Attention-deficit/hyperactivity disorder (ADHD) is a prevalent childhood neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and/or impulsivity. Multiple etiologic contributors have been proposed, including genetic, environmental, and neurobiological factors. Iron is essential to brain development and acts as a cofactor for tyrosine hydroxylase, an enzyme that limits dopamine synthesis; therefore, iron stores may influence dopaminergic pathways implicated in ADHD. Prior individual studies examining the relationship between peripheral iron measures such as serum ferritin and ADHD have reported inconsistent results. To address this uncertainty, the authors conducted a systematic review and meta-analysis to compare serum ferritin concentrations in children with ADHD versus healthy controls.
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the protocol was registered in PROSPERO (CRD420261420475). The authors searched PubMed/MEDLINE, Scopus, ScienceDirect, Google Scholar, and institutional repositories for English-language studies published through June 10, 2026. Search terms combined concepts related to iron (eg, "serum ferritin", "iron deficiency"), ADHD (eg, "Attention Deficit Hyperactivity Disorder", "ADHD"), and children.
Eligible studies included case-control, comparative cross-sectional, or cohort designs that reported serum ferritin levels in children diagnosed with ADHD by standardized criteria and compared these values with healthy control groups. Exclusions were case reports, case series, studies involving other psychiatric diagnoses or known hematologic disorders, conference abstracts, reviews, and animal studies. Two investigators independently screened records, removed duplicates, and reviewed full texts; disagreements were resolved by a third author. The final analysis included 21 studies after screening 7,643 records and evaluating 37 full-text articles.
Two reviewers independently extracted study-level data including first author, publication year, country, study design, mean age, mean and SD of serum ferritin for cases and controls, and sample sizes. Study quality was appraised with Joanna Briggs Institute (JBI) critical appraisal tools for observational studies; items assessed included group comparability, measurement validity, identification of confounders, and appropriateness of statistical analysis. JBI scoring classified studies into high, moderate, and low quality categories.
Because of substantial heterogeneity across studies, the authors used a random-effects model in STATA v17 to calculate pooled mean differences (MD) and standardized mean differences (SMD) for serum ferritin. Heterogeneity was quantified with Higgins’ I² statistic. The investigators explored heterogeneity sources with Galbraith radial plots, subgroup analyses (by continent, publication year, sample size, study design, and diagnostic criteria), sensitivity analyses (leave-one-out), and random-effects meta-regression. Publication bias was assessed visually with funnel plots and tested with Egger’s weighted regression (p < 0.05 considered evidence of bias).
The meta-analysis included 21 studies comprising 4,058 children with ADHD and 4,533 healthy controls. Studies originated from diverse regions: Egypt (4 studies), Israel, France (2), China, Turkey (2), South Africa, USA (3), Indonesia, Qatar, Brazil, Italy, India, Finland, and Korea. Designs were primarily case-control and comparative cross-sectional. Extracted variables and methodological details were tabulated in the manuscript.
Across the 21 studies, the pooled mean difference in serum ferritin between ADHD cases and controls was −9.74 μg/L (95% CI: −16.50, −2.98), indicating lower ferritin concentrations in children with ADHD.
Subgroup analyses demonstrated variation in pooled MDs:
Heterogeneity across included studies was substantial, motivating the choice of a random-effects model. The authors used Galbraith radial plots to identify studies contributing to heterogeneity and performed leave-one-out sensitivity analyses to evaluate the influence of individual studies on pooled estimates. Publication bias was inspected with funnel plots and tested using Egger’s regression; the manuscript reports these investigations but specifics of Egger’s p-values and funnel plot asymmetry are contained in the full paper and supplementary files.
This meta-analysis of 21 observational studies found that children with ADHD had lower peripheral serum ferritin levels than healthy controls, with a pooled mean difference of −9.74 μg/L. The association varied by region, study size, publication period, design, and diagnostic criteria, and overall heterogeneity was high. The finding aligns with biological plausibility: iron is necessary for dopamine synthesis and brain function, and lower iron stores could relate to dopaminergic dysfunction implicated in ADHD symptomatology.
The authors note that some individual studies have linked low serum ferritin to greater ADHD symptom severity and that randomized trials of iron supplementation have reported symptom improvement in some samples. However, evidence has not been uniformly consistent across studies, and the cross-sectional or case-control designs included in the review cannot establish causality.
Based on the pooled association, the authors recommend consideration of serum ferritin screening in children with ADHD and suggest that enhanced iron supplementation should be considered where deficiency is identified. They emphasize, however, that the evidence does not establish causality and that clinical decisions should factor in individual patient assessment and existing guidelines.
Key limitations include high heterogeneity across studies, potential publication bias, restriction to English-language publications, and reliance on peripheral ferritin as a proxy for brain iron. The included study designs are largely observational, limiting causal inference. The authors call for longitudinal studies and well-conducted randomized trials to clarify whether iron deficiency contributes causally to ADHD onset or severity and to determine the clinical benefits and safety of iron supplementation in this population.
This systematic review and meta-analysis found that children with ADHD have lower serum ferritin compared with healthy controls (pooled MD −9.74 μg/L). The authors recommend considering ferritin screening and appropriate iron supplementation in affected children, while advocating for future longitudinal research to determine causality and inform clinical practice.