New Research: Pain Reliever Is Not the Cause of ADHD

Does a common pain reliever cause or contribute to ADHD in a developing baby when taken by the mother while pregnant? The risks and benefits of acetaminophen use during pregnancy have been debated for several years, leaving expectant parents unsure if they should take the medication at all.

Acetaminophen, also known in Europe as paracetamol, is found in the leading name-brand pain relievers and fever reducers in the United States and is a component in other combination medications for over-the-counter migraine medication. It can also be prescribed in higher dosages and is included as an ingredient in some prescription medications. Acetaminophen was long considered to be safe for use during pregnancy until studies between 2014 and 2019 indicated it could play a role in the prenatal development of ADHD or autism spectrum disorder.

Since then, medical professionals have urged caution for women who take the medication during pregnancy but have also pointed out that the studies showed casual association (two or more things happening at the same time) but not causative association (that one thing leads directly to another).

Now, a new study may be able to offer parents some reassurance and relief regarding this pain reliever. The proposed link between ADHD and acetaminophen does not seem to connect, meaning the pain reliever does not appear to play any role in the development of ADHD.

“We hope that our results provide reassurance to expectant parents when faced with the sometimes fraught decision of whether to take these medications during pregnancy when suffering from pain or fever,” says the study’s co-senior author Renee M. Gardner, PhD, of Sweden’s Karolinska Institutet.

A stronger genetic association with ADHD than acetaminophen during pregnancy

Dr. Gardner and colleagues reviewed the medical records of about two and a half million children in Sweden who had a diagnosis of ADHD and their mothers’ use of acetaminophen, similar to the original studies in the late 2010s. This time, though, they did a sibling control analysis of almost two million additional children.

When they analyzed matched full sibling pairs (one sibling has ADHD or ASD and the other does not), the sibling control analysis showed no evidence acetaminophen use during pregnancy was linked to autism, ADHD, or intellectual disability.

It has been shown in other studies, unrelated to the current one, that if a sibling already has ADHD, the second sibling has a 32% chance of also having ADHD. This increases to 70%-80% if the siblings are identical twins.

“Sibling comparisons allow us to control for familial characteristics that might explain an apparent relationship between acetaminophen use during pregnancy and risk of neurodevelopmental conditions,” says Brian Lee, PhD, from Drexel’s Dornsife School of Public Health. “Genetics likely play a role, but future work to elucidate this mechanism is crucial.”

Relief for expecting parents

When earlier research on a possible link between acetaminophen use during pregnancy and ADHD was first published, the worry of many parents was that by taking a common medication they had somehow “caused” their child to have ADHD. Medical professionals and researchers pointed out at that time there was not a definitive link, but that avoiding pain relievers in pregnancy might be a good thing to do.

“Recall bias is a real thing,” says Jeffrey Kuller, MD, a maternal-fetal medicine specialist from Duke University. “There’s this guilt. ‘Did I cause this?’ I think it’s quite unlikely that it was the [acetaminophen] somebody took during pregnancy that led to those outcomes. That’s a huge reach and just a way to make people who are already feeling badly about a difficult situation feel so much worse.”

The current research, Dr. Kuller says, should reassure mothers that the medication for pain relief or to relieve a fever they took when needed, was not the cause of ADHD in their children.

Dr. Gardner wants her research to be a relief to parents regarding ADHD and pain medication. Advertisements and repeated news articles and blogs based on the earlier research frequently presented a convincing case to parents that there is a connection. Her research, she says, points out that there is not a causative connection between acetaminophen and ADHD.

“We hope that our results provide reassurance to expectant parents when faced with the sometimes fraught decision of whether to take these medications during pregnancy when suffering from pain or fever,” she says.

“Acetaminophen is still the safest known drug to take during pregnancy for problems like fever and pain,” says Salena Zanotti, MD, an obstetrician at the Cleveland Clinic. “When you’re pregnant, it’s riskier to have an untreated fever than it is to take acetaminophen.”

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