In the largest epidemiologic study to date of the risk of giving birth to a child with autism, ADHD or intellectual disability following acetaminophen use during pregnancy, researchers found no association. The study is now published in JAMA.
The question of whether it is safe to take the pain-relieving and antipyretic drug paracetamol (sometimes called acetaminophen) during pregnancy flares up from time to time.
Most recently in 2021, a group of researchers, including several Swedish ones, warned in an article in Nature Reviews Endocrinology that paracetamol during pregnancy could increase the risk of autism, ADHD and intellectual disability.
Now comes a study that may add to the body of knowledge. Together with colleagues from Drexel University in Philadelphia, USA, researchers from Karolinska Institutet have conducted the largest epidemiological analysis to date of the use of paracetamol during pregnancy and the risk of giving birth to children with autism, ADHD or intellectual disability.
No difference between siblings
The researchers used registry data for 2.4 million children born in Sweden between 1995 and 2019. They then used the prescription register and reports to midwives during pregnancy to study the nearly 186,000 children whose mothers were treated with paracetamol during pregnancy.
These children were then compared with their own siblings in cases where the mother had not been treated with paracetamol when she was pregnant with them.
During the study's follow-up of up to 26 years, the researchers saw a slight increase in the prevalence of autism, ADHD and intellectual disability in the entire population.
However, when siblings exposed and unexposed to paracetamol in utero were compared, the researchers found no differences.
"We did not see any increased risk of ADHD, autism or intellectual disability in the children that could be attributed to paracetamol use during pregnancy," says Renee Gardner, associate professor of epidemiology and researcher at the Department of Global Public Health at Karolinska Institutet, and co-author of the study.
Listen to the doctor
The method of using non-exposed siblings helps the researchers control for many factors that might otherwise skew the results.
"Paracetamol users differ from non-users in a number of ways. These differences are difficult to capture using standard statistical methods. By comparing siblings, we can control for important family factors," says Brian Lee, an associate professor at Drexel University and a member of the A.J. Drexel Autism Institute in Philadelphia. Drexel Autism Institute in Philadelphia, and co-author of the study.
"We hope that our findings can reassure parents-to-be who are faced with the choice of whether or not to use paracetamol during pregnancy. However, you should always listen to your doctor's assessment of whether or not the medication is safe in each individual case," says Renee Gardner.
Since the use of paracetamol was obtained from the prescription register and from reporting by pregnant women to midwives, other non-prescription use of paracetamol was not captured in the analysis.
Also, the researchers did not investigate the side effects of maternal acetaminophen use during pregnancy on the children other than autism, ADHD and intellectual disability.
The research was funded by the US National Institute of Health (NIH).
Publication
"Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability", Viktor H. Ahlqvist, Hugo Sjöqvist, Christina Dalman, Håkan Karlsson, Olof Stephansson, Stefan Johansson, Cecilia Magnusson, Renee M. Gardner, Brian K. Lee, JAMA, online 9 April 2024, doi: 10.1001/jama.2024.3172.
Fass recommendations during pregnancy
Paracetamol is a pain-relieving and antipyretic drug sold under several different trade names such as Alvedon and Panodil. It is available in both non-prescription and prescription packaging.
In 2021, an article was published in Nature Reviews Endocrinology in which researchers warned of a link between paracetamol intake during pregnancy and an increased risk of autism, ADHD and intellectual disability.
However, they had not done any research of their own but made a consensus statement based on available epidemiological and animal studies. They also highlighted the increasing incidence of male genital malformations in the article.
The Fass text notes that neither malformations, fetal toxicity nor neonatal toxicity have been seen in data from pregnant women and that epidemiological studies in this area have not been able to show conclusive results.
The recommendation is that paracetamol can be used during pregnancy, but should be used at the lowest effective dose for the shortest possible time and with the lowest possible frequency.
Source: Fass, Nature.
