Vitamin A May Reduce Deaths From Measles and Diarrhea in Children

Laurie Barclay, MD

December 08, 2010

December 8, 2010 — Giving vitamin A capsules to children aged 6 months to 5 years may reduce deaths and incidence of measles and diarrhea, according to the results of a systematic review reported online December 8 in the Cochrane Database of Systematic Reviews.

"Giving vitamin A is associated with a reduction in the incidence of diarrhoea and measles, as well as the number of child deaths due to these diseases," said senior author Zulfiqar A. Bhutta, chairman of the Division of Women and Child Health at Aga Khan University in Karachi, Pakistan, in a news release. "However, the effects of supplementation on disease pathways are not well understood, so this could be a focus for further studies."

The reviewers note that vitamin A deficiency (VAD), which affects 190 million children younger than 5 years, causes a significant public health burden in low and middle income countries, with many adverse sequelae including death. The goal of this review was to determine the impact of vitamin A supplementation (VAS) in children aged 6 months to 5 years on prevention of death and morbidity.

To identify randomized controlled trials and clusters of these trials studying the effect of synthetic VAS in community-dwelling children aged 6 months to 5 years, the reviewers searched the Cochrane Central Register of Controlled Trials (CENTRAL 2010 Issue 2), MEDLINE (1950 to AprilWeek 2 2010), EMBASE (1980 to 2010 Week 16), Global Health (1973 to March 2010), Latin American and Caribbean Health Sciences (LILACS), the metaRegister of Controlled Trials, and the African Index Medicus (27 April 2010). Trials enrolling hospitalized children or those with disease or infection were excluded, as were trials looking at the effects of food fortification, dietary intake of vitamin A-rich foods, or beta-carotene supplementation.

Two review authors independently determined which studies would be included, with disagreements resolved by discussion. Data were double abstracted, and meta-analyses were carried out for all-cause and cause-specific mortality, disease, vision, adverse effects, and other outcomes.

Among 43 included trials enrolling a total of 215,633 children, a meta-analysis for all-cause mortality was performed in 17 trials enrolling a total of 194,795 children. At follow-up, there were a total of 3536 deaths in both groups. Compared with control groups, vitamin A-supplemented groups had a 24% observed reduction in the risk of all-cause mortality (relative risk [RR], 0.76; 95% confidence interval [CI], 0.69 - 0.83).

Among 7 trials reporting mortality from diarrhea, there was a 28% overall reduction for VAS (RR, 0.72; 95% CI, 0.57 - 0.91). Cause-specific mortality from measles, respiratory tract disease, and meningitis were not significantly affected by VAS. Although VAS was associated with a lower incidence of diarrhea (RR, 0.85; 95% CI, 0.82 - 0.87) and measles morbidity (RR, 0.50; 95% CI, 0.37 - 0.67), there was no significant impact on respiratory tract disease incidence or hospitalizations for diarrhea or pneumonia. Within the first 48 hours of VAS, the risk for vomiting was increased (RR, 2.75; 95% CI, 1.81 - 4.19).

"VAS is effective in reducing all-cause mortality by about 24% compared to no treatment," the review authors write. "In our opinion, given the evidence that VAS causes considerable reduction in child mortality, further placebo-controlled trials of VAS in children between 6 months and 5 years of age are not required. There is a need for further studies comparing different doses and delivery mechanisms (for example, fortification)."

Limitations of this review include some evidence of small-study bias for secondary outcomes and heterogeneity among included trials.

"Fortification, dietary diversification, food distribution programs and horticultural developments such as home gardening and bio-fortification may provide more permanent relief," Dr. Bhutta concluded. "For example, vitamin A content could be increased in staples such as rice or growers may aim to promote use of biofortified foods such as orange sweet potato."

This Cochrane review and its authors were supported by Aga Khan University, Karachi, Pakistan; the Centre for Evidence-Based Intervention, University of Oxford, United Kingdom; and/or the Department of Nutrition for Health and Development, World Health Organization, Switzerland. The review authors have disclosed no relevant financial relationships.

Cochrane Database Syst Rev. Published online December 8, 2010.


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