What We Know and Don’t Know About the Connection Between Painkillers and Autism

On Monday, the US government introduced two initiatives concerning autism. One update involves labeling for paracetamol, commonly known as acetaminophen, emphasizing that its use during pregnancy could elevate the risks of autism and ADHD in children. The government also approved leucovorin for certain children diagnosed with autism spectrum disorder (ASD). However, these actions are not strongly supported by scientific evidence and may have negligible effects on autism prevalence in the United States.

This announcement followed Robert F. Kennedy Jr.’s pledge, made in April, to uncover the causes of autism by the close of September. President Donald Trump later described this initiative at a press conference as “a historic step towards battling the autism crisis.”

This portrayal indicates a possible misunderstanding or distortion of existing knowledge about autism. There is no crisis as such. Autism rates began to surge rapidly since the 1980s, significantly influenced by increased awareness and recognition of its symptoms leading to more frequent diagnoses.

Evidence supporting the idea that paracetamol causes autism is limited. While several studies indicate a correlation between paracetamol use during pregnancy and an elevated risk of autism in children, causation should not be assumed. A recent investigation involving 46 studies found that 27 of them reported a significant link between paracetamol use in pregnancy and heightened risk for neurodevelopmental issues, including autism. Nevertheless, correlation does not imply causation; other underlying factors may also play a role.

Contrasting findings are evident in other studies. For instance, a 2024 evaluation analyzing around 2.5 million children determined that while those exposed to paracetamol during pregnancy faced a marginally higher autism risk, this effect diminished when comparing children exposed to painkillers with their siblings. “It wasn’t the paracetamol use, but rather family history that played a crucial role,” said Dimitrios Siasacos from University College London. “Although studies indicate a slight increase in autism outcomes related to paracetamol use during pregnancy, this tends to vanish when analyzing the more significant factors involved.”

During a press briefing, Trump advised that pregnant women should avoid taking paracetamol for pain or fever. However, the US Food and Drug Administration (FDA) issued a press release stating that no causal link between paracetamol and autism has been established. Additionally, in a notification to healthcare providers, the FDA confirmed that paracetamol remains the safest and most accessible pain relief option during pregnancy. “[It] is the only over-the-counter medication that is approved for use to treat fever during pregnancy, as a high fever can pose risks to the developing fetus,” emphasizing potential fetal brain or spinal cord defects.

The FDA also announced its approval of leucovorin for individuals with cerebral folate deficiency, a condition that affects the brain’s capability to absorb vitamin B9. Studies suggest that around 40% of people with autism may be affected by this deficiency, leading to similar symptoms, including difficulties with communication and sensory processing.

Leucovorin, a form of vitamin B9, is already utilized to address deficiencies of this vitamin and to mitigate side effects from certain cancer treatments. Preliminary evidence implies that it might aid in alleviating severe autism symptoms. For instance, a 2016 study involving 25 autistic children treated with leucovorin demonstrated that 65% showed meaningful improvements in verbal communication skills compared to only 24% in the placebo group after 12 weeks.

However, existing studies on leucovorin and autism have been relatively small, often yielding only modest positive results. Larger clinical trials are in progress, with results expected next year. “Currently available evidence is tentative and not yet deemed comprehensive,” stated Monique Botha at Durham University. “While these medications might offer benefits in specific areas, there are no treatments that effectively address or eliminate autism as a whole.”

Following the announcement, the U.S. Department of Health and Human Services reiterated that “while promising, it’s crucial to understand that leucovorin is not a cure for ASD but may help to enhance speech-related skills in a limited group of children with the condition.”

With Trump’s backing, Kennedy is positioning the “autism epidemic” as a cornerstone of U.S. public health policy. They are both framing these policy developments as substantial milestones achieved in a brief timeframe. However, scientific evidence suggests that avoiding paracetamol during pregnancy or utilizing leucovorin is unlikely to have the significant impact on autism that Trump and Kennedy claim. Instead, the most probable outcome of these initiatives pertains to how and when to manage pain and fever safely during pregnancy.