---
title: "Serum ferritin and ADHD in children: systematic review and meta-analysis findings"
id: "plos-one-11-serum-ferritin-in-children-with-attention-deficit-hyperactivity-disorder-adhd-a"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-11-serum-ferritin-in-children-with-attention-deficit-hyperactivity-disorder-adhd-a"
content_type: "clinical_feed_article"
specialty: "Pediatrics"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359790"
published_at: "2026-10-05T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Serum ferritin and ADHD in children: systematic review and meta-analysis findings
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-11-serum-ferritin-in-children-with-attention-deficit-hyperactivity-disorder-adhd-a
- **Specialty:** [Pediatrics](https://medichelpline.com/clinical-feed/pediatrics.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359790)
- **Published At:** 2026-10-05T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This systematic review and meta-analysis compared **serum ferritin** concentrations in children with ADHD versus healthy controls using 21 studies published through June 10, 2026. - The pooled dataset included 4,058 children with ADHD and 4,533 controls drawn from 21 case-control and cross-sectional studies across multiple continents. - The overall pooled mean difference (MD) in serum ferritin between ADHD cases and controls was −9.74 μg/L (95% CI: −16.50, −2.98), indicating lower ferritin in children with ADHD. - Subgroup analyses showed variation by continent, publication year, sample size, and study design: the largest negative MD was reported in African studies and in studies published after 2016; smaller studies (<199 participants) and comparative cross-sectional designs produced greater MDs. - DSM-IV-TR–based ADHD diagnoses produced the largest pooled MD (−16.56, 95% CI: −28.23, −4.89) among diagnostic-criteria subgroups. - Heterogeneity across studies was high, and the authors used a random-effects model; sensitivity, Galbraith plots, meta-regression, and publication-bias assessments (funnel plots and Egger’s test) were performed to explore sources of heterogeneity. - Authors conclude that lower serum ferritin is associated with ADHD in children and recommend consideration of **serum ferritin screening** and strengthened iron supplementation; they also call for longitudinal studies to clarify causality. - The review followed PRISMA, was registered in PROSPERO (CRD420261420475), included English-language studies only, and excluded reports with other psychiatric or hematologic disorders and non‑human studies. - Quality appraisal used Joanna Briggs Institute tools; study-level characteristics (country, design, age, ferritin mean ± SD, sample sizes) were extracted and reported in the manuscript.
## Clinical Analysis & Structured Key Points
Serum ferritin in children with Attention Deficit Hyperactivity Disorder (ADHD): A systematic review and meta-analysis | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Peer Review Reader Comments Figures Figures Abstract Background 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. Method 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’ I 2 test. Publication bias was evaluated visually using funnel plots and statistically via Egger’s weighted regression test. Results 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). Conclusion 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. Citation: Gedfie S, Gashaw M, Adisu A, Bazezew A, Jemal A, Alula MT, et al. (2026) Serum ferritin in children with Attention Deficit Hyperactivity Disorder (ADHD): A systematic review and meta-analysis. PLoS One 21(10): e0359790. https://doi.org/10.1371/journal.pone.0359790 Editor: Mu-Hong Chen, Taipei Veterans General Hospital, TAIWAN Received: July 7, 2026; Accepted: September 16, 2026; Published: October 5, 2026 Copyright: © 2026 Gedfie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All data generated or analyzed during this study are contained in this manuscript and its supplementary files. Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Abbreviations: ADHD, Attention Deficit Hyperactivity Disorder; CC, Case-control; CS, Cross-Sectional; DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; ID, Iron Deficiency; K-SADS-E, Kiddie Schedule for Affective Disorders and Schizophrenia–Epidemiological Version; K-SADS-PL, K-SADS–Present and Lifetime Version; MD, Mean Difference; MRI, Magnetic Resonance Imaging; PRISMA, Preferred Reporting Items for Systematic Review and Meta-Analysis; SMD, Standardized Mean Difference Introduction Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental brain disorder marked by a persistent and maladaptive pattern of inattention, as well as hyperactivity or impulsivity, that impairs functioning or development [ 1 , 2 ]. Among school-aged children, ADHD has a prevalence of 5–10%, and in 30–50% of these cases, the disorder continues into adolescence and adulthood [ 3 ]. Worldwide, the estimated prevalence