Paracetamol in infancy raises childhood asthma risk

Medical Tribune November 2008 SFXX
David Brill

Exposure to paracetamol during infancy could increase the subsequent risk of developing asthma, new research suggests.

Children aged 6 to 7 had a 46 percent increased risk of having asthma symptoms if they had received paracetamol for fever during their first year of life, data from the International Study of Asthma and Allergies in Childhood showed.

Use of the drug in infancy was also associated with an increased risk of rhinoconjunctivitis and eczema (odds ratios 1.48 and 1.35, respectively).

The authors of the Lancet study reviewed questionnaires completed by the parents or guardians of 205,487 children in 31 countries. [372(9643):1039-48]

“Because it was an epidemiological study we were unable to determine whether the relationship was causal … but when you put it together with all the other evidence we have it does suggest that paracetamol might be an important risk factor for the development of asthma,” said lead researcher Professor Richard Beasley, Medical Research Institute of New Zealand, Wellington.

Paracetamol should remain the preferred drug for relief of fever and pain in infancy but should be used sparingly, he said, noting that WHO guidelines recommend that the drug only be used for those with high fever (38.5°C or higher).

Beasley stressed that infants should not be switched to aspirin, which can cause the rare but potentially fatal Reye’s syndrome.

Current usage of paracetamol also increased the risk of asthma in a dose-dependent fashion. Children taking the drug on a regular basis were over three times as likely to have symptoms compared to those who were not taking it at all (odds ratio 3.23).

Dr. Chiang Wen Chin, an associate consultant in the department of pediatric allergy, immunology and rheumatology at KK Women’s and Children’s Hospital (KKH), Singapore, said that paracetamol use over the past 50 years has been safe and that the drug would remain first line for the majority of children (10mg/kg 4 to 6 hourly).

She added that ibuprofen can be given as a second line antipyretic, with tepid sponging also an option if the fever does not resolve.

Chiang noted, however, that there is a group of children who display angioedema and uticaria from high doses of paracetamol. [Pediatrics 2005 Nov;116(5):e675-80]

“We have demonstrated this in our own local patients that have presented to our clinic in KKH. Most of these children have allergic rhinitis, although not all of these have asthma,” she said.

“Our understanding of this pathophysiology is that paracetamol is a nonspecific COX-1 and COX-2 inhibitor, especially at high doses, and that this may result in a shunting of arachidonic acid production to predominantly leukotriene production, resulting in the release of various mediators such as mast cells and histamine release,” she said.

Beasley added that further studies – including randomized controlled trials of paracetamol in infancy – are needed to better understand the association with asthma.