title: 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.
abstract: Vitamin A supplementation (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 supplementation, 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, 95 % CI 1·07, 1·49, P=0·04), while spontaneous TNF-α production was lower in the VAS group (geometric mean ratio 0·54, 95 % CI, 0·37, 0·78, P=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=0·03 and P=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.
authors.affiliation: Bandim Health Project, INDEPTH Network, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Mathias J
authors.initials: MJ
authors.lastname: Jørgensen
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau.
authors.forename: Ane B
authors.initials: AB
authors.lastname: Fisker
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Erliyani
authors.initials: E
authors.lastname: Sartono
authors.affiliation: Bandim Health Project, INDEPTH Network, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Andersen
authors.affiliation: Department of Clinical Immunology, Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Erikstrup
authors.affiliation: Department of Clinical Immunology, Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark.
authors.forename: Ida M
authors.initials: IM
authors.lastname: Lisse
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Yazdanbakhsh
authors.affiliation: Bandim Health Project, INDEPTH Network, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.affiliation: Bandim Health Project, INDEPTH Network, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Benn
mesh_terms: D001500:BCG Vaccine / Q000276:immunology; D002478:Cells, Cultured; D002657:Child Development; D016207:Cytokines / Q000378:metabolism*; D019587:Dietary Supplements; D004224:Diterpenes; D004311:Double-Blind Method; D005260:Female; D006169:Guinea-Bissau; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D056747:Immunomodulation; D007231:Infant, Newborn; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000084562:Retinyl Esters; D012727:Sex Characteristics; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate