Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. A randomized controlled trial of the effect of zinc as adjuvant therapy in children 2-35 mo of age with severe or nonsevere pneumonia in Bhaktapur, Nepal. Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial. Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial. Zinc supplementation in severe acute lower respiratory tract infection in children: a triple-blind randomized placebo controlled trial. A double-blind, randomized, clinical trial of the effect of vitamin A and zinc supplementation on diarrheal disease and respiratory tract infections in children in Mexico City, Mexico. Zinc or multiple micronutrient supplementation to reduce diarrhea and respiratory disease in South African children: a randomized controlled trial. Zinc supplementation reduces the incidence of persistent diarrhea and dysentery among low socioeconomic children in India.
To evaluate the effect of daily zinc supplementation in children on the incidence of acute lower respiratory tract infections and pneumonia.
                Double masked, randomised placebo controlled trial.
                A slum community in New Delhi, India.
                2482 children aged 6 to 30 months.
                Daily elemental zinc, 10 mg to infants and 20 mg to older children or placebo for four months. Both groups received single massive dose of vitamin A (100 000 IU for infants and 200 000 IU for older children) at enrollment.
                All households were visited weekly. Any children with cough and lower chest indrawing or respiratory rate 5 breaths per minute less than the World Health Organization criteria for fast breathing were brought to study physicians.
                At four months the mean plasma zinc concentration was higher in the zinc group (19.8 (SD 10.1) v 9.3 (2.1) micromol/l, P<0.001). The proportion of children who had acute lower respiratory tract infection during follow up was no different in the two groups (absolute risk reduction -0.2%, 95% confidence interval -3.9% to 3.6%). Zinc supplementation resulted in a lower incidence of pneumonia than placebo (absolute risk reduction 2.5%, 95% confidence interval 0.4% to 4.6%). After correction for multiple episodes in the same child by generalised estimating equations analysis the odds ratio was 0.74, 95% confidence interval 0.56 to 0.99.
                Zinc supplementation substantially reduced the incidence of pneumonia in children who had received vitamin A. Increased acute lower respiratory infection incidence, severity, and mortality are associated with malnutrition, and reduced immunological competence may be a mechanism for this association. Because zinc deficiency results in impaired immunocompetence and zinc supplementation improves immune status, we hypothesized that zinc deficiency is associated with increased incidence and severity of acute lower respiratory infection.
                We evaluated the effect of daily supplementation with 10 mg of elemental zinc on the incidence and prevalence of acute lower respiratory infection in a double-blind, randomized, controlled trial in 609 children (zinc, n = 298; control, n = 311) 6 to 35 months of age. Supplementation and morbidity surveillance were done for 6 months.
                After 120 days of supplementation, the percentage of children with plasma zinc concentrations <60 microg/dL decreased from 35.6% to 11.6% in the zinc group, whereas in the control group it increased from 36.8% to 43.6%. Zinc-supplemented children had 0.19 acute lower respiratory infection episodes/child/year compared with 0.35 episodes/child/year in the control children. After correction for correlation of data using generalized estimating equation regression methods, there was a reduction of 45% (95% confidence interval, 10% to 67%) in the incidence of acute lower respiratory infections in zinc-supplemented children.
                A dietary zinc supplement resulted in a significant reduction in respiratory morbidity in preschool children. These findings suggest that interventions to improve zinc intake will improve the health and survival of children in developing countries. Pneumonia is a leading cause of illness and death in young children. Interventions to improve case management of pneumonia are needed.
                Our objective was to measure the effect of zinc supplementation in children with pneumonia in a population in which zinc deficiency is common.
                In a double-blind, placebo-controlled clinical trial, children aged 2-35 mo with severe (n = 149) or nonsevere (n = 2479) pneumonia defined according to criteria established by the World Health Organization were randomly assigned to receive zinc (10 mg for children aged 2-11 mo, 20 mg for children aged > or =12 mo) or placebo daily for 14 d as an adjuvant to antibiotics. The primary outcomes were treatment failure, defined as a need for change in antibiotics or hospitalization, and time to recovery from pneumonia.
                One of 5 children did not respond adequately to antibiotic treatment; the odds ratios between zinc and placebo groups for treatment failure were 0.95 (95% CI: 0.78, 1.2) for nonsevere pneumonia and 0.97 (95% CI: 0.42, 2.2) for severe pneumonia. There was no difference in time to recovery between zinc and placebo groups for nonsevere (median: 2 d; hazard ratio: 1.0; 95% CI: 0.96, 1.1) or severe (median: 4 d; hazard ratio: 1.1; 95% CI: 0.79, 1.5) pneumonia. Regurgitation or vomiting < or =15 min after supplementation was observed more frequently among children in the zinc group than among those in the placebo group during the supplementation period (37% compared with 13%; odds ratio: 0.25; 95% CI: 0.20, 0.30).
