Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months

  • Protocol
  • Intervention



This is the protocol for a review and there is no abstract. The objectives are as follows:

To evaluate the role of zinc supplementation in the prevention of pneumonia in children aged 2 months to 59 months.


Description of the condition

Zinc deficiency is common amongst children in developing countries due to a variety of factors such as low food intake, particularly from animal sources; limited zinc bioavailability from local diets; and loss of zinc during recurrent diarrhoeal illnesses (Bhutta 1999; Black 1998). Zinc deficiency is associated with decreased immunocompetence (Shankar 1998) and increased rates of serious infectious diseases (Bahl 1998; Black 1998). The deficiency is widely recognised as contributing to limited growth of children in both developing and developed countries (Ploysangam 1997).

Acute lower respiratory tract infections (LRIs) are among the leading causes of mortality in children under five years of age (Williams 2002) and account for nearly two million deaths annually, the majority of which occur in developing countries. Pneumonia is the largest cause of mortality, accounting for 18% of all childhood deaths in developing countries (WHO 2003). Interventions that affect mortality due to pneumonia are thus of great importance in any effort to improve childhood survival.

Description of the intervention

The effect of zinc supplementation on infections remains unclear. It is reported to prevent pneumonia (Bhutta 1999) and has also been found to be beneficial in reducing the duration and severity of diarrhoeal episodes in children with acute and persistent diarrhoea (Zinc Group 2000). Trials of zinc supplementation vary with regard to the magnitude of the effect demonstrated and the presence of a differential effect according to sex, age, nutritional status or baseline plasma zinc concentration.

Why it is important to do this review

The aim of this review is to evaluate the role of zinc supplementation in the prevention of pneumonia in children less than five-years old.


To evaluate the role of zinc supplementation in the prevention of pneumonia in children aged 2 months to 59 months.


Criteria for considering studies for this review

Types of studies

All randomised controlled trials evaluating supplementation of zinc for the prevention of pneumonia in children aged less than five-years will be included in this review. Studies that define an episode of pneumonia in the following ways will be considered for inclusion:

  1. reported cough or difficulty in breathing with a respiratory rate above the WHO-defined age-specific values (respiratory rate of 50 breaths per minute or more for children aged 2 to 11 months, or respiratory rate of 40 breaths per minute or more for children aged 12 to 59 months), and either documented fever of above 101 oF or chest in-drawing (WHO 1990);

  2. a diagnosis of pneumonia based on chest examination by a physician; or

  3. a diagnosis of pneumonia based on a chest radiograph.

Trials published in languages other than English will be included after translation into English. Non-randomised (quasi-randomised) trials will be excluded.

Types of participants

Children aged from 2 months to 59 months.

Types of interventions

Oral supplement containing at least the United States recommended daily allowance (RDA) of zinc versus either an oral supplement without zinc or placebo. Supplementation of zinc should be the only difference between the intervention and the control group. Trials in which additional supplements are given will be excluded. The RDA for infants is 5 mg of elemental zinc per day. For children aged from one to five-years it is 10 mg per day (RDA 1989). Trials in which supplements were administered for at least two weeks and outcome surveillance was carried out for at least four weeks will be included in this review

Types of outcome measures

Outcome measures will include the number of new episodes of pneumonia in children less than five-years old and the prevalence (number of days of illness per total days of observation) of pneumonia.

Search methods for identification of studies

Electronic searches

We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, latest issue) which contains the Acute Respiratory Infections Group's specialized register; MEDLINE (1966 to present); EMBASE (1974 to present); and LILACS (all years). The search terms will be combined with the highly sensitive search strategy devised by Dickersin et al (Dickersin 1994) and run in MEDLINE and CENTRAL. The terms will be adapted to search EMBASE and LILACS. The search terms are as follows.

((exp Pneumonia/ ) OR pneumonia OR lower respiratory tract infection$ OR LRTI OR lower respiratory infection$)
(exp Zinc/ OR zinc)
(exp Child/ OR child OR children exp Infant/ OR infant OR infants OR paediatric OR pediatric)

Searching other resources

There will be no language or publication restrictions (published, unpublished, in press, and in progress). We will also search the related conference proceedings for relevant abstracts. We will contact organisations and researchers in the field and pharmaceutical companies for information on unpublished and ongoing trials. We will also check the reference lists of all trials identified by the above methods.

Data collection and analysis

Selection of studies

Eligibility of the trials will be assessed independently by two authors. Authors will select studies as being potentially relevant by screening the titles and the abstracts, if available. If the relevance cannot be ascertained by screening the title and the abstract the full text of the article will be retrieved and reviewed. Authors will retrieve full texts of all potentially relevant articles and assess the eligibility independently by filling out eligibility forms designed in accordance with the specified inclusion criteria. Any disagreements will be resolved by discussion and consensus will be reached. Studies excluded from the review will be displayed in a table along with the reason of exclusion.

Data extraction and management

Two authors will pilot, test and subsequently use a data extraction form to collect data. Both authors will then compare the abstracted data to enable them to correct errors and resolve any disagreements. The form will be used to extract information regarding study setting (for example, country, type of population), dose of zinc and duration used, sample size, length of follow up, randomisation procedure, and outcomes mentioned above. For dichotomous outcomes, we will extract the total number of participants for each group and the number of participants experiencing an event. For continuous outcomes, we will extract the mean, standard deviation (or data required to calculate this) and the total number of participants for each group.

Assessment of risk of bias in included studies

Two authors will independently assess the methodological quality of the selected trials by using methodological quality assessment forms. Quality assessment of the trials will be undertaken using the standard criteria of: allocation concealment using the categories adequate, inadequate and unclear; assessment of the random allocation sequence including randomisation and evaluation of whether it was secure or not; blinding of care givers and outcome assessors divided into categories of yes, no and unclear; information on differential loss to follow up of participants and analysis of participants in their respective randomised groups. Any disagreements between the two authors will be resolved by discussion.

Unit of analysis issues

Data analysis will be undertaken using Review Manager software (RevMan 4.2). Analysis of the outcomes will be based on an intention-to-treat principle. For dichotomous outcomes, we will use the odds ratio (or relative risks); and for continuous outcomes, we will use the weighted mean difference. A sensitivity analysis will be performed for trials of varying methodological quality.

Heterogeneity among the trials will be measured by calculating the I2 statistic and by visual inspection of the forest plots. If I2 exceeds 50% and visual inspection of the forest plots is indicative then heterogeneity will be considered to be substantial and reasons for it will be sought, such as differences in dosage and duration of zinc used, age, supplementation in healthy children against that of children recovering from an episode of illness, pre-intervention zinc level and baseline characteristics of the study population.


The authors wish to thank the following people for commenting on the draft protocol: Anne Lyddiatt, José Luis Ferrero Albert, Robert Black, Sree Nair and George Swingler.

What's new

10 May 2009AmendedContact details updated.


Protocol first published: Issue 2, 2006

25 August 2008AmendedConverted to new review format.

Contributions of authors

Dr Batool A Haider wrote the protocol under the guidance of Dr Zulfiqar A Bhutta.
Mr Ammad Saeed assisted in writing the protocol.

Declarations of interest

Dr Bhutta has been involved in previous studies of zinc supplementation in diarrhoea and was part of the Zinc Investigators Collaborative Group that produced the initial meta-analysis of the preventive and therapeutic benefits of zinc. Dr Bhutta has not, however, been involved in any studies of zinc supplementation in acute respiratory infections.

Sources of support

Internal sources

  • The Aga Khan University, Pakistan.

External sources

  • No sources of support supplied