Department of Psychology, York University, Toronto, ON, Canada.
Department of Psychology, York University, Toronto, ON, Canada.
Neurotoxicol Teratol. 2023 Jul-Aug;98:107181. doi: 10.1016/j.ntt.2023.107181. Epub 2023 May 11.
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.
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.
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.
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.
Higher prenatal PFAS exposure was associated with lower performance IQ in males, suggesting that this association may be sex- and domain-specific.
实验研究表明，接触全氟烷基物质（PFAS）具有神经毒性，但将产前 PFAS 暴露与儿童神经发育联系起来的流行病学证据尚无定论且十分有限。
在加拿大妊娠和出生队列中，量化产前暴露于传统 PFAS 与儿童智力（智商）和执行功能（EF）之间的关系，并确定这些关系是否因儿童性别而异。
我们在母婴环境化学物质研究（MIREC）中测量了第一孕期血浆中全氟辛酸（PFOA）、全氟辛烷磺酸（PFOS）和全氟己烷磺酸（PFHxS）的浓度，并使用韦氏学前和小学智力量表（WPPSI-III）评估了儿童的全量表（n=522）、表现（n=517）和言语（n=519）智商。使用家长报告的问卷，行为评定量表的执行功能-学前版（BRIEF-P）评估了儿童的工作记忆（n=513）和计划和组织能力（n=514）。我们使用多元线性回归分析量化了个体 log2 转化后的 PFAS 暴露与儿童智商和 EF 之间的关系，并评估了儿童性别对其的影响。我们还使用了重复保留加权分位数总和（WQS）回归模型，评估了儿童性别对其的影响，以量化三种 PFAS 化学物质联合暴露对智商和 EF 的影响。所有模型均经过了关键社会人口特征的调整。
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，儿童性别对其存在显著的影响（p<0.01）。具体而言，PFOA、PFOS 和或 PFHxS 的每一次翻倍与表现智商呈负相关，但仅在男性中存在（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）。同样，WQS 指数的每个四分位数增加都与男性表现智商较差有关（B=-3.16，95%CI：-4.90，-1.43），其中 PFHxS 对该指数的贡献最大。相比之下，女性中未发现显著的关联（B=0.63，95%CI：-0.99，2.26）。在男性或女性中均未发现 EF 存在显著关联。
较高的产前 PFAS 暴露与男性的表现智商较低有关，表明这种关联可能具有性别和领域特异性。
