Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort

Abstract

Background-Acetaminophen has been associated with asthma and is in part metabolised via the glutathione pathway. Inner-city minority children have high asthma morbidity and a relatively high frequency of a minor allele variant in the glutathione S transferase Pi gene (GSTP1). We hypothesised that prenatal acetaminophen exposure would predict wheeze at age 5 years in an inner-city minority cohort and examined whether this association was modified by common polymorphisms in genes related to the glutathione pathway.

What does adolescent undiagnosed wheeze represent? Findings from the Isle of Wight Cohort

“…Paracetamol depletes glutathione levels, potentially facilitating airway damage and disease. Studies have suggested that paracetamol exposure at various stages of life increases asthma risk [11,21,38]. Assessment of paracetamol consumption has varied between studies.…”

“…Prospective studies have supported early life origins for childhood and early adult asthma [9][10][11][12][13][14][15][16]. More recently, attention has turned to early life as also being of possible relevance for the development of COPD [9,17,18].…”

Risk factors associated with wheezing in infants

“…29 A cohort study that evaluated the use of paracetamol during pregnancy observed that the use of this drug was associated with the presence of asthma at age five and the risk was higher in those who had a greater number of days of consumption, suggesting a possible dose-dependent association. 30 Therefore, the association between paracetamol and wheezing/asthma may simply reflect a reverse causality, i.e. children with a genetic predisposition to asthma or other allergies are more prone to febrile comorbidities, particularly URTI and therefore use more antipyretic medications such as acetaminophen.…”

Paracetamol Hypersensitivity: Clinical Features, Mechanism and Role of Specific IgE

“…The link between paracetamol and asthma has been extensively investigated [1,2,3,4,5,6], but the mechanism of hypersensitivity reactions is not well understood [7,8,9,10]. Discovered in 1878 and first used as an antipyretic in 1887, paracetamol has become increasingly popular due to the paucity of its adverse effects in therapeutic doses.…”