Li Qiu, Yang Ting, Chen Li, Dai Ying, Wu Li-Jie, Jia Fei-Yong, Hao Yan, Li Ling, Zhang Jie, Ke Xiao-Yan, Yi Ming-Ji, Hong Qi, Chen Jin-Jin, Fang Shuan-Feng, Wang Yi-Chao, Wang Qi, Jin Chun-Hua, Dong Zhi-Fang, Chen Jie, Li Ting-Yu
Chongqing Key Laboratory of Childhood Nutrition and Health, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing, China.
Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin, China.
Front Nutr. 2021 May 13;8:661223. doi: 10.3389/fnut.2021.661223. eCollection 2021.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Folate has been demonstrated to be associated with ASD. However, current studies on the correlation between folate and symptoms of children with ASD have inconsistent conclusions, use mainly small samples, and lack age-stratified analysis. This study aimed to explore the association between serum folate and symptoms of autistic children at different age groups from a multi-center perspective. We enrolled 1,300 children with ASD and 1,246 typically developing (TD) children under 7 years old from 13 cities in China. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS) were used to evaluate the symptoms of children with ASD. China neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) scale was used to evaluate the neurodevelopment of children with ASD. Serum folate was measured by chemiluminescence assay in the two groups. The serum folate levels of children with ASD were lower than that of TD children. In terms of core symptoms of ASD, we found that the serum folate levels were not associated with ABC, SRS, and CARS scores in ASD children of all ages but negatively associated with communication warning behavior scores of CNBS-R2016 in ASD children aged three and under. Concerning development quotients, it was at the age of three and under that serum folate levels were positively associated with gross motor, fine motor, language, and general quotient of ASD children. These ASD children aged three and under were further divided into two groups according to the median of serum folate (14.33 ng/mL); we found that compared to ASD children with folate ≤ 14.33 ng/mL, those with folate >14.33 ng/mL had lower communication warning behavior score and higher gross motor, fine motor, adaptive behavior, language, person-social, and general development quotients. We found that serum folate status was primarily associated with the neurodevelopment of children with ASD aged three and under. Furthermore, relatively higher serum folate levels may be more beneficial for children with ASD. Our results suggest that folate level should be paid more attention in ASD children, especially in early life, to better promote the intervention of ASD children.
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍。叶酸已被证明与ASD有关。然而，目前关于叶酸与ASD儿童症状之间相关性的研究结论不一致，主要使用小样本，且缺乏年龄分层分析。本研究旨在从多中心角度探讨血清叶酸与不同年龄组自闭症儿童症状之间的关联。我们招募了来自中国13个城市的1300名7岁以下的ASD儿童和1246名发育正常（TD）的儿童。使用自闭症行为量表（ABC）、社会反应量表（SRS）和儿童自闭症评定量表（CARS）来评估ASD儿童的症状。使用中国神经心理与行为量表2016修订版（CNBS-R2016）量表来评估ASD儿童的神经发育情况。通过化学发光法测定两组儿童的血清叶酸水平。ASD儿童的血清叶酸水平低于TD儿童。在ASD的核心症状方面，我们发现血清叶酸水平与各年龄段ASD儿童的ABC、SRS和CARS评分均无关联，但与3岁及以下ASD儿童的CNBS-R2016沟通警示行为评分呈负相关。关于发育商，在3岁及以下时，血清叶酸水平与ASD儿童的大运动、精细运动、语言和总商数呈正相关。将这些3岁及以下的ASD儿童根据血清叶酸中位数（14.33 ng/mL）进一步分为两组；我们发现，与叶酸≤14.33 ng/mL的ASD儿童相比，叶酸>14.33 ng/mL的儿童沟通警示行为评分更低，大运动、精细运动、适应行为、语言、人际社交和总体发育商数更高。我们发现血清叶酸状态主要与3岁及以下ASD儿童的神经发育有关。此外，相对较高的血清叶酸水平可能对ASD儿童更有益。我们的研究结果表明，应更加关注ASD儿童的叶酸水平，尤其是在生命早期，以更好地促进对ASD儿童的干预。
