Acetaminophen, found in over-the-counter products such as Excedrin and Tylenol, provides many people with relief from headaches and sore muscles. When used appropriately, it is considered mostly harmless. Over recent decades, the drug, which has been marketed since the 1950s, has become the medication most commonly used by pregnant women for fevers and pain.
Now, a long-term study by UCLA, in collaboration with the University of Aarhus in Denmark, has raised concerns about the use of acetaminophen during pregnancy.
In a report in the current online edition of JAMA Pediatrics, researchers from the UCLA Fielding School of Public Health show that taking acetaminophen during pregnancy is associated with a higher risk in children of attention-deficity/hyperactivity disorder and hyperkinetic disorder. The data raises the question of whether the drug should be considered safe for use by pregnant women.
ADHD, one of the most common neurobehavioural disorders worldwide, is characterised by inattention, hyperactivity, increased impulsivity, and motivational and emotional dysregulation. Hyperkinetic disorder is a particularly severe form of ADHD.
“The causes of ADHD and hyperkinetic disorder are not well understood, but both environmental and genetic factors clearly contribute,” said Dr. Beate Ritz, professor and chair of the department of epidemiology at the Fielding School and one of the senior authors of the paper. “We know there has been a rapid increase in childhood neurodevelopmental disorders, including ADHD, over the past decades, and it’s likely that the rise is not solely attributable to better diagnoses or parental awareness. It’s likely there are environmental components as well.”
“That gave us the motivation to search for environmental causes that are avoidable,” said the University of Aarhus’ Dr. Jørn Olsen, another senior author and former chair of the UCLA Fielding School’s epidemiology department. “Part of the neuropathology may already be present at birth, making exposures during pregnancy and/or infancy of particular interest. Because acetaminophen is the most commonly used medication for pain and fever during pregnancy, it was something we thought we should look at.”
More than half of all the mothers in the study reported using acetaminophen while pregnant. The researchers found that children whose mothers used acetaminophen during pregnancy were at a 13% to 37% higher risk of later receiving a hospital diagnosis of hyperkinetic disorder, being treated with ADHD medications or having ADHD-like behaviours at age 7. The longer acetaminophen was taken — that is, into the second and third trimesters — the stronger the associations. The risks for hyperkinetic disorder/ADHD in children were elevated 50% or more when the mothers had used the common painkiller for more than 20 weeks in pregnancy.
“It’s known from animal data that acetaminophen is a hormone disruptor, and abnormal hormonal exposures in pregnancy may influence fetal brain development,” Ritz said.
Acetaminophen can cross the placental barrier, Ritz noted, and it is plausible that acetaminophen may interrupt fetal brain development by interfering with maternal hormones or through neurotoxicity, such as the induction of oxidative stress, which can cause the death of neurons.
“We need further research to verify these findings, but if these results reflect causal associations, then acetaminophen should no longer be considered a ‘safe’ drug for use in pregnancy,” Olsen said.
(Source: UCLA, JAMA Pediatrics)