YSPH Research Identifies Pregnancy Risks Associated With Acetaminophen Use

Two recent studies by researchers at the Yale School of Public Health have identified potential risks when pregnant girls and women take pain relievers containing acetaminophen.

The research adds to a growing body of evidence that suggests more caution when prescribing and taking the medication, though more studies are needed to confirm the findings.

In one recent study, YSPH Assistant Professor Zeyan Liew, Ph.D., M.P.H., and Professor Andreas Ernst of Aarhus University in Denmark evaluated the epidemiological evidence surrounding acetaminophen and child development and raised concerns over the drug’s use. After reviewing existing literature, they concluded that a number of studies have linked the pain reliever with an increased risk of asthma, neurodevelopmental disorders and genital malformations in children.

In the peer-reviewed paper, however, the scientists said some issues need to be addressed in these studies, such as measurement errors and methods used. They also recommend additional research into the biological mechanisms associated with acetaminophen use.

Liew also was part of a team of researchers from across the world that published a consensus statement in Nature Reviews Endocrinology on Sept. 23, 2021, calling for specific changes in federal drug recommendations to reflect concerns about acetaminophen.

“Our lab was among the first to report a potential harmful effect of acetaminophen on fetal brain development in a large longitudinal human cohort study,” Liew said in September. “It is time to take the growing body of evidence seriously and consider precautionary measures.”

Acetaminophen is a chemical compound that is commonly used to relieve mild to moderate pain and fever and can be found in over-the-counter brands such as Tylenol. Researchers estimate that as many as 65% of women in the United States have used medication with acetaminophen during pregnancy.

In another study (published in his M.P.H. thesis and under peer review at press time), YSPH Environmental Health Sciences student Tristan Furnary used human pluripotent stem cells, RNA sequencing, and metabolomics to identify cellular mechanisms that may be involved in the development of autism spectrum disorder. After exposing the stem cells in culture to clinically relevant doses of acetaminophen for six days, Furnary found acetaminophen to elicit the same gene expression patterns and metabolic behaviors in the cultures as those known to be associated with autism spectrum disorder.

“We believe that our approach of assessing the impact of clinically relevant acetaminophen concentrations on genetic expression and the metabolome reveals more nuanced effects of therapeutic doses,” said Furnary, who worked on the study under the guidance of Vasilis Vasiliou, Ph.D., department chair and Susan Dwight Bliss Professor of Epidemiology at YSPH, and Abha Gupta, M.D., Ph.D., assistant professor of pediatrics at the Yale School of Medicine.

“Tristan’s research is the first to examine the developmental effects of acetaminophen using human stem cells,” Vasiliou said. “In addition, his efforts represent an important first step towards our laboratories (in collaboration with the Yale Stem Cell Center) developing 3D neuronal organoids to study the effects of drugs and environmental pollutants on the human brain.”