Effect of Daily Iron Supplementation in Healthy Exclusively Breastfed Infants: A Systematic Review with Meta-Analysis

Background: The literature on the iron requirements of exclusively breastfed infants contains conflicting data and contrary views. Objective: The purpose of this study was to summarize the evidence for both benefits and risks of daily oral iron supplementation with regard to hematologic, growth, cognitive parameters, and adverse effects in exclusively breastfed infants. Materials and Methods: Structured electronic searches were conducted using PubMed, Cochrane Library databases, and Google Scholar for randomized controlled trials (RCTs) involving daily iron supplementation in full-term healthy exclusively breastfed infants. Random- and fixed-effects models were used for calculating the pooled estimates. Results: Four RCTs with 511 infants were included in the meta-analysis. Iron interventions had no significant effect on iron deficiency or iron deficiency anemia, serum ferritin level, or hemoglobin level. Iron interventions did result in a significant increase in Bayley psychomotor developmental indices in later life (mean difference [MD]=7.00, confidence interval [95% CI] 0.99-13.01) and mean corpuscular volume (MD=2.17 fL; 95% CI 0.99-3.35 fL). Iron supplementation was associated with slower growth during the exclusive breastfeeding period, but the long-term effect is unclear. Conclusions: Limited available evidence suggests that daily iron supplementation has beneficial effects on hematologic parameters and cognitive development, but may delay physical growth in healthy exclusively breastfed infants. There was no evidence to suggest that iron supplementation could cause other adverse effects.