Vitamin A May Reduce Deaths From

Measles and Diarrhea in Children

Laurie Barclay, MD

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.

http://www.medscape.com/viewarticle/733832