'Clinicians and researchers continue to address unproven and debunked claims about the origins of autism — most notably that vaccines and prenatal acetaminophen use may increase the risk for the disorder.
'After the Trump administration released a controversial report on autism spectrum disorder (ASD) last month, many autism experts and medical societies pointed out that the rise in autism prevalence and its potential causes are not yet fully understood.
'Recent research has revealed new information on genetic, environmental, and other factors that influence risk, and projects funded through the recently announced National Institute of Health’s Autism Data Science Initiative (ASDI) could further clarify the disorder’s complex origins.
'Meanwhile, clinicians, patients, and caregivers are asking: What is currently known — and unknown — about the prevalence and causes of autism? '
Is Autism Prevalence Rising?
The CDC regularly compiles data on ASD prevalence through the Autism and Developmental Disabilities Monitoring (ADDM) Network. The findings are considered to be among the most reliable snapshots of autism rates in children.
The CDC’s most recent data from the 2022 ADDM surveillance cycle are based on 393,353 8-year-olds across 16 US sites. The report showed that ASD affected 1 in 31 children (32.2 per 1000) in 2022, up from 1 in 36 in 2020 and 1 in 150 in 2000. ASD continues to be more common in boys than girls (ratio 3.4:1).
ASD prevalence was higher among Asian or Pacific Islander, Black, and Hispanic children than White children, continuing a pattern first observed in 2020.
Children born in 2018 were more likely to be diagnosed by age 48 months compared with those born in 2014, suggesting increased early identification consistent with historical patterns.
CDC investigators noted several factors that may be driving the increase, including broader diagnostic criteria, increased screening, greater awareness among parents and pediatricians, reduced stigma and increase acceptance, and improved access to specialized services.
Together, these shifts mean children who may have been overlooked in previous decades are now being identified.
Other potential drivers include increasing paternal age (and to a lesser extent maternal age), which is a known risk factor: older fathers tend to accumulate more de novo mutations in sperm.
In addition, more preterm or low-birth-weight infants are surviving now than decades ago; prematurity is itself a risk factor for neurodevelopmental differences.
Acetaminophen-Autism Link: What’s the Evidence?
The autism report released by the Trump administration claimed that prenatal use of acetaminophen causes autism, but experts say a causal link between the two isn’t supported by evidence.
Studies suggest that acetaminophen can cross the placenta and may influence pathways involved in fetal brain development, including prostaglandin and endocannabinoid signaling. Oxidative stress and hormonal effects have also been proposed as potential mechanism, but none of these hypotheses have been proven.
One study cited in the Trump administration’s report was a comprehensive review of 46 studies that showed that the overall body of evidence is consistent with an association between prenatal acetaminophen exposure and increased neurodevelopmental diagnoses, including ASD. However, the researchers noted that “observational limitations preclude definitive causation.”
The report also pointed to results from a Johns Hopkins or NIH-funded study that measured cord-blood acetaminophen metabolites, which is an objective exposure marker. Researchers found higher metabolite levels were associated with an increased likelihood of subsequent attention-deficit/hyperactivity disorder (ADHD) or autism diagnoses but noted that the pattern was dose-dependent and highlighted that only one measurement of cord-blood acetaminophen levels, taken at birth, was used in the analysis.
“Given that the half-life of acetaminophen in adults is < 3 hours, the cord plasma measurement may at most reflect maternal use of acetaminophen during the peripartum period,” the researchers wrote.
Meanwhile, the largest, most rigorous epidemiological study to date showed no effect of prenatal acetaminophen exposure and ASD risk after accounting for family confounding — factors shared within families, such as genetics and environment, that could potentially influence neurodevelopmental outcomes.
This 2024 Swedish study of 2.4 million children (1995-2019) included sibling data to control for genetic and environmental factors. The researchers found no relationship between in utero exposure to acetaminophen and subsequent diagnoses of autism, ADHD, or intellectual disability. This suggests there is no causal link between acetaminophen and autism, they wrote.
Methodological concerns also exist in studies that do report a link. In a practice advisory published in late September, the American College of Obstetricians and Gynecologists highlighted recurring issues, including reliance on self-reported use (recall bias), inconsistent outcome measures, limited data on dose or timing, failure to fully control genetic or familial factors, and potential confounding by the indications for acetaminophen use, such as fever, infection, or pain — which themselves can influence neurodevelopment.
“Pregnant women have few safe, over-the-counter options available to them to treat pain and inflammation. Acetaminophen is one. Not using it judiciously and when needed may actually increase risks to pregnant women and their babies,” David Mandell, ScD, with the Coalition of Autism Scientists and Perelman School of Medicine, University of Pennsylvania, Philadelphia, told Medscape Medical News.
Vaccine-Autism Link: What’s the Evidence?
Decades of high-quality evidence has shown that vaccines do not cause autism.
A large Danish cohort of 657,461 children showed no increased autism risk after measles, mumps, and rubella (MMR) vaccine (fully adjusted hazard ratio, 0.93; 95% CI, 0.85-1.02), and no signal in children with autistic siblings and other high-risk subgroups or specific postvaccine time windows.
A US claims-based cohort of roughly 95,000 children showed that even among children who have an older sibling with autism, MMR was not associated with ASD risk.
Pooled data from cohort and case-control studies showed no association between vaccines, including MMR, vaccine components, or multiple vaccines and autism.
After thimerosal was removed from nearly all US childhood vaccines, a study from California showed that autism diagnoses continued to rise in the state — contradicting the hypothesis that thimerosal was a contributing factor.
