Jerusalem, Israel—Expectant mothers are encouraged to use acetaminophen for pain and fever reduction during pregnancy to avoid riskier drugs. A new study, however, questions whether the drug increases the possibility of neurodevelopmental disorders in the fetus if it is used for a longer duration.

A meta-analysis in the American Journal of Epidemiology points out that past studies have shown that long-term administration of low doses of acetaminophen may affect the development of the fetal nervous system and that this effect is often seen years after exposure during childhood.

Now, Hebrew University of Jerusalem researchers have conducted a systematic review and meta-analysis to assess the possible association between prolonged exposure to acetaminophen during pregnancy and the risk for attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Included were 132,738 mother-and-child pairs with a follow-up period of 3 to 11 years.

Results suggest that prolonged exposure to acetaminophen during pregnancy is associated with a 30% increase in relative risk for ADHD and a 20% increase in relative risk for ASD, compared with women who did not take acetaminophen during their pregnancy.

The meta-analysis was the first to be conducted, and researchers urge that the results be interpreted with caution because the studies had significant limitations, adding, “The available data is of observational nature only. Studies differed gravely in exposure and outcome assessment.” They also emphasized that pain and fever can be detrimental to a developing fetus, and there is no evidence that short-term use of acetaminophen is unsafe during pregnancy.

“Our study provides the first comprehensive overview of developmental outcomes following prolonged acetaminophen use during pregnancy,” said Ilan Matok, PhD, head of the Pharmacoepidemiology Research Lab, Institute for Drug Research, School of Pharmacy, Hebrew University Faculty of Medicine. “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.”