title: Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial.
abstract: To evaluate adverse reactions of the Bacillus Calmette-Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial.
  
  
  
  A randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG or no intervention. Follow-up until 13 months of age.
  
  
  
  Pediatric and maternity wards at three Danish university hospitals.
  
  
  
  All women planning to give birth at the three study sites (n=16,521) during the recruitment period were invited to participate in the study. Four thousand one hundred and eighty four families consented to participate and 4262 children, gestational age 32 weeks and above, were randomized: 2129 to BCG vaccine and 2133 to no vaccine. None of the participants withdrew because of adverse reactions.
  
  
  
  Trial-registered adverse reactions after BCG vaccination at birth. Follow-up at 3 and 13 months by telephone interviews and clinical examinations.
  
  
  
  Among the 2118 BCG-vaccinated children we registered no cases of severe unexpected adverse reaction related to BCG vaccination and no cases of disseminated BCG disease. Two cases of regional lymphadenitis were hospitalized and thus classified as serious adverse reactions related to BCG. The most severe adverse reactions were 10 cases of suppurative lymphadenitis. This was nearly a fivefold increase compared to what was expected based on the summary of product characteristics of the vaccine. All cases were treated conservatively and recovered. Six of 10 (60%) families of children experiencing suppurative lymphadenitis compared to 117/2071 (6%) of those with no lymphadenitis indicated that the vaccine had more adverse effects than expected (p-value <0.001).
  
  
  
  BCG vaccination was associated with only mild morbidity and no mortality. A higher incidence of suppurative lymphadenitis than expected was observed. All children were treated conservatively without sequelae or complications.
  
  
  
  Trial registration number NCT01694108 at www.clinicaltrials.gov.
authors.affiliation: Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: thomas.nissen@dadlnet.dk.
authors.forename: Thomas Nørrelykke
authors.initials: TN
authors.lastname: Nissen
authors.affiliation: Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: ninabirk@dadlnet.dk.
authors.forename: Nina Marie
authors.initials: NM
authors.lastname: Birk
authors.affiliation: The Child and Adolescent Clinic 4072, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Electronic address: Jesper.Kjaergaard@regionh.dk.
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjærgaard
authors.affiliation: Department of Pediatrics, Kolding Hospital, Skovvangen 2-8, DK-6000 Kolding, Denmark. Electronic address: lmje@dadlnet.dk.
authors.forename: Lisbeth Marianne
authors.initials: LM
authors.lastname: Thøstesen
authors.affiliation: Department of Pediatrics, Kolding Hospital, Skovvangen 2-8, DK-6000 Kolding, Denmark. Electronic address: Gitte.Thybo.Pihl@rsyd.dk.
authors.forename: Gitte Thybo
authors.initials: GT
authors.lastname: Pihl
authors.affiliation: Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: thoffmann@dadlnet.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoffmann
authors.affiliation: Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: Dorthe.Lisbeth.Jeppesen@regionh.dk.
authors.forename: Dorthe Lisbeth
authors.initials: DL
authors.lastname: Jeppesen
authors.affiliation: Department of Pediatrics, Kolding Hospital, Skovvangen 2-8, DK-6000 Kolding, Denmark. Electronic address: Poul.Erik.Kofoed@rsyd.dk.
authors.forename: Poul-Erik
authors.initials: PE
authors.lastname: Kofoed
authors.affiliation: The Child and Adolescent Clinic 4072, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Electronic address: Gorm.Greisen@regionh.dk.
authors.forename: Gorm
authors.initials: G
authors.lastname: Greisen
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark; Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: cb@ssi.dk.
authors.forename: Christine Stabell
authors.initials: CS
authors.lastname: Benn
authors.affiliation: Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. Electronic address: p.aaby@bandim.org.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.affiliation: Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: pryds@dadlnet.dk.
authors.forename: Ole
authors.initials: O
authors.lastname: Pryds
authors.affiliation: The Child and Adolescent Clinic 4072, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Electronic address: Lone.graff.stensballe@regionh.dk.
authors.forename: Lone Graff
authors.initials: LG
authors.lastname: Stensballe
mesh_terms: D001500:BCG Vaccine / Q000009:adverse effects* / Q000276:immunology; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006785:Hospitals, University; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008199:Lymphadenitis / Q000209:etiology; D008297:Male; D009026:Mortality; D009163:Mycobacterium bovis / Q000276:immunology; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control; D014611:Vaccination
chemical_list: D001500:BCG Vaccine
keywords: Adverse reactions; BCG; Children; Clinical trials; Non-specific effects; Vaccines