Effect of Low-Dose Iron Supplementation on Early Development in Breastfed Infants: A Randomized Clinical Trial.

Importance: Breastfed infants are at risk of iron deficiency, which is associated with suboptimal development. There is a paucity of evidence on the effects of iron supplementation on child development, and current guidelines are divergent.

Objective: To assess whether daily iron supplementation, 1 mg/kg, between 4 and 9 months in exclusively or predominantly breastfed infants improves psychomotor development at 12 months.

Design, Setting, And Participants: This was a randomized, double-blind, placebo-controlled trial conducted between December 2015 and May 2020 with follow-up through May 2023 in an outpatient setting in Poland and Sweden. Participants were healthy singleton infants born at term with birth weight greater than 2500 g who were exclusively or predominantly breastfed (>50%) and did not have anemia (hemoglobin >10.5 g/dL) at age 4 months. Exclusion criteria included major illness, congenital anomaly, food allergy, and difficulty communicating with caregivers.

Interventions: Iron (micronized microencapsulated ferric pyrophosphate), 1 mg/kg, or placebo (maltodextrin) once daily from age 4 to 9 months.

Main Outcomes And Measures: The primary outcome was psychomotor development assessed by motor score of Bayley Scales of Infant and Toddler Development III at 12 months, adjusted for gestational age, sex, and maternal education. Secondary outcomes included cognitive and language scores at 12 months; motor, cognitive, and language scores at 24 and 36 months; iron deficiency (serum ferritin <12 ng/mL), and iron deficiency anemia (iron deficiency and hemoglobin <10.5 g/dL) at 12 months.

Results: Of 221 randomized infants (111 female), 200 (90%) were included in the intention-to-treat analysis (mean [SD] age, 12.4 [0.8] months). Iron supplementation (n = 104) compared to placebo (n = 96) had no effect on psychomotor development (mean difference [MD] for motor score, -1.07 points; 95% CI, -4.69 to 2.55), cognitive score (MD, -1.14; 95% CI, -4.26 to 1.99), or language score (MD, 0.75; 95% CI, -2.31 to 3.82) at 12 months. There were no significant differences at 24 and 36 months. The intervention did not reduce the risk for iron deficiency (relative risk [RR], 0.46; 95% CI, 0.16 to 1.30) or iron deficiency anemia (RR, 0.78; 95% CI, 0.05 to 12.46) at 12 months.

Conclusion And Relevance: No benefit was found with daily low-dose iron supplementation between 4 and 9 months with respect to psychomotor development, risk of iron deficiency, or iron deficiency anemia among breastfed infants in a setting of low risk of anemia.

Trial Registration: ClinicalTrials.gov Identifier: NCT02242188.