Although the theoretical basis for a potential role of zinc has been postulated for quite some time, convincing evidence for its importance in child health has come only recently from randomized controlled trials of zinc supplementation. Episodes of childhood diarrhoea that last 14 days or more are associated with increased morbidity and growth retardation. Children who experience such episodes are more likely to have other serious infections and to die (1).

Zinc is essential for many cellular functions, including transcription of DNA and cell division (2) and is required for normal immune function (3). It has been shown to hasten mucosal recovery after diarrhoea. Zinc deficiency, as indicated by low plasma zinc concentrations, is associated with both an increased risk of diarrhoeal episodes and greater severity of these illnesses (4, 5).

The data from 10 trials evaluating preventive effects of zinc supplementation; three trials evaluating the therapeutic effects on acute diarrhoea; and four trials in therapy of persistent diarrhoea have now been subjected to a pooled analysis (6). This evaluation assessed studies carried out on the effects of zinc supplementation in the prevention of diarrhoea and pneumonia. Trials included those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance of zinc in children under 5 years of age and evaluated the prevention of serious infectious morbidity. The effects of supplements on diarrhoea and pneumonia were analysed overall and in subgroups, defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random effects hierarchical models to calculate odds ratios and confidence interval.

This analysis indicated that there is significant homogeneity in the results across the studies conducted throughout 10 developing countries. Zinc supplementation in these children in developing countries is associated with substantial reductions in the rates of diarrhoea and pneumonia, the two leading causes of death in these settings. These studies also provide by far the best evidence of widespread prevalence of zinc deficiency among preschool children.

However, although the available evidence is promising, it is still insufficient to formulate public health policies. Extrapolation of mortality impact from morbidity trial data is fraught with problems of both underestimating and overestimating the impact. Therefore, given its substantial potential to become a powerful intervention to promote child survival, the World Health Organization, in collaboration with UNICEF backed by funding from the United Nations Foundation, has initiated two large studies to determine whether zinc supplementation truly has an important role in decreasing child mortality and morbidity. These studies should provide conclusive new evidence on which to base interventions within the next 30 months and allow recommendations concerning the benefit of zinc supplementation in young children to be made.

References

1. Penny, M.E., Peerson, J.M., Marin, M. et al. Randomized, community-based trial of the effect of zinc supplementation, with and without other micronutrients, on the duration of persistent childhood diarrhoea in Lima, Peru. Journal of Pediatrics, 135: 208-217 (1999).

2. Berg, J.M., Shi Yigong. The galvanization of biology: a growing appreciation for the roles of zinc. Science, 27: 1081-1085 (1996).

3. Shankar, A.H., Prasad, A. Zinc and immune function: the biological basis of altered resistance to infection. American Journal of Clinical Nutrition, 68 (Suppl.): 447S-4463S (1998).

4. Roy, S.K., Behrens, R.G., Haider, R. et al. Impact of zinc supplementation on intestinal permeability in Bangladeshi children with acute diarrhoea and persistent diarrhoea syndrome. Journal of Paediatric Gastroenterology and Nutrition, 15: 289-296 (1992).

5. Alam, A.N., Sarkar, S.A., Wahed, M.A. et al. Enteric protein loss and intestinal permeability changes in children during acute shigellosis and after recovery: effect of zinc supplementation. Gut, 35: 1707-1711 (1994).

6. Zinc Investigators Collaborative Group. Therapeutic effects of oral zinc in persistent diarrhoea in children in developing countries: pooled analysis of randomized controlled trials. Journal of Pediatrics, 135: 689-697 (1999).