of ADHD in children below 18 years old varies between 8% and 12%, with boys showing higher rates than girls [ 4 , 5 ]. In children and adolescents, ADHD creates challenges in academic settings, studying, and social interactions. These difficulties result in developmental, educational, and social disadvantages, as well as a significant financial strain on both healthcare and education systems. Throughout life, ADHD serves as an ongoing risk factor for various comorbidities, including psychiatric conditions like depression, anxiety, and behavioral disorders, along with accidents, impaired social functioning, and obesity [ 2 , 6 ]. While the exact cause of ADHD remains unclear, the prevailing understanding is that it arises from a complicated network of interactions involving genetic, environmental, and social factors [ 7 ]. Thus, the suggested causes including prenatal and perinatal risks, genetic factors, and neurobiological impairments may each contribute to the underlying pathophysiology of ADHD, though their roles can vary from one individual to another [ 3 ]. Nevertheless, a wide range of studies employing diverse research methods have pointed to dopamine as a crucial factor in the pathophysiology of ADHD. Researchers have examined the link between ADHD and genes that regulate neurotransmitters such as dopamine, norepinephrine, serotonin, and gamma-aminobutyric acid (GABA). Among these, dopamine is likely to play a central role, given its involvement in controlling psychomotor activity and executive functions two core clinical features seen in individuals with ADHD [ 8 ]. Numerous molecular genetic studies on ADHD have focused on genes linked to dopamine function, with particular attention given to the dopamine D4 receptor gene and the dopamine transporter gene (DAT1). The connection between the dopamine transporter and ADHD is especially significant, as this site serves as the primary target for commonly prescribed ADHD medications, including methylphenidate, pemoline, and dexamphetamine. Additionally, iron acts as a cofactor for tyrosine hydroxylase, the enzyme that limits the rate of dopamine synthesis [ 9 ]. As a result, iron levels stored in the brain could impact dopamine production, which in turn may influence a range of behavioral characteristics especially those observed in individuals with ADHD [ 10 , 11 ]. Studies into the neurobiological underpinnings and treatment of ADHD indicate that dietary factors including glucose metabolism, fatty acid metabolism, and deficiencies in vitamins or minerals can influence brain function and play a role in the onset of the disorder [ 9 , 12 , 13 ]. Among these nutritional factors, iron deficiency (ID) has received particular attention because of iron’s essential role in regulating dopaminergic activity, which is linked to both the pathogenesis and symptoms of ADHD [ 14 ]. In a study by Sever et al., children with ADHD who were given iron supplements showed significantly increased serum ferritin levels and reduced scores on ADHD symptom scales, suggesting that even non-anemic individuals may benefit from iron therapy. This outcome spurred additional investigations into the relationship between ID and ADHD. However, findings from subsequent studies have often been inconsistent. For example, while some researchers reported lower average serum ferritin concentrations in children with ADHD compared to their healthy counterparts, other studies were unable to replicate these results [ 14 – 16 ]. One study found that the severity of ADHD is inversely related to serum ferritin levels [ 15 ], In contrast, another study [ 14 ] used magnetic resonance imaging (MRI) to compare brain iron levels between children with ADHD and healthy controls, finding that estimated brain iron was significantly lower in the bilateral thalami of those with ADHD. Likewise, one study [ 16 ] reported that medication-naïve individuals with ADHD exhibited lower estimated brain iron levels in both the striatum and thalamus compared to healthy controls. Nevertheless, other researchers have not identified any link between serum ferritin levels and ADHD [ 17 , 18 ]. Iron plays an essential role in numerous biological processes, especially during early development. Despite its importance in brain growth and function, the precise mechanisms through which iron operates and the full scope of its involvement in normal brain physiology remain unclear. According to the World Health Organization, ID is the most widespread nutritional deficiency globally [ 6 ]. The synthesis of dopamine is regulated by the enzyme tyrosine hydroxylase, which converts tyrosine into L-dopa; L-dopa is then transformed into dopamine through a decarboxylation process. Iron stored in the brain influences this dopamine production, thereby impacting various behaviors particularly in children with ADHD. One study found that brain ferritin levels were significantly lower in children with ADHD compared to control subjects [ 14 ]. In a study by Juneja et al., low