Pregnant women often take acetaminophen or paracetamol, better known by their brand names, Tylenol or Panadol, to relieve pain. These over-the-counter drugs are also recommended to reduce fevers in their newborns, despite the fact that animal and human studies suggest a link between prenatal acetaminophen exposure and neurodevelopment disorders such as attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

One reason why acetaminophen is still widely in use has to do with the fact that the U.S. Food and Drug Administration has not made recommendations about acetaminophen use during pregnancy, citing a lack of strong scientific evidence.

The findings, along with the results of previous studies, raise concerns about acetaminophen use during pregnancy.

That may soon change. Researchers from Johns Hopkins University have published a study of the association between acetaminophen use during pregnancy and the development of ADHD and ASD, analyzing objective, rather than self-reported, data. “Previous studies were based on self-reported maternal acetaminophen use. In our study, we measured acetaminophen and its metabolites in fetal cord blood as evidence of acetaminophen exposure in utero,” Xiaobin Wang, corresponding author on the study, told TheDoctor in an email. The findings, along with the results of previous studies, raise concerns about acetaminophen use during pregnancy.

The researchers measured levels of unchanged acetaminophen and two metabolites, or end products (acetaminophen glucuronide, and 3-[N-acetyl-L-cystein-S-yl]-acetaminophen), in samples of umbilical cord blood collected at birth from 996 mother-infant pairs enrolled in the Boston Birth Cohort. Study participants were followed prospectively at Boston Medical Center for almost 10 years.

By the time the children were about nine years old, 25.8 percent had been diagnosed with ADHD, 6.6 percent had been diagnosed with ASD, and 4.2 percent with ADHD and ASD. The researchers organized the samples into three tiers, according to levels of acetaminophen and acetaminophen metabolites detected in the samples.

Those women with samples in the middle tier had a 2.26 times greater risk for ADHD compared to the those in the lowest tier, while those with samples in the highest tier had a 2.86 times greater risk. Compared to those in the lowest tier, ASD risk was 2.14 times greater for those with samples in the middle tier and 3.62 times higher for those with samples in the highest tier.

“This information helps women and their providers weigh the risks and benefits of acetaminophen use during pregnancy and make an informed decision,” said Wang, a professor at Johns Hopkins Bloomberg School of Public Health.

Exactly how does acetaminophen use connect to attention deficit hyperactivity disorder and autistic spectrum disorder? Not all women who took acetaminophen during pregnancy had a child with ADHD or ASD, so identifying factors that contribute to acetaminophen toxicity is a topic for future research. Researchers also hope to identify the window of time during pregnancy when the fetus is most sensitive to acetaminophen exposure.

The study was published in JAMA Psychiatry.