◊ 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.
◊ FINDINGS:
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.
◊ INTERPRETATION:
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.
◊ Reviewed by F. Camu, MD, PhD
Prof. Emeritus of Anesthesiology,
Dept. of Anesthesiology, University of Brussels V.U.B., Nieuwerkerken Aalst , Belgium
Since 2005, several studies suggested the association between frequent use of paracetamol and the development of asthma and allergic disorders in infants and children. This report from a large-scale, international, worldwide study provides epidemiological evidence of the association between paracetamol and the occurrence of asthma and allergic diseases in childhood. The authors also investigated whether the association between symptoms and paracetamol use might be confounded by several potential environmental factors.
Their analyses indicated that the use of paracetamol for fever in the first year of life was associated with symptoms of asthma later in childhood. The risk of asthma symptoms increased in different countries worldwide (p<0.005) with a population-attributable risk of 21%. The study established a similar risk for symptoms of rhinoconjunctivitis and eczema at the age of 6-7 years with a population-attributable risk of 22% and 17%, respectively. This indicated that the effect of paracetamol was not restricted to the airways.
In children aged 6-7 years having used paracetamol in the past 12 months in comparison with children who never took paracetamol, the authors found a significantly increased risk of asthma symptoms of 40%. Moreover, there was a strong dose-dependent relationship with a three-fold increased risk of asthma symptoms with frequent paracetamol use (i.e. at least once per month). No difference was found between female and male children.
Although epidemiological studies do not establish causality, exposure to paracetamol appears to be a considerable risk factor for the development of asthma and allergic diseases in childhood. Physicians, pharmacists and healthcare professionals should be aware of these findings and reconsider the risk-benefit profile of administering paracetamol in infancy and childhood in comparison with other therapeutic approaches to fever and analgesia. A 20-40% increased risk of developing asthma or allergies is not a minor issue for children!
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