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加拿大学龄前儿童童年时期拟除虫菊酯暴露与神经发育

Childhood exposure to pyrethroids and neurodevelopment in Canadian preschoolers.

作者信息

Ntantu Nkinsa Patrick, Fisher Mandy, Muckle Gina, Guay Mireille, Arbuckle Tye E, Fraser William D, Boylan Khrista, Booij Linda, Walker Mark, Bouchard Maryse F

机构信息

Department of Environmental and Occupational Health, School of Public Health, Université de Montréal; CHU Sainte-Justine Research Centre Montréal, Quebec, Canada.

Population Studies Division, Health Canada, Ottawa, Ontario, Canada.

出版信息

Neurotoxicology. 2023 Dec;99:120-128. doi: 10.1016/j.neuro.2023.10.001. Epub 2023 Oct 5.

Abstract

BACKGROUND

Pyrethroid insecticides are used both residentially and agriculturally and their toxicity targets the nervous system of insects. They might also interfere with development and function of the human brain. A few epidemiological studies suggest that exposure to pyrethroids may be associated with neurobehavioral problems in children but there is little data on potential associations with cognitive outcomes. Furthermore, many studies showed that the neurotoxic effects of several pesticides are modified by sex, hence, considerations of potential sex-differences are important to investigate.

OBJECTIVE

To study the cross-sectional association between urinary levels of pyrethroid metabolites and neurodevelopment, including neurobehavioral and cognitive outcomes, in preschool-age children, and to examine whether sex might modify these associations.

METHODS

We used data from a follow-up examination of the Maternal-Infant Research on Environmental Chemicals (MIREC), the MIREC Child Development study (MIREC-CD Plus) on children at age 3-4 years living in 6 Canadian cities. For each participant, we collected a urine sample for measurements of pyrethroids metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA, 4-F-3-PBA). We assessed neurodevelopment with the Wechsler Primary and Preschool Scale of Intelligence-III (WPPSI-III) and two scales of the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). Parents reported children's behavior using the Behavior Assessment System for Children-2 (BASC-2) and the Social Responsiveness Scale-2 (SRS-2). We examined associations between children's urinary pyrethroid metabolite concentrations and neurodevelopmental scores with multiple linear regression models, adjusting for confounders, in boys and girls separately.

RESULTS

The study included 179 children (mean age: 3.2 y, range 2.8-4.0). The detection frequencies were high for most pyrethroid metabolites (83-100%), but lower for 4-F-3-PBA (36%). Higher concentrations of cis-DBCA were significantly associated with lower verbal, performance and full-scale IQ scores in boys (e.g., for a 2-fold increase in cis-DBCA, β = -2.0; 95% CI: -3.4, -0.6 for full-scale IQ). In girls, the only metabolite associated with cognitive scores was 3-PBA, which was associated with lower verbal IQ scores (β = -1.3, 95% CI: -2.6, -0.1). For neurobehavioral outcomes in boys, there were associations between poorer BASC-2 Adaptive Skills scores with higher concentrations of cis-DCCA (β = -1.6, 95% CI: -2.3, -0.9), trans-DCCA (β = -1.5, 95% CI: -2.2, -0.8), 3-PBA (β = -1.7, 95% CI: -2.5, -0.9), and sum of pyrethroid metabolites (β = -1.8, 95% CI: -2.6, -0.9). In girls, we observed a significant association between higher concentration of cis-DCCA and better BASC-2 Adaptive Skills score (β = 1.0; 95% CI, 0.2, 1.8), but not with other urinary pyrethroids metabolites. Scores on the SRS-2 and BRIEF-P were not associated with pyrethroid metabolites.

CONCLUSION

There were associations between some pyrethroid pesticide metabolites and indicators of neurodevelopmental disorder, especially among boys. These associations are in agreement with previous studies and could suggest that exposure to pyrethroid pesticides represents a risk of potential toxicity for the cognitive development of children, and a risk for behavioral development. However, the cross-sectional nature of this study limits causal inferences.

摘要

背景

拟除虫菊酯类杀虫剂在住宅和农业领域均有使用,其毒性作用于昆虫的神经系统。它们也可能干扰人类大脑的发育和功能。一些流行病学研究表明,接触拟除虫菊酯可能与儿童的神经行为问题有关,但关于与认知结果潜在关联的数据较少。此外,许多研究表明,几种农药的神经毒性作用存在性别差异,因此,考虑潜在的性别差异对于开展研究很重要。

目的

研究学龄前儿童尿中拟除虫菊酯代谢物水平与神经发育(包括神经行为和认知结果)之间的横断面关联,并检验性别是否会改变这些关联。

方法

我们使用了环境化学物质母婴研究(MIREC)的随访检查数据,即MIREC儿童发育研究(MIREC-CD Plus),该研究针对居住在加拿大6个城市的3-4岁儿童。对于每位参与者,我们收集了一份尿液样本,用于测量拟除虫菊酯代谢物(顺式-DBCA、顺式-DCCA、反式-DCCA、3-PBA、4-F-3-PBA)。我们使用韦氏学前和小学儿童智力量表第三版(WPPSI-III)以及执行功能学前行为评定量表(BRIEF-P)的两个分量表评估神经发育。父母使用儿童行为评估系统第二版(BASC-2)和社会反应量表第二版(SRS-2)报告孩子的行为。我们分别在男孩和女孩中使用多元线性回归模型,在调整混杂因素后,研究儿童尿中拟除虫菊酯代谢物浓度与神经发育评分之间的关联。

结果

该研究纳入了179名儿童(平均年龄:3.2岁,范围2.8-4.0岁)。大多数拟除虫菊酯代谢物的检出频率较高(83%-100%),但4-F-3-PBA的检出频率较低(36%)。顺式-DBCA浓度较高与男孩较低的语言、操作和全量表智商得分显著相关(例如,顺式-DBCA增加2倍时,全量表智商的β=-2.0;95%CI:-3.4,-0.6)。在女孩中,与认知评分相关的唯一代谢物是3-PBA,它与较低的语言智商得分相关(β=-1.3,95%CI:-2.6,-0.1)。对于男孩的神经行为结果,BASC-2适应技能得分较低与顺式-DCCA(β=-1.6,95%CI:-2.3,-0.9)、反式-DCCA(β=-1.5,95%CI:-2.2,-0.8)、3-PBA(β=-1.7,95%CI:-2.5,-0.9)以及拟除虫菊酯代谢物总和(β=-1.8,95%CI:-2.6,-0.9)浓度较高有关。在女孩中,我们观察到顺式-DCCA浓度较高与较好的BASC-2适应技能得分之间存在显著关联(β=1.0;95%CI,0.2,1.8),但与其他尿中拟除虫菊酯代谢物无关。SRS-2和BRIEF-P的得分与拟除虫菊酯代谢物无关。

结论

一些拟除虫菊酯类农药代谢物与神经发育障碍指标之间存在关联,尤其是在男孩中。这些关联与先前的研究一致,可能表明接触拟除虫菊酯类农药对儿童的认知发育和行为发育存在潜在毒性风险。然而,本研究的横断面性质限制了因果推断。

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