Is the Effect of Prenatal Paracetamol Exposure on Wheezing in Preschool Children Modified by Asthma in the Mother?

Abstract

Background: There seems to be an association between paracetamol consumption during late pregnancy and the prevalence of wheezing in infancy and childhood. The aim of the present study is to determine whether the aforementioned association is modified by the presence of asthma in the mother. Methods: A total of 1,741 children aged 3–5 years from an epidemiological survey performed in the province of Murcia (Spain) were included in the analysis. Data on paracetamol consumption (never, at least once during pregnancy or at least once per month during pregnancy), wheezing symptoms in the offspring (according to the International Study of Asthma and Allergies in Childhood protocol) and the presence of asthma in the mother, together with other known risk factors for asthma, were obtained by means of a questionnaire. Results: The mean age of the children was 4.08 ± 0.8 years and 51.1% were males. The overall prevalence of current wheezing was 20.2%. The frequency of paracetamol usage was similar among asthmatic and non-asthmatic mothers, and only a small proportion of them took this drug at least once a month (13.8% of asthmatics and 11.0% of non-asthmatics). Compared to the mothers who never took paracetamol, there was a significant association between the mother having taken paracetamol at least once per month during pregnancy and the offspring suffering from wheezing at preschool age, but only among non-asthmatic mothers (odds ratio 1.94, 95% confidence interval 1.34–2.79 vs. odds ratio 1.05, 95% confidence interval 0.21–5.08). This association was maintained after controlling for potential confounders (odds ratio 1.74, 95% confidence interval 1.15–2.61). Conclusions: The frequent usage of paracetamol during pregnancy is associated with the prevalence of wheezing in offspring during preschool years. Asthma in the mother might modify this association.

Asthma and pregnancy: emerging evidence of epigenetic interactions in utero

“…In the last year, a series of publications [74 , [75][76][77] have focused attention on the use of paracetamol in pregnancy as a risk factor for childhood asthma, supporting earlier observations [78]. As paracetamol depletes antioxidant glutathione levels, it has been implicated in the development of both abnormal lung function and immune function.…”

Monster Phase of Acetaminophen Use in Pregnancy: Current Vision of an Old Drug

“…From 1990s onwards APAP replaced aspirin as painkiller of choice since aspirin was found to be allied with Reyes syndrome [26]. Induction of asthma by APAP is biologically plausible, as APAP has been found to diminish glutathione, a key airway antioxidant [27][28][29][30]. More than 95% of glutathione is present in the reduced form as an antioxidant in respiratory tract lining fluid.…”

The acetaminophen and asthma hypothesis 10 years on: A case to answer

“…[2][3][4][5][6][7][8] This association is present for persistent wheezing rather than transient infant wheezing, extends to asthma at the age of 7 years, and is observed with hospital admissions for asthma in childhood, suggesting an effect on both the occurrence and severity of asthma. The observation that the association between the frequent use of acetaminophen in pregnancy and wheeze in preschool children is restricted to nonasthmatic mothers 6 indicates that this association cannot be due to mothers with asthma using acetaminophen in preference to aspirin or other nonsteroidal anti-inflammatory drugs. In 3 studies 2,7,8 data suggest that the effects might depend on the timing of prenatal exposure to acetaminophen; however, there are also data to suggest that the risk of childhood asthma might be present with acetaminophen use at any time during pregnancy.…”

“…1 Another potential mechanism for which there is conflicting evidence 32,33 is that by suppressing fever, acetaminophen might reduce the predominant T H 1 cytokine storm that occurs as part of the febrile response. Table I, [2][3][4][5][6][7][8][9][10][11][12][13][14][15]19,22,[25][26][27][28][29][30][31][34][35][36][37][38][39] there is evidence to suggest that acetaminophen use might be an important risk factor for the development of asthma and might have contributed to the increasing prevalence of asthma and allergic disorders over recent decades. Although further epidemiologic and laboratorybased studies will undoubtedly be informative, the priority is to undertake randomized controlled trials to explore the association of acetaminophen with both the development and maintenance of …”

“…Increased asthma risk of up to 2.1 (paracetamol exposure in utero), 2-8 1.5 to 3.2 (paracetamol use in infancy or childhood), 2,9 and up to 2.9 (paracetamol use in adults) [10][11][12][13][14][15] Dose response Present for paracetamol exposure in utero, 2,3 in childhood, 9 and in adults 10,12-14 Consistency/coherence Consistency between different studies in different age groups in different populations worldwide [2][3][4][5][6][7][8][9][10][11][12][13][14][15]22 Exposure before response Observed in studies of paracetamol exposure in the intrauterine environment, 2-8 in infancy, 9 and in adult life 14,15 Biologic plausibility Through increased oxidant-induced inflammation and potentially enhanced T H 2 response 27-31 Removal of exposure prevents disease Not yet examined Specificity…”