title: Randomized controlled trial of asthma risk with paracetamol use in infancy--a feasibility study.
abstract: BACKGROUND
  There is non-experimental evidence that paracetamol (acetaminophen) use may increase the risk of developing asthma. However, numerous methodological issues need to be resolved before undertaking a randomized controlled trial to investigate this hypothesis.
  
  
  OBJECTIVE
  To establish the feasibility of a randomized controlled trial of liberal paracetamol as usually given by parents/guardians vs. a comparator (restricted paracetamol in accordance with WHO guidelines, ibuprofen or placebo), and childhood asthma risk.
  
  
  METHODS
  Questionnaires were completed by parents/guardians of infants admitted to Wellington Hospital with bronchiolitis to assess views about comparator treatments. Subsequently, infants of parents/guardians who provided informed consent were randomized to restricted or liberal paracetamol use for 3 months with paracetamol use recorded.
  
  
  RESULTS
  Of 120 eligible participants, 72 (60%) parents/guardians completed the questionnaire. Ibuprofen, restricted paracetamol and placebo were acceptable to 42 (58%), 29 (40%) and 9 (12%) parents/guardians, respectively. 36 (30%) infants were randomized to restricted or liberal paracetamol. Paracetamol use was greater for the liberal vs. restricted group for reported [Hodges-Lehmann estimator of difference 0.94 mg/kg/day (95% CI 0.2-3.52), P = 0.02] and measured use [Hodges-Lehmann estimator of difference 2.11 mg/kg/day (95% CI 0.9-4.18), P = 0.004]. The median reported and measured use of paracetamol was 2.0-fold and 3.5-fold greater in the liberal vs. restricted group.
  
  
  CONCLUSIONS
  Although separation in paracetamol dosing is likely to be achieved with a liberal vs. restricted paracetamol regime, ibuprofen is the preferred comparator treatment in the proposed RCT of paracetamol use and risk of asthma in childhood.
authors.affiliation: Medical Research Institute of New Zealand, Wellington, New Zealand.
authors.forename: J
authors.initials: J
authors.lastname: Riley
authors.forename: I
authors.initials: I
authors.lastname: Braithwaite
authors.forename: P
authors.initials: P
authors.lastname: Shirtcliffe
authors.forename: R
authors.initials: R
authors.lastname: Caswell-Smith
authors.forename: A
authors.initials: A
authors.lastname: Hunt
authors.forename: V
authors.initials: V
authors.lastname: Bowden
authors.forename: S
authors.initials: S
authors.lastname: Power
authors.forename: T
authors.initials: T
authors.lastname: Stanley
authors.forename: J
authors.initials: J
authors.lastname: Crane
authors.forename: T
authors.initials: T
authors.lastname: Ingham
authors.forename: M
authors.initials: M
authors.lastname: Weatherall
authors.forename: E A
authors.initials: EA
authors.lastname: Mitchell
authors.forename: R
authors.initials: R
authors.lastname: Beasley
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000367:Age Factors; D001249:Asthma / Q000453:epidemiology* / Q000209:etiology*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D063868:Patient Outcome Assessment; D012306:Risk; D011795:Surveys and Questionnaires
chemical_list: D000082:Acetaminophen
keywords: acetaminophen; asthma; bronchiolitis; comparator arm; feasibility; infants; paracetamol