Source : Medscape Publication
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.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
1. Report whether paracetemol use in the first year of life is associated with a higher risk for asthma symptoms in childhood.
2. 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.
Paracetamol or acetaminophen use has been proposed to play a role in the development of asthma. Lesko and colleagues reported in the February 2002 issue of Pediatrics that children with asthma had a higher risk for asthma-related outpatient visits linked with acetaminophen vs ibuprofen use.
In the January 2005 issue of the International Journal of Tuberculosis and Lung Disease, Ellwood and colleagues described phase 3 of the multicenter, cross-sectional ISAAC, which involved children aged 6 to 7 years and children aged 13 to 14 years.
This study uses the ISAAC results from the 6-to 7-year age group to assess whether acetaminophen use in the first year of life or ages 6 to 7 years is linked with asthma symptoms, rhinoconjunctivitis, and eczema at ages 6 to 7 years.
* Data were available for 205,487 children aged 6 to 7 years from 73 centers in 31 countries.
* Exclusion criteria were centers that had data for fewer than 1000 subjects and response rate less than 60%.
* Parents completed a prevalence questionnaire about symptoms of asthma, rhinoconjunctivitis, and eczema and an environmental questionnaire about protective and risk factors for the development of asthma and allergic disorders.
* Questionnaire data included frequency of paracetemol use in the first 12 months of life and in the past 12 months; a history of wheezing or whistling in the chest in the past 12 months; sneezing, runny nose, or blocked nose aside from cold or influenza; itchy, watery eyes; or intermittent itchy skin rash in typical eczematous areas for at least 6 months.
* Severe asthma was defined as at least 4 wheezing attacks, at least 1 night per week of sleep disturbance from wheezing; or wheezing affecting speech in the past 12 months.
* Analyses were adjusted for sex, region, language, and gross national income.
* Multivariate analysis adjusted for covariates: maternal education, antibiotic use in the first year of life, ever breast-fed, parental smoking, current diet, and siblings.
* Primary outcome measure showed an association between paracetemol use for fever in the first year of life and increased risk for asthma symptoms at age 6 to 7 years (OR, 1.46; 95% CI, 1.36 - 1.56).
* Current paracetemol use (in the past 12 months) had a dose-dependent link to a higher risk for asthma symptoms at ages 6 to 7 years (OR for at least once-a-month use, 3.23; 95% CI, 2.91 - 3.60 vs OR for once-a-year use, 1.61; 95% CI, 1.46 - 1.77).
* Higher risk for severe asthma symptoms at ages 6 to 7 years had a dose-dependent link with paracetemol use in the first year (OR, 1.43; 95% CI, 1.30 - 1.58) and paracetemol use at ages 6 to 7 years.
* Paracetemol use in the first year of life was associated with a dose-dependent increased risk for rhinoconjunctivitis (OR, 1.48; 95% CI, 1.38 - 1.60) and eczema (OR, 1.35; 95% CI, 1.26 - 1.45) at ages 6 to 7 years.
* There were no differences in findings between boys and girls.
* Limitations of the study included retrospective and cross-sectional design and that most infants have an indication to take paracetemol for fever in the first year of life.
Pearls for Practice
* Paracetemol use for fever in the first year of life is associated with a greater risk for asthma and severe asthma symptoms at ages 6 to 7 years.
* Paracetemol use for fever in the first year of life or at ages 6 to 7 years is associated with a greater risk for rhinoconjunctivitis and eczema at ages 6 to 7 years.
Paracetemol use for fever in the first year of life is most likely to be associated with which of the following outcomes at ages 6 to 7 years?
Lower risk for both asthma symptoms and severe asthma symptoms
Higher risk for both asthma symptoms and severe asthma symptoms
Higher risk for asthma symptoms and lower risk for severe asthma symptoms
Lower risk for asthma symptoms and higher risk for severe asthma symptoms
A 9-month-old infant is given paracetemol for fever, and a 6-year-old child also is given paracetemol for fever. Both children are most likely to have which of the following outcomes at ages 6 to 7 years?
Higher risk for eczema
Lower risk for rhinoconjunctivitis
No effect on risk for rhinoconjunctivitis
No effect on risk for eczema
Instructions for Participation and Credit
There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.
This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.
FOLLOW THESE STEPS TO EARN CME/CE CREDIT*:
1. Read the target audience, learning objectives, and author disclosures.
2. Study the educational content online or printed out.
3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. Medscape encourages you to complete the Activity Evaluation to provide feedback for future programming.
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 5 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.
*The credit that you receive is based on your user profile.
This article is intended for primary care clinicians, allergists, pulmonologists, dermatologists, infectious disease specialists, and other specialists who provide care to children with asthma, rhinoconjunctivitis, and eczema.
The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.
Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Medscape, LLC designates this educational activity for a maximum of 0.25 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Medscape Medical News has filed an application for up to 350 Prescribed credits by the American Academy of Family Physicians.
AAFP Accreditation Questions
For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity: CME [at] medscape.net. For technical assistance, contact CME [at] webmd.net.
Medscape is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation.
Awarded 0.25 contact hour(s) of continuing nursing education for RNs and APNs; 0.25 contact hours are in the area of pharmacology.
Authors and Disclosures
As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.
Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.
Laurie Barclay, MD
is a freelance reviewer and writer for Medscape.
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.
Penny Murata, MD
is a freelancer for Medscape.
Disclosure: Penny Murata, MD, has disclosed no relevant financial relationships.
Laurie E. Scudder, MS, NP-C
Nurse Planner, Medscape; Adjunct Assistant Professor, School of Health Sciences, George Washington University, Washington, DC; Curriculum Coordinator, Nurse Practitioner Alternatives, Inc., Ellicott City; Nurse Practitioner, Baltimore City School-Based Health Centers, Baltimore, Maryland
Disclosure: Laurie Scudder, MS, NP-C, has disclosed no relevant financial information.
Brande Nicole Martin
is the News CME editor for Medscape Medical News.
Disclosure: Brande Nicole Martin has disclosed no relevant financial information.