Impact of Zinc Supplementation on Child Mortality, Zanzibar

This 60,000+ child trial assessed the efficacy of 10 mg of zinc with or without 12.5 mg of iron and 50 µg of folic acid in reducing child mortality and severe morbidity. The yearlong study had four arms: zinc alone, iron alone, zinc and iron together, and placebo. All groups received Vitamin A.

The primary outcomes of the study were effect on total and cause specific mortality and total and cause specific severe disease incidence as assessed by hospitalizations. Additional outcomes addressed in substudies include the effect of supplementation on:

• malaria prevalence
• diarrhea and pneumonia morbidity
• zinc status and iron status (both in terms of hematological status and iron stores)

The original study plan was revised based on recommendations after review of prospective data by the Data Safety and Monitoring Board (DSMB), which has been regularly reviewing the project's progress. In July 2003, DSMB observed that there was some evidence of increased adverse reactions in iron supplemented groups. For safety considerations they recommended the iron supplementation be withdrawn and data analysis on iron effects be analyzed. The board further observed that the study would provide important data for zinc effects and should be converted into a two-celled design (zinc and control groups).

Following the recommendation, the study design was modified, iron was withdrawn from the supplements, and children were switched to zinc and control groups. The switch was initiated in August 2003 and completed in one week.

The first report of results for the iron supplementation arms was published in Lancet.

Principal Investigator:  Sunil Sazawal (JHSPH)

Publications:

Bhatnagar, S. (2007). Effects of zinc supplmeentation on child mortality [comment]. The Lancet. 369, 9565, 927-34.

Hiremath GS, Sullivan DJ, Tripathi AK, Black RE, Sazawal S. (2006). Effect of Plasmodium falciparum Parasitemia on Erythrocyte Zinc Protoporphyrin [Short Communication]. Clinical Chemistry 52, 4, 778-779.

Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A, Dhingra U, Kabole I, Deb S, Othman MK, Kabole FM. 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. Lancet. 2006 Jan 28;367(9507):302.