August 25, 2011 — Evidence that vitamin A supplementation for children saves lives and prevents illness is strong enough to deem further placebo-based trials to be unethical and to support supplementation for all children in low- and middle-income countries, according to a new meta-analysis published online August 25 in the British Medical Journal.
The analysis included 43 randomized trials involving a total of 215,633 children aged from 6 months to 5 years. The authors, based in the United Kingdom and Pakistan, excluded studies involving children with current illness or children who were hospitalized, or that involved food fortification or beta-carotene.
The results of 17 trials involving 194,483 participants showed a 24% reduction in all-cause mortality (rate ratio, 0.76; 95% confidence interval [CI], 0.69 - 0.83). Seven trials demonstrated a 28% reduction in mortality associated with diarrhea (rate ratio, 0.72; 95% CI, 0.57 - 0.91).
Vitamin A supplementation was also associated with a reduced incidence of diarrhea (rate ratio, 0.85; 95% CI, 0.82 - 0.87) and measles (rate ratio, 0.50; 95% CI, 0.37 - 0.67), and a reduced prevalence of vision problems, including night blindness (rate ratio, 0.32; 95% CI, 0.21 - 0.50) and xerophthalmia (rate ratio, 0.31; 95% CI, 0.22 - 0.45).
Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (rate ratio, 2.75; 95% CI, 1.81 - 4.19).
"Comparable with previous reviews, this review shows that vitamin A supplementation is associated with large and important reductions in mortality for children in low and middle income countries," the authors write.
"This adds substantively to previous reviews in providing a plausible pathway and indicating that vitamin A supplementation reduces the incidence of and mortality from diarrhea and measles."
The World Health Organization estimates that as many as 190 million children younger than 5 years may be vitamin A deficient globally. Because vitamin A is commonly obtained through a healthy diet, countries in which poor nutrition is common can benefit the most from supplementation, according to the authors.
A reduction of 24% of deaths in those 190 million children who are deficient could equate to more than 600,000 lives saved each year, and a gain of 20 million disability-adjusted life years, the authors note.
"Although vitamin A supplementation has been available in many countries for over a decade, direct evidence for its contribution to reducing child mortality is not available. Many countries have experienced significant reductions in child mortality, and vitamin A supplementation programmes might have contributed to these declines."
The authors suggest that an effective means for delivery on a large scale could be to provide vitamin A supplementation when children receive other services such as vaccinations, or to involve community health workers in distribution.
In an accompanying editorial, Andrew Thorne-Lyman, MHS, and Wafaie W. Fawzi, PhD, MPH, from the Harvard School of Public Health, Boston, Massachusetts, supported the recommendation for vitamin A supplementation, asserting that although more research is needed in how to more effectively provide supplementation to those who need it, placebo trials are no longer necessary.
"Most national vitamin A programmes supplement children twice a year, yet evidence suggests that more frequent supplementation could reduce mortality even further," they write.
"Research into alternative dosing approaches and delivery mechanisms, with proper evaluation, might enable programmes to be more effective."
However, they note, "as previous meta-analyses have stated, no more placebo controlled trials of preschool vitamin A supplementation are needed. Instead, effort should focus on finding ways to sustain this important child survival initiative and fine tune it to maximise the number of lives saved."
The review received funding from the Department of Nutrition for Health and Development, World Health Organization. Two authors of the article were supported by the University of Oxford's Department of Social Policy and Intervention and the Centre for Evidence-Based Intervention, and one also received funding from a Marshall scholarship. Other authors were supported by Aga Khan University, Karachi, Pakistan. The study authors and the editors have disclosed no relevant financial relationships.
BMJ. Published online August 25, 2011.
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