Blood zinc and copper levels in children with autism spectrum disorder: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental condition shaped by genetic, environmental, and biochemical influences. Among these, trace elements such as zinc (Zn) and copper (Cu) have attracted considerable interest due to their involvement in synaptic transmission, antioxidant defense mechanisms, and neuroinflammatory processes. This systematic review and meta-analysis aimed to assess whole blood, serum and plasma levels of Zn and Cu in children diagnosed with ASD compared to neurotypical controls.

METHODS

A comprehensive literature search was conducted in accordance with PRISMA guidelines across PubMed, Embase, Web of Science, and Scopus databases up to July 2025. Eligible studies included observational studies, including cross-sectional and case-control studies reporting whole blood, serum, or plasma concentrations of Zn and Cu in children with ASD. Two independent reviewers performed study selection and data extraction, and quality assessment using the modified Newcastle-Ottawa Scale (NOS). Meta-analyses were conducted using STATA version 17.0. Pooled effect sizes were calculated using Hedges's g. Heterogeneity was evaluated using the I2 statistic, and publication bias was assessed via funnel plots and Egger's test.

RESULTS

In total 15 studies comprising 2,537 participants (849 children with ASD and 1,688 controls) met the inclusion criteria. The meta-analysis revealed non-significant pooled differences between children with ASD and controls for Zn (SMD=-0.48, 95 % CI: -1.08 to 0.13; p=0.13) and Cu (SMD=-0.59, 95 % CI: -1.30 to 0.11; p=0.10). Substantial heterogeneity (I2>97 %) was observed for both analyses.

CONCLUSIONS

The children with ASD and the control groups did not significantly differ in blood Zn or Cu levels. Due to the possibility of publication bias and heterogeneity that existed between included studies, the results should be interpreted cautiously. Thus, existing evidence should be treated as an attempt to generate the hypothesis, and higher-quality studies are needed to uncover the role of trace elements homeostasis in ASD.