Report whether paracetemol use in the first year of life and at ages 6 to 7 years is associated with a higher risk for rhinoconjunctivitis and eczema in childhood.
Authors
News Author: Laurie Barclay, MDCME Author: Penny Murata, MD
September 22, 2008 — Use of paracetamol (acetaminophen) during the first year of life and in later childhood may increase the risk for asthma, rhinoconjunctivitis, and eczema at ages 6 to 7 years, according to the results of phase 3 of the International Study of Asthma and Allergies in Childhood (ISAAC) program reported in the September 20 issue of The Lancet.
"Exposure to paracetamol during intrauterine life, childhood, and adult life may increase the risk of developing asthma," write Richard Beasley, from the Medical Research Institute of New Zealand, Wellington, and colleagues from the ISAAC Phase 3 Study Group. "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."
ISAAC took place at 73 centers in 31 countries. Parents or guardians of 205,487 children aged 6 to 7 years completed written questionnaires regarding symptoms of asthma, rhinoconjunctivitis, and eczema in the children as well as exposure to several risk factors, including paracetamol use for fever in the child's first year of life and the frequency of paracetamol use in the previous 12 months. The main endpoint was the odds ratio (OR) of asthma symptoms in these children linked to paracetamol use for fever in the first year of life, calculated by logistic regression.
Multivariate analyses revealed that use of paracetamol for fever in the first year of life was linked to increased risk for asthma symptoms at ages 6 to 7 years (OR, 1.46; 95% confidence interval [CI], 1.36 - 1.56). The risk for asthma symptoms increased in a dose-dependent fashion with current use of paracetamol (OR, 1.61; 95% CI, 1.46 - 1.77 for medium use vs no use; and OR, 3.23; 95% CI, 2.91 - 3.60 for high use vs no use).
Population-attributable risks for severe asthma symptoms associated with use of paracetamol ranged from 22% to 38%. In the first year of life as well as at ages 6 to 7 years, paracetamol use was also associated with an increased risk for symptoms of rhinoconjunctivitis and eczema.
"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," the study authors write. "We suggest that exposure to paracetamol might be a risk factor for the development of asthma in childhood."
Limitations of this study include questionnaires completed by parents or guardians; retrospectively collected data, possibly causing recall bias; sources of bias arising from translations of the questionnaires into different languages; possible confounding by other factors that determine the risk for the development of childhood asthma or use of paracetamol; and cross-sectional design.
"Overall, this study provides further worldwide evidence that the use of paracetamol in childhood can increase the risk of developing asthma and related allergic disorders," the study authors conclude. "Although causality cannot be established from a study with this design, we suggest that exposure to paracetamol might be an important putative risk factor for the development of asthma. However, evidence is insufficient to advise parents and health-care workers of the risk-benefit of taking paracetamol in childhood, or its comparative efficacy and safety with other approaches."
In an accompanying comment, R. Graham Barr, MD, DrPH, from Columbia University Medical Center in New York, NY, calls this phase 3 study from ISAAC "the largest and most important contribution to date" on the growing evidence concerning paracetamol use and childhood asthma.
"The studies to date are suggestive but not definitive enough to recommend a wholesale change in antipyretic use in children," Dr. Barr writes. "I agree with Beasley that a population-based randomised trial of adequate power and duration to examine childhood asthma incidence, with paracetamol compared with an active control such as ibuprofen and placebo, is warranted. In view of the heterogeneous nature of asthma, the pharmacogenetics of such a study is likely to be fascinating."
The BUPA Foundation, the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the Hawke's Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, the New Zealand Lottery Board, AstraZeneca New Zealand, and Glaxo Wellcome International Medical Affairs supported this study. Dr. Beasley has disclosed various financial relationships with GlaxoSmithKline, the maker of paracetamol. The other study authors have disclosed no relevant financial relationships.
Dr. Barr has been funded by the Robert Wood Johnson Foundation on a project about acetaminophen, inflammation, and asthma.
Lancet. 2008;372:1011-1012, 1039-1048.
"Exposure to paracetamol during intrauterine life, childhood, and adult life may increase the risk of developing asthma," write Richard Beasley, from the Medical Research Institute of New Zealand, Wellington, and colleagues from the ISAAC Phase 3 Study Group. "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."
ISAAC took place at 73 centers in 31 countries. Parents or guardians of 205,487 children aged 6 to 7 years completed written questionnaires regarding symptoms of asthma, rhinoconjunctivitis, and eczema in the children as well as exposure to several risk factors, including paracetamol use for fever in the child's first year of life and the frequency of paracetamol use in the previous 12 months. The main endpoint was the odds ratio (OR) of asthma symptoms in these children linked to paracetamol use for fever in the first year of life, calculated by logistic regression.
Multivariate analyses revealed that use of paracetamol for fever in the first year of life was linked to increased risk for asthma symptoms at ages 6 to 7 years (OR, 1.46; 95% confidence interval [CI], 1.36 - 1.56). The risk for asthma symptoms increased in a dose-dependent fashion with current use of paracetamol (OR, 1.61; 95% CI, 1.46 - 1.77 for medium use vs no use; and OR, 3.23; 95% CI, 2.91 - 3.60 for high use vs no use).
Population-attributable risks for severe asthma symptoms associated with use of paracetamol ranged from 22% to 38%. In the first year of life as well as at ages 6 to 7 years, paracetamol use was also associated with an increased risk for symptoms of rhinoconjunctivitis and eczema.
"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," the study authors write. "We suggest that exposure to paracetamol might be a risk factor for the development of asthma in childhood."
Limitations of this study include questionnaires completed by parents or guardians; retrospectively collected data, possibly causing recall bias; sources of bias arising from translations of the questionnaires into different languages; possible confounding by other factors that determine the risk for the development of childhood asthma or use of paracetamol; and cross-sectional design.
"Overall, this study provides further worldwide evidence that the use of paracetamol in childhood can increase the risk of developing asthma and related allergic disorders," the study authors conclude. "Although causality cannot be established from a study with this design, we suggest that exposure to paracetamol might be an important putative risk factor for the development of asthma. However, evidence is insufficient to advise parents and health-care workers of the risk-benefit of taking paracetamol in childhood, or its comparative efficacy and safety with other approaches."
In an accompanying comment, R. Graham Barr, MD, DrPH, from Columbia University Medical Center in New York, NY, calls this phase 3 study from ISAAC "the largest and most important contribution to date" on the growing evidence concerning paracetamol use and childhood asthma.
"The studies to date are suggestive but not definitive enough to recommend a wholesale change in antipyretic use in children," Dr. Barr writes. "I agree with Beasley that a population-based randomised trial of adequate power and duration to examine childhood asthma incidence, with paracetamol compared with an active control such as ibuprofen and placebo, is warranted. In view of the heterogeneous nature of asthma, the pharmacogenetics of such a study is likely to be fascinating."
The BUPA Foundation, the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the Hawke's Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, the New Zealand Lottery Board, AstraZeneca New Zealand, and Glaxo Wellcome International Medical Affairs supported this study. Dr. Beasley has disclosed various financial relationships with GlaxoSmithKline, the maker of paracetamol. The other study authors have disclosed no relevant financial relationships.
Dr. Barr has been funded by the Robert Wood Johnson Foundation on a project about acetaminophen, inflammation, and asthma.
Lancet. 2008;372:1011-1012, 1039-1048.
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