Acetaminophen, a widely used painkiller found in Excedrin, Tylenol and other over-the-counter pain relievers, has been linked for the first time with attention deficit hyperactivity disorder (ADHD).
A large study conducted in Denmark found that women who took acetaminophen while pregnant had a 37 percent higher risk of having a child diagnosed with hyperkinetic disorder, a particularly severe form of ADHD. The study is published in the Journal of the American Medical Association (JAMA) Pediatrics.
“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,” said Jørn Olsen, MD, The Institute of Public Health, University of Aarhus in Denmark.
Researchers at UCLA and the University of Aarhus looked at over 64,000 children and mothers who were enrolled from 1996 to 2002 in the Danish National Birth Cohort, a nationwide study of pregnancies and children. Women were asked about their use of acetaminophen and other painkillers while pregnant.
Acetaminophen was the most commonly used medication for pain and fever, with over half (56%) of the mothers reporting they used acetaminophen while pregnant.
In addition to the 37% higher risk of having a child with hyperkinetic disorder, women who took acetaminophen while pregnant had a 29% higher chance of having a child prescribed medications for ADHD and a 13% higher chance of a child exhibiting ADHD-like behaviors by age seven.
The longer acetaminophen was taken — into the second and third trimesters — the stronger the associations. The risks for hyperkinetic disorder/ADHD in children were 50% or more when the mothers had used the painkiller for more than 20 weeks in pregnancy.
“Acetaminophen can cross the placenta barrier and recent studies suggested that maternal use of acetaminophen increases the risk for cryptorchidism (undescended testis) in boys due to its endocrine-disrupting properties,” said Olsen.
“Maternal hormones, such as sex hormones and thyroid hormones, play critical roles in regulating fetal brain development, and it is possible that acetaminophen may interrupt brain development by interfering with maternal hormones or via neurotoxicity such as the induction of oxidative stress that can cause neuronal death.”
ADHD is characterized by inattention, hyperactivity, increased impulsivity, and motivational and emotional dysfunction. Experts say the research points to a new potential cause for the worldwide rise in cases of ADHD. Acetaminophen, also known as paracetamol, has been marketed since the 1950’s.
“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 UCLA Fielding School of Public Health and one of the senior authors of the study.
“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.”
Others experts cautioned that the findings do not prove that taking acetaminophen causes ADHD, only that a preliminary link between the two has been found.
“Findings from this study should be interpreted cautiously and should not change practice,” said an accompanying editorial in JAMA Pediatrics by Miriam Cooper and colleagues at the Cardiff University School of Medicine in Wales.
“However, they underline the importance of not taking a drug’s safety during pregnancy for granted, and they provide a platform from which to conduct further related analyses exploring a potential relationship between acetaminophen use and altered neurodevelopment.”
A recent study in Norway found that long term use of acetaminophen by pregnant women may adversely affect the development of their children.
The study from the Norwegian Institute of Public Health found that children exposed to acetaminophen for more than 28 days during pregnancy had substantially poorer motor skills, poorer communication skills and more behavioral problems compared to their unexposed siblings.
Acetaminophen has long been associated with liver injury and allergic reactions such as skin rash. In the U.S. over 50,000 emergency room visits each year are caused by acetaminophen, including 25,000 hospitalizations and 450 deaths.
The Food and Drug Administration has cautioned parents to be careful about the dose of acetaminophen for their children, but there are no specific warnings for pregnant women or nursing mothers.