title: Is diphtheria-tetanus-pertussis (DTP) associated with increased female mortality? A meta-analysis testing the hypotheses of sex-differential non-specific effects of DTP vaccine.
abstract: Ten years ago, we formulated two hypotheses about whole-cell diphtheria-tetanus-pertussis (DTP) vaccination: first, when given after BCG, DTP increases mortality in girls and, second, following DTP there is an increase in the female/male mortality rate ratio (MRR). A recent review by WHO found no convincing evidence that DTP increases mortality in females.
  
  
  
  We used previous DTP reviews as well as the recent WHO review for assessing the hypotheses. As pre-specified we excluded studies with survival or frailty bias; if children had received BCG and DTP simultaneously; and if the children had received neonatal vitamin A.
  
  
  
  In seven studies of BCG-vaccinated children, DTP vaccination was associated with a 2.54 (95% CI 1.68-3.86) increase in mortality in girls (with no increase in boys [ratio 0.96, 0.55-1.68]). In 10 studies of BCG-vaccinated children, the female-to-male mortality ratio was 2.45 (1.48-4.06) times higher after DTP than before DTP. In 15 studies of children who had received DTP after previous BCG vaccination, mortality was 1.53 (1.21-1.93) times higher in girls than boys. The findings were similar in studies conducted before and after formulation of the hypotheses.
  
  
  
  The two hypotheses were confirmed in the studies that fulfilled pre-specified criteria.
authors.affiliation: Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau p.aaby@bandim.org.|Research Centre for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.affiliation: Research Centre for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.|OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ravn
authors.affiliation: Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.|Research Centre for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.|OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital.
authors.forename: Ane B
authors.initials: AB
authors.lastname: Fisker
authors.affiliation: Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.
authors.forename: Amabelia
authors.initials: A
authors.lastname: Rodrigues
authors.affiliation: Bandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau.|Research Centre for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.|OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Benn
mesh_terms: D002675:Child, Preschool; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D064887:Observational Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012727:Sex Characteristics; D012737:Sex Factors; D016019:Survival Analysis; D014611:Vaccination / Q000401:mortality*
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine
keywords: BCG; DTP; Diphtheria-tetanus-pertussis vaccine; Non-specific effects of vaccines; Sex-differential effects; Strategic Advisory Group of Experts on Immunization (SAGE)