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Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children

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  • Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children

    The Lancet 2005; 366:999-1004
    DOI:10.1016/S0140-6736(05)67109-7
    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

    Prof W Abdullah BrooksMPH a , Prof Mathuram SantoshamMPH b, Aliya NaheedMPH a, Doli GoswamiMBBS a, M Abdul WahedBA a, Prof Marie Diener-WestPhD c, Abu SG FaruqueMPH a and Prof Robert E BlackMPH b

    Summary
    Introduction
    Methods
    Results
    Discussion
    References

    Summary

    BackgroundPneumonia 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.

    Methods1665 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.

    Findings34 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.

    Interpretation70 mg of zinc weekly reduces pneumonia and mortality in young children. However, compliance with weekly intake might be problematic outside a research programme.
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    Introduction

    Globally, from 2000 to 2003, pneumonia caused about 2·0 million (19%) of 10·6 million deaths among children younger than 5 years,1 more than 90% of which occurred in less developed countries.2 Pneumonia prevention strategies typically rely on vaccines and are complicated by inadequate efficacy of non-conjugate vaccines for children younger than 2 years,3 the high cost of effective protein-conjugate vaccines, and incomplete serotype vaccine coverage for Streptococcus pneumoniae. An effective alternative is needed for very young children in high-risk populations.
    Mortality from diarrhoea has decreased from 4·5 million per year in 1979,4 mostly as a result of the introduction of oral rehydration therapy. However, diarrhoea causes 1·9 million (18%) deaths among children younger than 5 years,1 and about 20% of young child deaths in Bangladesh.5 Zinc deficiency is common where pneumonia and diarrhoea are common,6 and daily regimens of zinc prevent and treat pneumonia7–10 and diarrhoea8,11–13 and reduce child mortality.6,13,14
    Research into zinc for the prevention of pneumonia and diarrhoea has mostly included children older than 2 years,7–10,13,15 although younger children might be more vulnerable,2 particularly to pneumonia. In most of these studies zinc has been given daily,7–10,13,15 which can be impractical. Pneumonia and diarrhoea are the first and second leading causes of patient visits, respectively, to our urban field clinic in Kamalapur, Bangladesh.
    We studied whether a large weekly dose of zinc (70 mg) would reduce clinical pneumonia, diarrhoea, and other morbidity in children younger than 2 years. We also studied the ponderal and linear-growth effects of this regimen. Because long-term intake of supplemental zinc could affect iron and copper metabolism,16,17 we measured the effects on haemoglobin and serum copper.
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    Methods

    Participants

    We did the study in a poor, urban population: Kamalapur, southeastern Dhaka, Bangladesh. We included children aged 60 days to 12 months at the time of enrolment. We excluded those with known or suspected tuberculosis, chronic respiratory or congenital heart disease, or severe malnutrition requiring hospital admission. Children with suspected tuberculosis were referred to Dhaka's hospital for tuberculosis.
    The research review committee and ethical review committee of the International Centre for Diarrhoeal Disease Research approved the study. Parents or carers gave informed written consent at enrolment.

