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American Academy of Pediatrics
Article

Effects of Iron Supplementation of LBW Infants on Cognition and Behavior at 3 Years

Staffan K. Berglund, Björn Westrup, Bruno Hägglöf, Olle Hernell and Magnus Domellöf
Pediatrics January 2013, 131 (1) 47-55; DOI: https://doi.org/10.1542/peds.2012-0989
Staffan K. Berglund
aPediatrics and
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Björn Westrup
bDivision of Neonatology, Department of Women and Child Health, Karolinska Institute, Stockholm, Sweden
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Bruno Hägglöf
cChild and Adolescent Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden; and
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Olle Hernell
aPediatrics and
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Magnus Domellöf
aPediatrics and
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Abstract

OBJECTIVE: Low birth weight (LBW) infants are at increased risk of cognitive and behavioral problems and at risk for iron deficiency, which is associated with impaired neurodevelopment. We hypothesized that iron supplementation of LBW infants would improve cognitive scores and reduce behavioral problems.

METHODS: In a randomized controlled trial, 285 marginally LBW (2000–2500 g) infants received 0, 1, or 2 mg/kg/day of iron supplements from 6 weeks to 6 months of age. At 3.5 years of age, these infants and 95 normal birth weight controls were assessed with a psychometric test (Wechsler Preschool and Primary Scale of Intelligence) and a questionnaire of behavioral problems (Child Behavior Checklist; CBCL).

RESULTS: There were no significant differences in IQ between the LBW groups or LBW infants versus 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 groups, respectively (P = .924). However, for behavioral problems, there was a significant effect of intervention. The prevalence of children with CBCL scores above the US subclinical cutoff was 12.7%, 2.9%, and 2.7% in the placebo, 1-mg, and 2-mg groups, respectively (P = .027), compared with 3.2% in controls. Relative risk (95% confidence interval) for CBCL score above cutoff in placebo-treated children versus supplemented was 4.5 (1.4–14.2).

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 iron deficiency and later behavioral problems.

KEY WORDS
  • behavioral problems
  • children
  • cognitive score
  • iron
  • infant
  • iron deficiency
  • iron deficiency anemia
  • low birth weight
  • neurodevelopment
  • preterm
  • randomized controlled trial
  • small for gestational age
  • Abbreviations:
    CBCL —
    Child Behavior Checklist
    Hb —
    hemoglobin
    ID —
    iron deficiency
    IDA —
    iron deficiency anemia
    LBW —
    low birth weight
    MCV —
    mean corpuscular volume
    TfR —
    transferrin receptor concentration
    TS —
    transferrin saturation
    WPPSI-III —
    Wechsler Preschool and Primary Scale of Intelligence–Third Edition
    • Accepted August 31, 2012.
    • Copyright © 2013 by the American Academy of Pediatrics

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    Pediatrics
    Vol. 131, Issue 1
    1 Jan 2013
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    Effects of Iron Supplementation of LBW Infants on Cognition and Behavior at 3 Years
    Staffan K. Berglund, Björn Westrup, Bruno Hägglöf, Olle Hernell, Magnus Domellöf
    Pediatrics Jan 2013, 131 (1) 47-55; DOI: 10.1542/peds.2012-0989

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    Effects of Iron Supplementation of LBW Infants on Cognition and Behavior at 3 Years
    Staffan K. Berglund, Björn Westrup, Bruno Hägglöf, Olle Hernell, Magnus Domellöf
    Pediatrics Jan 2013, 131 (1) 47-55; DOI: 10.1542/peds.2012-0989
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    Keywords

    • behavioral problems
    • children
    • cognitive score
    • iron
    • infant
    • iron deficiency
    • iron deficiency anemia
    • low birth weight
    • neurodevelopment
    • preterm
    • randomized controlled trial
    • small for gestational age
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