酸酯代谢物。采用韦氏学龄前和小学智力量表第四版（WPPSI-Ⅳ CN）评估学龄前儿童的智商分数。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 IQ 分数的纵向影响。拟合多元线性回归模型，以确定关键窗口期的邻苯二甲酸酯暴露是否会影响儿童的认知发展。
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）和全智商指数（FSIQ）分别降低了 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），而每种代谢物浓度的 ln 转换增加。流体推理指数（FRI）和处理速度指数（PSI）分别增加了 0.30（95%CI：0.07，0.54；p=0.01）和 0.28（95%CI：0.06，0.51；p=0.01），而每种 MEP 的 ln 浓度增加。根据妊娠期间样本采集时间进行的三季特异性回归模型产生了一致的结果。在孕早期，每个 ln 转化的 MBP 增加与 VCI、VSI 和 FSIQ 的降低分别相关，降低幅度为 0.56（95%CI：-1.09，-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）。在孕晚期，我们发现只有 MBzP 暴露与 VCI 增加有关（β：0.48，95%CI：0.03，0.92；p=0.04）。性别分层分析表明，男孩驱动了这些关联。
我们的研究结果表明，产前邻苯二甲酸酯暴露会损害学龄前儿童的认知发展。由于邻苯二甲酸酯暴露导致的神经毒性，妊娠早期可能是最脆弱的时期。这些发现需要进一步证实。