serum ferritin levels were found in 92% of children with ADHD. Similarly, Konofal’s research reported low ferritin levels in 84% of children with ADHD, compared to only 18% of children without the disorder. Furthermore, a randomized controlled trial (RCT) that compared iron supplementation with a placebo over 12 weeks found a significant decrease in ADHD rating scores among children receiving iron [ 19 ]. In recent years, multiple studies have been conducted to assess whether serum ferritin levels serve as a reliable indicator of iron stores in body tissues including the brain in non-anemic children with ADHD. However, only a small number of these studies have identified a link between low ferritin levels and the presence of ADHD [ 15 , 17 , 20 ]. Although numerous studies have examined serum ferritin levels in children with ADHD versus healthy controls, results remain inconsistent. Some report significantly lower ferritin levels in children with ADHD, while others find no difference. Given these conflicting findings, determining the overall association between serum ferritin and ADHD is essential. Thus, we conducted a systematic review and meta-analysis to estimate this association. Method The study protocol and registration This systematic review and meta-analysis were conducted based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline [ 21 ]. The protocol for this systematic review and meta-analysis has been registered in the PROSPERO, an International Prospective Register of Systematic Reviews with a registration number of: CRD420261420475 . Review question : children ( population ) with ADHD ( exposure ) had lower levels of mean serum ferritin ( outcome ) than healthy controls ( comparison )? Search strategy Data were retrieved by searching for published articles in databases, such as Scopus, PubMed, Science direct, Google Scholar search engine, and other institutional repositories. There was no time restriction during article searching, articles published up to June 10, 2026, were included. The search terms were used separately and in combination using the Boolean operators like “OR” or/and “AND”. The search terms were “Iron deficiency”, “serum ferritin”, “serum iron”, “Iron deficiency anemia”, “Iron parameters”, “ADHD”, “Attention deficit hyperactivity disorder”, “Children”. The search strings used in PubMed was:- (((((((((((((serum ferritin) OR (ferritin level)) OR (serum iron)) OR (iron deficiency)) OR (ID)) OR (iron deficiency anemia)) OR (IDA)) AND (children)) AND (Attention Deficit Hyperactivity Disorder)) OR (ADHD)) OR (Attention Deficit Disorder)) OR (ADD)) OR (Hyperkinetic Disorder)) OR (Hyperkinesis). We identified additional articles by conducting a manual search and by examining the references cited in pertinent papers. The search strategy and number of articles retrieved from the searched databases are depicted in the additional file ( S1 Table in S1 File ). Inclusion and exclusion criteria This review included peer-reviewed articles as well as studies deposited in institutional electronic repositories or registries. Eligible studies involved children with ADHD and healthy controls, utilized case-control, comparative cross-sectional, or cohort designs, and reported serum ferritin levels. Moreover, studies were included only if they satisfied two further conditions: serum ferritin assessment in children with ADHD relative to non-ADHD controls, and ADHD diagnosis established according to standardized protocols. Only articles published in English before June 10, 2026, were included. The review excludes case reports, case series, studies involving children with psychiatric disorders other than ADHD, known hematological abnormalities, or iron homeostasis disorders. Conference abstracts, reviews, and animal studies were also excluded. Study selection and quality assessment : To organize search outcomes and to remove duplicate articles the searched articles were imported into EndNote X 21 (Thomson Reuters, New York, USA). Two investigators independently selected the studies. Initially, clearly irrelevant studies were excluded by scanning titles and abstracts. The full texts of the remaining articles were then evaluated carefully according to our eligibility criteria. Where required, any disagreement on eligibility for inclusion was resolved by a third author. Study quality was rated by two authors using the Joanna Briggs Institute (JBI) critical appraisal tools, which is recommended for quality assessment of cohort and case-control studies, and has a maximum score of ten. Studies scoring 7–10, 4–6, and 0–3 are regarded as high quality, moderate quality, and low quality, respectively [ 22 ]. The quality appraisal guideline contains ten evaluation domains or categories to evaluate the internal and external validity. The items are: (a) were the groups comparable other than the Presence of disease in cases or the absence of disease in controls?, (b) sampling frame Were cases and controls matched appropriately?, (c) Were