Interaction between neonatal vitamin A supplementation and timing of measles vaccination: a retrospective analysis of three randomized trials from Guinea-Bissau

Christine Stabell Benn, Cesario L Martins, Ane B Fisker, Birgitte R Diness, May-Lill Garly, Ibraima Balde, Amabelia Rodrigues, Hilton Whittle, Peter Aaby

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: In Guinea-Bissau we conducted three trials of neonatal vitamin A supplementation (NVAS) from 2002 to 2008. None of the trials found a beneficial effect on mortality. From 2003 to 2007, an early measles vaccine (MV) trial was ongoing, randomizing children 1:2 to early MV at 4.5 months or no early MV, in addition to the usual MV at 9 months. We have previously found interactions between vitamin A and vaccines.

OBJECTIVE: We investigated whether there were interactions between NVAS and early MV.

DESIGN: We compared the mortality of NVAS and placebo recipients: first, from 4.5 to 8 months for children randomized to early MV or no early MV; and second, from 9 to 17 months in children who had received two MV or one MV. Mortality rates (MR) were compared in Cox models producing mortality rate ratios (MRR).

RESULTS: A total of 5141 children were randomized to NVAS (N=3015) or placebo (N=2126) and were later randomized to early MV (N=1700) or no early MV (N=3441). Between 4.5 and 8 months, NVAS compared with placebo was associated with higher mortality in early MV recipients (MR=30 versus MR=0, p=0.01), but not in children who did not receive early MV (p for interaction between NVAS and early MV=0.03). From 9 to 17 months NVAS was not associated with mortality. Overall, from 4.5 to 17 months NVAS was associated with increased mortality in early MV recipients (Mortality rate ratio=5.39 (95% confidence interval: 1.62, 17.99)).

CONCLUSIONS: These observations indicate that NVAS may interact with vaccines given several months later. This may have implications for the planning of future child intervention programs.

Original languageEnglish
JournalVaccine
Volume32
Issue number42
Pages (from-to)5468-5474
ISSN0264-410X
DOIs
Publication statusPublished - 2014

Keywords

  • Children
  • Low-income countries
  • Measles vaccine
  • Mortality
  • Vitamin A

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