Prescribed analgesics in pregnancy and risk of childhood asthma

Many epidemiological studies have reported a positive association between prenatal exposure to paracetamol and childhood wheezing and asthma. We investigated whether the link between prenatal analgesic exposure and asthma/wheeze is specific to paracetamol, and whether it is causal or confounded.Using linked Swedish health register data we investigated the relation between various prescribed analgesics in pregnancy and the risk of childhood asthma/wheeze in a population of 492 999, and used negative paternal control and sibling comparison approaches to explore unmeasured confounding.After controlling for potential confounders, prescribed opioids, antimigraine drugs and paracetamol were all positively associated with childhood asthma/wheeze risk at all ages (e.g. for asthma/wheeze at age 4 years: adjusted OR 1.39 (95% CI 1.30-1.49), 1.19 (95% CI 1.01-1.40) and 1.47 (95% CI 1.36-1.59) for opioids, antimigraine drugs and paracetamol, respectively). The results of the paternal control analysis did not suggest the presence of unmeasured confounding by genetics or shared environment. However, the sibling control analysis broadly suggested that associations between prenatal exposure to the analgesics and asthma/wheeze were confounded by specific maternal factors (e.g. for asthma/wheeze at age 4 years: adjusted OR 0.91 (95% CI 0.62-1.31), 0.50 (95% CI 0.17-1.45) and 0.80 (95% CI 0.50-1.29) for opioids, antimigraine drugs and paracetamol, respectively).We propose that analgesic use in pregnancy does not cause childhood asthma/wheeze and that the association is confounded by unmeasured factors that are intrinsic to the mother, such as chronic pain or anxiety.