ARI on Prenatal Acetaminophen Use, Leucovorin, and Autism

ARI’s Commitment to Evidence-Based Research

ARI is committed to monitoring ongoing research and sharing accurate, evidence-based information with autistic people, families, researchers, and policymakers. This includes addressing questions about environmental influences and potential medical factors, such as the use of over-the-counter medications.

“We know there are subtypes of autism, with no single cause explaining the condition and no single intervention benefiting everyone on the spectrum. Research should focus on understanding these differences rather than generalizing findings to every autistic individual,” said ARI Chief Science Officer, Dr. Steve Edelson. “By identifying unique biological, developmental, and environmental factors within each subtype, we can begin to develop more targeted, effective approaches.”

Acetaminophen Research

The Autism Research Institute acknowledges that recent studies have examined potential associations between prenatal acetaminophen (commonly known as Tylenol in the U.S.) exposure and autism. While these studies contribute to our understanding of possible risk factors, ARI maintains that the current evidence does not establish a definitive causal relationship between acetaminophen use during pregnancy and autism.

Extensive studies, including a 2024 Swedish study analyzing nearly 2.5 million births, suggest that observed associations between prenatal acetaminophen use and autism may reflect familial confounding rather than a direct causal link. Research led by Dr. Mady Hornig of Columbia University underscores the complexity of these factors. Her work highlights the role of maternal immune responses and fever, showing that inflammation during pregnancy may affect neurodevelopment independently of medication use. Preliminary evidence also indicates that acetaminophen taken to reduce fever may be neutral—or even potentially protective—though these findings remain inconclusive.

Leucovorin (Folinic Acid) Research

ARI has supported Dr. Richard Frye’s research related to leucovorin (folinic acid) as a potential intervention in autism, particularly for individuals with metabolic differences such as impaired methylation or glutathione production. We are encouraged by the preliminary results suggesting that leucovorin supplementation may benefit certain subgroups of individuals with autism spectrum disorders.

Dr. Frye’s work represents potential progress in understanding possible biomarker-based approaches to intervention. However, we emphasize that this research is still evolving, and larger, controlled studies are needed to fully validate these findings and establish optimal treatment protocols.

It is important to note that Dr. Frye’s leucovorin research explores potential therapeutic interventions rather than causative factors and should not be interpreted as supporting any specific theory about acetaminophen causation.

Ongoing Commitment

ARI remains committed to supporting rigorous, scientifically sound research into all aspects of autism spectrum disorders. We encourage:

• Continued investigation of the interplay between genetic susceptibility, environmental factors, and critical developmental periods
• Well-controlled studies that distinguish association from causation
• Investigation of maternal immune responses and inflammation as pathways to neurodevelopmental differences
• Research that includes autistic people and focuses on appropriate medical care
• Transparent communication about both the promise and limitations of emerging research

Individuals, parents and healthcare providers are encouraged to make medical decisions based on established guidelines and consultation with qualified professionals, while staying informed about ongoing research developments. As Dr. Hornig notes, untreated fever during pregnancy carries known risks, and decisions regarding fever-reducing medications should be made carefully with medical guidance.

“Autism is complex, and much remains to be learned,” Dr. Edelson said. “As always, ARI is committed to following the evidence wherever it leads and to providing clear, trustworthy information as new knowledge emerges.”