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

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

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.

Trial registration: ClinicalTrials.gov NCT00168558 NCT00168597 NCT00168610.

Keywords: Children; Low-income countries; Measles vaccine; Mortality; Vitamin A.

Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1
Fig. 1
Cumulative mortality according to randomization to neonatal vitamin A supplementation (NVAS) and early measles vaccine (MV), from 4 to 8 months.
Fig. 2
Fig. 2
Cumulative mortality according to randomization to neonatal vitamin A supplementation (NVAS) and early measles vaccine (MV), from 9 to 17 months.

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Source: PubMed

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