Efficacy of zinc given as an adjunct in the treatment of severe and very severe pneumonia in hospitalized children 2–24 mo of age: a randomized, double-blind, placebo-controlled trial

Wadhwa, Nitya; Chandran, Aruna; Aneja, Satinder; Lodha, Rakesh; Kabra, Sushil Kumar; Chaturvedi, Mona K.; Sodhi, Jitender; Fitzwater, Sean; Chandra, Jagdish; Rath, Bimbadhar; Kainth, Udaypal S; Saini, Sharanjot; Black, Robert E.; Santosham, Mathuram; Bhatnagar, Shinjini

doi:10.3945/ajcn.112.052951

Cited by 32 publications

(48 citation statements)

References 21 publications

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“…This promising finding was consistently confirmed by three other RCT (10,11) . However, the study conducted by Wadhwa et al (11) demonstrated that only very severe pneumonia rather than all severe pneumonia could benefit from Zn.…”

Section: Introductionsupporting

confidence: 67%

“…Second, Zn might exacerbate the situation by the increased pro-inflammation while eradicating infection. Consistently, it was reported that Zn could decrease the case fatality and treatment failure without improving clinical recovery (11,35) , indicating that the benefit of Zn might be counteracted or alleviated by the detrimental effect from increased pro-inflammation. Third, the duration of Zn supplementation was relatively short, and the impaired immune response could not be reversed by such a short-time supplementation (17) .…”

Section: Potential Mechanismmentioning

confidence: 57%

“…Furthermore, other meaningful outcomes, such as treatment failure, change of antibiotics, death, vomiting and clinical deterioration, were also analysed. Basnet (2012) Bose (2006) Bose (2006) Bose (2006) Brooks (2004) Brooks (2004) Brooks (2004) Brooks (2004) Valentiner-Branth (2010) Valentiner-Branth (2010) Valentiner-Branth (2010) Wadhwa (2013) Wadhwa (2013) Wadhwa ( (9,11,14,16,17) 5 1414 0 0·41 0·03 −0·07, 0·14 0·53 Time to recovery from chest indrawing (9,14,17) 3 961 14 0·31 −0·07 −0·20, 0·07 0·33 Time to recovery from fever (10,11,14) 3 774 68 0·05 −0·14 −0·40, 0·12 0·29…”

Section: Comparison With Previous Studiesmentioning

confidence: 99%

“…Among the thirteen studies, four were excluded, of which one (23) was an advanced abstract of an included study, two (24,25) focused on children with severe acute lower respiratory tract infection (LRTI) but not severe pneumonia and one (26) used the same data from the included trial. Finally, nine RCT (9)(10)(11)(12)(13)(14)(15)(16)(17) were included.Baseline characteristics and risk of bias …”

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confidence: 99%

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Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials

et al. 2016

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The effect of Zn, as an adjunct to antibiotics, on the treatment of severe pneumonia in young children is still under debate; therefore, we performed a meta-analysis to evaluate the therapeutic role of Zn for severe pneumonia in children younger than 5 years. PubMed, Cochrane library and Embase databases were systematically searched from inception until October 2015 for randomised-controlled trials (RCT) that assessed the effect of Zn as an adjunct to antibiotics for severe pneumonia. Random-effects model was used for calculating the pooled estimates, and intention-to-treat principle was also applied. Nine RCT involving 2926 children were included. Overall, the pooled results showed that adjunct treatment with Zn failed to reduce the time to recovery from severe pneumonia (hazard ratios (HR) = 1·04; 95 % CI 0·90, 1·19; I 2 = 39 %; P = 0·58), hospital length of stay (HR = 1·04; 95 % CI 0·83, 1·33; I 2 = 57 %; P = 0·74), treatment failure (relative risk (RR) = 0·95; 95 % CI 0·79, 1·14; I 2 = 20 %; P = 0·58) or change of antibiotics (RR = 1·07; 95 % CI 0·79, 1·45; I 2 = 44 %; P = 0·67). In addition, continuous outcomes were consistent while meta-analysed with standard mean difference, and all outcomes remained stable in intention-to-treat analysis. No significant differences were observed in the two groups between death rate, adverse events or recovery times of severe pneumonia indicators. Our results suggested that adjunct treatment with Zn failed to benefit young children in the treatment of severe pneumonia. Considering the clinical heterogeneity, baseline characteristics of children, definition of severe pneumonia and Zn supplement way should be taken into consideration in future research. This study was registered at PRESPERO as CRD42015019798.Key words: Children: Meta-analyses: Severe pneumonia: ZincPneumonia is a leading disease and cause of death in children under 5 years in developing countries (1) . It is reported that 14·9 % of 6·3 million deaths of children <5 years old were caused by pneumonia worldwide (2) . With advances in medicine, economy and society, pneumonia with diarrhoea and measles was responsible for half of the reduction in mortality of children under 5 years from 2000 to 2013 (2) . Although great progress was achieved, only a few countries could reach the goal of Millennium Development Goal 4 to reduce under 5 child mortality by two-thirds between 1990 and 2015, and pneumonia is still the leading cause of child mortality (3) . Therefore, intensive effort should be made in the research of pneumonia.Under-nutrition has been reported to be strongly associated with impaired immune response, (4) and it has been proven to be responsible for greater severity of pneumonia, prolonged course of disease and increased mortality of pneumonia (5) .Zn, as an important micro-element, has an essential role in cellular growth and immune defence, and its deficiency is associated with significant increased susceptibility to various infection pathogens (6)(7)(8) . In a randomised-controlled trial (RCT...

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Section: Introductionsupporting

confidence: 67%

Section: Potential Mechanismmentioning

confidence: 57%

Section: Comparison With Previous Studiesmentioning

confidence: 99%

mentioning

confidence: 99%

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Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials

et al. 2016

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“…The difference between both groups was highly significant (P<0.05) But Wadhwa et al found that zinc therapy is given or placebo is given, the death rate will be equal i.e., 1.5% with either method [25].…”

Section: Discussionmentioning

confidence: 99%

Comparing the Effects of Zinc Supplementation as Adjunct to the Conventional Therapy and Placebo on Morbidity in Children with Pneumonia Between Ages 1 Year to 5 Years

Singh¹,

Sultan²

2017

J Pediatr Care

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Background: Pneumonia is one of the leading causes of morbidity and mortality in children younger than 5 years of age. Treatments are available for timely management of pneumonia but mortality is still high in developing countries like Pakistan. Zinc may have an important protective role in cases of childhood pneumonia and can help in reducing potential complications of pneumonia and can also help to reduce the incidence of mortality in children less than five years of age. So we conducted this study to find the therapeutic role of zinc as an adjunct to standard therapy for pneumonia in comparison to placebo.

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Zinc supplements for preventing otitis media

Gulani

Sachdev

2014

Cochrane Database of Systematic Reviews

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Efficacy of zinc given as an adjunct in the treatment of severe and very severe pneumonia in hospitalized children 2–24 mo of age: a randomized, double-blind, placebo-controlled trial

Cited by 32 publications

References 21 publications

Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials

Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials

Comparing the Effects of Zinc Supplementation as Adjunct to the Conventional Therapy and Placebo on Morbidity in Children with Pneumonia Between Ages 1 Year to 5 Years

Zinc supplements for preventing otitis media

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