BACKGROUND The etiology of autism spectrum disorder is poorly understood. Few studies have investigated the link between endocrine-disrupting chemicals and autistic traits. We examined the relationship between gestational phthalates and autistic traits in 3- to 4-y-old Canadian children. We also investigated potential effect modification by sex and folic acid supplementation. METHODS We enrolled 2,001 women>18 years of age during the first trimester of pregnancy between 2008 and 2011 from 10 cities in Canada. At 3-4 years of age, 610 children underwent neuropsychological assessments including the Social Responsiveness Scale-II (SRS-2) as a measure of autistic traits and social impairment. We measured 11 phthalate metabolites in maternal first trimester urine samples and assessed folic acid supplementation from reported intakes. We estimated covariate-adjusted differences in SRS-2 T-scores with a doubling in phthalate concentrations in 510 children with complete data. RESULTS Mean total SRS T-score was 45.3 (SD=6.1). Children with higher gestational exposure to mono-n-butyl (MBP) and mono-3-carboxypropyl (MCPP) concentrations exhibited significantly higher total SRS T-scores, indicating greater overall social impairment, as well as higher scores on subdomains, indicating deficits in social cognition, social communication, social motivation, and restricted interests/repetitive behaviors. A doubling in MBP or MCPP concentrations was associated with 0.6 (95% CI: 0.1, 1.0) and 0.5 (95% CI: 0.1, 0.8) higher total SRS T-scores. Associations were consistently and significantly stronger in boys (βMBP=1.0; 95% CI: 0.4, 1.6; n=252) compared with girls (βMBP=0.1; 95% CI: -0.6, 0.7; n=258) and among children who had lower prenatal folic acid supplementation (<400μg/d) (βMBP=1.3; 95% CI: 0.4, 2.3; n=59) compared with those who had adequate folic acid supplementation (≥400μg/d) (βMBP=0.4; 95% CI: -0.1, 0.8; n=451). CONCLUSIONS Higher gestational concentrations of some phthalate metabolites were associated with higher scores of autistic traits as measured by the SRS-2 in boys, but not girls; these small size effects were mitigated by first trimester-of-pregnancy folic acid supplementation. https://doi.org/10.1289/EHP5621.

中文翻译：

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加拿大儿童邻苯二甲酸酯和叶酸的妊娠暴露以及自闭症特征。

背景技术对自闭症谱系障碍的病因知之甚少。很少有研究调查破坏内分泌的化学物质与自闭症特征之间的联系。我们研究了3至4岁加拿大儿童的妊娠邻苯二甲酸酯与自闭症特征之间的关系。我们还研究了通过补充性别和叶酸对潜在效果的影响。方法我们在2008年至2011年期间，从加拿大10个城市招募了200名年龄在18岁以上，年龄在18岁以上的女性。在3-4岁时，对610名儿童进行了神经心理学评估，其中包括社会反应量表II（SRS-2），以衡量自闭症特征和社会障碍。我们测量了孕妇孕早期尿液样本中的11种邻苯二甲酸酯代谢物，并从报告的摄入量中评估了叶酸的补充量。我们用完整的数据估算了510名儿童中SRS-2 T分数的协变量调整后差异，其中邻苯二甲酸盐浓度增加了一倍。结果平均SRS总得分为45.3（SD = 6.1）。妊娠暴露于单正丁基（MBP）和单-3-羧丙基（MCPP）浓度较高的儿童表现出更高的总SRS T分数，表明更大的整体社会障碍，以及子域得分更高，表明社交认知，社交沟通，社交动机和受限制的兴趣/重复行为。MBP或MCPP浓度加倍与总SRS T分数高0.6（95％CI：0.1，1.0）和0.5（95％CI：0.1，0.8）有关。男孩（βMBP= 1.0; 95％CI：0.4，1.6; n = 252）与女孩（βMBP= 0.1; 95％CI：-0.6，0.7; n = 258）和相比补充叶酸（≥400μg/ d）较低的产前叶酸补充剂（<400μg/ d）（βMBP= 1.3; 95％CI：0.4，2.3; n = 59） d）（βMBP ＝ 0.4； 95％CI：-0.1，0.8； n ＝ 451）。结论：通过SRS-2测定的男孩中，某些邻苯二甲酸酯代谢物的较高妊娠浓度与较高的自闭性特征得分有关；而与女孩无关。孕早期补充叶酸可减轻这些小影响。https://doi.org/10.1289/EHP5621。结论：通过SRS-2测定的男孩中，某些邻苯二甲酸酯代谢物的较高妊娠浓度与较高的自闭性特征得分有关；而与女孩无关。孕早期补充叶酸可减轻这些小影响。https://doi.org/10.1289/EHP5621。结论：通过SRS-2测定的男孩中，某些邻苯二甲酸酯代谢物的较高妊娠浓度与较高的自闭性特征得分有关；而与女孩无关。孕早期补充叶酸可减轻这些小影响。https://doi.org/10.1289/EHP5621。