Serum folate and vitamin B12 levels and their association with neurodevelopmental features in preschool children with autism spectrum disorder
WU Yuan, YANG Ting, CHEN Hong-Yu, LONG Dan, XIANG Xue-Li, FENG Yu-Ru, WEI Qiu-Hong, CHEN Jie, LI Ting-Yu
Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University/Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders/Ministry of Education Key Laboratory of Child Development and Disorders/National Clinical Research Center for Child Health and Disorders, Chongqing 400014, China
Abstract Objective To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). Methods A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. Results The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). Conclusions Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.
Corresponding Authors:
(Li T-Y, Email:tyli@vip.sina.com)
E-mail: tyli@vip.sina.com
Cite this article:
WU Yuan,YANG Ting,CHEN Hong-Yu et al. Serum folate and vitamin B12 levels and their association with neurodevelopmental features in preschool children with autism spectrum disorder[J]. CJCP, 2024, 26(4): 371-377.
WU Yuan,YANG Ting,CHEN Hong-Yu et al. Serum folate and vitamin B12 levels and their association with neurodevelopmental features in preschool children with autism spectrum disorder[J]. CJCP, 2024, 26(4): 371-377.
Maenner MJ, Warren Z, Williams AR, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years: Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2020[J]. MMWR Surveill Summ, 2023, 72(2): 1-14. PMID: 36952288. PMCID: PMC10042614. DOI: 10.15585/mmwr.ss7202a1.
Zhou H, Xu X, Yan W, et al. Prevalence of autism spectrum disorder in China: a nationwide multi-center population-based study among children aged 6 to 12 years[J]. Neurosci Bull, 2020, 36(9): 961-971. PMID: 32607739. PMCID: PMC7475160. DOI: 10.1007/s12264-020-00530-6.
Al-Farsi YM, Waly MI, Deth RC, et al. Low folate and vitamin B12 nourishment is common in Omani children with newly diagnosed autism[J]. Nutrition, 2013, 29(3): 537-541. PMID: 23287069. DOI: 10.1016/j.nut.2012.09.014.
Altun H, Kuruta? EB, ?ahin N, et al. The levels of vitamin D, vitamin D receptor, homocysteine and complex B vitamin in children with autism spectrum disorders[J]. Clin Psychopharmacol Neurosci, 2018, 16(4): 383-390. PMID: 30466210. PMCID: PMC6245292. DOI: 10.9758/cpn.2018.16.4.383.
Saha S, Saha T, Rajamma U, et al. Analysis of association between components of the folate metabolic pathway and autism spectrum disorder in eastern Indian subjects[J]. Mol Biol Rep, 2022, 49(2): 1281-1293. PMID: 34792727. DOI: 10.1007/s11033-021-06956-z.
Yekta? ?, Alpay M, Tufan AE. Comparison of serum B12, folate and homocysteine concentrations in children with autism spectrum disorder or attention deficit hyperactivity disorder and healthy controls[J]. Neuropsychiatr Dis Treat, 2019, 15: 2213-2219. PMID: 31496704. PMCID: PMC6689552. DOI: 10.2147/NDT.S212361.
Liu X, Liu J, Xiong X, et al. Correlation between nutrition and symptoms: nutritional survey of children with autism spectrum disorder in Chongqing, China[J]. Nutrients, 2016, 8(5): 294. PMID: 27187463. PMCID: PMC4882707. DOI: 10.3390/nu8050294.
Mitchell ES, Conus N, Kaput J. B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline[J]. Neurosci Biobehav Rev, 2014, 47: 307-320. PMID: 25173634. DOI: 10.1016/j.neubiorev.2014.08.006.
Ali A, Waly MI, Al-Farsi YM, et al. Hyperhomocysteinemia among Omani autistic children: a case-control study[J]. Acta Biochim Pol, 2011, 58(4): 547-551. PMID: 22187679.
Zhu J, Guo M, Yang T, et al. Nutritional status and symptoms in preschool children with autism spectrum disorder: a two-center comparative study in Chongqing and Hainan province, China[J]. Front Pediatr, 2020, 8: 469. PMID: 33014918. PMCID: PMC7494825. DOI: 10.3389/fped.2020.00469.
Guo M, Li L, Zhang Q, et al. Vitamin and mineral status of children with autism spectrum disorder in Hainan Province of China: associations with symptoms[J]. Nutr Neurosci, 2020, 23(10): 803-810. PMID: 30570388. DOI: 10.1080/1028415X.2018.1558762.
Li Q, Yang T, Chen L, et al. Serum folate status is primarily associated with neurodevelopment in children with autism spectrum disorders aged three and under: a multi-center study in China[J]. Front Nutr, 2021, 8: 661223. PMID: 34055856. PMCID: PMC8155683. DOI: 10.3389/fnut.2021.661223.
Hyman SL, Levy SE, Myers SM, et al. Identification, evaluation, and management of children with autism spectrum disorder[J]. Pediatrics, 2020, 145(1): e20193447. PMID: 31843864. DOI: 10.1542/peds.2019-3447.
Beggiato A, Peyre H, Maruani A, et al. Gender differences in autism spectrum disorders: divergence among specific core symptoms[J]. Autism Res, 2017, 10(4): 680-689. PMID: 27809408. DOI: 10.1002/aur.1715.
Xiong X, Liu D, He W, et al. Identification of gender-related metabolic disturbances in autism spectrum disorders using urinary metabolomics[J]. Int J Biochem Cell Biol, 2019, 115: 105594. PMID: 31449876. DOI: 10.1016/j.biocel.2019.105594.
Aita C, Mizoguchi Y, Yamamoto M, et al. Oxytocin levels and sex differences in autism spectrum disorder with severe intellectual disabilities[J]. Psychiatry Res, 2019, 273: 67-74. PMID: 30640053. DOI: 10.1016/j.psychres.2018.12.139.
WANG Cai-Yun, XU Hong-Mei, LIU Gang, LIU Jing, YU Hui, CHEN Bi-Quan, ZHENG Guo, SHU Min, DU Li-Jun, XU Zhi-Wei, HUANG Li-Su, LI Hai-Bo, WANG Dong, BAI Song-Ting, SHAN Qing-Wen, ZHU Chun-Hui, TIAN Jian-Mei, HAO Jian-Hua, LIN Ai-Wei, LIN Dao-Jiong, WU Jin-Zhun, ZHANG Xin-Hua, CAO Qing, TAO Zhong-Bin, CHEN Yuan, ZHU Guo-Long, XUE Ping, TANG Zheng-Zhen, SU Xue-Wen, QU Zheng-Hai, ZHAO Shi-Yong, PANG Lin, DENG Hui-Ling, SHU Sai-Nan, CHEN Ying-Hu. A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020[J]. CJCP, 2024, 26(2): 131-138.