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.