A Randomised Trial of High-dose Vitamin A at Vaccination Contacts After 6 Months of Age: Sex-differential Effects on Mortality

Abstract

Objectives: Though VAS at vaccination contacts has been recommended for many years, the policy has never been evaluated for its effect on overall mortality in randomised controlled trials. We evaluated the effect of the WHO recommendation of vitamin A supplementation (VAS) at routine vaccination contacts after 6 months of age. Methods: We conducted a randomised controlled trial of VAS. Children aged 6-23 months were randomised 1:1 to VAS (100,000 IU if aged 6-11 months, 200,000 IU if aged 12-23 months) or placebo at vaccination contacts in Guinea-Bissau. Mortality rates were compared in Cox proportional-hazards models overall, and by sex and vaccine. Results: Between August 2007 and November 2010, 7587 children were enrolled. Within 6 months of follow-up there were 81 non-accident deaths (VAS: 39; placebo: 42). The mortality rate ratio (MRR) comparing VAS versus placebo recipients was 0.93 (95% CI: 0.60-1.44) and differed significantly between boys (MRR=1.92 (0.98-3.75)) and girls (MRR=0.49 (0.26-0.92)) (p=0.004 for interaction between VAS and sex). At enrolment 42% (3161/7587) received live measles vaccine, 29% (2154/7587) received inactivated diphtheria-tetanus-pertussis-containing vaccines and 21% (1610/7587) received both live and inactivated vaccines. The effect of VAS did not differ by vaccine group. Conclusions: This is the first randomised trial of the effect of VAS at routine vaccination contacts on mortality. VAS had no overall effect, but the effect differed significantly by sex. More trials to ensure an optimal evidence-based vitamin A policy are warranted.