So why does the vaccine-autism myth persist? Experts cite timing coincidence as one reason. Early symptoms of autism often emerge around the same age routine vaccines are administered.
This claim was further fueled by a study from the 1990s which sparked widespread concern and eroded trust in vaccines. That study was formally retracted and exposed as fraudulent, but its narrative lingers.
What About Genes and Environment?
A robust body of evidence dating back to the 1970s points to a substantial genetic component in autism etiology.
Recent research has identified four biologically and clinically distinct subtypes of autism, each with associated genetic signals. The subtypes are: Social and Behavioral Challenges, Mixed ASD with Developmental Delay, Moderate Challenges, and Broadly Affected.
Children in all four classes had a significant burden of common and rare genetic variants, but researchers found differing signals that defined each autism subtype. These four subtypes also differed in terms of the genetic variants’ effects on brain development.
Other recent research indicates that autism diagnosed in early childhood differs genetically and developmentally from autism identified later, challenging the view that autism is a single, uniform disorder.
Children diagnosed early are more likely to have social and behavioral challenges in infancy and early childhood, while those diagnosed later have higher rates of comorbid conditions such as ADHD and depression. The two subtypes also exhibit distinct genetic profiles.
“With advances in genetic technology and analytic methods, hundreds of specific genetic changes have now been identified and are commonly accepted to cause autism,” Alexander Kolevzon, MD, clinical director of the Seaver Autism Center at Mount Sinai in New York City, told Medscape Medical News.
Yet twin studies have shown that if one identical twin has autism, the other may not about 10% of the time, “leaving room for some environmental influence,” Kolevzon said.
“Environmental effects may be acting through epigenetic mechanisms where certain factors, as of yet unidentified, influence the expression of genes. However, despite being an active area of study, no widespread environmental effects have been reliably established to date,” he added.
Maternal metabolic conditions may also play a role. In April 2025, a meta-analysis of 202 studies including more than 56 million mother-child pairs showed that children born to mothers with gestational diabetes were 25% more likely to be diagnosed with autism. Researchers have also linked autism risk to preterm birth and advanced parental age.
It’s thought that these exposures likely act as modifiers — influencing gene expression, immune activation, or neuronal development — rather than standalone causes.
Gut-Brain Link?
An emerging area of research focuses on the gut microbiome and whether gut dysbiosis may contribute to autism risk.
“There have been several studies showing that there is gut dysbiosis in autism, and that it correlates with autism symptoms,” Lisa Aziz-Zadeh, PhD, professor, Department of Psychology, University of Southern California, Los Angeles, told Medscape Medical News. “However, we know that any behavioral differences must be via gut microbiome or metabolite interactions with the human nervous system,” she said.
In a study published earlier this year, Aziz-Zadeh’s team was the first to identify links between gut microbial tryptophan metabolites, autism symptoms, and brain activity in individuals with ASD, particularly in brain regions associated with interoceptive processing. This points to a “mechanistic model by which gut metabolites may impact autism,” she said.
Interventions targeting gut imbalances — such as dietary changes, probiotics, prebiotics, or fecal transplants — could potentially be beneficial, said Aziz-Zadeh. However, it remains unclear whether there is a critical window for such interventions, such as during prenatal development or early childhood. More research must be done to answer this question, she added.
In another recent study, microbiota transfer therapy led to significant improvements in gastrointestinal (GI) symptoms, autism-related symptoms, and gut microbiota in children with autism. The effects of the initial treatment on both gut microbiota and GI symptoms were maintained at 2-year follow-up, with continued improvement in autism-like behaviors, the researchers reported.
What Could the ADSI Reveal?
As the recipients of ADSI grants begin their work, the initiative’s $50 million investment holds promise for uncovering new insights into autism’s causes and mechanisms. By supporting these diverse research projects, ADSI aims to deepen understanding of ASD and ultimately guide more effective strategies for diagnosis, intervention, and care.
It also aims to leverage large-scale data to identify and investigate potential contributors to autism’s causes and rising prevalence and the efficacy of existing treatments.
Among the 13 funded projects is one examining how causal inference – the use of data to examine causal relationships – can be used to study early-life factors that may cause autism, influence prevalence, or explain variations in traits and functioning among individuals with autism.
“We are bringing in newer techniques from causal inference that do a better job of teasing apart cause from association,” principal investigator Amy Cochran, PhD, assistant professor, Departments of Population Health Sciences and Mathematics, University of Wisconsin-Madison, told Medscape Medical News.
“We want to generate stronger evidence about the early-life factors that may — or may not — be contributing to autism, and how they shape the diverse experiences of autistic people, so we can better prioritize public health resources and interventions,” Cochran added.
Another ASDI project will use large-scale data on genes and environmental exposures to examine the link between autism and environmental factors and identify specific genetic variants that may interact with those factors.
“If long-term clinical outcome of a genetic disorder is influenced by an environmental factor, that represents a condition that could be modified to improve outcomes,” principal investigator Jonathan Sebat, PhD, professor of psychiatry and cellular and molecular medicine, University of California San Diego (UCSD), told Medscape Medical News.
Sebat’s lab at UCSD has pioneered genetic approaches to identify autism genes.
“We were one of two groups that first showed how a father’s age causes mutations in sperm and we have since unraveled a variety of genetic factors that explain the effect of parental age on autism risk,” Sebat said. “So this grant gives us an opportunity to expand this work to rigorously determine which environmental factors have real causal effects, and what are the mechanisms.”
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