Peripheral iron levels in children with autism spectrum disorders vs controls: a systematic review and meta-analysis

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, and nutritional deficiency may play a role in the development of ASD. A relationship between ASD and iron levels/iron deficiency (ID) has been reported; however, the results have been inconsistent. Therefore, we conducted this meta-analysis to examine the relationship between ASD and ID following the Meta-Analysis of Observational Studies in Epidemiology guidelines. We performed a systematic search of PubMed, ScienceDirect, Embase, ProQuest, ClinicalTrials.gov, and Cochrane CENTRAL databases up to September 22, 2017. Studies providing data on peripheral iron levels and/or the prevalence of ID in children with ASD vs those without ASD (non-ASD) were included. Primary outcomes included the difference in peripheral iron levels in children with ASD compared with those without ASD, and the odds ratio of ASD in children with ID compared with those without ID. Twenty-five articles met the inclusion criteria. We found that peripheral iron levels were not significantly different between the ASD and non-ASD groups, including serum ferritin (k = 4, Hedges g = 0.016, 95% confidence interval [CI] = -0.482 to 0.515, P = .949) or hair iron (k = 12; Hedges g = -0.219, 95% CI = -0.551 to 0.113, P = .196). There was no significant difference in the amount of iron in food content between the ASD and non-ASD groups (k = 6; Hedges g = -0.458, 95% CI = -1.246 to 0.330, P = .254). However, the reciprocal comorbidity of ASD and ID was significantly higher than in the children without these disorders. Our analysis showed that the available evidence is inconsistent with regard to whether children with ASD have lower iron levels. Future longitudinal studies are required to confirm or refute these associations and elucidate potential mechanisms.