Prolonged Paracetamol Use in Pregnancy Linked to Higher Autism, ADHD Risk

A groundbreaking analysis covering over 130,000 women found a link between prolonged use of acetaminophen painkillers and a slight rise in the risk of autism spectrum disorder and ADHD in the child – but pregnant women shouldn’t throw away their Tylenol just yet.

This was the conclusion of the research leader, Dr. Ilan Matok, who heads the pharmacoepidemiology research lab at the Hebrew University of Jerusalem.

The paper describing the meta-analysis was published Tuesday in the American Journal of Epidemiology. The study was based on six papers on  the potential association between gestational use of acetaminophen and autism spectrum disorder, and five papers on attention deficit hyperactivity disorder, done in the United States and Europe, Matok told Haaretz. (No such work has been done in Israel, he says.)

But while the increase in risk that the analysis found might seem impressive, the increase is actually small, Matok says.

Prolonged exposure to acetaminophen during pregnancy was associated with a 30 percent increase in relative risk for ADHD (compared to women who didn't take acetaminophen during pregnancy). The increase in relative risk for ASD was 20 percent, the researchers write.

“In absolute terms, the risk for ASD is about 1 percent, and the risk from prolonged gestational acetaminophen use rises to about 1.2 percent,” Matok says.

As for ADHD, the argument over what constitutes the disorder, let alone how many people suffer from it, remains hotly debated. If, for the sake of argument, the absolute risk is about 6 percent, prolonged use in pregnancy would increase that “a little bit,” Matok says.

What is prolonged use? “Use of a few days to relieve pain or fever is fine,” Matok adds.

His cut-off point for longer use is that a pregnant woman suffering from either pain or fever for more than a few days should consult a doctor. She could have an underlying condition that could hurt the baby such as a bacterial or viral infection, which should be diagnosed and treated appropriately.

Acetaminophen is still considered a safe drug for use during pregnancy in the short term, but not for weeks.

Acetaminophen is sold in Israel and the United States chiefly as Tylenol and in Europe as paracetamol. There are some other brands around the world.

Though the product is usually considered safe for pregnant women, the studies that the analysis looked at indicated a slight increase in absolute risk resulting from prolonged exposure. The studies had significant limitations, Matok says.

He also stresses that the analysis focused on ADHD and ASD, and didn't consider other areas such as possible links between neonatal and natal use of acetaminophen and the risk of developing gestational asthma. Studies on that have been done in the U.K. and Norway, for instance.

For another example, a mouse study suggested links between gestational paracetamol exposure and disruption of males' reproductive organs. A 2016 opinion in The New York Times touches on various issues in "The Trouble with Tylenol and Pregnancy." 

The meta-study covered 132,738 mother-and-child pairs with a follow-up period of three to 11 years. It was written with doctoral student Reem Masarwa. Dr. Amichai Perlman and Dr. Hagai Levine of Hebrew University and Hadassah Medical Center took part in the research.