    Procedures

    Random assignment to zinc or placebo was done with permuted blocks of variable length between two and eight. Zinc was given orally as a syrup (35 mg zinc acetate per 5 mL). The placebo was non-nutritious and vitamin-free, designed to be identical to the zinc syrup in colour, odour, and taste. ACME Laboratories, Ltd (Dhamrai, Dhaka, Bangladesh) prepared, labelled, and masked the identity of both preparations.
    Field research assistants (FRAs) did active surveillance, visiting every enrolled child at home once weekly. They collected information about specific signs of respiratory disease and diarrhoea for each day since the last visit by use of a pre-coded calendar questionnaire standardised during training before deployment. To avoid bias, FRAs used a timer to count every child's respiratory rate for 60 s, irrespective of reported symptoms, at each visit. If the respiratory rate was above 50 breaths per min, they counted a second time and calculated the mean. FRAs also inspected any diarrhoeal-stool samples. The FRA recorded all reported and observed data on the questionnaire, referring children to the clinic for any observed or reported findings that were suggestive of respiratory disease or diarrhoea.
    At the end of each visit, the FRA observed the child take the syrup, and waited at least 5 min before leaving. Compliance required intake of two teaspoons of syrup (10 mL). If the child vomited within 5 min, the syrup was given again once.
    At the clinic, medical officers and nurses involved in this study assessed patients. Nurses collected vital signs (respiratory rate, axillary temperature by mercury thermometer, pulse rate, and blood pressure). Fever was defined as an axillary temperature of at least 38°C. During the assessment, clothing was removed from the child's torso to assess chest indrawing and cyanosis. The medical officers auscultated the chest by stethoscope. Danger signs, such as chest indrawing, cyanosis, lethargy, or inability to drink, were recorded. Inability to drink was assessed by having the mother offer the child oral rehydration solution. Children who were too lethargic to drink or unable to swallow were recorded as “unable to drink”. Dehydration was assessed with WHO criteria.18 The medical officer diagnosed pneumonia if crepitations were heard on inspiration with a respiratory rate greater than 50 breaths per minute; severe pneumonia was diagnosed if there was also chest indrawing, or at least one other danger sign. Children with wheezing or rhonchi with crepitations were also diagnosed with pneumonia. Children who had only wheezing or rhonchi without crepitations were not diagnosed with pneumonia, but with reactive airways disease or bronchiolitis (reversible lower airway obstruction).
    Diarrhoea was diagnosed if the child had three or more watery stools or one bloody stool in a 24-h period. A stool sample was required for diagnosis.
    Patients with purulent ear discharge were diagnosed with suppurative otitis media. Upper respiratory tract infection consisted of cough, rhinorrhoea, and fever without tachypnoea (ie, no sign of lower airway obstruction).
    We treated pneumonia with co-trimoxazole (10 mg/kg trimethoprim, twice daily for 5 days). Children with WHO-defined pneumonia18 were also treated, although their illness was not counted unless it met study criteria. Children on antibiotics were assessed within 72 h of starting treatment; those who did not improve (ie, the respiratory rate did not change by more than 5 breaths per min from baseline) were switched to treatment with amoxicillin (40 mg/kg, three times daily for 5 days). If oral treatment failed, or if they had severe pneumonia, we referred them to hospital for parenteral treatment (ceftriaxone 75 mg/kg intramuscularly per day). Children with only expiratory wheezes or rhonchi were managed with salbutamol syrup (0·3 mg/kg, three times daily), or referred to hospital for danger signs. Patients with blood in their diarrhoea were treated with co-trimoxazole for 5 days, or if ineffective, with nalidixic acid. Children with “some” dehydration were treated according to WHO guidelines with oral rehydration solution,18 and those with “severe” dehydration were admitted to hospital.
    FRAs followed up patients who were home and taking antibiotics within 72 h to document compliance (asking the caretaker to explain the dosing regimen, and checking the remaining volume) and the end of the illness episode. The end of an episode of respiratory illness was defined as 7 disease-free days after the last day of illness; for diarrhoea, the disease-free interval was 3 days. “Disease-free” for pneumonia meant a respiratory rate less than 50 breaths per min without danger signs or fever, for suppurative otitis media no ear discharge, and for diarrhoea no watery or bloody stool.
    Medical officers collected blood (3 mL) at baseline before zinc or placebo was given and again during the 10th month. The final sample was taken at 10 months rather than 12 months to minimise attrition. Trace-element-free vacutainers and storage tubes were used to measure serum zinc, haemoglobin, and copper concentrations. Serum was separated at the International Centre for Diarrhoeal Disease Research, Dhaka, within 3 h of collection. Serum samples (150 mL) in polypropylene tubes were diluted 1/12 with HNO3 and Brij35, a non-ionic detergent. Flame atomic absorption spectrophotometry was used to assess zinc and copper concentration, as previously described.19
    Similarly, measurements taken at baseline and at 10 months assessed growth; the mean of two consecutive measures of nude bodyweight and length were recorded. These measurements were analysed for only a small sample of the study population (329 in the zinc group and 309 in the placebo group) primarily because of logistical constraints of getting well children to clinic. We estimated that if there was a 10% difference in growth we would need 190 children per group if the SD were about 0·3 (a third of the growth velocity). Thus, we recruited 300 per group plus 20% for attrition. Power is thus 94·8%. Measurements were compared with population data at the National Center for Health Statistics.20

