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Early neonatal vitamin A supplementation and infant mortality: two alternative hypotheses
  1. Christine Stabell Benn
  1. OPEN, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
  1. Correspondence to Dr Christine Stabell Benn, Open, Department of Clincal Research, University of Southern Denmark, 5000 Odense C, Denmark; cb{at}

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In 2008, WHO hosted a technical consultation on neonatal vitamin A supplementation (NVAS).1 The investigators of the existing NVAS trials participated. At that time, six NVAS trials had been conducted, yielding conflicting results. Some investigators supported the prevailing ‘NVAS prevents vitamin A deficiency’ hypothesis; they proposed that the variability of effects was seen because there were differences in the prevalence of vitamin A deficiency (VAD) in different settings. Based on our NVAS trials in Guinea-Bissau, we put forward an alternative hypothesis; that NVAS interacted negatively with subsequent diphtheria–tetanus–pertussis (DTP) vaccine in females, the ‘Negative interaction between NVAS and DTP in females’ hypothesis.2–5 If true, this would lead to negative effects of NVAS in females in areas with high DTP coverage. We proposed to test the hypothesis in the other NVAS trials.

WHO conducted three new large NVAS trials. In the initial proposal, the NVAS and placebo recipients were only followed to age 6 months. Since much of a potential negative interaction between NVAS and DTP vaccine in females would only occur after 6 months, when most children would have received DTP vaccine, we suggested that the trials collect vaccination information and follow children to age 12 months. This was accepted in the final protocol.6

In 2014, the three trials were published.7–9 …

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  • Contributors CSB wrote the article.

  • Funding This study was funded by Danmarks Grundforskningsfond.

  • Competing interests None declared.

  • Patient consent for publication Not required.

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

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