Acetaminophen (the active ingredient in Tylenol and Excedrin) is the most common over-the-counter pain medication. A new, long-term study found that pregnant women who take the drug may be placing their unborn children at risk of developing attention deficit disorders.

In the report, “Acetaminophen Use During Pregnancy, Behavioral Problems, and Hyperkinetic Disorders,” published in JAMA Pediatrics, researchers found a compelling pattern of pregnant mothers taking acetaminophen and offspring who are later diagnosed with attention deficit hyperactivity disorder (ADHD), exhibiting ADHD-like behaviors, or taking ADHD medication.

Researchers looked at data on 64,322 children and mothers who were enrolled in a Danish study tracking pregnancies and children, from 1996 to 2002.

A series of computer-assisted telephone interviews taken throughout each pregnancy found that more than one-half of all the mothers reported using acetaminophen. Researchers discovered that children born to mothers taking the medication had up to a 37 percent higher risk of ADHD by age seven.

Mothers who continued to take acetaminophen into the second and third trimesters had the strongest associations with ADHD. According to the report, risks were elevated by 50 percent or more when the mothers used the painkiller for more than 20 weeks into their pregnancy.

According to the National Institutes of Health, ADHD is one of the most common childhood disorders. Symptoms include difficulty staying focused and uncontrollable hyperactive behavior.

The jury is still out about what causes ADHD—and why there are now so many cases. Some doctors insist that the epidemic is merely the result of better diagnosing, while others point to various environmental and genetic factors.

According Dr. Beate Ritz, professor and vice chair of the Epidemiology Department at the University of California, Los Angeles’ (UCLA) School of Public Health and one of the senior authors of the report, the impetus for the study was the drug’s emerging reputation as a hormonal disrupter.

“We know ADHD has to do with the balance of certain brain circuitry and systems that are interacting with each other,” she said. “If we disturb that, we could see how that would lead to some kind of neurodevelopmental disorder or shift.”

The preponderance of ADHD in boys, and general fetal sensitivity to hormonal changes, got researchers thinking about how a widely used hormonal disrupter might affect a developing fetus. Ritz’s colleague, Dr. Jørn Olsen, another senior author and chair of the UCLA Epidemiology Department, has seen previous patterns of fetal hormonal disturbance, with pregnant women and acetaminophen use showing a greater risk for children with undescended testicles.

Safety Reputation

In the 1950s, acetaminophen was a new over-the-counter alternative to remedy pain and headaches, but over the years it has come to dominate the market—not only due to its effectiveness but also its reputation for safety. Since the 1970s, doctors have favored the well-tolerated acetaminophen over aspirin or other painkillers, particularly for pregnant women.

While it may be the safest analgesic in the modern medical arsenal, acetaminophen still carries significant risks that some say require more caution.

In September 2013, ProPublica and NPR collaborated on a report on acetaminophen and found that for more than 30 years, the U.S. Food and Drug Administration (FDA) had either “delayed or failed to adopt measures designed to reduce deaths and injuries” related to the drug.

In that report, the big issue was dosage, which the FDA found to be a “persistent, important public health problem.” While relatively safe at recommended doses, even slight overdoses have been shown to cause liver damage, resulting in about 150 deaths a year, according to the Centers for Disease Control.

Fetal Vulnerability

The FDA recently announced that it will review its over-the-counter drug policy. However, the safety issue becomes even more complicated in regard to acetaminophen as a hormonal disrupter—where even relatively small doses may have a profound effect on the body’s endocrine system, especially in the midst of development.

“We know that during development the fetus actually prepares itself for the environment he or she may encounter after being born,” said Ritz. “That’s very true with nutrition, but there are also certain chemicals, stress hormones that the mother has in her body that can program the brain.”

Instead of traditional measures of toxicity where a high enough dose threshold triggers damage to cells, endocrine disruptive chemicals can interfere in delicate hormonal processes with doses previously considered benign. As a young life builds fine details of its neurological system toward the later stages of fetal development, the body can be particularly vulnerable to a chemical influence disrupting the process, according to Ritz.

“That can happen at much lower doses than what we would normally expect for toxicity,” said Ritz.

UCLA researchers want to see more tests with variations in the study design to see if the pattern holds up. But until that’s available in another decade or so, Ritz urges caution to pregnant mothers.

“I would want to be careful,” she said, adopting a pregnant mother’s perspective. “‘I had to deal with my headache in a different way, but at least I didn’t put my fetus at risk.’”