- Evan Mayo-Wilson, departmental lecturer1,
- Aamer Imdad, senior research officer2,
- Kurt Herzer, Marshall scholar1,
- Mohammad Yawar Yakoob, senior research officer2,
- Zulfiqar A Bhutta, Noordin Noormahomed Sheriff endowed professor and founding chair2
- 1Centre for Evidence-Based Intervention, Department of Social Policy and Intervention, University of Oxford, Barnett House, Oxford OX1 2ER, UK
- 2Division of Women and Child Health, Aga Khan University Hospital, Stadium Road, PO Box 3500, 74800 Karachi, Pakistan
- Correspondence to: Z A Bhutta
- Accepted 7 July 2011
Objective To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years.
Design Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects.
Data sources Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status.
Eligibility criteria for selecting studies Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or β carotene were excluded.
Results 43 trials with about 215 633 children were included. Seventeen trials including 194 483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19).
Conclusions Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other sources are available, vitamin A supplements should be given to all children at risk of deficiency, particularly in low and middle income countries.
We are grateful to the Cochrane Collaboration for their assistance in preparing this review. We particularly thank the Cochrane Developmental Psychosocial and Learning Problems Group, including Jo Abbott, Chris Champion, and Laura MacDonald. Margaret Anderson developed the search strategy and Geraldine Macdonald edited the review. We thank the Cochrane Editorial Unit, particularly Toby Lasserson, Rachel Murphy, and Karla Soares-Weiser for extracting data; we thank David Tovey and Harriet MacLehose for advice and for helping to manage the project. We are grateful to Toby Lasserson for the table summarising of findings. Henry Ebron from DistillerSR provided assistance managing the data. We thank Julian Higgins and the Cochrane Methods Group for statistical advice and assistance. Anonymous peer reviewers offered helpful feedback on the protocol and the review, for which we are grateful.
Contributors: All authors contributed to the planning, conduct, and reporting of this work, and to writing the abstract; specifically, the background (AI, EM-W), methods (EM-W, AI, KH), literature search (KH, AI, MYY), data extraction (EM-W, AI, KH, MYY), tables (AI, EM-W, MYY), data analysis (EM-W, KH), results (EM-W, KH), discussion (EM-W, AI, KH), and overall supervision (ZAB). In addition to the authors Margaret Anderson developed the search strategy. Toby Lasserson, Rachel Murphy, and Karla Soares-Weiser extracted data. Toby Lasserson made the summary of findings table. Julian Higgins provided statistical advice and calculated intracluster correlation coefficient values. ZAB is guarantor.
Funding: The preparation of this review was funded by the Department of Nutrition for Health and Development, WHO, Switzerland. EMW and KH were supported by the University of Oxford’s department of social policy and intervention and the centre for evidence-based intervention. KH received funding from a Marshall scholarship. AI, MYY, and ZAB were supported by Aga Khan University, Karachi, Pakistan.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: Not required.
Data sharing: Detailed tables and effects for each study are available from our Cochrane Review (www.cochrane.org).
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