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Acetaminophen, Asthma Link 'Overstated'http://www.medscape.com/viewarticle/835494Laurie Barclay, MD | DisclosuresThere is insufficient evidence of a link between early life exposure to acetaminophen (paracetamol) and asthma to warrant changing guidelines on early life paracetamol exposure, according to a systematic review and meta-analysis published online November 25 in the Archives of Diseases of Childhood.The included studies showed a highly variable association between asthma and exposure to acetaminophen in early pregnancy, as well as moderate confounding by respiratory tract infections for exposure during infancy."Paracetamol, a widely used analgesic and antipyretic, has historically been considered to be safe in both pregnancy and young children," write Mweene Cheelo, MSc, from the Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics at the Melbourne School of Population and Global Health, University of Melbourne, Australia, and colleagues. "However, paracetamol has recently been identified as a possible cause for the current asthma epidemic. Paracetamol replaced aspirin as analgesic of choice in the 1990s when aspirin was found to be associated with Reyes syndrome."To better understand the possible risk, Cheelo and colleagues reviewed longitudinal studies of the association between paracetamol exposure in utero or during pregnancy and the development of childhood asthma at age 5 years or older.Among 11 observational cohort studies meeting inclusion criteria (of 1192 potentially relevant studies), any use of acetaminophen during the first trimester was associated with increased risk for childhood asthma (five studies, pooled odds ratio [OR], 1.39; 95% confidence interval [CI], 1.01 – 1.91). However, only one of these studies adjusted for maternal respiratory tract infections, and between-study heterogeneity was considerable (I 2, 63%).Of six studies looking at infancy to age 2 years, three studies showed that increasing frequency of acetaminophen use during infancy was linked to greater odds of childhood asthma (pooled OR, 1.15 per doubling of days of exposure; 95% CI, 1.00 – 1.31). However, adjustment for respiratory tract infections in these studies attenuated the association (OR, 1.06, 95% CI, 0.92 – 1.22)."The evidence of an association between early life paracetamol and asthma is often overstated, and there is currently insufficient evidence to support changing guidelines in the use of this medicine," the review authors write.The authors note several limitations of the study include only a small number of studies for each exposure period, limited statistical power, inability to quantitate publication bias, and marked heterogeneity among studies looking at prenatal exposure."Further well designed clinical trials and/or cohort studies are required to definitely answer this question," the review authors write. "Respiratory tract infections appear to confound this association and it is essential that this be accounted for in future observational studies. Future studies should also assess the effect of paracetamol exposure on lung function outcomes given that paracetamol is proposed to induce oxidative stress on the airway."The authors have disclosed no relevant financial relationships. Arch Dis Child. Published online November 25, 2014.