Children who take paracetamol during their first two years of life may be at a higher risk of developing asthma by the age of 18, especially if they have a particular genetic makeup, a study has found.
Research presented at the European Respiratory Society International Congress in Paris showed the link between paracetamol use and asthma seemed strongest in those who had a particular variant of the glutathione S-transferase (GST) gene, GSTP1.
But the study authors stressed that the findings showed only that there was an association between paracetamol and asthma – not that paracetamol caused the lung condition.
Paracetamol is recommended by the NHS to treat most kinds of childhood ailments, including headache, stomach ache, ear ache, and cold symptoms, while it can also be used to reduce fever. The leading brand is Calpol.
The research, carried out at the University of Melbourne, Australia, looked at 620 children who had been followed from birth to 18 years old as part of the Melbourne Atopy Cohort Study.
They had been recruited to the study before they were born because they were considered to be potentially at high risk of developing an allergy-related disease as they had at least one family member (mother, father or sibling) with a self-reported allergic disease (asthma, eczema, hay fever or a severe food allergy).
After their birth, a research nurse rang the family every four weeks for the first 15 months, and then at 18 months and at two-years-old to ask how many days in the previous weeks had the child taken paracetamol.
When the children were 18-years-old they gave a blood or saliva sample, which was tested for variants of the GST genes: GSTT1, GSTM1 and GSTP1.
They were also assessed for asthma, and a spirometry test was performed to measure the amount of air inhaled and exhaled when breathing through a mouthpiece.
Researchers found one variant of the GSTP1 gene – GSTP1 Ile/Ile (in which the amino acid Isoleucine (Ile) is inherited from both parents) – was associated with almost twice the risk of developing asthma.
Xin Dai, a nurse and PhD student at the university, said: “We found that children with the GSTP1 Ile/Ile variant had 1.8 times higher risk of developing asthma by the age of 18 years for each doubling of the days of paracetamol exposure when compared to children who were less exposed.
“In contrast, increasing paracetamol exposure in children who had other types of GSTP1 did not alter the risk of asthma.
“We also found effects in children who had a variant of GSTM1 in which one part is not functioning.
“In these children increasing paracetamol use was associated with small, but significant reduction in the amount of air they could forcibly breathe out in one second at 18 years.
“Our findings provide more evidence that paracetamol use in infancy may have an adverse effect on respiratory health for children with particular genetic profiles and could be a possible cause of asthma.
“There is mounting evidence that the GST superfamily of genes, including three major classes, GSTM1, GSTT1 and GSTP1, are associated with various diseases, including cancers, asthma, atherosclerosis, allergies, Alzheimer’s and Parkinson’s disease. Our study adds to this body of evidence.”
Commenting on the study, Neil Pearce, professor of epidemiology and biostatistics at the London School of Hygiene and Tropical Medicine, said: “The idea that paracetamol use early in life may increase the risk of developing asthma has been around for about 20 years. It has been extraordinarily difficult to prove or disprove.
“The problem is that children are not given paracetamol early in life for no reason. They are often given it because they have respiratory infection.
“It may be the infection which increases the risk of asthma, not the paracetamol.
“The picture is further complicated because these children are often also given antibiotics, which is also a possible risk factor for developing asthma.
“This study adds one important finding, namely that the association between early life antibiotic use and subsequent asthma risk occurred in children with a particular genetic variant (the GSTM1 null genotype).
“This perhaps provides one more piece of evidence in support of the idea that the association between early life paracetamol use and asthma may be causal, but there is a long way to go before we can be more certain about this.”