In a first-of-its-kind meta-analysis, researchers at the Hebrew University of Jerusalem found a link between prolonged use of drugs containing acetaminophen (paracetamol or Tylenol) during pregnancy, and increased risk of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).

Acetaminophen is one of the most common medications used for treating pain and reducing fever during pregnancy and is considered safe if taken for a short period.

However, when taken over a longterm at low doses, acetaminophen has been shown in past studies as possibly having a detrimental effect on the development of the fetal nervous system. This effect is often seen years after exposure, during childhood.

The groundbreaking Israeli review and meta-analysis involving 132,738 mother-and-child pairs, with a follow-up period of three to 11 years, shows that prolonged exposure to acetaminophen during pregnancy is associated with a 30 percent increase in relative risk for ADHD (compared to those who did not take acetaminophen during pregnancy) and a 20% increase in relative risk for ASD.

No cause for alarm

Led by Ilan Matok at the Institute for Drug Research in the Hebrew University School of Pharmacy and doctoral student Reem Masarwa, the study was published April 24 in the American Journal of Epidemiology.

“Our study provides the first comprehensive overview of developmental outcomes following prolonged acetaminophen use during pregnancy,” said Matok, who heads the Pharmacoepidemiology Research Lab at the university’s Institute for Drug Research.

“Our findings suggest an association between prolonged acetaminophen use and an increase in the risk of autism and ADHD. However, the observed increase in risk was small, and the existing studies have significant limitations. While unnecessary use of any medication should be avoided in pregnancy, we believe our findings should not alter current practice and women should not avoid use of short-term acetaminophen when clinically needed.”

Also participating in the research were Einat Gorelik of the Hebrew University and the Health Ministry, Amichai Perlman and Hagai Levine of the Hebrew University of Jerusalem and Hadassah Medical Center, and Hadassah-Hebrew University Medical Center-Ein Kerem chief of pediatrics Dr. Shimon Reif.

The researchers emphasized that the results, which are based on analysis of observational data only, should not cause unnecessary anxiety and that it is important to treat pain and fever during pregnancy to avoid danger to the developing fetus. They suggest that if a pregnant woman has fever and/or pain that cannot be managed by short-term acetaminophen use, she should consult her physician regarding further treatment.