1. This meta-analysis could not conclusively attribute increased asthma risk to in utero or early life paracetamol exposure.
2. While initial analysis showed an association between paracetamol exposure and asthma risk, controlling for coincident upper respiratory tract infections negated the association.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Recent evidence has suggested that the early life environment may confer risk of developing asthma in pediatric populations. Some studies have suggested that exposure to paracetamol (acetaminophen) in utero or during the first two years of life may increase asthma risk. This study pooled results from cohort studies of paracetamol exposure during the first trimester to 2 years of life and asthma prevalence at 5 or more years of age. While a small increase in asthma risk was found during all three trimesters of in utero and two years post-natal paracetamol exposure, the association between exposure and risk of asthma was not significant when controlling for coincident upper respiratory tract infections. In addition, heterogeneity between studies precluded any clear risk that could be attributed to solely paracetamol exposure.
While this study attempted to conclusively assess the effect of early life paracetamol exposure on asthma, the lack of suitably rigorous studies and randomized controlled trials made this task difficult. Of note, this study was particular in its inclusion/exclusion criteria in only accepting cohort studies, making the conclusion that exposure likely does not increase asthma risk very plausible. A well-designed prospective cohort study with clearly defined exposure data and later asthma development (>5 years) would be of great benefit to support this meta-analysis’s findings.
In-Depth [meta-analysis]: Of the 1192 citations identified on the topic, only retrospective and prospective cohort studies that assessed paracetamol exposure before the 2nd year of life (including in utero) and assessed asthma development after at least 5 years of age were included in the analysis. Studies measuring wheezing as an endpoint were excluded, and only 11 studies were used for the subsequent analysis. Odds ratios of asthma risk at different exposure time points were, for first trimester 1.39 (CI95% 1.01-1.91), second trimester 1.17 (CI95% 1.04-1.31), third trimester 1.49 (CI95% 1.37-1.63), and during infancy 1.15 (CI95% 1.00-1.31). However, after adjusting or upper respiratory tract infections, the odds ratio of asthma risk during infancy fell to 1.06 (CI95% 0.90 to 1.22). While only 1 study assessed upper respiratory tract infections during pregnancy, the attenuation of risk was similar to those found during infancy.
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