Objective Low birth weight infants (LBW) are at increased risk of cognitive and behavioral problems and at risk of iron deficiency (ID) which is associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants would improve cognitive scores and reduce behavioral problems.
Patients and methods: In a randomized controlled trial, 285 marginally LBW (2000–2500g) infants received 0, 1, or 2 mg/kg/day of iron supplements from six weeks to six months of age. At 3.5 years of age these infants and 95 normal birth weight controls were assessed with a psychometric test (WIIPSI-III) and a questionnaire of behavioral problems (CBCL).
Results There were no significant differences in IQ between the LBW-groups, nor compared to controls. Mean (SD) full-scale IQ was 105.2 (14.5), 104.2 (14.7), and 104.5 (12.7) in the placebo, 1 mg, and 2 mg-group respectively (p=0.924). The prevalence of children with CBCL-scores above the US subclinical cut-off was 12.7%, 2.9%, 2.7%, and 3.2% in the placebo, 1mg, 2 mg, and control-group respectively. Relative risks (95% CI) for behavioral problems vs. controls were 4.01 (1.13–14.29) in the placebo-group. In a logistic regression model, adjusted for confounders, the odds ratio (95% CI) for CBCL score above US subclinical cut-off in placebo-treated children was 4.5 (1.3–15.8) compared to iron supplemented children (p=0.019).
Conclusions Early iron supplementation of marginally LBW infants does not affect cognitive functions at 3.5 years of age but significantly reduces the prevalence of behavioral problems. The study suggests a causal relation between infant ID and later behavioral problems.