title: Siblings, multiple births, and the incidence of allergic disease: a birth cohort study using the West Midlands general practice research database.
abstract: BACKGROUND
  The presence of older siblings reduces the risk of developing hay fever, eczema and atopy, but findings for asthma have been inconsistent. Whether twins have a reduced risk of allergic disease is also unclear. We have investigated these questions in a birth cohort analysis of the West Midlands General Practice Research Database (GPRD).
  
  
  METHODS
  Our birth cohort included 29,238 children. The incidence of allergic disease was examined according to the number of siblings, multiple births, and parental allergic disease and smoking habit using Cox regression.
  
  
  RESULTS
  There was a dose related decrease in the incidence of eczema and hay fever with increasing number of older siblings (hazard ratio for children with three or more older siblings compared with none 0.70 (95% CI 0.64 to 0.76) for eczema and 0.67 (95% CI 0.52 to 0.86) for hay fever). In contrast, the presence of older siblings increased the incidence of asthma (HR 1.17, 95% CI 1.06 to 1.29), although this effect was strongly dependent on age of diagnosis. For children diagnosed over the age of 2 years the presence of older siblings was protective (HR 0.66, 95% CI 0.52 to 0.82), while below this age the reverse was true (HR 1.38, 95% CI 1.24 to 1.54). Members of a multiple birth had a reduced incidence of all three allergic diseases. Birth order and multiple birth effects were independent of sex, maternal age, consulting behaviour, and parental allergy and smoking habit.
  
  
  CONCLUSIONS
  The presence of older siblings and being a member of a multiple birth appears to protect against the development of eczema, hay fever, and asthma diagnosed after the age of 2. In contrast, the presence of older siblings increases the incidence of early asthma.
authors.affiliation: Division of Respiratory Medicine, University of Nottingham, UK. Tricia.McKeever@nottingham.ac.uk
authors.forename: T M
authors.initials: TM
authors.lastname: McKeever
authors.forename: S A
authors.initials: SA
authors.lastname: Lewis
authors.forename: C
authors.initials: C
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Collins
authors.forename: H
authors.initials: H
authors.lastname: Heatlie
authors.forename: M
authors.initials: M
authors.lastname: Frischer
authors.forename: R
authors.initials: R
authors.lastname: Hubbard
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000453:epidemiology; D001722:Birth Order; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016208:Databases, Factual; D004485:Eczema / Q000453:epidemiology; D004739:England / Q000453:epidemiology; D005192:Family Health; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology*; D015994:Incidence; D007223:Infant; D008297:Male; D008423:Maternal Age; D011247:Pregnancy; D011272:Pregnancy, Multiple; D012044:Regression Analysis; D006255:Rhinitis, Allergic, Seasonal / Q000453:epidemiology; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology