Randomized controlled trial of asthma risk with paracetamol use in infancy--a feasibility study

Clin Exp Allergy. 2015 Feb;45(2):448-56. doi: 10.1111/cea.12433.

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 and clinical relevance: 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.

Keywords: acetaminophen; asthma; bronchiolitis; comparator arm; feasibility; infants; paracetamol.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / adverse effects*
  • Adult
  • Age Factors
  • Asthma / epidemiology*
  • Asthma / etiology*
  • Feasibility Studies
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Patient Outcome Assessment
  • Risk
  • Surveys and Questionnaires

Substances

  • Acetaminophen