The effect of at-birth vitamin A supplementation on differential leucocyte counts and in vitro cytokine production: an immunological study nested within a randomised trial in Guinea-Bissau

Mathias J Jørgensen, Ane B Fisker, Erliyani Sartono, Andreas Andersen, Christian Erikstrup, Ida M Lisse, Maria Yazdanbakhsh, Peter Aaby, Christine Stabell Benn

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Vitamin A SUPPL.ementation (VAS) at birth was not associated with improved survival in a randomised, placebo-controlled trial in Guinea-Bissau. However, a negative sex-differential effect, which became evident after diphtheria-tetanus-pertussis (DTP) vaccination, was noted; among girls who had received DTP, VAS at birth was associated with two-fold higher mortality than placebo. The objective of the present study was to investigate the immunological effects of VAS at birth within a subgroup of participants in the randomised trial. Guided by the mortality results, we further explored whether VAS had a differential effect according to sex and DTP status. At 6 weeks after randomisation and SUPPL.ementation, we measured differential leucocyte counts and TNF-α, interferon-γ, IL-10, IL-13 and IL-5 production in a whole-blood culture assay. A total of 471 children were included. VAS compared with placebo at birth was associated with a higher proportion of monocytes (relative risk ratio 1·26, 95Â % CI 1·07, 1·49, P=Â 0·04), while spontaneous TNF-α production was lower in the VAS group (geometric mean ratio 0·54, 95Â % CI, 0·37, 0·78, P=Â 0·001). Stratified analysis showed that VAS was associated with lower TNF-α and IL-10 production for girls without DTP and boys with DTP, resulting in significant three-way interactions between VAS, sex and DTP vaccination status (P=Â 0·03 and P=Â 0·04, respectively) for spontaneous TNF-α and IL-10 production. The results substantiate the potential role of VAS as an immunomodulatory intervention, which has different effects depending on concomitant health interventions and the sex of the recipient.

Original languageEnglish
JournalBritish Journal of Nutrition
Volume109
Issue number3
Pages (from-to)467-477
ISSN0007-1145
DOIs
Publication statusPublished - 14. Feb 2013

Keywords

  • BCG Vaccine
  • Cells, Cultured
  • Child Development
  • Cytokines
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Guinea-Bissau
  • Humans
  • Immunity, Cellular
  • Immunity, Innate
  • Immunomodulation
  • Infant, Newborn
  • Leukocyte Count
  • Leukocytes
  • Male
  • Monocytes
  • Sex Characteristics
  • Tuberculosis
  • Vitamin A
  • Whole-blood stimulation
  • Immunology
  • Vitamin A SUPPL.ementation
  • Diphtheria-tetanus-pertussis vaccination

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