Use of prescription paracetamol during pregnancy and risk of asthma in children: a population-based Danish cohort study

PURPOSE: Use of paracetamol during pregnancy may increase the risk of asthma in offspring. The association between prenatal exposure to maternal use of paracetamol and risk of asthma was investigated. METHODS: A cohort study of 197,060 singletons born in northern Denmark in 1996–2008 was conducted, with follow-up until the end of 2009. Maternal paracetamol use during pregnancy was defined as a redeemed prescription. Asthma in offspring was defined as at least two prescriptions of both a β-agonist and an inhaled glucocorticoid and/or a hospital diagnosis of asthma during follow-up. Absolute risk of asthma in offspring was estimated using the Kaplan–Meier method and incidence rate ratios adjusted for known risk factors were estimated using Cox proportional-hazards regression. RESULTS: Overall, 976 (0.5%) children were exposed prenatally to maternal use of prescription paracetamol. During follow-up, 24,506 (12.4%) children developed asthma. Absolute risk of asthma was 7.5% after 2 years and 14.4% after 10 years among the unexposed children. Corresponding risks were 12.7% and 21.6% among the exposed children. The adjusted incidence rate ratio was 1.35 (95% confidence interval: 1.17–1.57) for exposure in any trimester of pregnancy. A similar association was present for paracetamol exposure in each of the trimesters and for maternal use of prescription nonsteroidal anti-inflammatory drugs. Furthermore, maternal prescription use in the year following the relevant delivery also showed similar associations. CONCLUSION: A robust association was found between prenatal exposure to maternal use of prescription paracetamol and the risk of asthma; however, noncausal explanations could not be ruled out for such association.