Real-life effect of vitamin A supplementation campaigns on all-cause mortality: systematic review and meta-analysis

Introduction WHO recommends high-dose vitamin A supplementation (VAS) in vitamin A-deficient areas. Many countries deliver VAS in national campaigns. Based on randomised trials from the 1980s to 1990s, such campaigns are assumed to reduce all-cause mortality by 12–24%. There has been no analysis of the real-life effect of VAS campaigns on all-cause mortality.Methods We conducted a systematic review and a meta-analysis of the real-life effect of ‘VAS’ campaigns (defined as VAS±simultaneous deworming) on all-cause mortality. In November 2025 we searched PubMed, Embase and Web of Science for studies involving children <5 years of age that investigated VAS campaigns based on individual-level data and reported all-cause mortality. ROBINS-I was used to assess the methodological quality. Some campaigns provided VAS in combination with vaccines (oral polio vaccine (OPV) or measles vaccine). Meta-estimates were calculated as random (prioritised) and fixed effect estimates overall and by sex and age group.Results We identified five observational studies covering the period from 1999 to 2019, including a total of 163 996 children and 5449 deaths. Four studies were of moderate risk of bias, one of critical risk of bias. The meta-analysis showed no benefit of VAS campaigns on all-cause mortality, the random effect estimate being 1.07 (95% CI 0.82 to 1.38) (fixed effect estimate 1.17 (95% CI 1.03 to 1.32)). In males, the meta-estimate was 1.18 (95% CI 0.91 to 1.52) and in females 1.06 (95% CI 0.85 to 1.33). In comparison, the estimate for ‘OPV-only’ campaigns was 0.78 (95% CI 0.71 to 0.85) (p for same effect of ‘Any VAS’ vs ‘OPV-only’ campaigns <0.001).Conclusion The available low-certainty evidence did not support the assumption that current VAS campaigns reduce all-cause mortality. Contextual analyses of ‘OPV-only’ campaigns in the same settings showed beneficial effect. The effect of VAS may have changed over time. Contemporary randomised or robust quasi-experimental studies are needed to support the continued use of VAS campaigns.