Iron Supplementation in Management of Neurodevelopmental Disorders: Systematic Review, Meta-Analysis, and Qualitative Synthesis

J Neuropsychiatry Clin Neurosci. 2024 Feb 12:appineuropsych20230081. doi: 10.1176/appi.neuropsych.20230081. Online ahead of print.

Abstract

Objective: The authors sought to explore the role of iron supplementation in the management of neurodevelopmental disorders among children and youths.

Methods: A systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was undertaken. A subset of results was suitable for meta-analysis. The quality of the evidence and strength of the clinical recommendations were assessed by using the Grading of Recommendations, Assessment, Development, and Evaluation method, and critical appraisal was conducted with the Joanna Briggs Institute critical appraisal tools.

Results: Nine articles met inclusion criteria. These articles included studies of attention-deficit hyperactivity disorder (ADHD) (N=7), autism spectrum disorder (N=1), and Tourette's syndrome (N=1). Three randomized controlled trials evaluating iron supplementation for ADHD hyperactivity symptom severity (124 participants: placebo, N=56; supplement, N=68) met inclusion criteria for a meta-analysis. Effect sizes for the placebo and supplement groups were moderate (Cohen's d=0.76) and large (Cohen's d=1.70), respectively, although these differences were not significant. The impact of iron supplementation on inattentive ADHD symptom severity was examined in two trials (75 participants: placebo, N=31; supplement, N=44). Large, nonsignificant effect sizes were demonstrated for the placebo (Cohen's d=1.66) and supplementation (Cohen's d=3.19) groups. The quality of the evidence and strength of the clinical recommendations were considered very low.

Conclusions: Further research is needed to examine the role of iron supplementation in the management of ADHD and neurodevelopmental disorders more generally. Additionally, iron supplementation comes with risks, including death in the case of overdose.

Keywords: Attention-Deficit Hyperactivity Disorder; Autism Spectrum Disorder; Children; Iron Deficiency; Iron Supplementation; Neurodevelopmental Disorders.