Autism Announcement Fact Sheet

Today, President Trump held a press conference in the Roosevelt Room to announce progress in uncovering the root causes of autism, as promised by HHS Secretary Kennedy. The three announcements made today include: leucovorin as a promising treatment for symptoms of autism, a notice to physicians on the use of acetaminophen, and an announcement of recipients of the NIH Autism Data Science Initiative.

Autism Prevalence in the United States

Key Findings

• 1 in 31 U.S. children (3.2%) born in 2014 are diagnosed with autism spectrum disorder (ASD).
• Sharp increase from 1 in 36 just two years earlier.
• Prevalence nearly 5 times higher than when the CDC began tracking in 2000 (1 in 150).
• Boys disproportionately affected: 1 in 20 (5%).
• California highest prevalence: 1 in 12.5.

Source: Centers for Disease Control and Prevention (CDC), Morbidity and Mortality Weekly Report (MMWR), Surveillance Summaries, Vol. 74, No. SS-2, April 2025
Read the full CDC study

Leucovorin for Cerebral Folate Deficiency

The Condition: Cerebral Folate Deficiency (CFD)

• What it is: A neurological condition where the brain doesn't get enough folate (an essential B-vitamin), even when folate levels in the rest of the body are normal. Folate is essential for brain development and function. Deficiency of folate in the brain causes severe problems including autistic symptoms.
• Who it affects: CFD has multiple causes, including rare genetic forms and autoimmune forms, with the latter being more common. FOLR1 deficiency is a rare genetic form which may affect 1 in 1,000,000 individuals worldwide; however, the true prevalence is unknown. CFD presents in early childhood with severe neurological symptoms and developmental delay. Autoimmune forms are caused by autoantibodies that mistakenly attack the body's folate transport system, preventing folate from reaching the brain and yielding the same severe symptoms.
• Symptoms: Patients with genetic forms have symptoms, typically beginning around age 2, such as global developmental delays with autistic features and psychomotor regression, intractable seizures, and motor disorders. Patients with autoimmune forms have heterogeneous neuropsychiatric symptoms, including potentially severe autism features.

The Treatment: Leucovorin (Folinic Acid)

• What it does: Leucovorin bypasses the defective folate transport system and delivers the active form of folate directly to the brain.
• Current evidence and treatment response: Analysis across 23 publications from 2009-2024 demonstrated the effectiveness for CFD. Overall, 85% of patients experienced some type of clinical benefit including improved speech/communication capabilities. Efficacy data on the use of leucovorin in the autoimmune form of CFD suggest that these patients may also benefit from treatment; however, the data are limited and need to be replicated.
• Safety profile: Leucovorin is generally well-tolerated based on available data obtained over 40 years of use for other conditions. The safety in CFD patients appears consistent with leucovorin's established safety profile in these other approved indications.

Context

• Population impact: While the most common FOLR1 gene mutation is rare, it is a proven cause of this devastating but potentially treatable presentation of autistic symptoms. Leucovorin’s use in patients with autoimmune CFD could potentially have a larger impact on the U.S. population; however additional studies are needed. Usage data from the FDA has shown that off-label use of leucovorin has increased significantly due to growing awareness among the autism community. Ingesting more folate through over-the-counter supplements is not indicated and could be harmful.
• Regulatory considerations: The original NDA for leucovorin was approved in 1983 but withdrawn in 1999 when GlaxoSmithKline (GSK) stopped marketing the product after the entry of generic versions into the market. This withdrawal was not for safety or effectiveness reasons. Following review of the data from patients with genetically confirmed CFD who showed profound symptom improvement with oral leucovorin treatment, the FDA has announced that they are requesting from the innovator company updated prescribing information (PI) to include the new indication of CFD, a condition often associated with autistic symptoms. The PI of generic leucovorin products will be updated accordingly.
• Research landscape: The evidence base for efficacy of leucovorin in genetic forms of CFD consists entirely of case reports and case series due to the condition's rarity. However, the FDA has worked with the NIH to review the scientific evidence for its use in autoimmune forms, particularly in cases manifesting with clinical features of autism spectrum disorder (ASD). The NIH is committed to supporting follow-up research to understand the impact of the label change and the potential broader benefit in individuals with ASD, and to working with FDA and CMS on post-market surveillance and safety studies.

