Enteral iron supplementation in preterm and low birth weight infants.

Systematic review and meta-analysis of 26 trials including 2726 infants. The population was preterm and low birth weight infants, with some studies also including term low birth weight infants; feeding context varied across trials and included breast milk, formula, and fortified formula.

Prophylactic enteral iron supplementation in preterm and low birth weight infants, delivered in a variety of oral/enteral formulations including ferrous sulfate, ferric ammonium citrate, iron polymaltose complex, and iron-fortified formula. Across included trials, dosing and timing varied widely, but most regimens were in the range of about 1 to 6 mg/kg/day, started from about 2 weeks of age to later infancy, and continued for weeks to up to 1 year; some studies compared early versus delayed initiation or higher versus lower doses.

Enteral iron supplementation probably improves hematologic iron status, with slightly higher hemoglobin levels, better iron stores, and a lower risk of iron deficiency anemia than no supplementation. The review found no clear evidence that iron supplementation improves long-term neurodevelopment or growth. Doses greater than about 2 to 3 mg/kg/day did not appear to provide additional hematologic benefit, and earlier initiation may improve hematologic parameters, but the best timing and duration remain uncertain.

The evidence base was heterogeneous, with many small and older trials using different iron formulations, doses, start times, durations, and feeding contexts. Long-term neurodevelopmental and growth outcomes were sparse, and many clinical outcomes were inconsistently reported, limiting confidence in broader benefits and in the optimal supplementation strategy.