title: Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?
abstract: BACKGROUND
  Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG.
  
  
  METHODS
  In the period 2004-2008 we recruited 2320 LBW children in Bissau. The children were visited at home at 2, 6, and 12 months of age. With a pretrial infant mortality of 250 per 1000, we hypothesized a 25% reduction in infant mortality for LBW children.
  
  
  RESULTS
  Infant mortality was only 101 per 1000 during the trial. In the primary analysis, infant mortality was reduced insignificantly by 17% (mortality rate ratio [MRR] = .83 [.63-1.08]). In secondary analyses, early BCG vaccine was safe with an MRR of .49 (.21-1.15) after 3 days and .55 (.34-.89) after 4 weeks. The reduction in neonatal mortality was mainly due to fewer cases of neonatal sepsis, respiratory infection, and fever. The impact of early BCG on infant mortality was marked for children weighing <1.5 kg (MRR = .43 [.21-.85]) who had lower coverage for diphtheria-tetanus-pertussis vaccinations.
  
  
  CONCLUSIONS
  Though early BCG did not reduce infant mortality significantly, it may have a beneficial effect in the neonatal period. This could be important for public health because BCG is often delayed in low-income countries.
authors.affiliation: Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau. P.aaby@bandim.org
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.forename: Adam
authors.initials: A
authors.lastname: Roth
authors.forename: Henrik
authors.initials: H
authors.lastname: Ravn
authors.forename: Bitiguida Mutna
authors.initials: BM
authors.lastname: Napirna
authors.forename: Amabelia
authors.initials: A
authors.lastname: Rodrigues
authors.forename: Ida Maria
authors.initials: IM
authors.lastname: Lisse
authors.forename: Lone
authors.initials: L
authors.lastname: Stensballe
authors.forename: Birgitte Rode
authors.initials: BR
authors.lastname: Diness
authors.forename: Karen Rokkedal
authors.initials: KR
authors.lastname: Lausch
authors.forename: Najaaraq
authors.initials: N
authors.lastname: Lund
authors.forename: Sofie
authors.initials: S
authors.lastname: Biering-Sørensen
authors.forename: Hilton
authors.initials: H
authors.lastname: Whittle
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
mesh_terms: D001500:BCG Vaccine / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D005260:Female; D006169:Guinea-Bissau; D006801:Humans; D007226:Infant Mortality; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D014376:Tuberculosis / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*
chemical_list: D001500:BCG Vaccine