Acetaminophen Use in Pregnancy

The Condition: Acetaminophen Exposure in Utero

• What it is: Acetaminophen (Tylenol) is an over-the-counter analgesic and antipyretic widely used during pregnancy. Concerns have arisen regarding possible neurodevelopmental risks associated with chronic prenatal exposure and potential overuse for low-grade fevers in pregnant women.
• Who it affects: Chronic acetaminophen use in pregnant women, especially late in pregnancy, may cause long-term neurological effects in their children.   
• Evidence base: Large-scale cohort studies, including the Nurses’ Health Study II and the Boston Birth Cohort, report associations between in utero exposure and later diagnoses of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Scientists have proposed biological mechanisms linking prenatal acetaminophen exposure to altered brain development.
• Conflicting findings: Family-based Scandinavian studies, comparing exposed and unexposed siblings, have not shown significant associations. Critics from Icahn School of Medicine at Mt. Sinai and Harvard argue that statistical adjustments in these analyses may mask true effects.

Clinical Considerations: Chronic Use of Acetaminophen During Pregnancy

• What it does: Acetaminophen is the only over-the-counter medication considered safe for treating fever during pregnancy. Maternal fever itself carries risks, including neural tube defects and preterm birth.
• Current evidence and recommendations: Evidence does not definitively establish causality, but the consistent associations raise concern. An international consensus statement (2021) recommends pregnant women minimize use, consult providers before long-term use, and apply the lowest effective dose for the shortest duration.
• Safety profile: When used short-term and at appropriate dosages, acetaminophen remains widely regarded as safe. However, unresolved questions remain regarding chronic or late-pregnancy exposure.

Context

• Population impact: Because acetaminophen is one of the most common medications taken during pregnancy, even a modest increase in risk could have a significant public health impact.
• Balancing risks: Experts emphasize a balanced approach, acknowledging potential risks of acetaminophen exposure while recognizing the dangers of untreated maternal fever and pain.
• Research landscape: Randomized trials of drug exposure during pregnancy are generally infeasible. Thus, continued reliance on epidemiologic studies, mechanistic research, and meta-analyses will shape guidance moving forward.

NIH Autism Data Science Initiative (ADSI)

Overview

• The NIH has launched the Autism Data Science Initiative (ADSI) to strengthen and transform the nation’s autism research portfolio.
• Out of 248 applications, following rigorous NIH peer review, 13 new awards totaling >$50M will advance understanding of autism across prevalence (2 awards), etiology (7 awards), treatment and services (2 awards), replication and validation (2 awards).
• These projects focus on large-scale, integrated data resources, drawing on genomic, epigenomic, metabolomic, proteomic, clinical, behavioral, and service-use information.
• A defining feature is the exposomics approach, comprehensively studying environmental, medical, and lifestyle factors in combination with biology and genetics.

Key Features of the ADSI Portfolio

• The ADSI portfolio integrates a wide range of data types, combining genomic, epigenomic, metabolomic, proteomic, clinical, behavioral, and service-use information into comprehensive resources.
• The initiative emphasizes exposomics by studying a wide range of external influences, the sources, routes, and pathways that are important for children’s exposure, and their impact on autism risk and outcomes, including:
  • Environmental contaminants such as chemicals and other hazardous substances in the everyday environments of children and pregnant women
  • Nutrition and maternal diet factors such as folate intake, fish consumption, and ultra-processed foods
  • Medical and perinatal influences, including medications, vaccinations, obstetric complications, and neonatal intensive care experiences
  • Psychosocial stressors, infections, and immune responses during pregnancy and early development
• The awards employ advanced methodologies, including causal inference approaches, exposome-wide association studies, machine learning techniques, and human cell-based organoid models, to investigate exposures with precision.
• Most projects are anchored in large, U.S.-based cohorts, ensuring findings are directly relevant to domestic prevalence patterns and systems of care.
• The portfolio takes a lifespan approach by addressing not only childhood outcomes but also the needs of autistic adults, who have been historically understudied.
• Replication and validation hubs will enhance rigor and transparency by independently replicating findings, harmonizing workflows, and applying best practices in open science.
• All projects require community engagement plans that establish structured partnerships with autistic individuals, caregivers, clinicians, and other stakeholders to align research with community needs and values.