Iron supplementation of breastfed infants from an early age.

Randomized, placebo-controlled trial in healthy term infants who were exclusively breastfed at enrollment at 1 month of age in Iowa, United States. For the iron supplementation group, 37 infants were randomized and 31 completed the intervention at 5.5 months; the placebo group had 38 randomized and 32 completed. Participants were white, had birth weight >2500 g, and were followed with repeated iron-status assessments through 18 months.

Infants in the active arm received 7 mg/day of iron as ferrous sulfate in a multivitamin preparation (Tri-Vi-Sol with Iron), given orally as 0.7 mL drops directly into the mouth once daily at the beginning of a feeding from 1 to 5.5 months of age. The placebo group received an identical-appearing regimen without iron.

Iron supplementation transiently improved iron status during the supplementation period but did not improve hemoglobin or produce lasting hematologic benefit after supplementation ended. Plasma ferritin declined less in the iron group, with significant differences at 4 and 5.5 months for adjusted ferritin and at 5.5 and 7.5 months for unadjusted ferritin; soluble transferrin receptor was lower at 5.5 months (P = 0.005), and ln(sTfR/PF) was better at 5.5 months (P = 0.001) and 7.5 months (P = 0.006). Hemoglobin did not differ at any age, and later differences in RDW and MCV were modest. The supplement was generally well tolerated, with 3 infants (8%) reporting side effects, and there was no consistent overall adverse effect on growth, although a female-only subgroup showed reduced weight gain. The authors concluded that universal early iron supplementation may not be necessary and that selective screening and treatment may be more appropriate.

The trial was small and underpowered to determine whether early iron supplementation prevents iron deficiency or iron deficiency anemia. The cohort was restricted to healthy, exclusively breastfed, mostly white term infants in one U.S. setting, limiting generalizability. Complementary feeding and some formula use began during follow-up, which may have diluted or obscured longer-term effects.