Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial

Christine Stabell Benn, Birgitte Rode Diness, Adam Roth, Ernesto Nante, Ane Baerent Fisker, Ida Maria Lisse, Maria Yazdanbakhsh, Hilton Whittle, Amabelia Rodrigues, Peter Aaby, Christine Stabell Benn, Birgitte Rode Diness, Adam Roth, Ernesto Nante, Ane Baerent Fisker, Ida Maria Lisse, Maria Yazdanbakhsh, Hilton Whittle, Amabelia Rodrigues, Peter Aaby

Abstract

Objective: To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality.

Design: Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering approximately 90,000 inhabitants. Participants 4345 infants due to receive BCG.

Intervention: Infants were randomised to 50,000 IU vitamin A or placebo and followed until age 12 months.

Main outcome measure: Mortality rate ratios.

Results: 174 children died during follow-up (mortality=47/1000 person-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0.84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration.

Conclusions: Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting. Although little doubt exists that vitamin A supplementation reduces mortality in older children, a global recommendation of supplementation for all newborn infants may not contribute to better survival.

Trial registration: Clinical trials NCT00168597.