Investigators from multiple Canadian institutions conducted a randomized trial to compare the effect of oral iron supplementation versus diet advice alone on neurodevelopmental outcomes in children. Parents of children with health supervision visits at 1 of 8 primary care practices in Toronto, Canada, during the study period were eligible. Children were included if they were 12-40 months of age and met criteria for non-anemic iron deficiency (NAID), defined as a hemoglobin ≥110 g/L and serum ferritin <14 μg/L. Children were excluded if they had a developmental condition, were born at a gestational age of <35 weeks or birth-weight of <2,500 grams, had acute illness, had previous anemia or iron deficiency, were receiving iron, or had a c-reactive protein ≥10 mg/L. Child demographics were collected at baseline.
Participants were randomized to receive either liquid ferrous sulfate (6 mg elemental iron/kg/day) or liquid placebo in 2 divided doses daily by mouth for 4 months. All parents received diet advice on improving iron status via a written guide. Parents and researchers were blinded to treatment arm. Participants received a developmental assessment of gross motor and cognitive at baseline as well as 4 and 12 months after baseline using the Mullen Scales of Early Learning (MSEL).
The primary outcome was MSEL scores 4 and 12 months after baseline. Secondary outcomes included serum ferritin values at 4 and 12 months. The investigators used an intention-to-treat analysis to assess the effect of intervention arm on outcomes, adjusting for baseline score, baseline ferritin, and unbalanced demographic characteristics across treatment arms.
There were 60 participants randomized. Participants had a mean age of 24.2 months. Serum ferritin and mean MSEL scores were similar across treatment groups at baseline. The mean between-group difference in MSEL scores at 4 months was 1.1 points (95% CI, -4.2, 6.5) and at 12 months was 4.1 points (95% CI, -1.9, 10.1). The mean between-group difference in serum ferritin at 4 months was 16.9 μg/L (95% CI, 6.5, 27.2) and at 12 months was 3.9 μg/L (95% CI, -7.3, 15.1).
The investigators conclude that there is no important between-group difference in neurodevelopmental outcomes in young children NAID treated with ferrous sulfate plus diet advice versus diet advice alone, though serum ferritin values are higher among those who received ferrous sulfate 4 months later.
Dr Hogan has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
NAID is found in an estimated 11% of US children ages 6 months to 5 years.1 Approximately 25% to 42% of NAID eventually contributes to anemia in this age group.1 Duration, severity, and age onset of NAID may impact neurocognitive skills, breath-holding spells, restless...