(© luengo_ua – stock.adobe.com)

SEATTLE — Acetaminophen is one of the most commonly used medications by women during pregnancy. About 70% of expectant mothers in the United States, Europe, and Asia take this over-the-counter pain reliever, known by brand names like Tylenol and as paracetamol in some countries. But compelling new research suggests this widely used medication may be linked to a significantly increased risk of attention deficit hyperactivity disorder (ADHD) in children when taken during pregnancy.

A study published in Nature Mental Health found that children whose mothers had detectable levels of acetaminophen in their blood during pregnancy had more than three times the odds of receiving an ADHD diagnosis between ages 8-10. The effect appeared to be stronger in girls, with an odds ratio of 6.16, though researchers noted that the difference between boys and girls was not statistically significant due to the study’s sample size.

Unlike previous research that relied on mothers remembering and reporting their medication use—which can be unreliable—this study used biomarker analysis of maternal blood samples to measure acetaminophen exposure. “Most of the prior studies asked women to self-report whether they had taken Tylenol or anything that contained acetaminophen,” said lead author Brennan Baker, a researcher at Seattle Children’s Research Institute, in a statement. “This medication was also approved decades ago, and may need reevaluation by the FDA,” added senior author Dr. Sheela Sathyanarayana, a UW Medicine pediatrician.

Researchers from the University of Washington and several other institutions studied 307 African American mother-child pairs in Memphis, Tennessee, as part of the CANDLE study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood). Blood tests revealed acetaminophen in 62 mothers (20.2%) during their second trimester of pregnancy. When these children reached ages 8-10, 17.7% of them had received an ADHD diagnosis, compared to only 8.6% of children whose mothers showed no acetaminophen exposure. The exposed children were also more than twice as likely to be taking ADHD medications.

Moving beyond simply documenting this connection, the researchers investigated how acetaminophen might influence fetal development. They analyzed tissue samples from the placenta and discovered that acetaminophen exposure triggered significant changes in immune system activity and energy production at the cellular level.

These changes were particularly notable in female children. The drug appeared to increase the activity of certain immune-related genes that may influence brain development. The study found a 360% increase in IGHG1 gene expression in placental tissue of girls later diagnosed with ADHD, though this was not definitively linked to acetaminophen exposure. “We identified altered placental IGHG1 expression as a possible mechanism linking prenatal APAP exposure to child ADHD in females,” the study noted, while also cautioning that “causality cannot be inferred from these data.”

Public Health Implications

The findings raise important questions about current medication safety guidelines during pregnancy. While acetaminophen is presently considered the safest pain reliever for use during pregnancy, accumulating evidence suggests the need for further evaluation. “Medical societies and the FDA should update guidance on the use of acetaminophen as safety data emerges,” said Sathyanarayana.

The study’s results align with previous research showing that frequent or long-term acetaminophen use during pregnancy may carry more risks than occasional use. Several earlier studies found connections between prenatal acetaminophen exposure and various neurodevelopmental outcomes, but most relied on mothers’ memories of medication use rather than biological measurements.

Study Limitations and Next Steps

The study authors acknowledge several limitations. Acetaminophen levels were only measured once during pregnancy, meaning sporadic vs. frequent use could not be distinguished. Additionally, all participants were Black/African American from Memphis, which may limit broader applicability. The study also could not determine causation, as other genetic or environmental factors might contribute to ADHD risk. “There is obviously more work that needs to be done in this area,” said Baker. “And we need to continually update our guidance.”

Healthcare providers and expectant mothers now face complex decisions about pain management during pregnancy. The findings don’t necessarily mean that acetaminophen should never be used—fever and severe pain can themselves pose risks to fetal development. Instead, the research suggests the importance of carefully weighing the benefits and potential risks of acetaminophen use during pregnancy. “During prenatal visits, patients should discuss the dosage of a drug that contains acetaminophen or talk about what pain it is intended to help manage,” Baker advised.

This study represents a step forward in understanding the biological mechanisms that might underlie the observed link between acetaminophen and ADHD. Further research will be needed to confirm these findings in larger and more diverse populations and to determine whether alternative pain relief options should be considered for pregnant individuals.