Paracetamol, also called acetaminophen use in the first year of life or in early childhood has been associated with an increased risk of asthma, rhinoconjunctivitis (RC), and eczema between the ages of 6 and 7 years, according to an article released on September 19, 2008 in The Lancet.

Many hypotheses have been made about the cause of asthma, the common chronic respiratory condition which involves repeated inflammation and constriction of the airways. To investigate the risk factors for asthma, Professor Richard Beasley, of the Medical Research Institute of New Zealand, and colleagues performed a study as part of phase three of the International Study of Asthma and Allergies in Childhood (ISAAC) program.

In it, parents or guardians of more than 200,000 children in 73 centers in 31 countries between 6 and 7 years old were asked to complete written questionnaires regarding symptoms of several diseases including asthma, conjunctivitis, and eczema. Additionally, questions about several risk factors, including the use of paracetamol for the treatment of fever within the first year of life, and the frequency of paracetamol use in the previous year.

An increased risk of asthma symptoms in these children was associated with the use of paracetamol for fever in the first year of life. Paracetamol use in the last 12 months was associated with asthma symptoms, with a dose-response relationship. That is, medium use of paracetamol increased risk by 61% and a high dose caused an increased risk of more than 200%.

Severe asthma symptoms were also associated with paracetamol. Paracetamol use within a year of birth increased the risk of rhinoconjunctivitis by 48%, and increased the risk of eczema by 35%. A similar dose-response relationship was seen for these outcomes as well.

In conclusion, the authors point out that paracetamol should be further investigated to make better treatment recommendations. "Use of paracetamol in the first year of life, and in later childhood, is associated with risk of asthma, rhinoconjunctivitis, and eczema at age 6 to 7 years. We suggest that exposure to paracetamol might be a risk-factor for the development of asthma in childhood," they say. "We stress the findings do not constitute a reason to stop using paracetamol in childhood. Paracetamol remains the preferred drug to relieve pain and fever in children. However the findings do lend support to the current guidelines of the World Health Organization, which recommend that paracetamol should not be used routinely, but should be reserved for children with a high fever (38.5°C or above). The reason paracetamol became the preferred drug for treatment of fever in children was the risk of Reye's syndrome, a rare but serious complication of aspirin therapy in children. International asthma guidelines recommend that for both children and adults with asthma, paracetamol is the preferred drug to relieve pain or fever. Paracetamol is the preferred drug for asthmatics due to the risk that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) such as naproxen and ibuprofen may provoke attacks of asthma."

Professor R Graham Barr, Columbia University, New York, contributed an accompanying article that notes the importance of this controversial study."The report from ISAAC Phase Three is the largest and most important contribution to date on the growing literature, summarised well by Beasley and colleagues, on paracetamol use and childhood asthma. It ends, appropriately, with a question rather than a conclusion and that question is about causality," he says. Both the authors of the comment and those of the article indicate that further research is needed, including randomized control trials, which investigate the long-term effects of frequent paracetamol use.

Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase Three of the ISAAC programme
Richard Beasley, Tadd Clayton, Julian Crane, Erika von Mutius, Christopher K W Lai, Stephen Montefort, Alistair Stewart, for the ISAAC Phase Three Study Group
Lancet 2008; 372: 1039-48
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Anna Sophia McKenney