Effect of Zinc and Vitamin A Supplementation on Diarrhea, Physical Growth and Immune Response in Malnourished Children

Overview

Zinc deficiency is common in developing country children, as food intakes are often low, foods from animal sources are infrequently used, the bioavailability of zinc from staple cereal-based diets is limited and zinc losses occur during recurring diarrheal illnesses. Zinc deficiency is associated with impairment in immunological and other defenses against infection and increased rates of serious infections. Due to limitations in currently used biochemical markers, supplementation trials in populations likely to be deficient provide a reliable means of assessing health consequences of zinc deficiency. A significantly lower incidence and prevalence of diarrhea has been observed in zinc supplemented developing country children in several placebo-controlled trials. The effect of routine zinc supplementation on lower respiratory tract infection is still unclear. We, therefore, evaluated the impact of daily zinc supplementation in a representative sample of children aged 6 to 30 months enrolled from a New Delhi slum area, with a sample size sufficient to determine the impact on the incidence of severe diarrhea and acute lower respiratory infection.

Diarrheal disease is a major cause of child mortality in developing countries. Currently, the management of diarrhea focuses on oral rehydration therapy in acute diarrhea. However, acute diarrhea accounts for only 1/3 of the diarrhea-related deaths, the majority of the remaining being caused by persistent diarrhea. Currently persistent diarrhea treatment is complex, not yet adapted to community settings and, hence, has only a marginal impact on diarrheal mortality. A major challenge is to develop and implement cost-effective community-based interventions that can be applied to children with diarrhea to prevent persistence. The trial was implemented in the urban slum of Dakshinpuri comprising 15,000 dwellings and a population of about 75,000. Recent data from a neighboring community indicated that childhood malnutrition, zinc deficiency, diarrhea and lower respiratory tract infection were common. Children aged 6 to 30 months were identified through a door-to-door survey. Enrollment required that the parents give informed consent and that families did not intend to emigrate. Eligible children were individually randomized by a simple randomization scheme in blocks of 8 generated by a person at Statens Serum Institut, Denmark. The zinc and placebo syrups were prepared and packaged in unbreakable bottles by GK Pharma Aps (Koge, Denmark( and labeled with unique child number according to the randomization scheme. The zinc and placebo syrups were similar in appearance, taste and packaging. The enrolled children were randomized to receive zinc gluconate (10 mg elemental zinc/day to infants and 20 mg/day to older children) or placebo daily for a period of 4 months. All included subjects were given a massive dose of vitamin A at enrollment in addition to zinc or placebo. A field attendant administered the syrup daily at home for 4 months except on Sundays, when the mother was asked to administer it. One bottle containing 250 mL was kept in the child's home and replaced monthly. Field workers visited households every seventh day during the 4-month follow-up period. At each visit, information was obtained for the previous 7 days on history of fever, number and consistency of stools. If the child had diarrhea or vomiting, dehydration was assessed. Information was also obtained on cough, lower chest indrawing and on their illness characteristics and whether treatment was sought in the previous 7 days. Intervention impact was assessed on physician-diagnosed acute lower respiratory tract infections and pneumonia. Blood was collected at baseline in all children to measure micronutrient status. Cognitive development was measured at baseline and end study using Bayelys Scales of Infant Development version II.