Giving children paracetamol increases asthma risk

Giving children paracetamol during their first year of life can increase their risk of developing asthma according to new research to be published in Lancet.

Lancet podcast with Dr Richard Beasley, director of the Medical Research Institute of New Zealand and co-author of the research.

Currently over 600,000 New Zealaners have asthma and the incidence has been increasing over the last 50 years but we don’t exactly know why. This study found that use of paracetamol in the first year of life and in later childhood, is associated with increased risk of asthma, rhinoconjunctivitis, and eczema at age 6 to 7 years. The study also found a strong dose-dependent association, with the risk of asthma symptoms being three-fold higher in children with frequent paracetamol use.

The study included over 200,000 six and seven year-old children from over 30 countries, as part of the International Study of Asthma and Allergies in Childhood (ISAAC) programme.

Expert comment on the research:

Dr Robin Taylor, Medical Director, Asthma and Respiratory Foundation of New Zealand and Professor of Respiratory Medicine, University of Otago

“The paper by Beasley et al. published in this week’s Lancet provides a potentially important insight into the question ‘Why has the prevalence of asthma increased so substantially worldwide over the last 50 years’. Drawing on the very large international database of the ISAAC study, with nearly 200,000 participants in 34 countries, the authors have explored the relationship between paracetamol exposure in the first year of life and the presence of the allergic disorders asthma, rhinitis and eczema, in the same children at age 6-7. This question is not new, but after a trickle of papers on the topic, this is the most substantial investigation of the question ever conducted

“The results show that the risk of asthma symptoms 5 years later is increased by approximately 20-25% in paracetamol users. This suggests that even modest exposure may have a bearing on the “training” of the immune system in early childhood – this is considered to be crucial in terms of the development of allergies. The reason for this is not at all clear. The mechanisms for how paracetamol might modify immune responses are entirely speculative. Importantly, the results do not indicate that children in the first year of life should not use paracetamol especially if a high fever poses the threat of dehydration or convulsions. The benefits may strongly outweigh any potential risks

“The authors are hesitant to say that their findings represent is a causal relationship, and I agree with this. It remains possible that the use of paracetamol is a “marker” for some other “lifestyle” issue causing allergy, although in such a large study from so many varying countries with differing asthma and allergy prevalence rates, it is more difficult to suggest that this is the case.

“More compellingly, the authors have shown that there is a dose response relationship between paracetamol exposure in the previous 12 months and the severity of asthma at age 6-7. This result raises a different question, namely should children with an established diagnosis of active asthma avoid paracetamol particularly if it is poorly controlled? On an individual basis this may be so. Clinicans are required to assess the ‘triggers’ which might be causing either acute asthma, or more commonly, chronic low grade symptoms.

“For example, chronic exposure to cats may increase persistent airways “twitchiness” in some individuals even though they claim that such exposure does not cause acute ‘attacks’. Cat avoidance may be recommended. Based on the paper by Beasley et al., paracetamol avoidance may also now be relevant in managing patients with unstable asthma who have a history of paracetamol use, just in case exposure to the drug is contributing to the overall clinical problem. Parents and clinicians should now be alert to this possibility – just as we already are regarding the use of other drugs such as non-steroidal anti-inflammatories and beta-blockers and their potential to adversely affect asthma.”

Expert comment gathered by the Australian Science Media Centre:

Dr Adrian Lowe is a Research Fellow at the Centre for Molecular, Environmental, Genetic & Analytic Epidemiology, University of Melbourne.

“This is a very interesting paper as it is based on enormous numbers of participants and it is international which is quite unique in this area.

“These results do not definitively show that early exposure to paracetamol increases the risk of childhood asthma, due to the methods they have used. Specifically they have asked for parents to recall paracetamol use in early life when the child is 7 years of age. This opens up the risk of recall bias: parents of kids who have asthma might remember giving them paracetamol more readily than parents whose children are free of asthma.

“Secondly, you need to question why these kids are getting paracetamol in early life. The main reason is for treatment of infection. There are a number of early life infections that have been linked to increased risk of asthma. So in this type of observational study it is hard to separate whether it is the paracetamol or the underlying infection, for which the paracetamol was given, that is the cause for the increased risk of asthma. Furthermore, the increase in risk of asthma associated with early life paracetamol use is modest. Collectively these issues make it questionable whether or not these results are due to a cause and effect relationship.

“It is important to remember that high fevers in babies can have some very serious consequences. Paracetamol is very useful in managing high fevers in these kids. I would be very worried if these results stopped parents and doctors giving paracetamol to manage high fevers in young children.”

Dr Raymond Mullins is an Australian consultant physician practicing in the specialty of clinical immunology and allergy. He is President elect of the Australasian Society for Clinical Immunology and Allergy (ASCIA)

“This study shows a statistically significant increased risk of asthma symptoms (using ISAAC methodology) in children aged six to seven years with a history of paracetamol use during the first year of life and later infancy. This risk appears to be greater for those using high doses and using this medication more regularly to treat fever. The strength of the study lies in the large number of children studied (over 200,000), the number of centres and countries examined (73 and 31, respectively) and the reproducibility of this observation in multiple countries around the world both in developing and westernised countries.

“Interestingly, a similar trend was found linking paracetamol use with hay fever and eczema symptoms, suggesting that any influence of paracetamol was not just restricted to the lower airways. These findings represent a fascinating phenomenon, and while they may not explain all of the increases observed an allergic disease in the last couple of generations, they do have the potential to influence our approach to treating fever in young children. The exact mechanism by which paracetamol exerts this effect remains unclear at this time and merits further study. It will certainly also be interesting to see whether future studies show a similar relationship that might explain recent some of the food allergy trends as well.”

Professor Philip Thompson is Director of the Lung Institute of Western Australia

“This is an important landmark study assessing environmental links to childhood allergic disease including asthma. The finding that the use of paracetamol early in life is associated with these diseases is important and requires more studies to be undertaken to see if a mechanism can be found and if prospective studies can confirm these results. At this stage the evidence is not strong enough to change our current treatment recommendations.”

The SMC in partnership with the AusSMC will be hosting an online briefing with the New Zealand author of this paper on Friday 19 September at 12pm. Please contact the AusSMC for further information.

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