    Statistical analysis

    We used the clinical pneumonia incidence from Matlab, a rural surveillance site, to calculate sample size because urban data were not available. Among children age 2–59 months the rate was 0·2 episodes per child per year. To detect a 30% decrease in the incidence of pneumonia, with a type 1 error of 5%, a type 2 error of 20%, and 20% attrition, we needed 776 child-years of observation per group. Diarrhoea rates of 4·6 episodes per child per year were used. Allowing for 20% attrition, a type 1 error of 5%, and a type 2 error of 10%, we needed 163 child-years per group.
    Statistical analysis was done with StataSE Release 8·2.21 Each child's observation period started from the first FRA visit at which syrup was given and continued for 12 months. If a child was absent when the FRA visited, that week was removed from analysis owing to the absence of morbidity data. If the child was present, irrespective of zinc compliance, the week was included. Children who withdrew or emigrated were right-censored (ie, data were included in analysis up to the point of withdrawal, even though they did not complete the observation period) after the last visit date, and earlier data were kept for analysis. We did exit interviews for all withdrawals to identify possible biases, and for those who died we did verbal autopsies between 2 and 6 weeks after death.
    Disease incidence was the number of episodes divided by child-years of observation. Because outcomes were infrequent, we compared incidence rates by Poisson regression for relative risk with 95% CIs, controlling for clustering (multiple observations) within groups. Analysis of variance was used to compare mean serum zinc, copper, haemoglobin, and white-blood-cell concentrations, and growth before and after supplementation. For dichotomous variables, p values were calculated with a two-tailed Fisher's exact test.

    Role of the funding source

    The funding sources had no role in the study design, data collection, data analysis, interpretation of results, or decision to publish this research. The corresponding author had full access to the data and the final responsibility for the decision to submit for publication.
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    Results

    Between April 21, 1999, and August 29, 2000, 1655 children age 2–12 months were enrolled; 34 of these had tuberculosis and were excluded, leaving 1621 children to be randomised. 809 children were randomly assigned zinc, and 812 placebo (figure). 147 (9·1%) children withdrew from the study, and their demographic and illness characteristics were not different from those who completed it. Withdrawal from both groups was most commonly attributed to the child's reaction to the taste of the syrup, which sometimes resulted in regurgitation. Most of those who withdrew were young, primarily breastfed infants. The highest proportion (37·1%) of withdrawals for both groups occurred at age 2 months, with 77·1% younger than 6 months. The mean length of time in the study before withdrawal was 55 days, with no differences between groups (p=0·392). There was no difference between the number of children under age 6 months in the zinc (51·1%) and the placebo (47·0%) groups who completed the study (p=0·12).


    Click to enlarge image


    Figure. Trial profile


    There were no significant demographic differences between groups at baseline (table 1), except for a slightly higher proportion of boys in the zinc group. 16 children (2·1%) in the placebo group and 29 (4·1%) in the zinc group received less than 80% of the doses; mean proportion of doses received by each group was not different (94·3% in the placebo group compared with 93·2% in the zinc group; p=0·10). Before treatment, there were no differences between the groups in concentrations of serum zinc, haemoglobin, copper, or white blood cells, or in anthropometry; however, after 10 months of treatment, the zinc group had significantly greater serum-zinc concentrations than the placebo group (table 2). By contrast there were no differences between the groups at 10 months for haemoglobin, copper, white blood cells, or weight gain. In addition, the groups' white-blood-cell differential count did not differ at baseline and 10 months (data not shown).

