Beasley R, Clayton T, Crane J, et al; ISAAC Phase Three Study Group. Lancet. 2008;372(9643):1039–1048
PURPOSE OF THE STUDY. The authors evaluated the associations between exposure to paracetamol (acetaminophen) in infancy and childhood and development of asthma and other atopic conditions in early school-aged children.
STUDY POPULATION. The study included 205 487 children 6 to 7 years of age from 73 centers in 31 countries.
METHODS. Parents or guardians completed written questionnaires regarding the presence of asthma, rhinoconjunctivitis, and eczema symptoms; child and family demographic information; and exposure to environmental risk factors including medications, breastfeeding, diet, home exposures, and traffic pollution. Acetaminophen administration for fever in the child's first year of life and the frequency of acetaminophen use in the previous 12 months (none; medium, once per year or more; or high, once per month or more) were determined.
RESULTS. Acetaminophen use for fever in the first year of life was associated with symptoms of asthma (odds ratio [OR]: 1.46 [95% confidence interval [CI]: 1.36–1.56]), rhinoconjunctivitis (OR: 1.48 [95% CI: 1.38–1.60]), and eczema (OR: 1.35 [95% CI: 1.26–1.45]) for children 6 to 7 years of age and was associated with severe asthma symptoms and with rhinoconjunctivitis and eczema after exclusion of children with wheeze. The overall population attributable risk of asthma was 21% to 40%. The association between asthma and current acetaminophen use was dose dependent (medium frequency OR: 1.61 [95% CI: 1.46–1.77]; high frequency OR: 3.23 [95% CI: 2.91–3.60]); dose-response relationships were also seen for rhinoconjunctivitis and eczema.
CONCLUSIONS. Acetaminophen use in infancy and childhood was associated with the development of asthma, rhinoconjunctivitis, and eczema in 6- to 7-year-old children, and the associations seemed to be dose-responsive for childhood acetaminophen exposure.
REVIEWER COMMENTS. This large, multinational, retrospective study demonstrated an association between previous and current acetaminophen use and childhood atopic conditions that persisted across populations with different lifestyles, medical access and practices, and types of febrile childhood illnesses. Prospective studies of acetaminophen use during pregnancy and a randomized, controlled trial that compared acetaminophen with another antipyretic medication also suggested associations between acetaminophen and childhood asthma, although an association between decreased aspirin use and asthma development has also been hypothesized. Before these findings can be interpreted as causal, additional prospective observational or randomized studies should be performed and should include information on covariates such as parental atopy and asthma, types of febrile illnesses, and use of other antipyretic agents.
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