What we know, and don’t, about the link between painkillers and autism

In a significant announcement on Monday, the US government unveiled two new initiatives aimed at addressing concerns related to autism. The initiatives include updates to the labelling of paracetamol, also known as acetaminophen. The updated warnings will indicate that the use of this common painkiller during pregnancy may be associated with an increased risk of autism and ADHD in children. Additionally, the government has approved the drug leucovorin for treating specific symptoms in children diagnosed with autism spectrum disorder (ASD). However, it is essential to note that neither of these moves is supported by robust scientific evidence, and they are unlikely to have a significant impact on autism rates in the US.

The announcement coincides with a pledge from Robert F. Kennedy Jr., the nation’s highest-ranking public health official, who promised in April to identify the causes of autism by the end of September. President Donald Trump hailed these initiatives as “historic steps” in addressing what he described as the autism crisis during a press conference.

This statement reflects either a misunderstanding or a misrepresentation of the prevailing understanding of autism. The notion of a crisis is misleading; the rate of autism has notably risen since the 1980s primarily due to expanded diagnostic criteria and increased awareness of the condition’s symptoms.

Regarding the etiology of autism, there exists little evidence implicating paracetamol as a causative factor. While multiple studies have indicated a potential link between paracetamol use during pregnancy and an increased risk of autism in offspring, correlation does not imply causation. A recent analysis of 46 studies found that 27 indicated a significant association, but it remains unclear if other contributing factors play a more critical role.

Conflicting results from other research further complicate this landscape. For example, a 2024 study analyzing nearly 2.5 million children found a marginally elevated risk of autism among those exposed to paracetamol during pregnancy. However, upon comparing children exposed to paracetamol with their unexposed siblings, the perceived effect vanished. Dimitrios Siassakos from University College London pointed out, “It was the family history that mattered and not the use of paracetamol.” This underscores that any evident increase in autism linked to paracetamol tends to disappear when accounting for significant factors, such as genetics, a well-established contributor to autism.

During the press conference, Trump urged pregnant women to avoid paracetamol for pain or fever unless absolutely necessary, recommending they consult their doctors for further guidance. Notably, the US Food and Drug Administration (FDA) confirmed in a press release that a causal relationship between paracetamol and autism has yet to be established, maintaining that it remains the safest readily available painkiller for use during pregnancy. The agency highlighted that paracetamol is the only over-the-counter medication approved for treating fever in pregnant women, as elevated maternal fever can jeopardize fetal health, potentially leading to preterm birth or developmental defects.

Moreover, the FDA has granted approval for leucovorin to be used for patients with cerebral folate deficiency, a condition hindering vitamin B9 uptake in the brain and which some research suggests may affect as many as 40% of autistic individuals. Early studies indicate leucovorin may alleviate certain severe symptoms of autism. For instance, a 2016 study assessing 23 children with language impairments found that 65% of those receiving leucovorin experienced meaningful improvements in verbal communication after 12 weeks, compared to only 24% in the placebo group.

Despite these promising early indications, most investigations on leucovorin have involved small sample sizes and revealed only modest improvements. A larger clinical trial is currently ongoing, with results expected in the coming year. Monique Botha at Durham University noted that “any evidence available at this point is exceptionally tentative and would not be considered robust.” It’s crucial to emphasize that while medications like leucovorin may assist with specific symptoms, there is currently no medication or treatment capable of curing or eliminating autism.

The US Department of Health & Human Services reiterated in a statement following the announcement that “although promising, it is important to understand that leucovorin is not a cure for ASD and may only lead to improvements in speech-related deficits for a subset of children with ASD.”

Kennedy, with Trump’s endorsement, has prioritized addressing the “autism epidemic” within US public health policy, portraying these recent developments as significant accomplishments achieved swiftly. However, the prevailing science indicates that neither the avoidance of paracetamol during pregnancy nor the adoption of leucovorin will substantially influence autism rates, contrary to the claims made by Trump and Kennedy. Instead, there is a considerable risk these initiatives could induce confusion regarding the safe treatment of pain or fever during pregnancy.