Prenatal paracetamol exposure and risk of wheeze at preschool age

Aim: To analyse the association between prenatal paracetamol exposure and preschool wheeze. Methods: Data were obtained from a prospective, longitudinal study of a cohort of children born in the region of western Sweden in 2003; 8176 families were randomly selected. The parents answered questionnaires at 6 and 12 months and at 4.5 years of age. The response rate was 55%, i.e. 4496 of the 5398 questionnaires distributed at 4.5 years (83%). Inhaled corticosteroid (ICS) treated wheeze during the last year was regarded as a proxy for doctor-diagnosed asthma. Episodic viral wheeze was defined as wheezing only with viral infections and multiple-trigger wheeze as wheezing also in between infections. Results: In the multivariate analysis, the risk of ICS-treated wheeze was increased by paracetamol (OR 1.6; 95% CI 1.01-2.6). Within the ICS-treated group, the effect was significant for multiple-trigger wheeze (OR 2.4; 1.2-4.8) but not for episodic viral wheeze (OR 1.1; 0.5-2.3). Conclusion: Prenatal paracetamol exposure was an independent risk factor for ICS-treated wheeze at preschool age, especially among children with ICS-treated multiple-trigger wheeze. Although the analysis adjusted for e. g. maternal asthma and antibiotic use, the possibility of residual confounding by maternal indication (respiratory illness) should be acknowledged.