Results of the search
Through the search strategy we identified six trials that fulfilled the eligibility criteria of inclusion.
We included six trials in the pooled analysis. However, we included Sazawal and Bhandari twice in the analysis, because the investigators in the trials reported ALRI in two different ways.
The trial from Lima, Peru, Penny 2004, was a randomised, double-masked, placebo-controlled community-based trial. Children aged six to 36 months with diarrhoea for more than 14 days were randomly assigned and were given zinc daily for two weeks. Characteristics of the children at baseline was similar except for sex and length-for-age Z scores.
Brooks 2005 was also conducted in a poor population in an urban setting of Dhaka, Bangladesh. The study included 1665 children aged 60 days to 12 months who were randomly allocated to the zinc (70 mg) or placebo orally once weekly group. In this study, children were assessed every week by field research assistants at their homes. On finding children with suggestive respiratory disease or diarrhoea, children were referred to clinics where medical officers and nurses were involved in their assessment and diagnosis was made based on the WHO criteria. At the outset, no significant demographic differences were found between the two groups, except for a slightly higher proportion of boys in the zinc group.
The trial from the urban slums of New Delhi, India (Bhandari 2002a; Bhandari 2002b) included 2482 children aged six to 30 months. These children were given daily elemental zinc, 10 mg to infants and 20 mg to older children, or placebo for four months. Both these groups also received a single massive dose of vitamin A (100,000 IU for infants and 200,000 IU for older children) at enrolment. Both these groups were comparable in age, anthropometry, child feeding practices, morbidity in the previous 24 hours, socioeconomic characteristics, and plasma zinc concentration.
The trial from the KwaZulu-Natal Province of South Africa by Luabeya 2007 included children four to six months of age and was divided into two intervention arms and one control arm. In the control arm, children were given vitamin A alone; in the first intervention arm they were given vitamin A plus zinc; and in the second intervention arm they were given vitamin A, zinc and multiple micronutrients. Children in this study were given supplements until 24 months of age, thus each child was given with supplement for the period of 18 to 20 months. In the study sample 32 children were born with HIV positive status, while 154 were born without HIV infection to HIV positive mothers. Baseline characteristics of the treatment groups in the three cohorts did not significantly differ with the exception of weight-for-length.
The trial conducted by Sazwal et al (Sazawal 1998a; Sazawal 1998b) was in a low socioeconomic population of urban India. It was a double-blind controlled trial in which 609 children (zinc, n = 298; control, n = 311) aged six to 35 months were recruited and assigned to supplementation and placebo groups. The treatment group received 10 mg elemental zinc and the placebo group a substance similar in colour and taste. The fixed dose of 5 mL per child was given daily for six months to the all enrolled children, while it was increased to 10 mL in the case of diarrhoeal illnesses. The baseline characteristics of children included into the two groups were similar for age, sex, nutritional status, and baseline plasma zinc.
The trial from South Africa by Bobat et al (Bobat 2005) was a randomised, double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg. In this trial 96 children aged from six to 60 months with HIV 1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for six months. Baseline characteristics of included children assigned into the two treatment groups were similar.
Please refer to the Characteristics of included studies table for more details.
We excluded 19 studies as they did not satisfy the inclusion criteria for this review. Five studies included children outside the age limits of our review criteria (Lira 1998; Osendarp 2002; Sur 2003; Taneja 2009; Tielsch 2007). We excluded another five studies as they supplemented their participants for less than three months (Baqui 2002; Castillo-Duran 1987; Rahman 2001; Roy 1999; Sempértegui 1996). We found eight studies that had a case definition for ALRI/pneumonia which was different from what we had reported (Baqui 2003; Long 2006; Lind 2004; Ninh 1996; Reul 1997; Richard 2006; Rosado 1997; Umeta 2000). We excluded one study because the investigators supplemented children by using a fortified drink (Bates 1993).
Please refer to the Characteristics of excluded studies table for more details.