SYSTEMATIC REVIEW article
Front. Nutr.
Sec. Clinical Nutrition
Association between Zinc Status and Autism Spectrum Disorder in Children and Adolescents: A Systematic Review and Meta-Analysis of Case-Control Studies
Provisionally accepted
- 1Ninghai Maternal and Child Health Hospi, Zhejiang, China
- 2Fourth Affiliated Hospital of China Medical University, Shenyang, China
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Background: This study aimed to further corroborate a previously reported connection between zinc nutritional status and the occurrence of autism spectrum disorder (ASD) in children and adolescents. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a systematic review with meta-analysis was conducted. PubMed, Embase, Web of Science, Scopus and PsyclNFO were searched for all relevant case-control studies published until January 2024. Cohen's kappa was computed to assess reviewer agreement. This meta-analysis used a random-effects model to summarize the overall association between zinc levels and ASD. The Q-test and I2 statistics were used to evaluate the heterogeneity of the studies, while funnel plot, Begg's test and Egger's test were used to evaluate publication bias. Results: We included 25 case-control studies with 4763 children and adolescents, comprising 2499 cases and 2264 typical controls. The random-effects meta-analysis showed that whole blood and plasma/serum zinc levels were negatively associated with ASD (standardized mean difference [SMD] = −0.44, 95% confidence interval [CI]: −0.63 to −0.25; SMD = −1.79, 95% CI: −2.74 to -0.84), whereas hair (SMD = −0.01, 95% CI: −0.40 to 0.37) and urinary (SMD = −0.17, 95% CI: −0.87 to 0.53) zinc levels were not associated with ASD. Moreover, we observed statistically significant heterogeneity among the included studies (plasma/serum zinc: I2 =98.8%, P<0.001; hair zinc: I2 =88.4%, P<0.001; urinary zinc: I2 =88.0%, P<0.001). Conclusions: Blood zinc levels were associated with ASD in children and adolescents. Therefore, screening blood zinc levels in children with ASD could be reasonable. Further prospective studies are warranted to elucidate the role of zinc in the etiology of ASD.
Keywords: zinc deficiency, Autism Spectrum Disorder, Children, adolescents, Meta-analysis
Received: 23 Sep 2025; Accepted: 03 Nov 2025.
Copyright: © 2025 Liu, Chen, He and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jia He, 7284813@qq.com
Xuening Li, xningli@cmu.edu.cn
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