How Does the Risk of Iron-deficiency Anemia Compare between Exclusively Breastfed and Non-exclusively Breastfed Infants?

Abstract

Exclusive breastfeeding (EBF) for the first 6 months of life is recommended worldwide for optimal infant health. However, the comparative efficacy of breast milk versus iron-fortified formula in preventing iron-deficiency anemia (IDA) remains debated due to breast milk's lower total iron content. This meta-analysis aims to evaluate the risk of anemia in exclusively breastfed infants compared to those receiving mixed or formula feeding (MF/FF) during the first year of life. A systematic literature search was conducted across PubMed, Scopus, and Web of Science. Observational studies comparing anemia risk or hemoglobin (Hb) levels between EBF and MF/FF infants were included. Data were pooled using a random-effects model to calculate Odds Ratios (OR) and Mean Differences (MD). Subgroup and sensitivity analyses were performed to explore heterogeneity. 17 studies were included. The overall pooled analysis for anemia risk (n=4869) showed a non-significant trend towards higher risk in the EBF group (OR = 1.58, 95% CI: 0.91–2.75, p=0.105). However, subgroup analysis by age revealed a critical divergence: EBF was protective/safe in infants <6 months (OR = 1.05, p=0.83) but doubled the risk of anemia in infants ≥6 months (OR = 2.10, 95% CI: 1.29–3.40, p=0.002). Sensitivity analysis demonstrated that excluding one large study of 4-month-old infants shifted the overall results to high statistical significance (OR = 1.88, p=0.001). The pooled mean difference in Hb levels was clinically negligible (MD = -0.09 g/dL, p=0.52). EBF provides adequate iron status during the first six months of life. However, prolonged EBF beyond six months without the timely introduction of iron-rich complementary foods significantly increases the risk of iron-deficiency anemia. Adherence to guidelines for timely complementary feeding is crucial globally.