Effects of Early Life Paracetamol Use on the Incidence of Allergic Disease and Sensitization: 5 Year Follow-Up of an Ethiopian Birth Cohort

Alemayehu Amberbir,Gail Davey,Charlotte Hanlon,John Britton,Andrea Venn,Girmay Medhin

doi:10.1371/journal.pone.0093869

Abstract

IntroductionThe hypothesis that paracetamol, one of the most widely used medicines, may increase the risk of asthma and allergic disease is of obvious importance but prospective cohort data looking at dose and timing of exposure are lacking.ObjectiveThe aim of the study is to investigate the role of paracetamol use in early life on the prevalence and incidence of wheeze, eczema, rhinitis and allergic sensitization, prospectively over 5 years in an Ethiopian birth cohort.MethodsIn 2005/6 a birth cohort of 1006 newborns was established in Butajira, Ethiopia. Questionnaire data on allergic disease symptoms, paracetamol use and numerous potential confounders were collected at ages 1, 3 and 5, and allergen skin sensitivity measured at ages 3 and 5. Multivariate logistic regression was used to determine independent effects of paracetamol exposure on the incidence of each outcome between ages 3 and 5, and prevalence at age 5.FindingsParacetamol use in the first 3 years of life was reported in 60% of children and was associated with increased incidence of wheeze, eczema, rhinitis and allergic sensitisation between ages 3 and 5 which was statistically significant for wheeze and eczema. High exposure (reported use in the past month at age 1 and 3) was associated with a more than 3-fold increased risk of new onset wheeze (adjusted odds ratio (OR) 3.64; 95% confidence interval, 1.34 to 9.90) compared to never users. Use in the past year at age 3 but not age 1 was associated with ORs at least as large as those for use in first year of life only. Significant positive dose-response effects of early life use were seen in relation to the prevalence of all outcomes at age 5.ConclusionsUse of paracetamol in early life is a strong risk factor for incident allergic disease in childhood.

Highlights

The hypothesis that paracetamol, one of the most widely used medicines, may increase the risk of asthma and allergic disease is of obvious importance but prospective cohort data looking at dose and timing of exposure are lacking
The other longitudinal study in children was our follow-up of an Ethiopian cohort, in which we saw an adverse effect of paracetamol use in the first year of life on incident wheeze at age 3 which we concluded was unlikely to be due to reverse causation or confounding by indication; no adverse effect on eczema was seen and other allergic outcomes were not available for analysis[9]
Children who were lost to follow up were not different to those followed in terms of paracetamol exposure or the outcomes collected

Summary

Introduction

The hypothesis that paracetamol, one of the most widely used medicines, may increase the risk of asthma and allergic disease is of obvious importance but prospective cohort data looking at dose and timing of exposure are lacking. Of the few longitudinal studies that have been conducted, only three have looked at personal use rather than in utero exposure, one in adults[14] and two in children [9,15], Lowe et al reported an adverse effect of paracetamol use on incident childhood asthma, but the effect diminished following control for confounding by early respiratory infections[15]. The other longitudinal study in children was our follow-up of an Ethiopian cohort, in which we saw an adverse effect of paracetamol use in the first year of life on incident wheeze at age 3 which we concluded was unlikely to be due to reverse causation or confounding by indication; no adverse effect on eczema was seen and other allergic outcomes were not available for analysis[9]

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Conclusion