title: Neonatal vitamin A supplementation associated with a cluster of deaths and poor early growth in a randomised trial among low-birth-weight boys of vitamin A versus oral polio vaccine at birth.
abstract: BACKGROUND
  The effect of oral polio vaccine administered already at birth (OPV0) on child survival was not examined before being recommended in 1985. Observational data suggested that OPV0 was harmful for boys, and trials have shown that neonatal vitamin A supplementation (NVAS) at birth may be beneficial for boys. We set out to test this research question in a randomised trial.
  
  
  METHODS
  The trial was carried out at the Bandim Health Project, Guinea-Bissau. We planned to enrol 900 low-birth weight (LBW) boys in a randomised trial to investigate whether NVAS instead of OPV0 could lower infant mortality for LBW boys. At birth, the children were randomised to OPV (usual treatment) or VAS (intervention treatment) and followed for 6 months for growth and 12 months for survival. Hazard Ratios (HR) for mortality were calculated using Cox regression. We compared the individual anthropometry measurements to the 2006 WHO growth reference. We compared differences in z-scores by linear regression. Relative risks (RR) of being stunted or underweight were calculated in Poisson regression models with robust standard errors.
  
  
  RESULTS
  In the rainy season we detected a cluster of deaths in the VAS group and the trial was halted immediately with 232 boys enrolled. The VAS group had significantly higher mortality than the OPV0 group in the rainy season (HR: 9.91 (1.23 - 80)). All deaths had had contact with the neonatal nursery; of seven VAS boys enrolled during one week in September, six died within two months of age, whereas only one died among the six boys receiving OPV (p = 0.05). Growth (weight and arm-circumference) in the VAS group was significantly worse until age 3 months.
  
  
  CONCLUSIONS
  VAS at birth instead of OPV was not beneficial for the LBW boys in this study. With the premature closure of the trial it was not possible to answer the research question. However, the results of this study call for extra caution when testing the effect of NVAS in the future.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov NCT00625482. Registered 18 February 2008.
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark. najaaraq@dadlnet.dk.
authors.forename: Najaaraq
authors.initials: N
authors.lastname: Lund
authors.forename: Sofie
authors.initials: S
authors.lastname: Biering-Sørensen
authors.forename: Andreas
authors.initials: A
authors.lastname: Andersen
authors.forename: Ivan
authors.initials: I
authors.lastname: Monteiro
authors.forename: Luis
authors.initials: L
authors.lastname: Camala
authors.forename: Mathias Jul
authors.initials: MJ
authors.lastname: Jørgensen
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
mesh_terms: D000284:Administration, Oral; D002423:Cause of Death; D002657:Child Development / Q000187:drug effects*; D003906:Developing Countries; D019587:Dietary Supplements / Q000009:adverse effects*; D057239:Early Termination of Clinical Trials; D005500:Follow-Up Studies; D006169:Guinea-Bissau / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007230:Infant, Low Birth Weight / Q000254:growth & development*; D007231:Infant, Newborn; D008297:Male; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage; D016016:Proportional Hazards Models; D011891:Rain; D012621:Seasons; D014801:Vitamin A / Q000008:administration & dosage / Q000009:adverse effects*; D014815:Vitamins / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D011055:Poliovirus Vaccine, Oral; D014815:Vitamins; D014801:Vitamin A