title: Therapeutic evaluation of zinc and copper supplementation in acute diarrhea in children: double blind randomized trial.
abstract: 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 diarrhea in children.
  
  
  METHODS
  In a randomized, double blind, placebo controlled trial children aged 6 months to 59 months in an urban hospital with acute diarrhea, were assigned to receive the intervention of once daily 40 mg of zinc sulfate and 5 mg of copper sulfate dissolved in a liter of standard ORS (n = 102) or placebo (50 mg of standard ORS powder) dissolved in a liter of ORS (n = 98).
  
  
  RESULTS
  The baseline characteristics in the two groups were similar. The mean survival time (days) (SE) with diarrhea 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 diarrhea 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 diarrhea > 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 diarrhea > 4 days was diarrheal duration prior to enrollment with OR = 6.25 (3.7, 11.1). The supplemented group however had less severity of diarrhea 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 diarrhea in children was the severity of the disease at enrollment, 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 diarrhea.
authors.affiliation: Clinical Epidemiology Unit, Indira Gandhi Medical College, Nagpur 440 018, Maharashtra, India. archana_patel@vsnl.com
authors.forename: Archana B
authors.initials: AB
authors.lastname: Patel
authors.forename: Leena A
authors.initials: LA
authors.lastname: Dhande
authors.forename: Manwar S
authors.initials: MS
authors.lastname: Rawat
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D002675:Child, Preschool; D019327:Copper Sulfate / Q000627:therapeutic use*; D003967:Diarrhea / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005440:Fluid Therapy / Q000379:methods*; D006801:Humans; D007223:Infant; D008297:Male; D016016:Proportional Hazards Models; D014131:Trace Elements / Q000627:therapeutic use*; D019287:Zinc Sulfate / Q000627:therapeutic use*
chemical_list: D014131:Trace Elements; D019287:Zinc Sulfate; D019327:Copper Sulfate