Abstract / Summary
Attention-deficit/hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder of uncertain etiology. Iron is crucial for brain function and dopamine regulation, but prior studies examining its association with ADHD have produced inconsistent results. This systematic review and meta-analysis aimed to compare serum ferritin concentrations in children with ADHD versus healthy controls.
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, Science Direct, and Google Scholar to identify eligible studies. Statistical analyses were performed using STATA version 17, and a random-effects model was applied to estimate the pooled mean difference (MD) and standardized mean difference (SMD). Heterogeneity across included studies was assessed using Higgins' I2 test. Publication bias was evaluated visually using funnel plots and statistically via Egger's weighted regression test.
A total of 7643 articles were identified, of which 21 studies (including 4,058 ADHD cases and 4,533 controls) were included in the final meta-analysis. The pooled mean difference (MD) in serum ferritin levels between children with ADHD and healthy controls was -9.74 (95% CI: -16.50, -2.98). Subgroup analyses were conducted to explore heterogeneity. By continent, the highest pooled MD was observed in Africa (-19.28, 95% CI: -40.73, 2.17) and the lowest in North America (-1.42, 95% CI: -6.98, 4.13). By publication year, studies published before 2015 showed a pooled MD of -1.94 (95% CI: -2.31, -1.58), compared to -19.43 (95% CI: -34.37, -4.49) for those published after 2016. By sample size, smaller studies (<199 participants) yielded a higher MD (-12.12, 95% CI: -21.91, -2.34) than larger studies (≥200 participants; -7.64, 95% CI: -17.33, 2.05). By study design, the pooled MD was -1.95 (95% CI: -2.31, -1.59) for case-control studies and -14.85 (95% CI: -27.07, -2.63) for comparative cross-sectional studies. In the subgroup analysis based on ADHD diagnostic criteria, the DSM-IV-TR criteria yielded the largest mean difference (-16.56, 95% CI: -28.23, -4.89).
Lower serum ferritin levels (pooled MD: -9.74) are associated with ADHD in children. Accordingly, screening for serum ferritin and enhanced iron supplementation should be considered in this population. Future longitudinal studies are needed to clarify the causal relationship between iron deficiency and ADHD severity.