Effect of iron supplementation on brain myelination and neurodevelopmental outcomes in children aged 0–3 years: a systematic review protocol
Iron deficiency is one of the most prevalent micronutrient deficiencies globally, affecting nearly 40% of children aged 6–59 months. Iron plays an essential role in early brain development, particularly in myelination, neurotransmitter synthesis and energy metabolism. Deficiency during critical developmental periods may impair cognitive, motor and behavioral outcomes. Although iron supplementation improves hematological parameters, its effects on brain myelination and neurodevelopmental outcomes in children aged 0–3 years remain unclear. To evaluate the effects of iron supplementation administered during pregnancy or early childhood (0–3 years) on brain myelination and neurodevelopmental outcomes in children. This systematic review protocol follows PRISMA 2020 and Cochrane Handbook recommendations and has been prospectively designed for registration in PROSPERO. We will search PubMed, EMbase, Scopus, CENTRAL, PsycINFO, CINAHL and Web of Science for randomized controlled trials, quasi-experimental studies, cohort studies, and observational studies evaluating iron supplementation in pregnant women or children aged 0–3 years. Interventions will include iron supplementation in any form and dosage, compared with placebo, standard care, or alternative interventions. Primary outcomes include cognitive, motor, language, executive function, memory and myelination outcomes assessed through validated neurodevelopmental tools and neuroimaging modalities. Secondary outcomes include adverse events. Risk of bias will be assessed using ROB 2 and ROBINS-I tools and certainty of evidence will be evaluated using the GRADE approach. This review will synthesize current evidence regarding the role of iron supplementation in brain myelination and neurodevelopment during early childhood. The findings may inform clinical practice and public health policy, particularly in low- and middle-income settings where iron deficiency is highly prevalent. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261388359 , Registration ID: CRD420261388359.