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Intermittent iron supplementation for improving nutrition and development in children under 12 years of age.

Abstract

BACKGROUND

Approximately 600 million children of preschool and school age are anaemic worldwide. It is estimated that half of the cases are due to iron deficiency. Consequences of iron deficiency anaemia during childhood include growth retardation, reduced school achievement, impaired motor and cognitive development, and increased morbidity and mortality. The provision of daily iron supplements is a widely used strategy for improving iron status in children but its effectiveness has been limited due to its side effects, which can include nausea, constipation or staining of the teeth. As a consequence, intermittent iron supplementation (one, two or three times a week on non-consecutive days) has been proposed as an effective and safer alternative to daily supplementation.

OBJECTIVES

To assess the effects of intermittent iron supplementation, alone or in combination with other vitamins and minerals, on nutritional and developmental outcomes in children from birth to 12 years of age compared with a placebo, no intervention or daily supplementation.

SEARCH METHODS

We searched the following databases on 24 May 2011: CENTRAL (2011, Issue 2), MEDLINE (1948 to May week 2, 2011), EMBASE (1980 to 2011 Week 20), CINAHL (1937 to current), POPLINE (all available years) and WHO International Clinical Trials Registry Platform (ICTRP). On 29 June 2011 we searched all available years in the following databases: SCIELO, LILACS, IBECS and IMBIOMED. We also contacted relevant organisations (on 3 July 2011) to identify ongoing and unpublished studies.

SELECTION CRITERIA

Randomised and quasi-randomised trials with either individual or cluster randomisation. Participants were children under the age of 12 years at the time of intervention with no specific health problems. The intervention assessed was intermittent iron supplementation compared with a placebo, no intervention or daily supplementation.

DATA COLLECTION AND ANALYSIS

Two authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies and assessed the risk of bias of the included studies.

MAIN RESULTS

We included 33 trials, involving 13,114 children (˜49% females) from 20 countries in Latin America, Africa and Asia. The methodological quality of the trials was mixed.Nineteen trials evaluated intermittent iron supplementation versus no intervention or a placebo and 21 studies evaluated intermittent versus daily iron supplementation. Some of these trials contributed data to both comparisons. Iron alone was provided in most of the trials.Fifteen studies included children younger than 60 months; 11 trials included children 60 months and older, and seven studies included children in both age categories. One trial included exclusively females. Seven trials included only anaemic children; three studies assessed only non-anaemic children, and in the rest the baseline prevalence of anaemia ranged from 15% to 90%.In comparison with receiving no intervention or a placebo, children receiving iron supplements intermittently have a lower risk of anaemia (average risk ratio (RR) 0.51, 95% confidence interval (CI) 0.37 to 0.72, ten studies) and iron deficiency (RR 0.24, 95% CI 0.06 to 0.91, three studies) and have higher haemoglobin (mean difference (MD) 5.20 g/L, 95% CI 2.51 to 7.88, 19 studies) and ferritin concentrations (MD 14.17 µg/L, 95% CI 3.53 to 24.81, five studies).Intermittent supplementation was as effective as daily supplementation in improving haemoglobin (MD -0.60 g/L, 95% CI -1.54 to 0.35, 19 studies) and ferritin concentrations (MD -4.19 µg/L, 95% CI -9.42 to 1.05, 10 studies), but increased the risk of anaemia in comparison with daily iron supplementation (RR 1.23, 95% CI 1.04 to1.47, six studies). Data on adherence were scarce and it tended to be higher among those children receiving intermittent supplementation, although this result was not statistically significant.We did not identify any differential effect of the type of intermittent supplementation regimen (one, two or three times a week), the total weekly dose of elemental iron, the nutrient composition, whether recipients were male or female or the length of the intervention.

AUTHORS' CONCLUSIONS

Intermittent iron supplementation is efficacious to improve haemoglobin concentrations and reduce the risk of having anaemia or iron deficiency in children younger than 12 years of age when compared with a placebo or no intervention, but it is less effective than daily supplementation to prevent or control anaemia. Intermittent supplementation may be a viable public health intervention in settings where daily supplementation has failed or has not been implemented. Information on mortality, morbidity, developmental outcomes and side effects, however, is still lacking.

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  • Authors+Show Affiliations

    ,

    Micronutrients Unit, Department of Nutrition for Health and Development, World Health Organization, 20 Avenue Appia, Geneva, Switzerland, 1211.

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    Source

    MeSH

    Anemia, Iron-Deficiency
    Child
    Child Development
    Child Nutritional Physiological Phenomena
    Child, Preschool
    Dietary Supplements
    Drug Administration Schedule
    Female
    Glycated Hemoglobin A
    Humans
    Iron, Dietary
    Male
    Randomized Controlled Trials as Topic
    Trace Elements
    Vitamins

    Pub Type(s)

