Iron in breastfed infants and behavior at 3 years: a randomized trial.

Breastfed infants are particularly vulnerable to iron deficiency, which is associated with impaired neurodevelopment. Iron supplementation reduces behavioral problems in certain risk groups, but effects in healthy infants are uncertain. This randomized, double-blind, placebo-controlled trial evaluated whether daily low-dose iron supplementation (7, 10, or 15 mg micronized microencapsulated ferric pyrophosphate, approximating 1 mg/kg, from 4 to 9 months of age) affects behavioral outcomes at 3 years. The study was conducted in Warsaw, Poland and Umeå, Sweden and included full-term, healthy, predominantly breastfed infants who were non-anemic at baseline. Behavioral problems were assessed using the Child Behavior Checklist (CBCL) at 3 years as a pre-specified secondary outcome. Of the 221 participants randomized, 133 (60%) completed the CBCL. Iron supplementation compared to placebo significantly reduced CBCL externalizing T-scores (mean [SD], 45.6 [8.5] vs. 48.6 [8.9], adjusted P = .006). Lower scores were also observed for aggressive behaviors (adjusted P = .0329). This pre-specified secondary outcome analysis found that low-dose iron supplementation in predominantly breastfed healthy infants between 4 and 9 months of age may contribute to fewer behavioral problems at 3 years of age. These findings suggest a potential beneficial effect, though cautious interpretation is warranted until replicated in future studies.Trial registration: clinicaltrials.gov; identifying number: NCT02242188; URL: http://www.clinicaltrials.gov/study/NCT02242188 ; Date of registration: 2014-09-14.