title: Two different doses of supplemental vitamin A did not affect mortality of normal-birth-weight neonates in Guinea-Bissau in a randomized controlled trial.
abstract: Whether neonatal vitamin A supplementation (NVAS) should be policy in areas with vitamin A deficiency is debated. We observed that a smaller dose of vitamin A may decrease mortality more than a larger dose and conducted a randomized, double-blind, placebo-controlled trial in Guinea-Bissau with the primary aim of comparing the effect of 50,000 with 25,000 IU neonatal vitamin A on infant mortality. The secondary aim was to study the effect of NVAS vs. placebo, including a combined analysis of NVAS trials. Between 2004 and 2007, normal-birth-weight neonates were randomly assigned in a 1:1:1 ratio to be administered 2 different doses of vitamin A (50,000 or 25,000 IU) or placebo. Infant mortality rates (MRs) were compared in Cox models providing MR ratios (MRRs). Among 6048 children enrolled, there were 160 deaths in 4125 person-years (MR = 39/1000). There was no difference in mortality between the 2 dosage groups: the MRR for 25,000 vs. 50,000 IU was 0.96 (95% CI: 0.67, 1.38). Neither dose of NVAS was associated with lower mortality than placebo (MRR = 1.28; 95% CI: 0.91, 1.81). In a combined analysis of the present trial and 2 previous NVAS trials in Guinea-Bissau, the effect of receiving NVAS (any dose) vs. placebo was 1.13 (95% CI: 0.94, 1.36) and differed significantly (P = 0.01) between boys (0.80; 95% CI: 0.58, 1.09) and girls (1.35; 95% CI: 1.04, 1.75). We could not confirm that a smaller dose of neonatal vitamin A reduces mortality more than a larger dose. We confirmed 2 other trials in Guinea-Bissau that showed no beneficial effect of NVAS. This trial was registered at clinicaltrials.gov as NCT00168610.
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; Odense Patient data Explorative Network, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital, Odense, Denmark cb@ssi.dk.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Benn
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark;
authors.forename: Birgitte R
authors.initials: BR
authors.lastname: Diness
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau; and.
authors.forename: Ibraima
authors.initials: I
authors.lastname: Balde
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau; and.
authors.forename: Amabelia
authors.initials: A
authors.lastname: Rodrigues
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark;
authors.forename: Karen R
authors.initials: KR
authors.lastname: Lausch
authors.affiliation: Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau; and.
authors.forename: Cesario L
authors.initials: CL
authors.lastname: Martins
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark;
authors.forename: Ane B
authors.initials: AB
authors.lastname: Fisker
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau; and.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
mesh_terms: D001724:Birth Weight; D002675:Child, Preschool; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006169:Guinea-Bissau; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D008297:Male; D012016:Reference Values; D012737:Sex Factors; D014801:Vitamin A / Q000008:administration & dosage / Q000494:pharmacology*; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014815:Vitamins; D014801:Vitamin A