Using common painkiller in pregnancy might raise ADHD risk in children

Children whose mothers used paracetamol, also known as acetaminophen, during pregnancy are more likely to develop ADHD than those whose mothers didn’t, suggests a small study. While far from conclusive, the finding lends weight to the contested idea that the widely used pain reliever may affect fetal brain development.

Previous studies on paracetamol and neurodevelopmental conditions have provided conflicting findings. For instance, a 2019 study involving more than 4700 children and their mothers linked use of the painkiller in pregnancy with a 20 per cent greater risk of children developing ADHD. However, an analysis published last year of nearly 2.5 million kids showed no such association when comparing siblings who either were or were not exposed to paracetamol before birth.

One issue is that most of these studies rely on self-reported medication use, a significant limitation given that people may not remember taking paracetamol while pregnant. For example, only 7 per cent of participants in the 2019 study reported using paracetamol during pregnancy – far below the 50 per cent seen in other studies. “A lot of people take [paracetamol] without knowing it,” says Brennan Baker at the University of Washington in Seattle. “It could be the active ingredient in some cold medication you’re using, and you don’t necessarily know.”

So, Baker and his colleagues used a more accurate metric instead. They looked for markers of the medicine in blood samples collected from 307 women, all of whom were Black and lived in Tennessee, during their second trimester. None of them were taking medications for chronic conditions or had known pregnancy complications. The researchers then followed up with participants once their children were between 8 and 10 years old. In the US, about 8 per cent of children between 5 and 11 years old have ADHD.

On average, children whose mothers had markers of paracetamol in their blood were three times as likely to be diagnosed with ADHD than children born to mothers who did not – even after adjusting for factors like the mother’s age, pre-pregnancy body mass index (BMI), socioeconomic status and mental health conditions among their immediate family members. This suggests that using paracetamol during pregnancy may raise children’s risk of developing ADHD.

It is, however, also possible that the actual factor raising ADHD risk is whatever led someone to take paracetamol in the first place, rather than the drug itself. “They haven’t been able to account for things like the mother’s reason for taking [paracetamol], such as headaches or fevers or pains or infections, which we know are risk factors for adverse child development,” says Viktor Ahlqvist at the Karolinska Institute in Sweden.

But Baker believes it is the drug itself that is responsible. A subsequent analysis of tissue samples from 174 of the participants’ placentas showed that those using paracetamol had distinct metabolic and immune system changes. These changes are similar to those seen in studies that tested the effects of paracetamol in pregnant animals without an infection or underlying health condition.

“The fact we see the immune upregulation in animal models as well, I think, really strengthens the case for causality,” says Baker. “There is a lot of prior work showing that elevated immune activation during pregnancy is linked with adverse neurodevelopment.”

Still, these findings are far from conclusive. For one thing, the study included a small number of participants, all of whom were Black and lived in the same city – limiting the generalisability of the findings. For another, it only measured blood markers of paracetamol at one moment in time. These markers stick around for about three days, so the study probably captured more frequent users, and there may be a dose-dependent effect, says Baker.

“[Paracetamol] is currently the first-line therapeutic option for pain and fever in pregnancy,” says Baker. “But I think agencies like the [US Food and Drug Administration] and different obstetric and gynaecology associations need to be continually reviewing all available research and updating their guidance.”

Meanwhile, people should talk with their doctors if they are uncertain whether they should take paracetamol during pregnancy, says Baker.