Division of Climate and Environmental Health, Norwegian Institute of Public Health, 0456, Oslo, Norway; Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Chemical Neuroscience Group, Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine, University of Oslo, Oslo, Norway.
Environ Int. 2023 Nov;181:108271. doi: 10.1016/j.envint.2023.108271. Epub 2023 Oct 18.
The etiology of autism spectrum disorder (ASD) is multifactorial, involving genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs).
To evaluate the association between perinatal exposure to 27 potential EDCs and ASD among Norwegian children, and to further examine the neurodevelopmental toxicity of associated chemicals using zebrafish embryos and larvae.
1,199 mothers enrolled in the prospective birth-cohort (HUMIS, 2002-2009) study. Breastmilk levels of 27 chemicals were measured: polychlorinated biphenyls, organochlorine pesticides, polybrominated diphenyl ethers, and perfluoroalkyl substances as a proxy for perinatal exposure. We employed multivariable logistic regression to determine association, utilized elastic net logistic regression as variable selection method, and conducted an in vivo study with zebrafish larvae to confirm the neurodevelopmental effect.
A total of 20 children had specialist confirmed diagnosis of autism among 1,199 mother-child pairs in this study. β-Hexachlorocyclohexane (β-HCH) was the only chemical associated with ASD, after adjusting for 26 other chemicals. Mothers with the highest levels of β-HCH in their milk had a significant increased risk of having a child with ASD (OR = 1.82, 95 % CI: 1.20, 2.77 for an interquartile range increase in ln-transformed β-HCH concentration). The median concentration of β-HCH in breast milk was 4.37 ng/g lipid (interquartile range: 2.92-6.47), and the estimated daily intake (EDI) for Norwegian children through breastfeeding was 0.03 µg/kg of body weight. The neurodevelopmental and social behavioral effects of β-HCH were established in zebrafish embryos and larvae across various concentrations, with further analysis suggesting that perturbation of dopaminergic neuron development may underlie the neurotoxicity associated with β-HCH.
Prenatal exposure to β-HCH was associated with an increased risk of specialist-confirmed diagnoses of ASD among Norwegian children, and the EDI surpasses the established threshold. Zebrafish experiments confirm β-HCH neurotoxicity, suggesting dopaminergic neuron disruption as a potential underlying mechanism.
自闭症谱系障碍（ASD）的病因是多因素的，涉及遗传和环境因素，如内分泌干扰化学物质（EDCs）。
评估挪威儿童围产期接触 27 种潜在 EDC 与 ASD 之间的关联，并进一步使用斑马鱼胚胎和幼虫研究相关化学物质的神经发育毒性。
1199 名母亲参加了前瞻性出生队列研究（HUMIS，2002-2009 年）。测量了 27 种化学物质的母乳水平：多氯联苯、有机氯农药、多溴联苯醚和全氟烷基物质作为围产期暴露的替代物。我们采用多变量逻辑回归来确定关联，利用弹性网络逻辑回归作为变量选择方法，并进行了斑马鱼幼虫的体内研究以证实神经发育效应。
在这项研究的 1199 对母婴中，共有 20 名儿童被专家确诊为自闭症。β-六氯环己烷（β-HCH）是唯一与 ASD 相关的化学物质，在调整了 26 种其他化学物质后。母乳中β-HCH 水平最高的母亲，其子女患 ASD 的风险显著增加（OR=1.82，95%CI：1.20，2.77，ln 转化的β-HCH 浓度增加一个四分位距）。母乳中β-HCH 的中位数浓度为 4.37ng/g 脂质（四分位距：2.92-6.47），通过母乳喂养，挪威儿童的每日估计摄入量（EDI）为 0.03µg/kg 体重。β-HCH 在不同浓度下对斑马鱼胚胎和幼虫的神经发育和社会行为均有影响，进一步的分析表明，多巴胺能神经元发育的干扰可能是β-HCH 神经毒性的潜在机制。
围产期接触β-HCH 与挪威儿童专家确诊的 ASD 风险增加有关，而 EDI 超过了既定阈值。斑马鱼实验证实了β-HCH 的神经毒性，表明多巴胺能神经元破坏可能是潜在的机制。