the same criteria used for identification of cases and controls?, (d) Was exposure measured in a standard, valid and reliable way?, (e) Was exposure measured in the same way for cases and controls, (f) Were confounding factors identified?, (g) Were strategies to deal with confounding factors stated?, (h) Were outcomes assessed in a standard, valid and reliable way for cases and controls?, (i) Was the exposure period of interest long enough to be meaningful?, and (j) Was appropriate statistical analysis used?. Each category was evaluated as Yes, No, unclear and not applicable. Unclear was considered as a high risk of bias. Data extraction : Two reviewers independently extracted key data, including first author, publication year, country, study design, age (mean ± SD), mean and standard deviation of serum ferritin for cases and controls, and sample sizes for both groups. Extracted information was compiled into an MS Excel spreadsheet. Any disagreements were resolved by consensus or through discussion involving a third author ( Table 1 ). Download: PNG larger image TIFF original image Table 1. Characteristics of included studies for Serum Ferritin in Children with Attention Deficit Hyperactivity Disorder (ADHD). https://doi.org/10.1371/journal.pone.0359790.t001 Statistical analysis : The data were checked for completeness in Microsoft Excel before being transferred to STATA version 17 for final analysis. Due to the high heterogeneity between studies, we chose a random effects model to calculate the pooled SMD [ 23 ]. The standardized mean difference (SMD) was used to assess the association between serum ferritin level and ADHD. Forest plots were generated to display the overall pooled SMD, along with the relative weight assigned to each included study. The degree of heterogeneity was assessed using Higgins’ I² statistic, with I 2 values categorized as low (25%), moderate (50%), and high (75%) [ 24 ]. We also used Galbraith radial plots to explore which studies may be contributing to heterogeneity. To explore potential sources of heterogeneity, sub-group analyses were performed based on country, year of publication, study design, and sample size. A sensitivity analysis was conducted by sequentially excluding individual studies to assess whether any single study had a significant influence on the pooled estimate. To assess potential publication bias, funnel plots were visually inspected, and Egger’s weighted regression test was performed. We also performed random-effects meta-regressions. In Egger’s test, a p-value < 0.05 was considered indicative of statistically significant publication bias [ 25 ]. Ethics approval and consent to participate As this study is a systematic review and meta-analysis of previously published data, it did not involve direct patient contact or primary data collection. Therefore, ethical approval and informed consent were not required. Results Literature search and identified studies This systematic review and meta-analysis included articles on serum ferritin level among children with ADHD and healthy controls. Pubmed/MEDLINE, ScienceDirect, Scopus, and Google Scholar were among the databases used in the searching strategy. The review identified 7643 studies. After removing 521 duplicate records, 7085 studies were excluded following title and abstract screening. After screening 37 full-text articles for eligibility, 16 were excluded as they did not report the relevant outcome. Consequently, 21 studies met all inclusion criteria and were included in the final meta-analysis ( Fig 1 ). Download: PNG larger image TIFF original image Fig 1. PRISMA flow diagram showing the results of the search and reasons for exclusion on systematic review and meta-analysis of Serum Ferritin in Children with Attention Deficit Hyperactivity Disorder (ADHD) [ 26 ]. https://doi.org/10.1371/journal.pone.0359790.g001 Characteristics of included studies A total of 21 studies met the inclusion criteria for this systematic review and meta-analysis Among the included studies, four were conducted in Egypt [ 27 – 30 ], one were conducted in Israel [ 31 ], two were conducted in France [ 14 , 17 ], one conducted in China [ 32 ], two study were conducted in Turkey [ 33 , 34 ], one in South Africa [ 35 ], three were in USA [ 16 , 19 , 20 ], one in Indonesia [ 36 ], one in Qatar [ 37 ], one in Brazil [ 38 ], one in Italy [ 18 ], one in India [ 15 ], one in Finland [ 39 ] and one study in Korea [ 40 ] ( Table 1 ). Methodological quality and risk-of-bias assessment All potential papers were assessed for quality using the recommended quality assessment tool, the Joanna Briggs Institute (JBI), for prevalence data/observational studies. Two reviewers independently performed a critical appraisal of each paper. This involved a thorough examination using the JBI appraisal domains as follows: (a) were the groups comparable other than the Presence of disease in cases or the absence of disease in controls?, (
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