Meta-analysis links lower Fe, Zn, Mg and higher Cu levels to iron deficiency anemia in children

OBJECTIVES: Iron deficiency anemia (IDA) remains the most prevalent form of anemia in children and adolescents globally. In addition to iron (Fe), other trace elements, such as zinc (Zn), copper (Cu), and magnesium (Mg), may influence hematopoiesis, yet the extent of their dysregulation in IDA remains unclear. METHODS: We conducted a systematic review and meta-analysis of observational studies assessing the serum levels of Fe, Zn, Cu, and Mg in pediatric IDA populations. The literature was searched in PubMed, Scopus, Embase, and Web of Science up to January 2025. The data were standardized to consistent units (μmol/L), and pooled weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated. Subgroup, sensitivity, and publication bias analyses were performed. The study protocol was registered online (PROSPERO number: CRD42024578704). RESULTS: Eight articles encompassing twelve datasets and 1105 participants were included. Compared to controls, IDA patients had significantly lower levels of Fe (WMD: -13.07 μmol/L, 95% CI: -16.09 to -10.05), Zn (WMD: -4.33 μmol/L, 95% CI: -5.30 to -3.35), and Mg (WMD: -18.17 μmol/L, 95% CI: -21.00 to -15.33) but higher levels of Cu (WMD: 4.33 μmol/L, 95% CI: 2.21-6.46). High heterogeneity (² > 95%) was noted for Fe, Zn, and Cu. Subgroup analyses confirmed consistent trends across age, gender, and geography. CONCLUSION: Pediatric IDA is associated with broad alterations in trace elements, highlighting potential roles for Fe, Zn, Cu, and Mg in the pathophysiology of anemia. These findings may inform comprehensive nutritional strategies in managing IDA.