Investigators from the University of Toronto and Hospital for Sick Children, both in Toronto, Canada, conducted a prospective study to assess the association between chronic iron deficiency and later cognitive function in young children. Study participants were healthy children attending health supervision visits between the ages of 12 and 36 months at 1 of 8 primary care practices in Toronto. At enrollment, baseline hemoglobin (Hb) and serum ferritin levels were obtained, and study children were classified as: iron sufficient (IS) if Hb was ≥11.0 g/dL and serum ferritin was ≥14 μg/L, nonanemic iron deficiency (NAID) if Hb was ≥11.0 g/dL and serum ferritin was <14 μg/L, or iron deficiency anemia (IDA) if Hb was <11.0 g/dL and serum ferritin was <14 μg/L. IDA patients were treated with oral ferrous sulfate (6 mg elemental iron/kg/day) for 4 months. NAID children were randomized (as part of another study) to receive oral ferrous sulfate, using the same dosing regimen as was used in those with IDA, or placebo. Hb and ferritin levels were repeated at 4 months after enrollment, and study participants were classified as IS if Hb was ≥11.0 g/dL and serum ferritin was ≥14 μg/L, or chronic iron deficiency if they had IDA at baseline or if Hb was <11.0 g/dL and/or ferritin was <14 μg/L. Ferritin levels also were obtained at 12 months following enrollment. Four and 12 months after enrollment, cognitive function was assessed using the Learning Composite (ELC) from the Mullen Scales of Early Learning. The primary study outcome was the ELC scores at 4 and 12 months. Secondary outcomes were ferritin levels at 4 and 12 months. Outcomes among children with IS and chronic iron deficiency were compared using linear regression after adjusting for age, sex, and baseline ferritin levels.
A total of 130 children were enrolled in the study, including 37 with IDA, 63 with NAID, and 30 with IS. Data were available for analysis on 116 children (41 with chronic iron deficiency and 75 with IS) at 4 months and 91 at 12 months (31 with chronic iron deficiency and 60 with IS). Mean ELC scores at 4 months were 107.9 ±13.4 for children with chronic iron deficiency and 112.5 ±14.5 for those with IS (adjusted mean differences, -6.4; 95% CI, -12.4, -0.3; P = 0.04), and mean scores were 110.2 ±15.0 and 114.8 ±13.7, respectively, (adjusted mean difference, -7.4; 95% CI, -14.0, -0.8; P = 0.03) at 12 months. Ferritin levels were significantly higher at 4 months in those with chronic iron deficiency compared to IS children (mean values, 48.1 ±41.0 μg/L and 31.4 ±21.6 μg/L, respectively; P = 0.03), but there was no significant difference between groups at 12 months.
The authors conclude that children with chronic iron deficiency had lower cognitive scores at...