Children of women who take paracetamol during pregnancy may be at higher risk of developing attention-deficit hyperactivity disorder (ADHD), a new pilot-style study suggests. But experts warn this should not prompt a change in recommendations around paracetamol use.
Paracetamol is the most commonly used medication for pain and fever in Australia, including among pregnant women. Although it readily crosses the placenta, it is considered safe when taken at the recommended dose.
The study is published today in the journal JAMA Pediatrics, alongside an editorial which concludes the authors have made an “interesting observation” but it would be wrong for women and doctors to change their practices based on the findings.
The joint US-Danish research team, led by Zeyan Liew from the University of California, set out to test the hypothesis that paracetamol affected sex and other hormones which could impact on brain development and cause behavioural dysfunction.
The researchers studied 64,000 children and mothers from the Danish National Birth Cohort born between 1996 and 2002. The mothers described their paracetamol use, along with a list of other pain relievers, in three phone interviews during pregnancy and again after childbirth.
After the children turned seven, the researchers asked the parents to complete a questionnaire about any behavioural problems their child might have. The researchers also collected data about ADHD diagnoses and medication prescriptions from Danish registries.
More than half of the mothers (56%) reported using paracetamol during pregnancy.
Children of women who took paracetamol during pregnancy were 13% to 37% more likely to have a diagnosed hyperkinetic disorder (the European equivalent of ADHD), to be taking ADHD medication, or to have ADHD-like symptoms, compared with children of mothers who took none.
The researchers said the risk increased when the women used paracetamol in more than one trimester.
Adjunct senior lecturer at Monash University George Halasz said the research was best described as a pilot study. “It’s so preliminary that I wouldn’t expect the findings to have any direct impact on anything else other than the formation of a substantial study,” he said.
“To have a policy and practice change on intervention during pregnancy, the onus is on the research to prove, within the realms of science, the high probability that there is a causative link. This doesn’t even go to the earlier level of an associative link.”
Dr Halasz said the idea of testing for ADHD risk factors was also a hornet’s nest because researchers still don’t know what caused the disorder, though some suggest it might have a genetic base.
“No one disputes that children have a whole range of behavioural and emotional problems that are linked to hyperactivity, but what is it still remains an open question.”
Clinical senior lecturer at Deakin University Michael Vagg said the JAMA Pediatrics study “may be a random finding which will go away when attempts to replicate it are made” and should not cause women to stop using paracetamol.
“We don’t have a firm idea exactly how paracetamol works, so the idea it could influence developing foetal brains in some way is not inherently implausible.
"There is, however, a huge amount of experience with paracetamol in pregnancy which has not previously suggested a link.”
Dr Vagg said expectant mothers should try to manage day-to-day pains with hot or cold packs, rest and pacing of activities before using medications.
But those with chronic pain problems who become pregnant should discuss their options with their GP or pain specialist, he said.
“There are health risks to mother and foetus associated with not treating headaches, backaches and fevers effectively during pregnancy, so changes to practice should not be made until the risk (if it is real) from paracetamol is more thoroughly understood.”
University of Western Sydney professor of midwifery Hannah Dahlen said there were many reasons women may take paracetamol that could make the outcome of ADHD an association, not a cause.
“For example, women who are anxious or stressed get more headaches and may take panadol for this, with the anxiety and stress being more of a causal factor than the paracetamol,” she said.
“It is unlikely that one environmental or genetic trigger is at play, with ADHD it is likely to be far more complex than being due to paracetamol use.
"Women tend to either take no drugs or use several during pregnancy so polypharmacy may be an issue.”
One of the major weaknesses of the study was the exclusion of 28,254 women because they missed one or more telephone calls, Prof Dahlen said. The inability of many women (28%) to remember when paracetamol was taken during their pregnancy also reduced accuracy.
Prof Dahlen said the fact that half the women in the study used paracetamol during pregnancy suggests “we may be getting complacent about its use”.
“Bottom line is, if you don’t really need a medication in pregnancy then don’t take it. Never presume any drug is completely safe in pregnancy,” she said.