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

BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39542.509444.AE (Published 19 June 2008) Cite this as: BMJ 2008;336:1416
  1. Christine Stabell Benn, senior researcher1,
  2. Birgitte Rode Diness, clinician1,
  3. Adam Roth, clinician12,
  4. Ernesto Nante, clinician3,
  5. Ane Bærent Fisker, student3,
  6. Ida Maria Lisse, senior registar 4,
  7. Maria Yazdanbakhsh, professor 5,
  8. Hilton Whittle, professor 6,
  9. Amabelia Rodrigues, research director3,
  10. Peter Aaby, director3
  1. 1Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark
  2. 2Department of Medical Microbiology, Lund University, 205 02 Malmö, Sweden
  3. 3Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau
  4. 4Department of Pathology, Herlev University Hospital, 2730 Herlev, Denmark
  5. 5Department of Immunoparasitology, Leiden University Medical Centre, Leiden 2333 AZ, Netherlands
  6. 6MRC Laboratories, Fajara, POB 273, Gambia
  1. Correspondence to: C S Benn cb{at}ssi.dk
  • Accepted 19 March 2008

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.

Footnotes

  • Contributors: CSB was the chief investigator and is the guarantor. CSB, ARoth, MY, HW, ARodrigues, and PA designed the study. CSB, ARoth, and PA initiated the study. BRD, EN, ABF, and IML were responsible for the recruitment and follow-up of participants. CSB was responsible for the statistical analysis and wrote the first draft of the paper. All authors contributed to and approved the final version of the paper.

  • Funding: The study was funded by the EU (ICA4-CT-2002-10053), the Danish Medical Research Council, University of Copenhagen, March of Dimes, and the Ville Heise Foundation. The Bandim Health Project received support from DANIDA and the Danish National Research Foundation. PA holds a research professorship grant from the Novo Nordisk Foundation. The sponsors had no role in the study design, data collection, data analysis, data interpretation, or the writing of the report.

  • Competing interests: None declared.

  • Ethical approval: Ministry of Health in Guinea-Bissau; Danish Central Ethical Committee (624-02-0010).

  • Provenance and peer review: Not commissioned; externally peer reviewed.

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