Acetaminophen is still safe in pregnancy, despite controversy

By Robyn Horsager-Boehrer, M.D.

Acetaminophen is one of the few pain medications that is generally considered safe to take during pregnancy. It is preferred to nonsteroidal anti-inflammatory (NSAID) drugs, such as ibuprofen, which are proven to pose pregnancy risks such as low amniotic fluid or fetal kidney problems.

But a mass tort lawsuit has raised concerns about whether exposure to acetaminophen in utero could cause neurological problems in children.

According to news reports, 66 cases have been filed in which plaintiffs accuse major pharmacy retailers of failing to warn them that taking acetaminophen (such as Tylenol) during pregnancy could cause autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in children. The lawsuit does not name any pharmaceutical manufacturers.

Patients often ask about the safety of taking acetaminophen and other medications while pregnant. National guidelines and recommendations from the Society for Maternal-Fetal Medicine and the American College of Obstetricians and Gynecologists have not changed.

But patients are understandably concerned, so we took a closer look at what sparked the misperception that acetaminophen is unsafe in pregnancy – starting with wobbly research that created the initial concerns about the medication in 2018.

What the original research says

A meta-analysis published in the American Journal of Epidemiology about acetaminophen use during pregnancy combined information from 121 small studies. After eliminating duplicate and irrelevant information, researchers ended up with just seven studies’ worth of data. From that data set, they suggested a potential increased risk of ASD (20%) and ADHD (30%) in children whose mothers reported taking acetaminophen in pregnancy.

One of the studies analyzed found no association between the disorders and acetaminophen. And none found an increased risk for ADHD when acetaminophen was used for less than a week.

In short, no causal associations were found between acetaminophen and ASD or ADHD. While the data raise opportunities for further research, they don’t point to acetaminophen as a proven cause of either condition.

In the final paragraph of the meta-analysis, the authors clearly state, “…we believe care should be taken to avoid overstating the significance of the results of our analysis, because this could promote unnecessary anxiety among pregnant women.”

3 primary concerns with the data

1. The studies relied on patient recall of information.

About 60% of study participants remembered taking acetaminophen during pregnancy, after their children were old enough to be diagnosed with a condition – the mean age of children with ADHD, for example, was 3 years old.

When a family is faced with an upsetting diagnosis, they rack their brains for any possible exposure or event that might have led to the outcome. And, when presented with the possibility that taking acetaminophen might have been the culprit, it is not uncommon for people to misremember or overestimate their use of it to try to explain a neurological diagnosis.

2. Increased risk appeared to be skewed toward mothers over age 31.

Pregnancies after age 35 are generally considered higher risk for birth defects. This may be because older patients are more likely to have preexisting conditions that cause chronic stress and inflammation, which might explain the increased risk of ADHD and ASD.

3. No research was conducted on why participants were taking acetaminophen.

Having an extended high fever may be a sign of a viral or bacterial infection – and the infection, not the treatment, may be the actual culprit in contributing to neurological or developmental conditions.

The meta-analysis looked at durations of use from four days to more than 28. If participants were taking acetaminophen for more than a week at a time, the underlying condition driving the need for relief might have been the true risk factor.

While research has shown that occasional use is unlikely to harm the patient or fetus, taking acetaminophen long term is not advised during pregnancy.

While no causal association was found between acetaminophen and ADHD or ASD, the study raises important opportunities for more research – namely that clinical studies and meta-analyses still lack real-time data from pregnant patients.