Association of urinary polycyclic aromatic hydrocarbon metabolites with symptoms among autistic children: A case–control study in Tianjin, China

Association of urinary polycyclic aromatic hydrocarbon metabolites with symptoms among autistic children: A case–control study in Tianjin, China
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DOI:
10.1002/aur.2788
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发表时间:
2022-08
期刊:
影响因子:
4.7
通讯作者:
Peiying Li;Qiaoyun Yang;Yao Li;Yu Han;Zhiyi Qu;Lei Gao;T. Cui;W. Xiong;W. Xi;Xin Zhang
Peiying Li;Qiaoyun Yang;Yao Li;Yu Han;Zhiyi Qu;Lei Gao;T. Cui;W. Xiong;W. Xi;Xin Zhang
中科院分区:
医学2区
文献类型:
--
作者:
Peiying Li;Qiaoyun Yang;Yao Li;Yu Han;Zhiyi Qu;Lei Gao;T. Cui;W. Xiong;W. Xi;Xin Zhang

文献摘要

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多环芳烃(PAHs)是一种普遍存在的污染物,与神经发育改变和各种神经发育障碍有关。然而,根据自闭症谱系障碍(ASD)症状和自闭症行为的严重程度来评估PAH暴露的内部生物标志物的研究很少。因此,我们进行了一项病例对照研究,根据性别和年龄按1:1的比例匹配,对101名自闭症儿童和101名神经正常儿童进行了12种尿羟基多环芳烃代谢产物(即羟基多环芳烃)的评估。采用儿童自闭症评定量表(CARS)和自闭症行为量表(ABC)对自闭症儿童的症状严重程度和自闭症行为进行评估。我们发现,除2-羟基萘(2-OHNap)和4-羟基菲(4-OHPhe)外,ASD组有9种羟基多环芳烃的尿中含量显著高于对照组。此外,尿羟基-PAH水平与ASD风险相关,优势比从1.86到17.19不等。在调整协变量后,接触1-羟基萘(1-OHNAP,β=3.32)、羟基菲(1/2/3+9-OHPhes,β=3.41-5.12)、1-羟基吡喃(1-OH-PYR;β=3.91)、2-羟基苯并呋喃(2-OHDBF;β=3.93)和∑羟基多环芳烃(β=4.67)与CARS评分呈正相关(P均<0.05)。当使用ABC量表时,1-OHPYR水平与ABC总分呈正相关(β=18.54),其中社交关系(β=6.51)和语言领域(β=6.51)的相关性最强(均p&lt;0.05)。贝叶斯核机器回归(BKMR)显示,对于CARS得分,1-OHNap、1-OHPhe和3+9-OHPhe水平的暴露反应一致,对于ABC总分,1-OHPyr水平的暴露反应一致。我们的发现表明,患有自闭症的儿童可能有更高的尿羟基多环芳烃水平,这些生物标记物水平与自闭症儿童患自闭症的几率增加、自闭症症状的严重性增加以及自闭症儿童的自闭症行为增加有关。
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous pollutants that are associated with altered neurodevelopment and various neurodevelopmental disorders. However, studies evaluating internal biomarkers of PAH exposure in reference to the severity of autism spectrum disorder (ASD) symptomology and autistic behaviors are scarce. Hence, we conducted a case–control study evaluating 12 urinary hydroxylated PAH metabolites (i.e., hydroxy‐PAHs) in 101 children with autism and 101 neurotypical children, matching according to sex and age in a 1:1 ratio. In children with ASD, the severity of symptomology and autistic behaviors were assessed using the child autism rating scale (CARS) and the autism behavior checklist (ABC). We found that urinary levels of nine of the hydroxy‐PAHs were statistically significantly higher in the ASD group, with the exception of 2‐hydroxynaphthalene (2‐OHNap) and 4‐hydroxyphenanthrene (4‐OHPhe). Moreover, urinary hydroxy‐PAH levels were associated with ASD risk, with odds ratios ranging from 1.86 to 17.19. Exposures to 1‐hydroxynaphthalene (1‐OHNap, β = 3.32), hydroxyphenanthrenes (1/2/3 + 9‐OHPhes, β = 3.41–5.12), 1‐hydroxypyrene (1‐OH‐Pyr; β = 3.91), 2‐hydroxybenzofuran (2‐OHDBF; β = 3.93), and ∑OH‐PAHs (β = 4.67) were positively associated with CARS scores after adjusting for covariates (all p < 0.05). When applying the ABC scale, 1‐OHPyr levels were positively associated with ABC total scores (β = 18.54), with the strongest associations evidenced in regard to the social relatedness (β = 6.51) and language domains (β = 6.51) (all p < 0.05). Bayesian kernel machine regression (BKMR) showed consistent positive exposure responses for 1‐OHNap, 1‐OHPhe, and 3 + 9‐OHPhe levels in regard to CARS scores, and for 1‐OHPyr levels in regard to ABC total scores. Our findings suggest that children with ASD may have higher urinary levels of hydroxy‐PAHs, and that these biomarker levels are associated with an increased odds of ASD, an increased severity of autism symptomology, and increased autistic behaviors in children with autism.