Paracetamol and antibiotics in childhood and subsequent development of wheezing/asthma: association or causation?

Background Several studies found an association between early administration of paracetamol and antibiotics and development of wheezing. This could be due to confounding: wheeze and asthmatic symptoms in early childhood are difficult to distinguish from respiratory tract infections that are widely t...

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Bibliographic Details
Published in:International journal of epidemiology 2011-06, Vol.40 (3), p.662-667
Main Authors: Rusconi, Franca, Gagliardi, Luigi, Galassi, Claudia, Forastiere, Francesco, Brunetti, Luigia, La Grutta, Stefania, Piffer, Silvano, Talassi, Fiorella
Format: Article
Language:English
Subjects:
Acetaminophen - adverse effects
Acetaminophen - therapeutic use
Adolescent
Age Distribution
Age of Onset
Anti-Bacterial Agents - adverse effects
Anti-Bacterial Agents - therapeutic use
Asthma - epidemiology
Asthma - etiology
Biological and medical sciences
Child
Cross-Sectional Studies
Female
Follow-Up Studies
General aspects
Humans
Incidence
Infant
Infant, Newborn
Italy - epidemiology
Logistic Models
Male
Medical sciences
Miscellaneous
Odds Ratio
Public health. Hygiene
Public health. Hygiene-occupational medicine
Respiratory Sounds - etiology
Risk Assessment
Sex Distribution
Surveys and Questionnaires
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Summary:Background Several studies found an association between early administration of paracetamol and antibiotics and development of wheezing. This could be due to confounding: wheeze and asthmatic symptoms in early childhood are difficult to distinguish from respiratory tract infections that are widely treated with these drugs; in case of persistence of symptoms up to school age, this could explain the observed relationship. Methods We investigated the association between paracetamol and antibiotics use in the first year of life and wheezing phenotypes, i.e. wheezing starting in different time periods (early, persistent and late-onset) in the SIDRIA-2 study, a cross-sectional survey of 16 933 children aged 6-7 years. Directed acyclic graph (DAG) was used to depict the causal structure. Results Paracetamol and antibiotics administration in the first year were associated with early wheezing (first 2 years of life only) [odds ratio (OR): 2.27; 95% confidence interval (95% CI): 1.98-2.62 and OR = 3.76, 95% CI: 3.31-4.27] and with persistent wheezing (first 2 years + last 12 months) (OR = 1.77, 95% CI: 1.49-2.10 and OR = 3.06, 95% CI: 2.60-3.60), whereas the association with late-onset wheezing (in the last 12 months only) was weak (OR = 1.12, 95% CI: 0.97-1.31 and OR = 1.18, 95% CI: 1.02-1.38 for paracetamol and antibiotics, respectively). DAG shows that even in the absence of a direct (causal) arrow from early drugs use to wheezing at school age, the two are associated due to confounding (through the 'infection' node). Conclusions It is important to take into account different phenotypes in order to disentangle the association of paracetamol and antibiotics with wheezing.
ISSN:0300-5771
1464-3685
DOI:10.1093/ije/dyq263