A research team including two Yale researchers have cautioned pregnant women against the use of the common pain reliever acetaminophen, brand name Tylenol. They cited the growing body of research that suggests the drug might alter fetal development. 

In a consensus statement, the 13-member research team called for greater precaution against taking acetaminophen when pregnant and to forgo using the pain reliever unless its use is medically necessary. Lead author Ann Bauer, a researcher at University of Massachusetts Lowell Center for Autism Research and Education, was the primary contributor behind writing the statement. Zeyan Liew, assistant professor of epidemiology at the Yale School of Public Health, and Hugh S. Taylor, chair of Obstetrics, Gynecology and Reproductive Sciences at the Yale School of Medicine, both helped write the statement as well.

“The period of fetal development is a very vulnerable stage,” Taylor explained in an interview with the News. “Things are moving, changing quickly. The changes that occur during that time period are then programmed for the rest of our lives. Things that don’t affect adults may affect these crucial developmental windows.”

He said that up to 65 percent of women in the United States and more than 50 percent of women worldwide use acetaminophen when pregnant. 

The consensus statement was published in Nature Reviews Endocrinology on Sept. 23, and was the result of reviewing currently available literature on the effects of acetaminophen in pregnant women. In addition, the statement included support by signatories from 91 researchers, clinicians and public health experts across the world. 

The statement shared the growing body of experimental and epidemiological research that suggests prenatal exposure to acetaminophen could alter fetal development, which could in turn lead to neurodevelopmental, reproductive and urogenital disorders. Animal studies and epidemiological research involving humans were analyzed when writing the statement, supporting the team’s concern about the potential developmental risks associated with prenatal exposure to acetaminophen.

“We are interested in [Tylenol] exposure because we realized how commonly these medications are used by women,” Liew said. “And overall we are interested in medication intake and supplement intake.” 

The team reported that some risks associated with prenatal exposure to acetaminophen include reproductive and urogenital disorders, primarily affecting males. These disorders include cryptorchidism — a condition when one or both of the testes fail to descend — hypospadias — a birth defect marked by the misplacement of the urethra in boys — and testicular germ cell cancer. These could be accompanied by early puberty, decreased sperm counts and decreased fertility. 

In addition, the statement cited papers that suggested the use of acetaminophen during pregnancy had 26 identified positive associations with neurodevelopmental outcomes, primarily attention deficit hyperactivity disorder, or ADHD, but also including autism spectrum disorder, or ASD, language delays and decreased IQ. Sixteen out of 19 studies analyzing dose-response association corroborated the possible risk of these outcomes. 

Consistent with epidemiological data and studies, experimental animal studies suggested that prenatal acetaminophen exposure, even at low doses, increased the risk of brain and behavioral abnormalities in rodents and also caused disorders of the male urogenital tract.

Liew and Bauer both said that while there is considerable evidence demonstrating a relation between prenatal acetaminophen exposure and altered fetal development, it is still only correlative evidence.

“We can’t say there is a causal link yet, but it is compelling,” Bauer said. “It makes us all concerned that the animal data and the human data is quite consistent. It is consistent in the reproductive realms of suggesting that male reproductive function may be impacted.” 

Liew explained that the challenge ahead is to draw a causal link, but it remains very difficult as historically and currently, it is very hard to set up a study for vulnerable populations such as pregnant women. Bauer reiterated this point, sharing that they can’t do clinical trials with pregnant women when it could cause harm, and as a result, can only rely on animal and observational studies to find causal links. 

While a causal link has not yet been drawn, Bauer, Liew and Taylor hope this statement will inform pregnant women, as well as the broader obstetrics and gynecology community, about the associated risks of taking acetaminophen while pregnant. 

“My bias has always been that even if there is a cause for concern, we should at least take it seriously and think about it,” Taylor said. 

Bauer also shared that she hopes that the U.S. Food and Drug Administration will review these new findings because of the released statement. According to her, the FDA last reviewed the neuroscience data in 2015 when there were three studies and determined the results to be inconclusive. In 2021, there are now 30 human epidemiology studies. 

Bauer, Liew, and Taylor all reiterated and emphasized the same message: as with any other drug or medication, take acetaminophen only when necessary, in the lowest dose possible, for the shortest duration possible. That is not to say don’t take acetaminophen at all, but only when necessary, and if pregnant women have any concern or questions, they should always consult their physicians first, they said.

According to the CDC, between 2015 to 2017, a 17.8 percent increase was observed in the overall rate of developmental disabilities among U.S. children ages 3-17.

 

 

 

 

BRANDON WU