title: Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase Three of the ISAAC programme.
abstract: BACKGROUND
  Exposure to paracetamol during intrauterine life, childhood, and adult life may increase the risk of developing asthma. We studied 6-7-year-old children from Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) programme to investigate the association between paracetamol consumption and asthma.
  
  
  METHODS
  As part of Phase Three of ISAAC, parents or guardians of children aged 6-7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis, and eczema, and several risk factors, including the use of paracetamol for fever in the child's first year of life and the frequency of paracetamol use in the past 12 months. The primary outcome variable was the odds ratio (OR) of asthma symptoms in these children associated with the use of paracetamol for fever in the first year of life, as calculated by logistic regression.
  
  
  RESULTS
  205 487 children aged 6-7 years from 73 centres in 31 countries were included in the analysis. In the multivariate analyses, use of paracetamol for fever in the first year of life was associated with an increased risk of asthma symptoms when aged 6-7 years (OR 1.46 [95% CI 1.36-1.56]). Current use of paracetamol was associated with a dose-dependent increased risk of asthma symptoms (1.61 [1.46-1.77] and 3.23 [2.91-3.60] for medium and high use vs no use, respectively). Use of paracetamol was similarly associated with the risk of severe asthma symptoms, with population-attributable risks between 22% and 38%. Paracetamol use, both in the first year of life and in children aged 6-7 years, was also associated with an increased risk of symptoms of rhinoconjunctivitis and eczema.
  
  
  CONCLUSIONS
  Use of paracetamol in the first year of life and in later childhood, is associated with risk of asthma, rhinoconjunctivitis, and eczema at age 6 to 7 years. We suggest that exposure to paracetamol might be a risk factor for the development of asthma in childhood.
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand.
authors.forename: Richard
authors.initials: R
authors.lastname: Beasley
authors.forename: Tadd
authors.initials: T
authors.lastname: Clayton
authors.forename: Julian
authors.initials: J
authors.lastname: Crane
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Christopher K W
authors.initials: CK
authors.lastname: Lai
authors.forename: Stephen
authors.initials: S
authors.lastname: Montefort
authors.forename: Alistair
authors.initials: A
authors.lastname: Stewart
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000293:Adolescent; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001249:Asthma / Q000139:chemically induced* / Q000453:epidemiology; D002648:Child; D003231:Conjunctivitis / Q000139:chemically induced / Q000453:epidemiology; D003430:Cross-Sectional Studies; D004485:Eczema / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D005334:Fever / Q000188:drug therapy; D014943:Global Health; D006801:Humans; D007223:Infant; D008297:Male; D015337:Multicenter Studies as Topic; D015995:Prevalence; D012220:Rhinitis / Q000139:chemically induced* / Q000453:epidemiology; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen