Acetaminophen is the main ingredient in Tylenol and many other pain medicines. It's often one of the only pain relievers doctors recommend to pregnant women for pain or fever. It’s long been viewed as safe during pregnancy and is used by a large number of pregnant women in the U.S. and abroad.
Experts are divided on the strength of the studies linking the medication to behavioral problems. None of them proved that the medications caused any of the health problems -- they only showed an association. And untreated pain or fever in pregnancy can also carry risks to an unborn child.
Hal C. Lawrence, MD, the CEO and executive vice president of the American College of Obstetricians and Gynecologists, says the studies “show no clear evidence that proves a direct relationship between the prudent use of acetaminophen during any trimester and developmental issues in children."
But researcher John Thompson, PhD, associate professor of pediatrics at the University of Auckland, says "evidence appears to be building” linking acetaminophen and behavior problems. In a 2014 study of 871 children, Thompson linked acetaminophen to ADHD symptoms in children ages 7 and 11.
Thompson says more study is still needed but “the results are consistent.”
Here’s what some of the studies showed.
Acetaminophen and Behavioral Problems
In the most recent study, researchers looked at data from nearly 7,800 mothers.
They asked mothers about their acetaminophen use at 18 and 32 weeks during their pregnancies, and again when their children were 5 years old. Each time, they were asked if they’d used the pain reliever in the past 3 months. At 18 weeks, more than half the mothers reported using acetaminophen; about 40% reported its use by week 32.
Overall, the children whose mothers took acetaminophen during pregnancy were about 1.4 times more likely to have behavioral problems and 1.3 times more likely to be hyperactive.
The fathers also reported their acetaminophen use. Their use of the drug was not linked with increased risks of behavioral issues; nor was the mothers' use after giving birth. That strengthens the link, the researchers say, and suggests the risk cannot be explained by other things.
"I would say we have evidence [acetaminophen use] is linked to behavioral difficulties," says Evie Stergiakouli, PhD, a lecturer in genetic epidemiology at the University of Bristol in the U.K. and leader of the recent study. "However, we should point out that the increased risk is quite small. That is a very important point."
She points out the study had limitations -- it didn’t look at how much acetaminophen the women took or for how long. The women also did not report why they used acetaminophen.
Stergiakouli can't explain the link, but she says that some evidence from animal studies suggests the medications might lead to abnormal brain development. Researchers found the strongest links to behavioral problems when acetaminophen was taken during the third trimester, a period of active brain development and growth.
The Consumer Healthcare Products Association (CHPA), which represents manufacturers and marketers of over-the-counter medicines, pointed out that ''the study has many limitations" and found only associations.
Several previous studies have focused on acetaminophen in pregnancy and later risks to children. Among the findings:
- Children whose mothers took acetaminophen during pregnancy were about 1.3 times more likely to be taking ADHD (attention deficit hyperactivity disorder) medications or have ADHD-like behaviors at age 7.
- Children born to women who had taken acetaminophen during pregnancy were about 1.4 times more likely to have hyperactivity and impulsivity symptoms than those whose mothers did not, according to Spanish researchers who followed more than 2,600 mother-child pairs for 5 years. They also found the boys had more symptoms of autism if their mothers took acetaminophen during pregnancy. The study did look at frequency of acetaminophen use and found higher risk with more use.
- A study released this year of more than 53,000 children in Norway showed a link between acetaminophen use in pregnancy and childhood asthma, although it didn’t look at the amount of acetaminophen taken. Study authors found acetaminophen use for colds, flu, fever, and pain in pregnancy all showed a “modest association” with asthma in 3- and 7-year-olds. But the study found untreated pain was also associated with an increase in asthma.
All those studies relied on women to report their acetaminophen use.
"The data seem to at least point to a correlation or link," says Rebecca Hoover, PharmD, assistant professor of pharmacy at Idaho State University, who led the study about ADHD behaviors at age 7.
But, she adds, “I think there is not enough evidence there to change practice. ... I would no longer say it's 100% safe, but nothing is 100% safe.”
The FDA agrees. In a 2015 review of pain medicine use during pregnancy, including acetaminophen, the agency said “reliable conclusions” could not be drawn from all the studies it reviewed because of design limitations or other problems. The agency recommends pregnant women talk to their doctor before using any prescription or over-the-counter medicines.
McNeil Consumer Healthcare, the maker of Tylenol, also notes that no studies have definitively proved that taking acetaminophen while pregnant causes developmental problems in children.
Aisling Murphy, MD, an assistant clinical professor in maternal-fetal medicine with UCLA Obstetrics and Gynecology, says another problem with the research is that it relies on parents’ reports of medication use and their children's behavior issues.
"Generally speaking, I always try to tell pregnant patients to avoid medication when possible," Murphy says.
Alternatives for pain relief include massage, hot or cold packs, or sitting in a chair with good back support to relieve back pain, Murphy says. If medication is needed, she says she advises her patients to take the lowest effective dose for the shortest time.
But "in situations where something is needed, acetaminophen would be our first-line medication,” she says.