Mortality Benefits of Vitamin A Are Not Affected by Varying Frequency, Total Dose, or Duration of Supplementation

Abstract

Background: Although vitamin A supplementation reduces child mortality, it remains unclear whether dosing frequency, total dose, or duration modifies effectiveness. Objective: Determine whether mortality effects of vitamin A vary by dosing frequency, total dose, or duration. Methods: Meta-analysis of randomized controlled trials, identified by systematic review and expert opinion, utilizing relatively standard World Health Organization doses in children <5 years. Meta-regression evaluated whether mortality effects varied by dosing frequency, total dose, or supplementation duration. Results: Identified 17 trials, including 1,180,718 children, mean (standard deviation [SD]) age 31.5 (15.4) months at baseline. Supplementation frequency ranged every 3 months-every 2 years, supplementation duration 4-60 months (mean = 15.4; SD = 12.8), and total dose 134,361-2,200,000 IU (mean = 667,132 IU; SD = 540,795). Compared with control, vitamin A reduced mortality 22% (95% confidence interval [CI] = 10-32; P = 0.002). This protective effect was not modified by increasing supplementation frequency (dose/year: relative risk [RR] = 1.02; 95% CI = 0.98-1.06; P = .22), total dose (per 200,000 IU: RR = 1.02; 95% CI = 0.97-1.06; P = .31), nor supplementation duration (per year: RR = 1.06; 95% CI = 0.97-1.15; P = 0.14). Multivariate meta-regression showed similar results. Sensitivity analyses excluding 1 controversial trial (Aswathi 2013) did not alter findings. Conclusion: Results confirm benefits of vitamin A supplementation in children <5 years in nations with vitamin A deficiency, without influence of frequency, total dose, or dosing duration within ranges evaluated. These findings inform design and efficiency of vitamin A supplementation policies.