Prenatal and infant paracetamol exposure and development of asthma: the Norwegian Mother and Child Cohort Study

BACKGROUND:
Paracetamol exposure has been positively associated with asthma development. The relative importance of prenatal vs infant exposure and confounding by indication remains elusive. We examined the association of prenatal and infant (first 6 months) paracetamol exposure with asthma development while addressing confounding by indication.

METHODS:
We used information from the Norwegian Mother and Child Cohort Study, including 53169 children for evaluation of current asthma at 3 years, 25394 for current asthma at 7 years and 45607 for dispensed asthma medications at 7 years in the Norwegian Prescription Database. We calculated adjusted relative risks (adj. RR) and 95% confidence intervals (CI) using log-binomial regression.

RESULTS:
There were independent modest associations between asthma at 3 years with prenatal paracetamol exposure (adj. RR 1.13; 95% CI: 1.02-1.25) and use of paracetamol during infancy (adj. RR 1.29; 95% CI: 1.16-1.45). The results were consistent for asthma at 7 years. The associations with prenatal paracetamol exposure were seen for different indications (pain, respiratory tract infections/influenza and fever). Maternal pain during pregnancy was the only indication that showed an association both with and without paracetamol use. Maternal paracetamol use outside pregnancy and paternal paracetamol use were not associated with asthma development. In a secondary analysis, prenatal ibuprofen exposure was positively associated with asthma at 3 years but not asthma at 7 years.

CONCLUSIONS:
This study provides evidence that prenatal and infant paracetamol exposure have independent associations with asthma development. Our findings suggest that the associations could not be fully explained by confounding by indication.