                Adjuvant treatment with zinc neither reduced the risk of treatment failure nor accelerated recovery in episodes of nonsevere or severe pneumonia. This trial was registered at clinicaltrials.gov as NCT00148733. Pneumonia and diarrhoea cause much morbidity and mortality in children younger than 5 years. Most deaths occur during infancy and in developing countries. Daily regimens of zinc have been reported to prevent acute lower respiratory tract infection and diarrhoea, and to reduce child mortality. We aimed to examine whether giving zinc weekly could prevent clinical pneumonia and diarrhoea in children younger than 2 years.
                1665 poor, urban children aged 60 days to 12 months were randomly assigned zinc (70 mg) or placebo orally once weekly for 12 months. Children were assessed every week by field research assistants. Our primary outcomes were the rate of pneumonia and diarrhoea. The rates of other respiratory tract infections were the secondary outcomes. Growth, final serum copper, and final haemoglobin were also measured. Analysis was by intention to treat.
                34 children were excluded before random assignment to treatment group because they had tuberculosis. 809 children were assigned zinc, and 812 placebo. After treatment assignment, 103 children in the treatment group and 44 in the control group withdrew. There were significantly fewer incidents of pneumonia in the zinc group than the control group (199 vs 286; relative risk 0.83, 95% CI 0.73-0.95), and a small but significant effect on incidence of diarrhoea (1881 cases vs 2407; 0.94, 0.88-0.99). There were two deaths in the zinc group and 14 in the placebo group (p=0.013). There were no pneumonia-related deaths in the zinc group, but ten in the placebo group (p=0.013). The zinc group had a small gain in height, but not weight at 10 months compared with the placebo group. Serum copper and haemoglobin concentrations were not adversely affected after 10 months of zinc supplementation.
                70 mg of zinc weekly reduces pneumonia and mortality in young children. However, compliance with weekly intake might be problematic outside a research programme. Pneumonia is a leading cause of morbidity and mortality in young children. Early reversal of severity signs--chest indrawing, hypoxia, and tachypnoea--improves outcome. We postulated that zinc, an acute phase reactant, would shorten duration of severe pneumonia and time in hospital.
                In a double-blind placebo-controlled clinical trial in Matlab Hospital, Bangladesh, 270 children aged 2-23 months were randomised to receive elemental zinc (20 mg per day) or placebo, plus the hospital's standard antimicrobial management, until discharge. The outcomes were time to cessation of severe pneumonia (no chest indrawing, respiratory rate 50 per min or less, oxygen saturation at least 95% on room air) and discharge from hospital. Discharge was allowed when respiratory rate was 40 per minute or less for 24 consecutive hours while patients were maintained only on oral antibiotics.
                The group receiving zinc had reduced duration of severe pneumonia (relative hazard [RH]=0.70, 95% CI 0.51-0.98), including duration of chest indrawing (0.80, 0.61-1.05), respiratory rate more than 50 per min (0.74, 0.57-0.98), and hypoxia (0.79, 0.61-1.04), and overall hospital duration (0.75, 0.57-0.99). The mean reduction is equivalent to 1 hospital day for both severe pneumonia and time in hospital. All effects were greater when children with wheezing were omitted from the analysis.
                Adjuvant treatment with 20 mg zinc per day accelerates recovery from severe pneumonia in children, and could help reduce antimicrobial resistance by decreasing multiple antibiotic exposures, and lessen complications and deaths where second line drugs are unavailable. To evaluate the efficacy of zinc supplementation on duration of illness in children with severe acute lower respiratory tract infection (ALRTI).
                This randomized triple-blind placebo-controlled trial was conducted in pediatric emergency of a teaching referral hospital. Children in the age group of 2-24 months presenting to pediatric emergency with severe ALRTI were included. Eligible children were randomly allocated to zinc (n=53) or control (n=53) groups. Zinc group received 20 mg of elemental zinc per day (5 ml syrup per day) as a single daily dose for 5 days. Control group received an equal amount of placebo which was appropriately modified to give the taste, smell, color and consistency similar to zinc mixture. Primary outcome was 'time to be asymptomatic', a composite outcome defined as resolution of all four of the following: danger signs, respiratory distress, tachypnea and hypoxia in room air.
                Age, gender, nutritional status, pretreatment zinc levels and other demographic and clinical variables were similar in the two groups. 'Time to be asymptomatic' was comparable in the two groups (h; median (IQR): 60 (24-78) vs. 54 (30-72), P=0.98]. At any time point a similar proportion of children were symptomatic in both the groups. Time to resolution of respiratory distress, tachypnea, dangers signs and hypoxia were also similar in two groups. Duration of hospital stay was shorter by 9 h in the zinc group but the difference was statistically insignificant.
                Zinc supplementation did not reduce recovery time and duration of hospital stay in children with ALRTI. Larger randomized controlled trials are needed to evaluate role of zinc in ALRTI. The efficacy of micronutrient supplementation in improving childhood health and survival in developing countries may be specific to the micronutrient used and health outcome measured.
