Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.
The Real-Life Effect of Vitamin a Supplementation Campaigns on All-Cause Mortality. Systematic Review and Meta-Analysis
Background: WHO recommends high-dose vitamin A supplementation (VAS) in vitamin A-deficient areas. Many countries deliver VAS in national campaigns. Based on randomised trials conducted in the 1980s-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 March 2024 we searched Pubmed and Embase for studies involving children<5 years of age, that investigated VAS campaigns based on individual-level data and reported all-cause mortality. We did not include modelling studies. ROBINS-I was used to assess the methodological quality. Some campaigns provided VAS in combination with vaccines (oral polio vaccine (OPV) or measles vaccine (MV)). Meta-estimates were calculated as random (prioritized) and fixed effect estimates, overall and by biological sex and age group.
Findings: We identified five observational studies covering the period from 1999-2019, including a total of 163,996 children and 5,449 deaths. Four studies were of median risk of bias, one of critical risk of bias. Overall, the meta-analysis showed no benefit of VAS campaigns on all-cause mortality, the random effect estimate being 1.07 (0.82-1.38)(fixed effect estimate 1.17 (1.03-1.32)). In males, the meta-estimate was 1.18 (0.91-1.52) and in females 1.06 (0.85-1.33). Among infants between 6-11 months, the effect estimate was 1.24 (1.00-1.54). In combined “VAS+OPV” campaigns the effect estimate was 1.05 (0.97-1.14); for “VAS+MV” it was 1.17 (0.88-1.57). For “Any VAS” (VAS +/- deworming and vaccines), the estimate was 1.07 (0.99-1.16). In comparison, the estimate for “OPV-only” campaigns across the same studies was 0.78 (0.71-0.85)(p for same effect of “Any VAS” vs “OPV-only” campaigns<0.001; p for same effect of “VAS+OPV” vs “OPV-only”<0.001).
Interpretation: There was no evidence that VAS campaigns contribute to lowering all-cause mortality. On the contrary, there were signals of harm in the youngest children. In the same settings, “OPV-only” campaigns had markedly beneficial effect. The effect of VAS may have changed over time. VAS campaigns should be stopped until randomised trials have documented their current effect.
Funding: No funding was available for the work.
Declaration of Interest: The authors have no conflicts of interest that are directly relevant to the content of this article.
Keywords: Vitamin A supplementation, low- and middle income countries, children, all-cause mortality, oral polio vaccine, campaigns
Nielsen, Sebastian and Aaby, Peter and Welaga, Paul and Hanifi, Syed Manzoor Ahmed and Benn, Christine Stabell, The Real-Life Effect of Vitamin a Supplementation Campaigns on All-Cause Mortality. Systematic Review and Meta-Analysis. Available at SSRN: https://ssrn.com/abstract=4994078 or http://dx.doi.org/10.2139/ssrn.4994078
Subscribe to this fee journal for more curated articles on this topic
FOLLOWERS
58
PAPERS
1,756
Feedback
Feedback to SSRN
If you need immediate assistance, call 877-SSRNHelp (877 777 6435) in the United States, or +1 212 448 2500 outside of the United States, 8:30AM to 6:00PM U.S. Eastern, Monday - Friday.
Download This Paper