Zinc as adjunct treatment in infants aged between 7 and 120 days with probable serious bacterial infection: a randomised, double-blind, placebo-controlled trial

Bhatnagar, Shinjini; Wadhwa, Nitya; Aneja, Satinder; Lodha, Rakesh; Kabra, Sushil Kumar; Natchu, Uma Chandra Mouli; Sommerfelt, Halvor; Dutta, A. K.; Chandra, Jagdish; Rath, Bimbadhar; Sharma, Mamta; Sharma, Vinod; Kumari, Mohini; Strand, Tor A.

doi:10.1016/s0140-6736(12)60477-2

Cited by 79 publications

(81 citation statements)

References 20 publications

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“…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: 58%

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: Potential Mechanismmentioning

confidence: 58%

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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“…These results agree with those of previous studies that support an advantage of zinc supplementation early in life. Twelve randomized controlled trials (RCTs) were conducted in subjects aged ,28 d of life (13,15,19,(31)(32)(33)(34)(35)(36)(37)(38)(39). Seven studies had a double-blind design, and most of these trials enrolled slightly preterm or small-for-gestational-age neonates (13,15,19,32,34,37,38).…”

Section: Discussionmentioning

confidence: 99%

“…In a large trial, Sazawal et al (15) showed a reduction in mortality in the first 9 mo of life in an RCT that enrolled full-term small-for-gestational-age infants who received oral zinc supplementation at high doses (5 mg/d). A dose of 10 mg/d was adopted in other studies involving neonates early in life to prevent bacterial infections (18,19). Our study was the first trial to use high doses of zinc in VLBW neonates.…”

Section: Discussionmentioning

confidence: 99%

“…There is a wealth of evidence that zinc, at different doses, has a positive influence on morbidity, mortality, and growth in infants and children (15)(16)(17). Recent trials have suggested that high doses of zinc as co-treatment against infections early in the life (18,19). In this trial we aimed to investigate the efficacy of high zinc doses to reduce morbidity and mortality and promote growth in preterm neonates.…”

Section: Introductionmentioning

confidence: 99%

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Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country

Terrin¹,

Canani²,

Passariello³

et al. 2013

The American Journal of Clinical Nutrition

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Background: Zinc plays a pivotal role in the pathogenesis of many diseases and in body growth. Preterm neonates have high zinc requirements. Objective: The objective of the study was to investigate the efficacy of zinc supplementation in reducing morbidity and mortality in preterm neonates and to promote growth. Design: This was a prospective, double-blind, randomized controlled study of very-low-birth-weight preterm neonates randomly allocated on the seventh day of life to receive (zinc group) or not receive (control group) oral zinc supplementation. Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate of neonates with $1 of the following morbidities: lateonset sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality and body growth. Results: We enrolled 97 neonates in the zinc group and 96 in the control group. Morbidities were significantly lower in the zinc group (26.8% compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was significantly higher in the control group (6.3% compared with 0%; P = 0.014). Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08, 5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 6 5.6 g $ kg 21 $ d 21 ) and control (17.0 6 8.7 g $ kg 21 $ d 21

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“…A recent double-blind, randomized, placebo-controlled trial has confirmed the utility of zinc as an adjunct treatment of young infants with probable severe bacterial infections [53]. Zinc supplementation could have additional benefits in reducing duration and severity of diarrhea [54,55].…”

Section: Back To Realitymentioning

confidence: 97%

Better Drug Therapy for the Children of Africa: Current Impediments to Success and Potential Strategies for Improvement

et al. 2013

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A commentary is presented on the urgent need for a comprehensive effort to improve the practice of pediatric therapeutics in Africa. A call for action is addressed to a variety of practitioners internationally, many of whom possess skills that could be fruitfully applied to the improvement of health outcomes for African children. Successful engagement with the many challenges requires the complementary effort of researchers in basic and clinical pharmacology and toxicology, nurses, pharmacists, physicians, clinical pharmacologists, clinical pharmacists, and political leaders and civil servants. While a comprehensive or systematic review of the relevant literature has not been attempted, the authors have highlighted promising initiatives driven by international agencies and academic networks. Two African perspectives are presented to reinforce the prospect of child health gains that can be achieved through consistent pursuit of optimal therapy for conditions such as respiratory infection, diarrhea, malaria, and HIV/AIDS. There is an imperative for development of north-south and south-south partnerships that will amplify current research efforts and mobilize existing knowledge concerning pediatric drugs. The overall goal is a multidisciplinary commitment to making essential medicines available at the right time, the right place, and in the right formulation for African children from infancy to adolescence.

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Zinc as adjunct treatment in infants aged between 7 and 120 days with probable serious bacterial infection: a randomised, double-blind, placebo-controlled trial

Cited by 79 publications

References 20 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

Zinc supplementation reduces morbidity and mortality in very-low-birth-weight preterm neonates: a hospital-based randomized, placebo-controlled trial in an industrialized country

Better Drug Therapy for the Children of Africa: Current Impediments to Success and Potential Strategies for Improvement

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