                We evaluated the effect of vitamin A and zinc supplementation on overall rates of childhood diarrheal disease and respiratory tract infections and rates stratified by household and personal characteristics.
                A double-blind, randomized, placebo-controlled trial was carried out in which 736 children aged 6-15 mo living in a periurban area of Mexico City were assigned to receive vitamin A every 2 mo, zinc daily, vitamin A and zinc together, or placebo. Children were followed for 12 mo to determine overall counts of diarrheal episodes and respiratory tract infections.
                Vitamin A supplementation was associated with a 27% increase in diarrheal disease [risk ratio (RR): 1.27; 95% CI: 1.10, 1.45; P < 0.001] and a 23% increase in cough with fever (RR: 1.23; 95% CI: 1.02, 1.47; P = 0.02), whereas zinc had no effect on these outcomes. Vitamin A supplementation decreased diarrhea in children from households with dirt floors but increased diarrhea in children from households with nondirt floors, piped water, and indoor bathrooms. Zinc supplementation decreased diarrhea in children from households with dirt floors and whose mothers were more educated. Vitamin A supplementation increased cough with fever in children from less-crowded households that lacked indoor bathrooms and in children of less-educated mothers.
                Vitamin A increases diarrheal disease and respiratory tract infections in young children in periurban areas of Mexico City. Vitamin A and zinc have more heterogeneous effects in different subgroups of children. Prophylactic zinc supplementation has been shown to reduce diarrhea and respiratory illness in children in many developing countries, but its efficacy in children in Africa is uncertain.
                To determine if zinc, or zinc plus multiple micronutrients, reduces diarrhea and respiratory disease prevalence.
                Randomized, double-blind, controlled trial.
                Rural community in South Africa.
                THREE COHORTS: 32 HIV-infected children; 154 HIV-uninfected children born to HIV-infected mothers; and 187 HIV-uninfected children born to HIV-uninfected mothers.
                Children received either 1250 IU of vitamin A; vitamin A and 10 mg of zinc; or vitamin A, zinc, vitamins B1, B2, B6, B12, C, D, E, and K and copper, iodine, iron, and niacin starting at 6 months and continuing to 24 months of age. Homes were visited weekly.
                Primary outcome was percentage of days of diarrhea per child by study arm within each of the three cohorts. Secondary outcomes were prevalence of upper respiratory symptoms and percentage of children who ever had pneumonia by maternal report, or confirmed by the field worker.
                Among HIV-uninfected children born to HIV-infected mothers, median percentage of days with diarrhea was 2.3% for 49 children allocated to vitamin A; 2.5% in 47 children allocated to receive vitamin A and zinc; and 2.2% for 46 children allocated to multiple micronutrients (P = 0.852). Among HIV-uninfected children born to HIV-uninfected mothers, median percentage of days of diarrhea was 2.4% in 56 children in the vitamin A group; 1.8% in 57 children in the vitamin A and zinc group; and 2.7% in 52 children in the multiple micronutrient group (P = 0.857). Only 32 HIV-infected children were enrolled, and there were no differences between treatment arms in the prevalence of diarrhea. The prevalence of upper respiratory symptoms or incidence of pneumonia did not differ by treatment arms in any of the cohorts.
                When compared with vitamin A alone, supplementation with zinc, or with zinc and multiple micronutrients, did not reduce diarrhea and respiratory morbidity in rural South African children.
                ClinicalTrials.gov NCT00156832. Persistent diarrhea (PD) and dysentery (DD) account for most diarrhea-associated deaths among children in developing countries. Zinc deficiency can cause stunting and impaired immune function, both of which are risk factors for these diarrheal illnesses. We investigated the effect of zinc supplementation on the incidence of PD and DD in a community-based, double-blind randomized trial in children 6-35 mo of age. Increase over baseline in plasma zinc concentrations in the supplemented group compared with a control group (3.61 vs. 0.009 mumol.L-1), indicated successful supplementation. The overall reductions in the zinc supplemented group of 21% in the incidence of PD (95% CI -6 to 42%) and 14% in the incidence of dysentery (95% CI -15 to 36%) were not significant. There was a significant interaction of treatment effect with baseline plasma zinc concentration and age for PD and with gender for DD. In the zinc-supplemented group compared with the control group, the incidence of PD was reduced by 73% (P < 0.05; 95% CI 34 to 91%) in children with a baseline zinc < 7.65 mumol.L-1 and by 49% (P < 0.05; 95%CI 24 to 66%) in children > 11 mo of age. Zinc supplementation resulted in a 38% (P < 0.05 95%CI 8 to 59%) reduction in the incidence of DD in boys. There was no effect on PD among children 6-11 mo old or on DD in girls. In conclusion, zinc supplementation had a significant impact on the incidence of persistent diarrhea in children > 1 y old and in children with low plasma zinc, as well as on dysentery in boys. These findings may have important implications for reducing diarrhea-related morbidity and mortality.
Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia, the leading cause of death in children.