Therapeutic evaluation of zinc and copper supplementation in acute diarrhea in children: double blind randomized trial
Patel, A.B.; Dhande, L.A.; Rawat, M.S.
Indian Pediatrics 42(5): 433-442
2005
ISSN/ISBN: 0019-6061 PMID: 15923689 Document Number: 254311
Objective: To test the hypothesis that daily supplementation of zinc and copper mixed with the oral rehydration solution (ORS) reduces the duration and the severity of acute diarrhoea in children. Methods: In a randomized, double blind, placebo controlled trial children aged 6 months to 59 months in an urban hospital (Government Medical College, Nagpur, India) with acute diarrhoea, were assigned to receive the intervention of once daily 40 mg of zinc sulfate and 5 mg of copper sulfate dissolved in a litre of standard ORS (n=102) or placebo (50 mg of standard ORS powder) dissolved in a litre of ORS (n=98). Results: The baseline characteristics in the two groups were similar. The mean survival time (days) (SE) with diarrhoea was not significantly different in the treatment (4.34) (0.2) as compared to the placebo group (4.48) (0.2), nor was there any difference in the median time to cure. Cure was less likely with longer duration of diarrhoea prior to enrollment (P<0.001), if the time taken for rehydration was more (P=0.001) and if intravenous fluids were used (P=0.03) regardless of the micronutrient supplementation. The proportion of children with diarrhoea >4 days was 46% in the placebo group with an adjusted odds ratio (OR) (95%CI) of 1.19 (1.58, 0.9; P=0.2) as compared to 39% in the supplemented group. The most important risk factor for diarrhoea >4 days was diarrhoeal duration prior to enrolment with OR=6.25 (3.7, 11.1). The supplemented group however had less severity of diarrhoea with a lower proportion of children requiring unscheduled intravenous fluids (OR=0.4; 95% CI 0.05, 2.2), with weight loss (OR=0.7; 95% CI; 0.4, 1.3), with complications (OR=0.15; 0.01, 1.3) and had no deaths as compared to two in the placebo group. Conclusions: This study showed that the most important predictor for duration of diarrhoea in children was the severity of the disease at enrolment, and, not the supplementation. There were clinical beneficial effects of supplementation on rate of any complications and mortality. A larger trial is warranted before supplementation of micronutrients mixed with ORS are recommended for management of acute diarrhoea.