Table 2_Association between zinc status and autism spectrum disorder in children and adolescents: a systematic review and meta-analysis of case–control studies.docx

BackgroundThis study aimed to further corroborate a previously reported connection between zinc nutritional status and the occurrence of autism spectrum disorder (ASD) among children and adolescents.
MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a systematic review and meta-analysis was conducted. The PubMed, Embase, Web of Science, Scopus, and PsyclNFO databases 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 plots, Begg’s test, and Egger’s test were used to evaluate publication bias.
ResultsWe included 25 case–control studies with 4,763 children and adolescents, comprising 2,499 cases and 2,264 typical controls. The random-effects meta-analysis revealed 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).
ConclusionBlood zinc levels were associated with ASD among children and adolescents. Therefore, screening blood zinc levels in children with ASD may be warranted. Further prospective studies are warranted to elucidate the role of zinc in the etiology of ASD.

背景 本研究旨在进一步验证此前报道的儿童青少年锌营养状况与孤独症谱系障碍（Autism Spectrum Disorder, ASD）发病之间的关联。
方法 本研究遵循《系统评价与Meta分析首选报告条目（Preferred Reporting Items for Systematic Reviews and Meta-Analyses, PRISMA）2020》指南，开展了一项系统评价与Meta分析。检索截至2024年1月发表于PubMed、Embase、Web of Science、Scopus及PsycINFO数据库的所有相关病例对照研究。计算科恩κ值以评价评价者间的一致性。本Meta分析采用随机效应模型汇总锌水平与ASD之间的总体关联。采用Q检验与I²统计量评估研究间异质性，同时通过漏斗图、Begg检验及Egger检验评价发表偏倚。
结果 本研究共纳入25项病例对照研究，涉及4763名儿童青少年，其中病例组2499人，典型发育对照组2264人。随机效应Meta分析结果显示，全血及血浆/血清锌水平与ASD呈负相关（标准化均数差（standardized mean difference, SMD）= −0.44，95%置信区间（confidence interval, CI）：−0.63 至 −0.25；SMD = −1.79，95%CI：−2.74 至 −0.84）；而毛发锌（SMD = −0.01，95%CI：−0.40 至 0.37）与尿液锌（SMD = −0.17，95%CI：−0.87 至 0.53）水平与ASD无显著关联。此外，纳入研究间存在统计学意义上的显著异质性（血浆/血清锌：I²=98.8%，P<0.001；毛发锌：I²=88.4%，P<0.001；尿液锌：I²=88.0%，P<0.001）。
结论 儿童青少年的血锌水平与ASD存在关联。因此，对孤独症谱系障碍患儿开展血锌水平筛查或具有必要性。未来需开展进一步的前瞻性研究，以阐明锌在ASD病因学中的作用。