    Journal Article
    Meta-Analysis
    Review
    Systematic Review

    Language

    eng

    PubMed ID

    22161444

    Citation

    De-Regil, Luz Maria, et al. "Intermittent Iron Supplementation for Improving Nutrition and Development in Children Under 12 Years of Age." The Cochrane Database of Systematic Reviews, 2011, p. CD009085.
    De-Regil LM, Jefferds ME, Sylvetsky AC, et al. Intermittent iron supplementation for improving nutrition and development in children under 12 years of age. Cochrane Database Syst Rev. 2011.
    De-Regil, L. M., Jefferds, M. E., Sylvetsky, A. C., & Dowswell, T. (2011). Intermittent iron supplementation for improving nutrition and development in children under 12 years of age. The Cochrane Database of Systematic Reviews, (12), p. CD009085. doi:10.1002/14651858.CD009085.pub2.
    De-Regil LM, et al. Intermittent Iron Supplementation for Improving Nutrition and Development in Children Under 12 Years of Age. Cochrane Database Syst Rev. 2011 Dec 7;(12)CD009085. PubMed PMID: 22161444.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Intermittent iron supplementation for improving nutrition and development in children under 12 years of age. AU - De-Regil,Luz Maria, AU - Jefferds,Maria Elena D, AU - Sylvetsky,Allison C, AU - Dowswell,Therese, Y1 - 2011/12/07/ PY - 2011/12/14/entrez PY - 2011/12/14/pubmed PY - 2012/1/31/medline SP - CD009085 EP - CD009085 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 12 N2 - BACKGROUND: Approximately 600 million children of preschool and school age are anaemic worldwide. It is estimated that half of the cases are due to iron deficiency. Consequences of iron deficiency anaemia during childhood include growth retardation, reduced school achievement, impaired motor and cognitive development, and increased morbidity and mortality. The provision of daily iron supplements is a widely used strategy for improving iron status in children but its effectiveness has been limited due to its side effects, which can include nausea, constipation or staining of the teeth. As a consequence, intermittent iron supplementation (one, two or three times a week on non-consecutive days) has been proposed as an effective and safer alternative to daily supplementation. OBJECTIVES: To assess the effects of intermittent iron supplementation, alone or in combination with other vitamins and minerals, on nutritional and developmental outcomes in children from birth to 12 years of age compared with a placebo, no intervention or daily supplementation. SEARCH METHODS: We searched the following databases on 24 May 2011: CENTRAL (2011, Issue 2), MEDLINE (1948 to May week 2, 2011), EMBASE (1980 to 2011 Week 20), CINAHL (1937 to current), POPLINE (all available years) and WHO International Clinical Trials Registry Platform (ICTRP). On 29 June 2011 we searched all available years in the following databases: SCIELO, LILACS, IBECS and IMBIOMED. We also contacted relevant organisations (on 3 July 2011) to identify ongoing and unpublished studies. SELECTION CRITERIA: Randomised and quasi-randomised trials with either individual or cluster randomisation. Participants were children under the age of 12 years at the time of intervention with no specific health problems. The intervention assessed was intermittent iron supplementation compared with a placebo, no intervention or daily supplementation. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies and assessed the risk of bias of the included studies. MAIN RESULTS: We included 33 trials, involving 13,114 children (˜49% females) from 20 countries in Latin America, Africa and Asia. The methodological quality of the trials was mixed.Nineteen trials evaluated intermittent iron supplementation versus no intervention or a placebo and 21 studies evaluated intermittent versus daily iron supplementation. Some of these trials contributed data to both comparisons. Iron alone was provided in most of the trials.Fifteen studies included children younger than 60 months; 11 trials included children 60 months and older, and seven studies included children in both age categories. One trial included exclusively females. Seven trials included only anaemic children; three studies assessed only non-anaemic children, and in the rest the baseline prevalence of anaemia ranged from 15% to 90%.In comparison with receiving no intervention or a placebo, children receiving iron supplements intermittently have a lower risk of anaemia (average risk ratio (RR) 0.51, 95% confidence interval (CI) 0.37 to 0.72, ten studies) and iron deficiency (RR 0.24, 95% CI 0.06 to 0.91, three studies) and have higher haemoglobin (mean difference (MD) 5.20 g/L, 95% CI 2.51 to 7.88, 19 studies) and ferritin concentrations (MD 14.17 µg/L, 95% CI 3.53 to 24.81, five studies).Intermittent supplementation was as effective as daily supplementation in improving haemoglobin (MD -0.60 g/L, 95% CI -1.54 to 0.35, 19 studies) and ferritin concentrations (MD -4.19 µg/L, 95% CI -9.42 to 1.05, 10 studies), but increased the risk of anaemia in comparison with daily iron supplementation (RR 1.23, 95% CI 1.04 to1.47, six studies). Data on adherence were scarce and it tended to be higher among those children receiving intermittent supplementation, although this result was not statistically significant.We did not identify any differential effect of the type of intermittent supplementation regimen (one, two or three times a week), the total weekly dose of elemental iron, the nutrient composition, whether recipients were male or female or the length of the intervention. AUTHORS' CONCLUSIONS: Intermittent iron supplementation is efficacious to improve haemoglobin concentrations and reduce the risk of having anaemia or iron deficiency in children younger than 12 years of age when compared with a placebo or no intervention, but it is less effective than daily supplementation to prevent or control anaemia. Intermittent supplementation may be a viable public health intervention in settings where daily supplementation has failed or has not been implemented. Information on mortality, morbidity, developmental outcomes and side effects, however, is still lacking. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/22161444/Intermittent_iron_supplementation_for_improving_nutrition_and_development_in_children_under_12_years_of_age_ L2 - https://doi.org/10.1002/14651858.CD009085.pub2 DB - PRIME DP - Unbound Medicine ER -