Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial

Abstract Objective: To evaluate the effect on morbidity and mortality of providing daily zinc for 14 days to children with diarrhoea. Design: Cluster randomised comparison. Setting: Matlab field site of International Center for Diarrhoeal Disease Research, Bangladesh. Participants: 8070 children aged 3-59 months contributed 11 881 child years of observation during a two year period. Intervention: Children with diarrhoea in the intervention clusters were treated with zinc (20 mg per day for 14 days); all children with diarrhoea were treated with oral rehydration therapy. Main outcome measures: Duration of episode of diarrhoea, incidence of diarrhoea and acute lower respiratory infections, admission to hospital for diarrhoea or acute lower respiratory infections, and child mortality. Results: About 40% (399/1007) of diarrhoeal episodes were treated with zinc in the first four months of the trial; the rate rose to 67% (350/526) in month 5 and to >80% (364/434) in month 7 and was sustained at that level. Children from the intervention cluster received zinc for about seven days on average during each episode of diarrhoea. They had a shorter duration (hazard ratio 0.76, 95% confidence interval 0.65 to 0.90) and lower incidence of diarrhoea (rate ratio 0.85, 0.76 to 0.96) than children in the comparison group. Incidence of acute lower respiratory infection was reduced in the intervention group but not in the comparison group. Admission to hospital of children with diarrhoea was lower in the intervention group than in the comparison group (0.76, 0.59 to 0.98). Admission for acute lower respiratory infection was lower in the intervention group, but this was not statistically significant (0.81, 0.53 to 1.23). The rate of non-injury deaths in the intervention clusters was considerably lower (0.49, 0.25 to 0.94). Conclusions: The lower rates of child morbidity and mortality with zinc treatment represent substantial benefits from a simple and inexpensive intervention that can be incorporated in existing efforts to control diarrhoeal disease. What is already known on this topic Zinc deficiency is highly prevalent in children in developing countries Zinc supplements given during diarrhoea reduce the duration and severity of treated episodes If given for 14 days during and after diarrhoea, zinc reduces the incidence of diarrhoea and pneumonia in the subsequent two to three months What this study adds Zinc used as a treatment for diarrhoea reduces mortality in children Zinc reduces admissions to hospital for diarrhoea The impact of zinc on mortality and morbidity can be achieved in a realistic large scale public health programme

[1]  C. McClain,et al.  The effect of severe zinc deficiency on activity of intestinal disaccharidases and 3-hydroxy-3-methylglutaryl coenzyme A reductase in the rat. , 1983, The Journal of nutrition.

[2]  B. L. O’dell,et al.  A critical physiological role of zinc in the structure and function of biomembranes. , 1981, Life sciences.

[3]  M. Alpers,et al.  The influence of zinc supplementation on morbidity due to Plasmodium falciparum: a randomized trial in preschool children in Papua New Guinea. , 2000, The American journal of tropical medicine and hygiene.

[4]  R. Black,et al.  Zinc and childhood infectious disease morbidity and mortality , 2001, British Journal of Nutrition.

[5]  P. Galan,et al.  Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. , 1999, Archives of internal medicine.

[6]  R. Black,et al.  Zinc Supplementation Reduces the Incidence of Acute Lower Respiratory Infections in Infants and Preschool Children: A Double-blind, Controlled Trial , 1998, Pediatrics.

[7]  S. Vermund,et al.  Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomised double blind controlled trial , 2001, BMJ : British Medical Journal.

[8]  J. Rivera,et al.  Impact of zinc supplementation on morbidity from diarrhea and respiratory infections among rural Guatemalan children. , 1997, Pediatrics.

[9]  G. Darmstadt,et al.  Zinc supplementation during pregnancy and effects on growth and morbidity in low birthweight infants: a randomsied placebo controlled trial , 2001, The Lancet.

[10]  R. Martorell,et al.  Effectiveness of vitamin A supplementation in the control of young child morbidity and mortality in developing countries. Revised ed. , 1993 .

[11]  G. Daston,et al.  Effect of copper deficiency on prenatal development and pregnancy outcome. , 1998, The American journal of clinical nutrition.

[12]  R. Martorell,et al.  Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. , 2000, The American journal of clinical nutrition.

[13]  D. Clayton Poisson regression with a random effect , 1999 .

[14]  J. Hauth,et al.  The effect of zinc supplementation on pregnancy outcome. , 1995, JAMA.

[15]  R. Black,et al.  Causes of childhood deaths in Bangladesh: results of a nationwide verbal autopsy study. , 1998, Bulletin of the World Health Organization.

[16]  A Donner,et al.  Randomization by cluster. , 1991, Nursing research.

[17]  R. Gibson,et al.  A growth-limiting, mild zinc-deficiency syndrome in some southern Ontario boys with low height percentiles. , 1989, The American journal of clinical nutrition.

[18]  R. Black,et al.  Efficacy of zinc supplementation in reducing the incidence and prevalence of acute diarrhea--a community-based, double-blind, controlled trial. , 1997, The American journal of clinical nutrition.

[19]  S G Thompson,et al.  The design and analysis of paired cluster randomized trials: an application of meta-analysis techniques. , 1997, Statistics in medicine.

[20]  R. Black,et al.  Zinc supplementation in young children with acute diarrhea in India. , 1995, The New England journal of medicine.

[21]  H. Sandstead Zinc deficiency. A public health problem? , 1991, American journal of diseases of children.

[22]  R Martorell,et al.  Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group. , 1999, The Journal of pediatrics.

[23]  D. Macdonald,et al.  Zinc deficiency and zinc repletion: effect on the response of rats to infection with Trichinella spiralis. , 1990, The American journal of clinical nutrition.

[24]  R. Uauy,et al.  Trace mineral balance during acute diarrhea in infants. , 1988, The Journal of pediatrics.

[25]  C. F. Mills,et al.  Trace elements in man and animals TEMA 5 , 1985 .

[26]  F. Forastiere,et al.  The Effect of Zinc and Vitamin A Supplementation on Immune Response in an Older Population , 1998, Journal of the American Geriatrics Society.

[27]  L. Caulfield,et al.  Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival. , 1998, The American journal of clinical nutrition.

[28]  A S Prasad,et al.  Zinc and immune function: the biological basis of altered resistance to infection. , 1998, The American journal of clinical nutrition.

[29]  A. Donner,et al.  Randomization by cluster. Sample size requirements and analysis. , 1981, American journal of epidemiology.

[30]  P. Lavori,et al.  Analysis of randomized controlled trials. , 2002, Epidemiologic reviews.

[31]  S. Roy,et al.  Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea , 1997, Archives of disease in childhood.

[32]  L. Allen,et al.  Zinc supplementation reduced morbidity, but neither zinc nor iron supplementation affected growth or body composition of Mexican preschoolers. , 1997, The American journal of clinical nutrition.

[33]  L. Caulfield,et al.  Zinc supplementation in infants born small for gestational age reduces mortality: a prospective, randomized, controlled trial. , 2001, Pediatrics.