Fetal acetaminophen exposure increases the likelihood that a child will develop attention-deficit/hyperactivity disorder ( ADHD ), according to a study published Feb. 6 in Nature Mental Health.
Prior research shows that upward of 70% of pregnant women use acetaminophen during pregnancy to control pain or reduce fever. The drug, which is the active ingredient of many pain-relief medications, is one of the few considered safe to take during pregnancy by the U.S. Food and Drug Administration.
The new findings suggest, however, that doctors should reconsider prescribing medications with acetaminophen to mothers during pregnancy, the researchers said.
"Most of the prior studies asked women to self-report whether they had taken Tylenol or anything that contained acetaminophen," said lead author Brennan Baker , a researcher at Seattle Children's Research Institute. Baker also works in the lab of Dr. Sheela Sathyanarayana , a UW Medicine pediatrician.
"This medication was also approved decades ago, and may need reevaluation by the FDA," said Sathyanarayana, the paper's senior author. "Acetaminophen was never evaluated for fetal exposures in relations to long-term neurodevelopmental impacts."
Acetaminophen is widely used during pregnancy, with 41–70% of pregnant individuals in the United States, Europe and Asia reporting use. Despite acetaminophen's classification as low risk by regulatory agencies such as the FDA, accumulating evidence suggests a potential link between prenatal acetaminophen exposure and adverse neurodevelopmental outcomes, including ADHD and ADHD autism spectrum disorder, the researchers noted.
This research tracked a cohort of 307 women from 2006 to 2011, who agreed to give blood samples during their pregnancy. The researchers tracked plasma biomarkers for acetaminophen in the samples.
The children born to these mothers were followed for 8 to 10 years. Among the women who did not use acetaminophen during pregnancy, the rate of ADHD was 9%, but for the women who used acetaminophen, the ADHD rate among their offspring was 18%.
Acetaminophen metabolites were detected in 20.2% of maternal plasma samples. Children whose mothers had these biomarkers present in their plasma had a 3.15 times higher likelihood of an ADHD diagnosis compared with those without detected exposure.
The association was stronger among daughters than sons, with the daughters of acetaminophen-exposed mothers showing a 6.16 times higher likelihood of ADHD while the association was weaker and nonsignificant in males. Researchers did not know why the association was stronger in females.
The investigators' analysis used data from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) research cohort , which comprised 1,031 pregnant individuals in Memphis, Tenn., who were enrolled between 2006 and 2011.
By happenstance, and not by design, the study cohort included only Black women, Baker said, adding that the results could be generalized to woman and children of any race or ethnicity.
Mothers often are advised to turn to acetaminophen, the primary agent in Tylenol, rather than ibuprofen, which is more likely to adversely affect the fetal kidney or heart, Baker said.
"(Acetaminophen) is really the only option to control fever or pain during pregnancy," he said.
So, what is a mother to do?
"There is obviously more work that needs to be done in this area," he said. "And we need to continually update our guidance."
For example, he suggested, during prenatal visits, patients should discuss the dosage of a drug that contains acetaminophen or talk about what pain it is intended to help manage, he said. Another drug class, such as triptans , is safe and effective for managing migraines, he added.
More work needs to be done to find out if some people can tolerate acetaminophen during pregnancy with no ill effects on the fetus while others cannot, he said.
He added that research findings on the effects of the drug and its potential risks during pregnancy have not been consistent.
One study recently released in Sweden, showed no link between maternal acetaminophen use and ADHD in their children; while another study out of Norway, did in fact find a link. The study out of Sweden, however, relied on self-reported data, Baker noted.
"The study out of Sweden, however, reported that only 7% of pregnant individuals used acetaminophen," Baker noted. "And that study could have underestimated the exposure.
"I think it goes back to how the data was collected," he added. "The conflicting results means that more research is needed."
Medical societies and the FDA should update guidance on the use of acetaminophen as safety data emerges, Sathyanarayana said.
