The case of drug causation of childhood asthma: antibiotics and paracetamol

European Journal of Clinical Pharmacology© The Author(s) 201210.1007/s00228-012-1463-7

Review ArticleThe case of drug causation of childhood asthma: antibiotics and paracetamol

Konrad Heintze¹ and Karl-Uwe Petersen²  

(1)

RWTH Aachen University, Aachen, Germany

(2)

Institute of Pharmacology and Toxicology, RWTH Aachen University, 52072 Aachen, Germany

 

 

Karl-Uwe Petersen

Email: karluwe.petersen@post.rwth-aachen.de

Received: 5 October 2012Accepted: 27 November 2012Published online: 5 January 2013

Abstract

Aim

The rising prevalence of bronchial asthma has led to world-wide efforts to understand and stem this development. Cross-sectional studies appear to show that early childhood use of antibiotics may be an important contributory factor, with paracetamol as an additional suspected cause. However, mounting evidence, which is reviewed here, points to various confounding factors as the major reasons for these reported associations.

Methods

PubMed and EMBASE were systematically searched for studies on associations between antibiotics and/or paracetamol with asthma and/or wheezing, published up to November 2012. A total of 64 pertinent studies were identified, 35 focusing on antibiotics, 19 on paracetamol, and ten addressing both antibiotics and paracetamol, bringing the number of relevant datasets to 74.

Results

Numerous studies were cross-sectional and made no adjustment for the indication of antibiotics or paracetamol; consequently, they were unable to dismiss possible confounding by indication. Where such adjustments could be performed (mostly in longitudinal studies), they substantially weakened or entirely eliminated the association with asthma or asthma surrogates present in the unadjusted data.

Conclusion

The weight of evidence of the collected studies in our review strongly suggests that the association of antibiotics with childhood asthma reflects various forms of bias, the most prominent of which is confounding by indication. Recent studies and meta-analyses support the same conclusion for paracetamol. Truly indicated antibiotics should not be withheld from infants or young children for fears they might develop asthma. Likewise, there is no sound reason to replace paracetamol as the preferred pain relief and fever medication in this age group.

Electronic supplementary material

The online version of this article (doi:10.1007/s00228-012-1463-7) contains supplementary material, which is available to authorized users.

Keywords

 Antibiotics Paracetamol Acetaminophen Childhood asthma Wheeze Epidemiologic studies

Open access: http://link.springer.com/article/10.1007/s00228-012-1463-7/fulltext.html