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产前暴露于全氟烷基物质与学龄前儿童注意缺陷多动障碍症状和认知功能的关联。

Prenatal exposure to perfluoroalkyl substances and associations with symptoms of attention-deficit/hyperactivity disorder and cognitive functions in preschool children.

机构信息

Norwegian Institute of Public Health, PO Box 222, Skøyen, N-0213, Oslo, Norway.

Norwegian Institute of Public Health, PO Box 222, Skøyen, N-0213, Oslo, Norway.

出版信息

Int J Hyg Environ Health. 2020 Jan;223(1):80-92. doi: 10.1016/j.ijheh.2019.10.003. Epub 2019 Oct 22.

Abstract

BACKGROUND

Perfluoroalkyl substances (PFASs) are persistent organic pollutants that are suspected to be neurodevelopmental toxicants, but epidemiological evidence on neurodevelopmental effects of PFAS exposure is inconsistent. We investigated the associations between prenatal exposure to PFASs and symptoms of attention-deficit/hyperactivity disorder (ADHD) and cognitive functioning (language skills, estimated IQ and working memory) in preschool children, as well as effect modification by child sex.

MATERIAL AND METHODS

This study included 944 mother-child pairs enrolled in a longitudinal prospective study of ADHD symptoms (the ADHD Study), with participants recruited from The Norwegian Mother, Father and Child Cohort Study (MoBa). Boys and girls aged three and a half years, participated in extensive clinical assessments using well-validated tools; The Preschool Age Psychiatric Assessment interview, Child Development Inventory and Stanford-Binet (5th revision). Prenatal levels of 19 PFASs were measured in maternal blood at week 17 of gestation. Multivariable adjusted regression models were used to examine exposure-outcome associations with two principal components extracted from the seven detected PFASs. Based on these results, we performed regression analyses of individual PFASs categorized into quintiles.

RESULTS

PFAS component 1 was mainly explained by perfluoroheptane sulfonate (PFHpS), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorooctanoic acid (PFOA). PFAS component 2 was mainly explained by perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA) and perfluorononanoic acid (PFNA). Regression models showed a negative association between PFAS component 1 and nonverbal working memory [β = -0.08 (CI: -0.12, -0.03)] and a positive association between PFAS component 2 and verbal working memory [β = 0.07 (CI: 0.01, 0.12)]. There were no associations with ADHD symptoms, language skills or IQ. For verbal working memory and PFAS component 2, we found evidence for effect modification by child sex, with associations only for boys. The results of quintile models with individual PFASs, showed the same pattern for working memory as the results in the component regression analyses. There were negative associations between nonverbal working memory and quintiles of PFOA, PFNA, PFHxS, PFHpS and PFOS and positive associations between verbal working memory and quintiles of PFOA, PFNA, PFDA and PFUnDA, with significant relationships mainly in the highest concentration groups.

CONCLUSIONS

Based on our results, we did not find consistent evidence to conclude that prenatal exposure to PFASs are associated with ADHD symptoms or cognitive dysfunctions in preschool children aged three and a half years, which is in line with the majority of studies in this area. Our results showed some associations between PFASs and working memory, particularly negative relationships with nonverbal working memory, but also positive relationships with verbal working memory. The relationships were weak, as well as both positive and negative, which suggest no clear association - and need for replication.

摘要

背景

全氟烷基物质(PFAS)是持久性有机污染物,被怀疑具有神经发育毒性,但有关 PFAS 暴露对神经发育影响的流行病学证据并不一致。我们研究了产前暴露于 PFAS 与学龄前儿童注意力缺陷/多动障碍(ADHD)症状和认知功能(语言技能、估计智商和工作记忆)之间的关系,以及儿童性别对其的影响。

材料与方法

本研究纳入了 944 对母子,他们参加了 ADHD 症状的纵向前瞻性研究(ADHD 研究),参与者是从挪威母婴队列研究(MoBa)中招募的。三岁半的男孩和女孩使用经过充分验证的工具进行广泛的临床评估;使用学前年龄精神病评估访谈、儿童发展量表和斯坦福-比内特(第 5 版)进行评估。在妊娠第 17 周时,测量了母亲血液中 19 种 PFAS 的水平。使用两个从检测到的七种 PFAS 中提取的主成分的多变量调整回归模型来检查暴露-结局关系。基于这些结果,我们对分类为五分位数的个体 PFAS 进行了回归分析。

结果

PFAS 成分 1 主要由全氟庚烷磺酸(PFHpS)、全氟辛烷磺酸(PFOS)、全氟己烷磺酸(PFHxS)和全氟辛酸(PFOA)解释。PFAS 成分 2 主要由全氟癸酸(PFDA)、全氟十一烷酸(PFUnDA)和全氟壬酸(PFNA)解释。回归模型显示,PFAS 成分 1 与非言语工作记忆呈负相关[β=−0.08(CI:−0.12,−0.03)],PFAS 成分 2 与言语工作记忆呈正相关[β=0.07(CI:0.01,0.12)]。PFAS 与 ADHD 症状、语言技能或智商之间没有关联。对于言语工作记忆和 PFAS 成分 2,我们发现儿童性别存在效应修饰作用,仅在男孩中存在关联。对于单独的 PFAS 进行五分位数模型的结果与成分回归分析的结果一致。非言语工作记忆与 PFOA、PFNA、PFHxS、PFHpS 和 PFOS 的五分位数呈负相关,言语工作记忆与 PFOA、PFNA、PFDA 和 PFUnDA 的五分位数呈正相关,在最高浓度组中存在显著关系。

结论

根据我们的结果,我们没有发现一致的证据表明产前暴露于 PFAS 与 3 岁半学龄前儿童的 ADHD 症状或认知功能障碍有关,这与该领域的大多数研究一致。我们的结果显示 PFAS 与工作记忆之间存在一些关联,特别是与非言语工作记忆呈负相关,但与言语工作记忆也呈正相关。这些关系很微弱,既有正相关也有负相关,这表明没有明确的关联,需要进一步研究。

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