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    Table 1. Demographic characteristics of children at enrolment



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    Table 2. Clinical and laboratory results before treatment and after 10 months of treatment


    Children given zinc grew a mean of 0·9 cm taller during 10 months than those given placebo (table 2). Mean monthly linear-growth velocity was higher (p=0·003) in the zinc group (1·4 cm, SD 0·4) than in the placebo group (1·3 cm, SD 0·3).
    Follow-up per child was for a mean duration of 324 days (SD 97) for the zinc group and 320 days (78) for the placebo group (p=0·332). The overall incidence of pneumonia that met our study definitions in the placebo group was 0·56 episodes per child-year. The power for the observed sample size was thus 84·9% for pneumonia. There were significantly fewer incidents of pneumonia in the zinc group than in the placebo group (table 3). Fewer children in the treatment group (274, 38·8%) than in the control group (394, 51·3%) contracted pneumonia more than once (p<0·0001). There was a small but significant difference between groups in the incidence of diarrhoea; 681 (96·4%) in the zinc group and 743 (96·7%) in the placebo group had more than one episode (p=0·775). All other illnesses diagnosed by medical officers were significantly less frequent in the zinc group than the placebo group (table 3). The preventive effects of zinc increased with disease severity: zinc reduced upper respiratory infections by 8%, reactive airways disease or bronchiolitis by 12%, pneumonia by 17%, severe pneumonia by 49%, and pneumonia mortality by 100%. Adjustment of the Poisson model for the proportion of doses received (compliance) had no effect on outcome.

    Click to view table


    Table 3. Number of medical officer diagnoses in the clinic


    Mortality was significantly lower for the zinc group than the placebo group. Although ten of 14 deaths in the placebo group were pneumonia related (table 4), there were no pneumonia-related deaths in the zinc group.

    Click to view table


    Table 4. Cause of death


    Children younger than 6 months who took zinc had less pneumonia (relative risk 0·76, 0·22–2·29), severe pneumonia (0·63, 0·06–1·44), and diarrhoea (0·90, 0·63–1·28) than those who took the placebo. Children younger than 12 months also had less pneumonia (0·85, 0·62–1·17) and diarrhoea (0·95, 0·86–1·06) but not severe pneumonia (1·01, 0·39–2·56).
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    Discussion

