Paracetamol exposure and asthma: What does the evidence say? An overview of systematic reviews

To conduct an umbrella review collating the existing evidence to determine whether there is an association between exposure of Paracetamol in-utero or in infancy and the development of childhood Asthma.

In this review, systematic reviews with or without meta-analysis that reported the association between paracetamol and asthma in children were included. To identify relevant reviews, a search was performed in the electronic databases PubMed, the Cochrane Library, and Ovid MEDLINE. The protocol was registered in PROSPERO CRD42020156023. A separate search was conducted for primary studies from the last 5 years not yet included in systematic reviews reporting the association from January 2016 to March 2021.

The electronic searches identified 1966 review titles. After the removal of 493 duplicates, 1475 titles and abstracts were screened against the eligibility criteria. Full-text screening yielded six systematic reviews to be included in this review. The search for primary studies in the last 5 years yielded 1214 hits, out of which 5 studies were found suitable for inclusion. Three of them, that were not included in the systematic reviews, and have been summarised in this paper. The odds ratios (ORs) for the outcome of asthma in offspring of mothers with prenatal paracetamol consumption in any trimester were 1.28 (1.13-1.39) and 1.21 (1.02-1.44). For first trimester exposures, they were 1.12 (0.99-1.27), 1.39 (1.01-1.91), and 1.21 (1.14-1.28), for the second or third trimester, they were 1.49 (1.37-1.63) and 1.13 (1.04-1.23). For the third trimester only, the figure was 1.17 (1.04-1.31). Of the six reviews included, 1 had a low risk of bias, 2 had an unclear risk while 3 had a high risk of bias assessed using the ROBIS tool. There was no significant increased risk of asthma with early infancy exposure. The inter-study heterogeneity varied from I²  = 41% to I²  = 76% across reviews. In the primary studies, the OR for prenatal exposure ranged from 1.12 (0.25-4.98) to 4.66 (1.92-11.3) and for infancy exposure was 1.56 (1.06-2.30). All three included primary studies were adjudged to be of high quality using the Newcastle Ottawa scale.

There is a modest association between paracetamol exposure in-utero and the future development of asthma. Exposure in infancy has a less consistant association. All the studies done thus far are observational in nature, with their inherent biases. Further research, preferably randomized controlled trials are recommended to answer this pertinent question.