Paracetamol Use in Early Life and Link to Childhood Asthma: A Systematic Review

Abstract

Background: Exposure to paracetamol in the first two years of life may increase the risk of developing asthma in childhood. Recent epidemiologic studies have identified an increased risk of asthma with paracetamol use. Quantifying the relationship between paracetamol use and risk of asthma in children was investigated. In previous systematic reviews and metaanalysis, results have been conflicting; studies have had inconsistent confounders, size, and no use of control groups. Method: An exhaustive search of all the available medical literature was conducted using 4 databases, Medline-OVID, CINAHL, EBMR Multifile and Web of Science to identify pertinent articles. All clinical trials and observational studies were considered. For observational studies, those that clearly defined paracetamol exposure in the first two years of life and asthma diagnosis as a child (5-7) years were selected. Study quality was assessed with GRADE criteria. Results: Three birth cohort studies, and one multicenter cross-sectional ranging from 469 to 205 487 participants, from birth up to two years of life were included in the review that were later followed up between 5-7.5 years of age. In the large multicenter study after adjustments for sex, region of world, language and income, multivariate analysis with complete data only and risk of asthma in childhood and total days of paracetamol use in early life for fever was (OR 1.46 [95%CI 1.36-1.56]). In the largest birth cohort when adjusted for maternal factors in pregnancy and postnatal factors there was no significant effects of paracetamol use and childhood asthma (OR 1.11 [95%CI 1.00-1.23]). In this same study when children who had preexisting wheeze versus no wheeze, and effects of paracetamol and childhood asthma, there was a significant association for child with wheeze (OR 1.44[95%CI 1.13-1.83]). When adjustments were made for frequency of respiratory tract infections and total days of paracetamol use any indication in the other smaller birth cohort, there was no significance in a child with family history of atopy (OR 1.08 [95% CI 0.91-1.29]). In the smallest of studies included, after adjustments for chest infections, antibiotic use, and family history of atopy, there was no significance of childhood asthma and exposure to paracetamol (OR 1.78[95%CI .75-4.21]). Conclusion: The results from the review are inconsistent. It is suggested that exposure to paracetamol in the first years of life might be a risk factor for the development of asthma in childhood and direct causation is still questionable. Results do suggest that children with family history of atopy, or current asthma, and the use of paracetamol may precipitate asthma. Future RCT studies are needed. Keywords: Paracetamol, acetaminophen, asthma, child, infant