    Zinc substantially reduced the incidence of pneumonia and other upper and lower respiratory tract disease, and modestly reduced that of diarrhoea. However, the effect of zinc on mortality was strong. This finding in a study of young children in urban Bangladesh extends those of earlier studies, which found a 68% decrease in mortality in full-term infants who were small for their gestational age and treated with daily zinc in India,14 and a 50% reduction in mortality in children younger than 5 years in rural Bangladesh for daily zinc used for 14 days to treat diarrhoea.13 The effect on diarrhoea is modest compared with other reports,8,13 but supports the preventive benefit described in management recommendations for acute diarrhoea.4 Daily zinc doses might have had more effect on diarrhoea.
    We found a small but significant effect on linear growth, but not ponderal growth, which supports the results of meta-analyses.22,23
    Five factors are relevant to the use of zinc for respiratory infection control: age, disease severity, disease aetiology, safety of long-term intake of zinc, and dosing interval. First, regarding age, the study showed that zinc substantially reduces illness among children aged 2–24 months; these children are vulnerable and ineligible for the non-conjugate vaccine. Rates of reduction for age-specific subgroups were probably not significant because of inadequate numbers studied.
    Second, the incidence of clinically confirmed pneumonia, severe pneumonia, and other respiratory illnesses was lower in the treatment group. Zinc might be progressively protective against more invasive and severe disease, leading to an 85% reduction in overall mortality, primarily owing to pneumonia. Zinc supplementation was associated with a reduction in otitis-media incidence. Otitis media is a common paediatric infection, particularly in less developed countries,24,25 with important sequelae.26–29 Our findings suggest that zinc could result in substantial treatment-cost savings, reduction in hearing-related disabilities, and improved quality of life.
    Third, although we have no aetiological data, bronchiolitis and upper respiratory tract infection are likely to be viral, whereas most cases of severe pneumonia and pneumonia-related deaths are more likely to be bacterial; the incidence of all these disorders was reduced by zinc. Zinc could have a substantial effect, independent of aetiology, but may have larger effects on more severe (possibly bacterial) disease.
    Fourth, zinc was found to be safe in young children at a weekly dose of 70 mg. Apart from vomiting in a small subpopulation, which may have caused early dropouts, there has been concern that long-term zinc supplementation may interfere with iron and copper absorption. If this were the case we would expect to see decreased serum haemoglobin, copper, and white blood cells, none of which we observed.
    Fifth, our findings with a weekly dose are an important step forward in our thinking about, and programmatic use of, zinc. Daily regimens, though promising, might not be practical for long-term use. This study suggests that weekly dosing is beneficial and cost effective, even with reduced compliance. A previous study found a 40% reduction in the rate of acute lower respiratory infection in malnourished children receiving both iron and zinc (20 mg once weekly);30 these results could be more modest than ours because of the dose. Dosing intervals that are even longer than weekly might be protective against certain diseases, because 20 mg zinc for 2 weeks significantly reduced subsequent diarrhoea up to 3 months in children younger than 59 months.13 Exclusive breastfeeding is encouraged for the first 4–6 months of life,18 but is uncommon in this age-group.31 Thus, we did not attempt to address the effect of breastfeeding on zinc.
    A limitation of our study is that more children in the zinc group than in the control group withdrew. We do not believe that these withdrawals affect our results for several reasons. First, they occurred early, typically within 2 months of randomisation. By withdrawing early their risk would be less likely affected by treatment assignment. Early dropouts in both groups should have had similar risk profiles. Second, they did not significantly change the proportion of young children in each group. Third, there was less than 15% attrition from either group and less than 10% attrition overall, well below the projected rate of 20%. Finally, blinding of FRAs was not affected because a proportion of children in both zinc and placebo groups reacted to the taste such that the treatment could not be distinguished. The astringent taste of the concentrated zinc syrup, and attempts to duplicate the taste in the placebo, probably contributed to regurgitation among young children, and their withdrawal. Present strategies for giving zinc orally are dispersible tablets, which seem to be well tolerated.
    Our findings suggest that among young children zinc has a substantial protective effect against pneumonia, severe pneumonia, suppurative otitis media, and most importantly, mortality secondary to pneumonia. Treatment with zinc had a modest effect on diarrhoea and growth, and no measurable adverse effects on copper or haemoglobin. Future studies should assess the optimum dose and length of protection after periodic zinc supplementation.
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    Conflict of interest statement
    We declare that we have no conflict of interest.
    Contributors
    WAB was the principal investigator and provided primary conception, design, execution, data analysis, and preparation of the paper. MS was the co-principal investigator, and was involved in the design, execution, data analysis, and paper preparation. AN oversaw the daily execution of the study, data collection and entry, and the field staff. DG was the chief medical officer responsible for clinical protocol adherence. MAW did the assays of zinc and copper. MD-W assisted with data analysis and paper preparation. ASGF assisted with study conception, design, training, and completion, and helped to prepare the paper. REB was the senior team member and contributed to the design, interim discussions of the research progress, data analysis, and paper preparation.

