Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 35294044 · doi:10.1002/14651858.CD008524.pub4
What was done
This Cochrane review update searched databases up to March 2021 for randomized and cluster-randomized controlled trials evaluating synthetic vitamin A supplementation in community-dwelling children aged six months to five years. Trials involving hospitalized children, children with active infections or diseases, and food fortification or dietary interventions were excluded. Meta-analyses were conducted for all-cause and cause-specific mortality, disease incidence, vision outcomes, and adverse effects, with evidence quality evaluated using the GRADE approach.
What was found
No new trials were identified in this update, maintaining 47 included studies (approximately 1,223,856 children across 19 countries). Vitamin A supplementation reduced all-cause mortality by 12% (RR 0.88, 95% CI 0.83 to 0.93; 19 trials, 1,202,382 children; high certainty) and diarrhea mortality by 12% (RR 0.88, 95% CI 0.79 to 0.98; 9 trials, 1,098,538 children; high certainty). No significant effect was found for measles mortality (RR 0.88, 95% CI 0.69 to 1.11; 6 trials; low certainty), respiratory disease mortality (RR 0.98, 95% CI 0.86 to 1.12; 9 trials; low certainty), or meningitis mortality. Supplementation lowered the incidence of diarrhea (RR 0.85, 95% CI 0.82 to 0.87; 15 trials; low certainty), measles (RR 0.45, 95% CI 0.30 to 0.69; 2 trials; low certainty), Bitot's spots (RR 0.42, 95% CI 0.33 to 0.53; 5 trials; moderate certainty), night blindness (RR 0.32, 95% CI 0.21 to 0.50; 2 trials; moderate certainty), and vitamin A deficiency (RR 0.71, 95% CI 0.65 to 0.78; 4 trials; moderate certainty). It had no effect on respiratory disease incidence (RR 0.99, 95% CI 0.92 to 1.06; 11 trials) or hospitalizations for diarrhea or pneumonia, but increased the risk of vomiting within 48 hours (RR 1.97, 95% CI 1.44 to 2.69; 4 trials, 10,541 children; moderate certainty).
Why it matters
This review reaffirms high-certainty evidence that periodic vitamin A supplementation in children under five living in populations at risk of deficiency meaningfully prevents child mortality. It solidifies global policy recommendations, indicating that further placebo-controlled trials are both unnecessary and unethical in deficient populations.
Limits
Included studies showed variable overall risk of bias across secondary outcomes. Geographic representation was skewed toward Asia (63% of studies, including 16 in India alone), with only 17% in Africa. Evidence certainty remained low for measles mortality, respiratory mortality, and respiratory disease incidence, and no newly published randomized trials met inclusion criteria since the 2017 review update.
Cited by
- supports Vitamin A deficiency causes approximately 1 million deaths per year worldwide.