Blood homocysteine levels in children with autism spectrum disorder: An updated systematic review and meta-analysis.

Results of studies on peripheral blood levels of homocysteine (Hcy) in children with autism spectrum disorder (ASD) are inconsistent, and conclusions from two previous meta-analyses on this subject published in 2012 are already outdated. Therefore, we conducted an updated systematic review and meta-analysis to quantitatively summarize the peripheral blood Hcy data in children with ASD compared with healthy controls (HC). We searched PubMed, EMBASE, PsycINFO, PsycARTICLES, Web of Science, and Cochrane Library databases from inception to September 2019 for eligible studies, with no language restriction. Using random-effects model, we computed summary statistics. Thirty-one studies (3304 participants including 1641 cases) were included. The pooled results showed that the peripheral blood Hcy levels were significantly elevated in children with ASD when compared to HC (Hedges's g = 0.56, 95% CI = 0.36 to 0.76, P < 0.001). By sensitivity analyses, we confirmed that our results were quite robust. Additionally, no publication bias was observed in this meta-analysis. In conclusion, our study support the association of increased circulating Hcy levels with ASD in children, and the involvement of Hcy in the occurrence of ASD. However, in view of the significant between-study heterogeneity, the conclusions should be interpreted cautiously and more investigation is required.