    Acknowledgments
    The research was funded by Johns Hopkins Family Health and Child Survival Cooperative Agreement with the US Agency for International Development, the Swiss Development Corporation, and a cooperative agreement between the US Agency for International Development (HRN-A-00-96-90005-00) and core donors to the Centre for Health and Population Research. We are grateful to ACME Laboratories Ltd for preparation of the zinc and placebo syrups.
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    <!--start tail=--> References

    1. Bryce J, Boschi-Pinto C, Shibuya K, Black RE. WHO estimates of the causes of death in children. Lancet 2005; 365: 1147-1152. Abstract | Full Text | PDF (611 KB) | CrossRef
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    3. Ledwith M. Pneumococcal conjugate vaccine. Curr Opin Pediatr 2001; 13: 70-74. MEDLINE
    4. United Nations Childrens Fund/World Health Organization. In: WHO/UNICEF joint statement: clinical management of acute diarrhoea. New York/Geneva: UNICEF/WHO, 2004: 1-8.
    5. Baqui AH, Black RE, Arifeen SE, Hill K, Mitra SN, al Sabir A. Causes of childhood deaths in Bangladesh: results of a nationwide verbal autopsy study. Bull World Health Organ 1998; 76: 161-171. MEDLINE
    6. Black RE, Sazawal S. Zinc and childhood infectious disease morbidity and mortality. Br J Nutr 2001; 85 (suppl 2): S125-S129.
    7. Bhandari N, Bahl R, Taneja S, et al. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum. BMJ 2002; 324: 1358. CrossRef
    8. Bhutta ZA, Black RE, Brown KH, et al. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. J Pediatr 1999; 135: 689-697. Abstract | Full Text | PDF (90 KB) | MEDLINE | CrossRef
    9. Ninh NX, Thissen JP, Collette L, Gerard G, Khoi HH, Ketelslegers JM. Zinc supplementation increases growth and circulating insulin-like growth factor I (IGF-I) in growth-retarded Vietnamese children. Am J Clin Nutr 1996; 63: 514-519. MEDLINE
    10. Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatrics 1998; 102: 1-5. MEDLINE | CrossRef
    11. Roy SK, Tomkins AM, Akramuzzaman SM, et al. Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea. Arch Dis Child 1997; 77: 196-200.
    12. Bhutta ZA, Bird SM, Black RE, et al. Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials. Am J Clin Nutr 2000; 72: 1516-1522. MEDLINE
    13. Baqui AH, Black RE, Arifeen SE, et al. Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ 2002; 325: 1059. CrossRef
    14. Sazawal S, Black RE, Menon VP, et al. Zinc supplementation in infants born small for gestational age reduces mortality: a prospective, randomized, controlled trial. Pediatrics 2001; 108: 1280-1286. CrossRef
    15. Rosado JL, Allen LH, Lopez P. The effect of zinc and/or iron supplementation on morbidity: a double blind, randomised community trial in preschoolers. FASEB J 1995; 9: 157(abstr).
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    18. WHO/UNICEF. In: Management of the child with a serious infection or severe malnutrition: guidelines for care at the first-referral level in developing countries. Geneva: Department of Child and Adolescent Health and Development UNICEF, 2000: 162.
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    22. Brown KH, Peerson JM, Allen LH. Effect of zinc supplementation on children's growth: a meta-analysis of intervention trials. Bibl Nutr Dieta 1998; 54: 76-83.
    23. Brown KH, Peerson JM, Rivera J, Allen LH. Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2002; 75: 1062-1071. MEDLINE
    24. Berman S. Otitis media in developing countries. Pediatrics 1995; 96: 126-131. MEDLINE
    25. Hatcher J, Smith A, Mackenzie I, et al. A prevalence study of ear problems in school children in Kiambu district, Kenya, May 1992. Int J Pediatr Otorhinolaryngol 1995; 33: 197-205. Abstract | Abstract + References | PDF (652 KB) | MEDLINE | CrossRef
    26. Attallah MS, al-Essa A. Hearing results in tympanoplasty in Riyadh. Otolaryngol Pol 1996; 50: 145-151. MEDLINE
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    28. Smith A, Hatcher J. Preventing deafness in Africa's children. Afr Health 1992; 15: 33-35. MEDLINE
    29. Smith AW, Hatcher J, Mackenzie IJ, et al. Randomised controlled trial of treatment of chronic suppurative otitis media in Kenyan schoolchildren. Lancet 1996; 348: 1128-1133. Abstract | Full Text | PDF (53 KB) | MEDLINE | CrossRef
    30. Baqui AH, Zaman K, Persson LA, et al. Simultaneous weekly supplementation of iron and zinc is associated with lower morbidity due to diarrhea and acute lower respiratory infection in Bangladeshi infants. J Nutr 2003; 133: 4150-4157. MEDLINE
    31. Brooks WA, Santosham M, Roy SK, et al. Efficacy of zinc in young infants with acute watery diarrhoea. Am J Clin Nutr (in press)
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    <!--end tail-->Affiliations
    "May the long time sun
    Shine upon you,
    All love surround you,
    And the pure light within you
    Guide your way on."

