The press conference on September 22, 2025 raised two very big questions: Does Tylenol cause autism? And what does leucovorin’s new approval mean for children with autism? These are complicated issues, and I will do my best to share what we know, what we don’t know, and the way forward – without fear or guilt or blame.
And here’s one thing we know – there is not one, single, “root cause” of autism. Research suggests an underlying genetic vulnerability, with multiple potential influences, including medications, environmental toxins, infections, vaccines, mitochondrial dysfunction, methylation defects, nutrient deficiencies, and the gut microbiome.
Some studies suggest that Tylenol use in pregnancy may be associated with a higher likelihood of autism or ADHD, while other studies find no link. I have patients whose moms used Tylenol during pregnancy, and their children did not develop autism. And I have patients who were never exposed to Tylenol or vaccines, and still developed autism.
There are many nuances and complexities here, and the full truth is yet to be revealed. But one thing is clear – no parent should feel guilty for the decisions they made with the information they had at hand.
Now is our opportunity to keep the dialogue open, pave the way for unbiased research, provide proactive health optimization solutions, and move forward with knowledge. Knowledge is power. And I’m so grateful to be on this journey with you as a fellow mom and practitioner, trying to do the best we can for our children.
xo Elisa Song, MD
Tylenol (Acetaminophen) and Autism/ADHD risk
What the evidence says
- Some studies show increased risk: A 2025 systematic review of 46 studies found that higher-quality research more often showed a link between prenatal acetaminophen exposure and increased likelihood of autism or ADHD. (1)
- Some studies show no risk: A Swedish cohort of nearly 2.5 million children found no increased likelihood when comparing siblings (which controls for shared genetics and environment). (2)
- Cord blood study: In the Boston Birth Cohort, higher cord blood acetaminophen metabolites were linked to increased likelihood of autism and ADHD. (3)
Why this makes biological sense
- Tylenol depletes glutathione — the body’s master antioxidant and detoxifier. When glutathione is low, oxidative stress rises, which can affect brain development. (4)
What remains unknown
- Association ≠ Causation. Confounding factors like fever, infection, dose, and timing during pregnancy all matter.
- We don’t yet know which trimesters or doses carry the most risk, or which children are most vulnerable because of their genetic susceptibilities.
What you can do now
- Use Tylenol only when truly necessary.
- Learn evidence-based alternatives that reduce the need for Tylenol. For fever, review the integrative tools I discuss in Part IV of my book, Healthy Kids, Happy Kids: An Integrative Pediatrician’s Guide to Whole Child Resilience. I share evidence-based natural ways to manage fever – including homeopathy, essential oils, and acupressure points. The biggest myth that needs to be dispelled is that fever is something to be feared. In my next newsletter, I will review everything you need to know about fever. In the meantime, you can download my free resource: Top 5 Mistakes Parents Make When Their Child Has a Fever — and What You Can Do Instead.
- If you do use Tylenol, know how to support glutathione levels. In Healthy Kids, Happy Kids (pp. 238–241), I explain ways to rebuild glutathione if Tylenol is used, including: Sulfur-rich foods (broccoli, cauliflower, Brussels sprouts, kale, onions, garlic), Vitamin C-rich fruits, Epsom salt baths, Glutathione supplements when extra detox support is needed. We carry a variety of highly-absorbable, Dr. Song-approved glutathione supplements to meet your family’s needs. Suggested dosage guidelines are included in the Resources section of my book (p. 419-420).
Leucovorin (Folinic Acid) and Autism
What it is
- Leucovorin (folinic acid) is a reduced form of folate that bypasses certain metabolic blocks, including folate receptor autoantibodies (FRAA), that are more commonly seen in children with neurodevelopmental concerns, including autism and PANS/PANDAS. It has long been used in oncology and specific folate-related conditions.
What the research shows
- Frye et al., 2016: 48 children with autism + language impairment received leucovorin (0.5–2 mg/kg/day, up to 50 mg/day) for 12 weeks. Result: significant improvements in verbal communication, especially in FRAA-positive children. (5)
- EFFET Trial (France): Lower dose (5 mg twice daily for 12 weeks) improved autism severity scores, especially communication. (6)
- Meta-analyses: A systematic review & meta-analysis found that in autistic children with cerebral folate deficiency or folate receptor alpha autoantibodies, treatment with folinic acid (leucovorin) was associated with improvements in communication, irritability, and other core symptoms. (7)
What approval means
- The FDA has approved leucovorin for the treatment of symptoms associated with cerebral folate deficiency. Insurance coverage may require testing, such as the Folate Receptor Antibody Test (FRAT). How this plays out with public and private insurance is yet to be seen.
How to talk with your doctor
- Ask if folate receptor autoantibodies (FRAT) testing is appropriate for your child with autism or PANS/PANDAS. Share a link to FRAT NOW so your provider has information to order the appropriate testing.
- If positive, discuss leucovorin at studied dosages (0.5–2 mg/kg/day, up to 50 mg/day).
- Monitor improvements in speech, social engagement, and behavior, as well as side effects (mild in most studies).
- Regardless of treatment, continue to focus on nutrition, detox, and microbiome support – the foundation for every child.
Takeaways
- Autism and ADHD are complex and multifactorial – not caused by one trigger.
- Tylenol may play a role in some children, but the bigger picture includes genetics, microbiome, toxins, methylation, mitochondrial function, and nutrients.
- Don’t feel guilty if you’ve used Tylenol. Focus on what you can do: support detox, strengthen glutathione reserves, and nurture the microbiome.
- Leucovorin offers new hope for supporting communication and development in some autistic children, especially those with folate receptor autoantibodies. Talk with your doctor about whether testing and treatment may be right for your child.
- Every child with autism is unique, with their own strengths and challenges. These studies are not about “curing autism,” but about exploring ways to support children who may benefit from extra help with communication, development, or daily functioning.
With hope and clarity,
xo Elisa Song, MD
P.S. If you found this helpful, please share this newsletter with friends, family, or your parent community – together we can spread knowledge and hope. And don’t forget to get your free guide, Top 5 Mistakes Parents Make When Their Child Has a Fever — and What You Can Do Instead. Refer to my book, Healthy Kids, Happy Kids: An Integrative Pediatrician’s Guide to Whole Child Resilience, for even more practical tools to support your child’s health every day.
References
- Baccarelli A, et al. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health. 2025;24(1):22. doi:10.1186/s12940-025-01208-0.
- Ahlqvist VH, Sjöqvist H, Dalman C, et al. Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability. JAMA. 2024;332(5):452-461. doi:10.1001/jama.2024.11054.
- Ji Y, Azuine RE, Zhang Y, et al. Cord plasma biomarkers of in-utero acetaminophen exposure and risk of ADHD and autism. JAMA Psychiatry. 2020;77(2):180-189. doi:10.1001/jamapsychiatry.2019.3259.
- Chen Y, et al. Acetaminophen metabolism, glutathione depletion, and oxidative stress. Int J Mol Sci. 2025;26(17):8585. doi:10.3390/ijms26178585.
- Frye RE, Slattery J, Delhey L, et al. Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Mol Psychiatry. 2018;23(2):247-256. doi:10.1038/mp.2016.168.
- Renard E, Leheup B, Guéant-Rodriguez RM, et al. The EFFET pilot trial: folinic acid improves autism symptom scores in children. J Autism Dev Disord. 2020;50:1-12. doi:10.1016/S0300-9084(20)30089-4.
- Rossignol DA, Frye RE. Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis. J Pers Med. 2021;11(11):1141. Published 2021 Nov 3. doi:10.3390/jpm11111141
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