Sep 23, 2025

Coalition of autism scientists oppose links between Tylenol and Autism; use of Leucovorin

Posted Sep 23, 2025 10:00 AM

Coalition of Autism Scientists

The vast majority of autism researchers understand that there is not a singular cause of autism. Our collective body of global research going back decades means that we have encyclopedic knowledge about the risks for autism, its possible causes, and the highly variable experience of autistic individuals.  

The September 22 press conference held by U.S. Health and Human Services alarms us researchers who committed our entire careers to better understanding autism. The data cited do not support the claim that Tylenol causes autism and leucovorin is a cure, and only stoke fear and falsely suggest hope when there is no simple answer.

In brief response to this report, the Coalition of Autism Scientists makes the following points:

Regarding a possible link between acetaminophen and autism:

While a recent summary analysis found some evidence for a weak association, it does not evaluate the quality of the studies informing the analysis. Importantly, these studies fail to address the fact that fevers during pregnancy are known to increase risk for autism, and that’s why mothers take acetaminophen in the first place. Rather, the most recent, rigorous study that controlled for unmeasured familiar risks found that acetaminophen did not cause autism.

Given that use of acetaminophen during pregnancy  has not increased (Ahlqvist VH, et al., Fig 2A in reference) over the past two decades alongside rates of autism, it’s clearly not the cause of the increased diagnoses of autism and the American College of Obstetricians and Gynecologists agrees.

Regarding folinic acid (leucovorin):

There are only a handful of clinical trials of leucovorin and evidence connecting treatment to improvements in outcomes is very weak. (See references) All of them are very small, and the study designs and approaches to statistical analyses of the data are not all of high quality.   It is premature to claim that leucovorin is an effective treatment for autism and add autism as a secondary indication.  

The Coalition of Autism Scientists reviewed these studies and found that the researchers aren’t using high quality study designs or statistical analysis. Most of these studies test many outcomes, without statistically adjusting for the fact that they are doing so along the way. Some of them use statistics that are inappropriate for a randomized trial (e.g., showing that there is statistically significant change in the intervention group but not in the control group, without actually comparing the groups). Others attempt to conduct analyses separately for children that they say have a gene or antibody that would suggest that they have folate deficiency, meaning that they are conducting the analysis on even smaller groups.

With this in mind, we do not support any recommendation from the HHS or FDA regarding increased use of folinic acid. Instead, we call for a well-designed, large scale clinical trial of leucovorin (folinic acid) with all of the rigor needed (biomarkers, proper endpoints) and most importantly a pre-registered analysis plan.

Vaccines and Autism:

Dozens of studies demonstrate the role vaccination plays to protect individuals, particularly the most vulnerable in our community, against potentially fatal diseases. There is no evidence that routine vaccinations have any connection to autism at all.

Secretary Kennedy is using his position to push forward his well-known anti-vaccination views, which does not align with Americans’ broad support of vaccines. Outbreaks and epidemics are inevitable if access to free, safe vaccines is reduced.

Is HHS wants to speed up autism research, then investment in gold-standard, peer-reviewed research – that which was already in progress before the rulebook suddenly changed – must continue. Regarding the grants awarded as part of the Autism Data Science Initiative (ADSI), the Coalition of Autism Scientists calls for an independent external advisory board of autism scientists and community members to support the ADSI and analyze methodologies, which will facilitate earning the trust of researchers and the public.

The Coalition of Autism Scientists will continue to speak factually and forcefully about the science that should inform our public understanding of autism and support autistic individuals and their families.

References:

  1. Prada D, Ritz B, Bauer AZ, Baccarelli AA. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health. 2025 Aug 14;24(1):56. doi: 10.1186/s12940-025-01208-0. PMID: 40804730; PMCID: PMC12351903.
  2. Ahlqvist VH, Sjöqvist H, Dalman C, et al. Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability. JAMA. 2024;331(14):1205–1214. doi:10.1001/jama.2024.3172 (See figure 2A)
  3. Zhang C, Chen Y, Hou F, Li Y, Wang W, Guo L, Zhang C, Li L, Lu C. Safety and Efficacy of High-Dose Folinic Acid in Children with Autism: The Impact of Folate Metabolism Gene Polymorphisms. Nutrients. 2025 May 7;17(9):1602. doi: 10.3390/nu17091602. PMID: 40362912; PMCID: PMC12073535.
  4. ACOG Response to Consensus Statement on Paracetamol Use During Pregnancy. 9-21-21. https://www.acog.org/news/news-articles/2021/09/response-to-consensus-statement-on-paracetamol-use-during-pregnancy
  5. Panda PK, Sharawat IK, Saha S, Gupta D, Palayullakandi A, Meena K. Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial. Eur J Pediatr. 2024 Nov;183(11):4827-4835. doi: 10.1007/s00431-024-05762-6. Epub 2024 Sep 7. PMID: 39243316.
  6. Batebi N, Moghaddam HS, Hasanzadeh A, Fakour Y, Mohammadi MR, Akhondzadeh S. Folinic Acid as Adjunctive Therapy in Treatment of Inappropriate Speech in Children with Autism: A Double-Blind and Placebo-Controlled Randomized Trial. Child Psychiatry Hum Dev. 2021 Oct;52(5):928-938. doi: 10.1007/s10578-020-01072-8. Epub 2020 Oct 7. PMID: 33029705.
  7. Renard E, Leheup B, Guéant-Rodriguez RM, Oussalah A, Quadros EV, Guéant JL. Folinic acid improves the score of Autism in the EFFET placebo-controlled randomized trial. Biochimie. 2020 Jun;173:57-61. doi: 10.1016/j.biochi.2020.04.019. Epub 2020 May 7. PMID: 32387472.
  8. Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, Tippett M, Sailey A, Wynne R, Rose S, Melnyk S, Jill James S, Sequeira JM, Quadros EV. Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Mol Psychiatry. 2018 Feb;23(2):247-256. doi: 10.1038/mp.2016.168. Epub 2016 Oct 18. PMID: 27752075; PMCID: PMC5794882.
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