    "Where your talents and the needs of the world cross, lies your calling."
    Aristotle

    “In a gentle way, you can shake the world.”
    Mohandas Gandhi

    Be the light that is within.

  • #2
    Re: Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in chil

    .....Zinc substantially reduced the incidence of pneumonia and other upper and lower respiratory tract disease, and modestly reduced that of diarrhoea. However, the effect of zinc on mortality was strong. This finding in a study of young children in urban Bangladesh extends those of earlier studies, which found a 68% decrease in mortality in full-term infants who were small for their gestational age and treated with daily zinc in India,14 and a 50% reduction in mortality in children younger than 5 years in rural Bangladesh for daily zinc used for 14 days to treat diarrhoea.....
    "May the long time sun
    Shine upon you,
    All love surround you,
    And the pure light within you
    Guide your way on."

    "Where your talents and the needs of the world cross, lies your calling."
    Aristotle

    “In a gentle way, you can shake the world.”
    Mohandas Gandhi

    Be the light that is within.

    Comment


    • #3
      Figure

      "May the long time sun
      Shine upon you,
      All love surround you,
      And the pure light within you
      Guide your way on."

      "Where your talents and the needs of the world cross, lies your calling."
      Aristotle

      “In a gentle way, you can shake the world.”
      Mohandas Gandhi

      Be the light that is within.

      Comment


      • #4
        Table 1

        "May the long time sun
        Shine upon you,
        All love surround you,
        And the pure light within you
        Guide your way on."

        "Where your talents and the needs of the world cross, lies your calling."
        Aristotle

        “In a gentle way, you can shake the world.”
        Mohandas Gandhi

        Be the light that is within.

        Comment


        • #5
          Table 2

          "May the long time sun
          Shine upon you,
          All love surround you,
          And the pure light within you
          Guide your way on."

          "Where your talents and the needs of the world cross, lies your calling."
          Aristotle

          “In a gentle way, you can shake the world.”
          Mohandas Gandhi

          Be the light that is within.

          Comment


          • #6
            Table 3

            "May the long time sun
            Shine upon you,
            All love surround you,
            And the pure light within you
            Guide your way on."

            "Where your talents and the needs of the world cross, lies your calling."
            Aristotle

            “In a gentle way, you can shake the world.”
            Mohandas Gandhi

            Be the light that is within.

            Comment


            • #7
              Table 4

              "May the long time sun
              Shine upon you,
              All love surround you,
              And the pure light within you
              Guide your way on."

              "Where your talents and the needs of the world cross, lies your calling."
              Aristotle

              “In a gentle way, you can shake the world.”
              Mohandas Gandhi

              Be the light that is within.

              Comment


              • #8
                Re: Table 4

                good catch, F1, thanks!
                Upon this gifted age, in its dark hour,
                Rains from the sky a meteoric shower
                Of facts....They lie unquestioned, uncombined.
                Wisdom enough to leech us of our ill
                Is daily spun, but there exists no loom
                To weave it into fabric..
                Edna St. Vincent Millay "Huntsman, What Quarry"
                All my posts to this forum are for fair use and educational purposes only.

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