Prenatal exposure to legacy PFAS and neurodevelopment in preschool-aged Canadian children: The MIREC cohort

IF 2.6 3区医学 Q3 NEUROSCIENCES Neurotoxicology and teratology Pub Date : 2023-07-01 DOI:10.1016/j.ntt.2023.107181

Carly V. Goodman , Christine Till , Rivka Green , Jana El-Sabbagh , Tye E. Arbuckle , Richard Hornung , Bruce Lanphear , Jean R. Seguin , Linda Booij , Mandy Fisher , Gina Muckle , Maryse F. Bouchard , Jillian Ashley-Martin

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引用次数: 2

Abstract

Background

Exposure to perfluoroalkyl substances (PFAS) has been shown to be neurotoxic in experimental studies, but epidemiological evidence linking prenatal PFAS exposure to child neurodevelopment is equivocal and scarce.

Objective

To quantify associations between prenatal exposure to legacy PFAS and children's intelligence (IQ) and executive functioning (EF) in a Canadian pregnancy and birth cohort and to determine if these associations differ by child sex.

Methods

We measured first-trimester plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) in the Maternal-Infant Research on Environmental Chemicals (MIREC) study and assessed children's full-scale (n = 522), performance (n = 517), and verbal (n = 519) IQ using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Children's working memory (n = 513) and ability to plan and organize (n = 514) were assessed using a parent-reported questionnaire, the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P). We quantified associations between individual log2-transformed PFAS exposure and children's IQ and EF using multiple linear regression analyses and evaluated effect modification by child sex. We also used Repeated Holdout Weighted Quantile Sum (WQS) regression models with effect modification by child sex to quantify the effect of combined exposure to all three PFAS chemicals on IQ and EF. All models were adjusted for key sociodemographic characteristics.

Results

Geometric mean plasma concentrations (IQR) for PFOA, PFOS and PFHxS were 1.68 (1.10–2.50), 4.97 (3.20–6.20) and 1.09 (0.67–1.60) μg/L respectively. We found evidence of effect modification by child sex in all models examining performance IQ (p < .01). Specifically, every doubling of PFOA, PFOS, and or PFHxS was inversely associated with performance IQ, but only in males (PFOA: B = −2.80, 95% CI: −4.92, −0.68; PFOS: B = −2.64, 95% CI: −4.77, −0.52; PFHxS: B = −2.92, 95% CI: −4.72, −1.12). Similarly, every quartile increase in the WQS index was associated with poorer performance IQ in males (B = −3.16, 95% CI: −4.90, −1.43), with PFHxS contributing the largest weight to the index. In contrast, no significant association was found for females (B = 0.63, 95% CI: −0.99, 2.26). No significant associations were found for EF in either males or females.

Conclusions

Higher prenatal PFAS exposure was associated with lower performance IQ in males, suggesting that this association may be sex- and domain-specific.

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加拿大学龄前儿童产前暴露于遗留PFAS与神经发育：MIREC队列

背景在实验研究中，接触全氟烷基物质（PFAS）已被证明具有神经毒性，但将产前接触PFAS与儿童神经发育联系起来的流行病学证据是模棱两可的，而且很少。目的量化加拿大妊娠和出生队列中产前暴露于遗留PFAS与儿童智力（IQ）和执行功能（EF）之间的相关性，并确定这些相关性是否因儿童性别而异。方法我们在母婴环境化学品研究（MIREC）研究中测量了妊娠早期全氟辛酸（PFOA）、全氟辛烷磺酸（PFOS）和全氟己磺酸（PFHxS）的血浆浓度，以及使用韦克斯勒学前和小学智力量表（WPPSI-III）的语言智商（n=519）。儿童的工作记忆（n=513）和计划和组织能力（n=514）使用父母报告的问卷，即执行功能行为评定量表-学前版（BRIEF-P）进行评估。我们使用多元线性回归分析量化了个体log2转化的PFAS暴露与儿童IQ和EF之间的相关性，并评估了儿童性别的影响修正。我们还使用了重复保持加权分位数和（WQS）回归模型，并根据儿童性别进行了影响修正，以量化联合暴露于所有三种PFAS化学物质对IQ和EF的影响。所有模型都根据关键的社会人口特征进行了调整。结果PFOA、PFOS和PFHxS的几何平均血浆浓度（IQR）分别为1.68（1.10–2.50）、4.97（3.20–6.20）和1.09（0.67–1.60）μg/L。我们发现，在所有检查表现智商的模型中，儿童性别都有影响修正的证据（p<；.01）。具体而言，全氟辛烷磺酸、全氟辛烷酸和/或全氟辛烷值每增加一倍，都与表现智商呈负相关，但仅在男性中（全氟辛烷甲酸：B=−2.80，95%置信区间：−4.92，−0.68；全氟辛烷酸:B=−2.64，95%可信区间：−4.77，−0.52，WQS指数的每四分位数增加都与男性较差的表现智商有关（B=−3.16，95%CI：−4.90，−1.43），PFHxS对该指数的贡献最大。相反，女性没有发现显著的相关性（B=0.63，95%CI：−0.99，2.26）。无论男性还是女性，EF都没有发现显著相关性。结论产前PFAS暴露量越高，男性表现智商越低，这表明这种联系可能是性别和领域特异性的。

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来源期刊

Neurotoxicology and teratology 医学-毒理学

CiteScore

5.60

自引率

10.30%

发文量

审稿时长

58 days

期刊介绍： Neurotoxicology and Teratology provides a forum for publishing new information regarding the effects of chemical and physical agents on the developing, adult or aging nervous system. In this context, the fields of neurotoxicology and teratology include studies of agent-induced alterations of nervous system function, with a focus on behavioral outcomes and their underlying physiological and neurochemical mechanisms. The Journal publishes original, peer-reviewed Research Reports of experimental, clinical, and epidemiological studies that address the neurotoxicity and/or functional teratology of pesticides, solvents, heavy metals, nanomaterials, organometals, industrial compounds, mixtures, drugs of abuse, pharmaceuticals, animal and plant toxins, atmospheric reaction products, and physical agents such as radiation and noise. These reports include traditional mammalian neurotoxicology experiments, human studies, studies using non-mammalian animal models, and mechanistic studies in vivo or in vitro. Special Issues, Reviews, Commentaries, Meeting Reports, and Symposium Papers provide timely updates on areas that have reached a critical point of synthesis, on aspects of a scientific field undergoing rapid change, or on areas that present special methodological or interpretive problems. Theoretical Articles address concepts and potential mechanisms underlying actions of agents of interest in the nervous system. The Journal also publishes Brief Communications that concisely describe a new method, technique, apparatus, or experimental result.