Abstract
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 N=492 999, and used negative paternal control and sibling comparison approaches to explore unmeasured confounding.
After controlling for potential confounders, prescribed opioids, anti-migraine drugs and paracetamol were all positively associated with childhood asthma/wheeze risk at all ages (for example, odds ratios (95% Confidence Intervals) for asthma/wheeze at four years were: 1.39 (1.30–1.49), 1.19 (1.01–1.40) and 1.47 (1.36–1.59), respectively). The results of the paternal control analysis did not suggest the presence of unmeasured confounding by genetics or shared environment However, the sibling comparison analysis broadly suggested that associations between prenatal exposure to the analgesics above and asthma/wheeze were confounded by specific maternal factors (for example, ORs (95% CI) for asthma/wheeze at 4 years were: 0.91 (0.62–1.31), 0.50 (0.17–1.45) and 0.80 (0.50–1.29) for opioids, anti-migraine 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 which are intrinsic to the mother, such as chronic pain or anxiety.
Footnotes
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Conflict of interest: Dr. Shaheen has nothing to disclose.
Conflict of interest: Dr. Lundholm has nothing to disclose.
Conflict of interest: Dr. Brew has nothing to disclose.
Conflict of interest: Dr. Almqvist reports grants from Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM) framework grant no 340-2013-5867, grants from Stockholm County Council (ALF-projects), grants from Swedish Heart-Lung Foundation, grants from FORTE (grant no 2015-00289) , grants from Swedish Asthma and Allergy Association's Research Foundation, during the conduct of the study.
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