Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: Community-based, randomised, placebo-controlled trial

Sunil Sazawal, Robert E Black, Mahdi Ramsan, Hababu M. Chwaya, Rebecca J. Stoltzfus, Arup Dutta, Usha Dhingra, Ibrahim Kabole, Saikat Deb, Mashavi K. Othman, Fatma M. Kabole

Research output: Contribution to journalArticle

Abstract

Background: Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa. However, there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful. Methods: We did a randomised, placebo-controlled trial, of children aged 1-35 months and living in Pemba, Zanzibar. We assigned children to daily oral supplementation with: iron (12·5 mg) and folic acid (50 μg; n=7950), iron, folic acid, and zinc (n=8120), or placebo (n=8006); children aged 1-11 months received half the dose. Our primary endpoints were all-cause mortality and admission to hospital. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59549825. Findings: The iron and folic acid-containing groups of the trial were stopped early on Aug 19, 2003, on the recommendation of the data and safety monitoring board. To this date, 24 076 children contributed a follow-up of 25 524 child-years. Those who received iron and folic acid with or without zinc were 12% (95% CI 2-23, p=0·02) more likely to die or need treatment in hospital for an adverse event and 11% (1-23%, p=0·03) more likely to be admitted to hospital; there were also 15% (-7 to 41, p=0·19) more deaths in these groups. Interpretation: Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death. In the presence of an active programme to detect and treat malaria and other infections, iron-deficient and anaemic children can benefit from supplementation. However, supplementation of those who are not iron deficient might be harmful. As such, current guidelines for universal supplementation with iron and folic acid should be revised.

Original languageEnglish (US)
Pages (from-to)133-143
Number of pages11
JournalThe Lancet
Volume367
Issue number9505
DOIs
StatePublished - Jan 14 2006

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Preschool Children
Hospital Mortality
Folic Acid
Malaria
Iron
Randomized Controlled Trials
Placebos
Zinc
Indian Ocean Islands
Clinical Trials Data Monitoring Committees
Eastern Africa
Intention to Treat Analysis
Tanzania
Iron-Deficiency Anemias
Guidelines
Mortality
Infection

ASJC Scopus subject areas

  • Medicine(all)

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Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting : Community-based, randomised, placebo-controlled trial. / Sazawal, Sunil; Black, Robert E; Ramsan, Mahdi; Chwaya, Hababu M.; Stoltzfus, Rebecca J.; Dutta, Arup; Dhingra, Usha; Kabole, Ibrahim; Deb, Saikat; Othman, Mashavi K.; Kabole, Fatma M.

In: The Lancet, Vol. 367, No. 9505, 14.01.2006, p. 133-143.

Research output: Contribution to journalArticle

Sazawal, Sunil ; Black, Robert E ; Ramsan, Mahdi ; Chwaya, Hababu M. ; Stoltzfus, Rebecca J. ; Dutta, Arup ; Dhingra, Usha ; Kabole, Ibrahim ; Deb, Saikat ; Othman, Mashavi K. ; Kabole, Fatma M. / Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting : Community-based, randomised, placebo-controlled trial. In: The Lancet. 2006 ; Vol. 367, No. 9505. pp. 133-143.
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abstract = "Background: Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa. However, there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful. Methods: We did a randomised, placebo-controlled trial, of children aged 1-35 months and living in Pemba, Zanzibar. We assigned children to daily oral supplementation with: iron (12·5 mg) and folic acid (50 μg; n=7950), iron, folic acid, and zinc (n=8120), or placebo (n=8006); children aged 1-11 months received half the dose. Our primary endpoints were all-cause mortality and admission to hospital. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59549825. Findings: The iron and folic acid-containing groups of the trial were stopped early on Aug 19, 2003, on the recommendation of the data and safety monitoring board. To this date, 24 076 children contributed a follow-up of 25 524 child-years. Those who received iron and folic acid with or without zinc were 12{\%} (95{\%} CI 2-23, p=0·02) more likely to die or need treatment in hospital for an adverse event and 11{\%} (1-23{\%}, p=0·03) more likely to be admitted to hospital; there were also 15{\%} (-7 to 41, p=0·19) more deaths in these groups. Interpretation: Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death. In the presence of an active programme to detect and treat malaria and other infections, iron-deficient and anaemic children can benefit from supplementation. However, supplementation of those who are not iron deficient might be harmful. As such, current guidelines for universal supplementation with iron and folic acid should be revised.",
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T1 - Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting

T2 - Community-based, randomised, placebo-controlled trial

AU - Sazawal, Sunil

AU - Black, Robert E

AU - Ramsan, Mahdi

AU - Chwaya, Hababu M.

AU - Stoltzfus, Rebecca J.

AU - Dutta, Arup

AU - Dhingra, Usha

AU - Kabole, Ibrahim

AU - Deb, Saikat

AU - Othman, Mashavi K.

AU - Kabole, Fatma M.

PY - 2006/1/14

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N2 - Background: Anaemia caused by iron deficiency is common in children younger than age 5 years in eastern Africa. However, there is concern that universal supplementation of children with iron and folic acid in areas of high malaria transmission might be harmful. Methods: We did a randomised, placebo-controlled trial, of children aged 1-35 months and living in Pemba, Zanzibar. We assigned children to daily oral supplementation with: iron (12·5 mg) and folic acid (50 μg; n=7950), iron, folic acid, and zinc (n=8120), or placebo (n=8006); children aged 1-11 months received half the dose. Our primary endpoints were all-cause mortality and admission to hospital. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59549825. Findings: The iron and folic acid-containing groups of the trial were stopped early on Aug 19, 2003, on the recommendation of the data and safety monitoring board. To this date, 24 076 children contributed a follow-up of 25 524 child-years. Those who received iron and folic acid with or without zinc were 12% (95% CI 2-23, p=0·02) more likely to die or need treatment in hospital for an adverse event and 11% (1-23%, p=0·03) more likely to be admitted to hospital; there were also 15% (-7 to 41, p=0·19) more deaths in these groups. Interpretation: Routine supplementation with iron and folic acid in preschool children in a population with high rates of malaria can result in an increased risk of severe illness and death. In the presence of an active programme to detect and treat malaria and other infections, iron-deficient and anaemic children can benefit from supplementation. However, supplementation of those who are not iron deficient might be harmful. As such, current guidelines for universal supplementation with iron and folic acid should be revised.

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