Publication Q&A: Associations of Maternal Blood Biomarkers of Prenatal APAP Exposure With Placental Gene Expression and Child Attention Deficit Hyperactivity Disorder

March 4, 2025 – Brennan Baker, PhD, researcher in the lab of Sheela Sathyanarayana, MD, MPH at Seattle Children’s Research Institute’s Center for Child Health, Behavior and Development published a recent study that shows placental correlations between the use of acetaminophen in pregnant persons and potential diagnosis of ADHD in late childhood.  

While these findings build upon previous research into the links between acetaminophen use and child neurodevelopment, specifically for ADHD, this is the first study to show that the placenta plays a role in the connection.  

The paper is authored by Seattle Children’s researchers Brennan Baker (first author), Brent Collett, PhD, Alison Paquette, PhD and Sheela Sathyanarayana in collaboration with research colleagues. These findings were availed by study participants from CANDLE, birth cohort study in Memphis, Tennessee. The placental gene analysis was supported by ECHO Pathways grant, spearheaded by investigators from University of Washington, Seattle Children’s Research Institute, University of Tennessee and University of California, San Francisco.

This study was funded in part by the National Institutes of Health.

Read the full article in Nature Mental Health (published Feb. 6, 2025)

Is this research a first in any way?

Research has been previously conducted in cohorts of pregnant persons to examine the potential effects of acetaminophen and other common over-the-counter medications. While these findings have pointed towards a positive link, this research measured acetaminophen use by surveying participants through standardized questionnaires.  Often, voluntary disclosure of dosage taken is recalled by memory, which could leave room for inaccuracy in data. 

This study is the first to look at the link between prenatal acetaminophen exposure and placental gene expression in humans. The placenta is a very important organ that can share a lot about the parent-child connection. It mediates the transfer of nutrients, oxygen and waste products between the parent and the fetus. Measuring gene expression in the placenta could better track molecular processes that are important for fetal development and could be disrupted by prenatal acetaminophen exposure.

How can this research lead to better ways to treat/prevent/diagnose? What is the potential impact?

With over 50% of pregnant individuals using acetaminophen in most populations worldwide, this research has the potential for substantial public health impact. These findings point to acetaminophen use in pregnancy being a potential risk factor contributing to the development of childhood ADHD, and the placental molecular mechanisms uncovered here could be targets for ADHD prevention. These results could impact future clinical recommendations for informing patients about potential risks.

What are the next steps and long-term goals for this research?

While this research continues, our team hopes to better understand how acetaminophen could cause harm to the developing brain through further studies. A few factors our team is hoping to explore include studying if the impact of acetaminophen use differs based on genetics and nutrition during pregnancy.

How can this research impact future care?

It is possible that mothers or children with specific genetic differences could be more adversely impacted by acetaminophen. It is also possible that acetaminophen could cause more harm among those with poor nutrition. It is important for our team to continue investigating these factors as answering these questions has the potential to shape acetaminophen recommendations based on the genetics or nutrition of a pregnant individual. While acetaminophen may still be the best first-line option for pain/fever in general, pregnant individuals should consult with their physician or pharmacist if they are uncertain whether acetaminophen is indicated and would actually provide relief, and before using it on a long-term basis.