U.S. study charts changing prevalence of profound and non-profound autism

Community traits: Children with profound autism are more likely to be girls than are their peers with non-profound autism.

Laurence Mouton / Getty Images

More than a quarter of autistic 8-year-olds in the United States have profound autism, according to a study published today in Public Health Reports. Although the overall prevalence of profound autism in this age group increased from 2002 to 2016, the prevalence of non-profound autism did so at a sharper rate, the findings show.

The results align with the idea that much of autism’s dramatic rise over the past three decades stems from diagnostic changes. “We are now finding people with autism who don’t have intellectual disability and who have more fluent language” — and who may not have been diagnosed 20 or 30 years ago, says Catherine Lord, distinguished professor of psychiatry and education at the University of California, Los Angeles, who was not involved in the work.

The term profound autism, introduced in December 2021 by Lord and her colleagues as part of the Lancet Commission on the Future of Care and Clinical Research in Autism, describes autistic people who likely need lifelong 24/7 care, many of whom have intellectual disability, limited communication abilities or both. The commission estimated at the time that anywhere from 18 to 48 percent of the autistic population might fit this description, according to an analysis of three separate datasets from the U.S., the United Kingdom and Norway.

The new estimate — the first based on data from 20,135 autistic children, collected by the U.S. Centers for Disease Control and Prevention’s Autism and Developmental Disabilities Monitoring (ADDM) Network — falls in the middle of that range at 26.7 percent.

But non-white autistic children are more likely than their white peers to have profound autism, the work shows. The prevalence is 76 percent higher for Black children, 55 percent higher for children from Asian, Native Hawaiian or other Pacific Islander backgrounds, 50 percent higher for Hispanic children and 33 percent higher for American Indian (Native American) and Alaska Native children. Children with profound autism are also more likely to come from low socioeconomic backgrounds compared with their peers with non-profound autism.

Those differences point to disparities in how clinicians diagnose autism across different communities, Lord says.

“We probably are not picking up the more able kids with autism in minority ethnic groups,” she says. “It tells us more about who’s not there than who’s there.”

Profound autism prevalence also varies by gender and region, the study shows. The results can help researchers and clinicians plan for the services and supports that people who meet the criteria for profound autism may need over their lifetime, says study investigator Michelle Hughes, an epidemiologist at the CDC. “We saw this as an opportunity to bring data to the conversation,” she says.

The ADDM Network has released reports on autism prevalence at study sites in the U.S. every two years since 2000. For those reports, the researchers use data from medical and educational records to estimate the number of 4- and 8-year-olds with autism in a given year. The network is continuing to track autism prevalence at its current sites and announced yesterday that it plans to expand its surveillance to 5 additional sites — including one in Puerto Rico — for the next funding cycle.

In the new study, CDC researchers used a similar approach to estimate the number of 8-year-olds with profound autism across 15 sites for the surveillance years between 2000 and 2016, excluding 2012 and 2014 because they did not have information on children’s verbal abilities for those years. They classified children as having profound autism if a clinician reviewing their records determined they fit the diagnostic criteria for autism and their records indicated that they were nonverbal, minimally verbal or had an IQ below 50.

In 2000, about 27 of every 10,000 children within the network had profound autism, and 39 in 10,000 had non-profound autism, the team found. And although prevalence increased for both groups over the next 16 years, that of non-profound autism did so more rapidly — reaching 143 per 10,000, compared with 46 per 10,000 for profound autism.

Group change: As more children with non-profound autism are diagnosed over time, the proportion of the autistic population with profound autism decreases.

Courtesy Hughes et al. / CDC

Profound autism prevalence is also relatively stable across regions, whereas the prevalence of children with non-profound autism varies more widely, the study shows: from 260 per 10,000 in New Jersey to 104 per 10,000 in Colorado for the 2016 surveillance year.

Those regional differences may be explained by how accessible services are in a given state, as well as the site’s racial and ethnic makeup, Lord says.

Autistic girls are about 25 percent more likely to be classified as having profound autism than their male peers, the findings show. Although it is possible that many autistic girls with non-profound autism are not diagnosed, it may also be that girls are more likely than boys to survive with the genetic mutations that cause this presentation of autism, Lord says.

The findings fit, to a large degree, with what the Lancet commission expected, Lord says. For example, most of the children with profound autism have low adaptive-functioning scores, the new study shows, and they are more likely than children with non-profound autism to have self-injurious behaviors and seizures. Having a more complete picture of who these children are and what traits they have will help researchers and clinicians provide better recommendations for their well-being, she says.

But the study is the first of its kind and needs to be replicated, Lord adds, noting methodological challenges such as incomplete records. “The numbers could be high — or low,” she says, because the researchers had to make inferences on data that was not systematically collected.

Moving forward, it will also be important to gain a better understanding of autism in the non-white population, says Santhosh Girirajan, associate professor of genomics at Pennsylvania State University in University Park, who was not involved in the work.

“What we use in white populations might not be applicable in non-white populations,” Girirajansays. Addressing that might take redefining some of the assessments to account for cultural and familial differences, he says — and may ultimately help the field better understand autism as a whole.

Cite this article: https://doi.org/10.53053/TCER1579

A questionable study linked epidurals to autism. Then what?

Scientific reflection: A seemingly simple epidemiology paper prompted researchers to consider what publishing is for.

The spread of misinformation — and the way fear can burn through a landscape — was forefront in Tor-Arne Hegvik’s mind when, in October 2020, he opened up his web browser and found a new autism paper in JAMA Pediatrics. Hegvik is a gynecologist and researcher at the University of Bergen in Norway, and the study, co-led by biostatistician Anny Xiang of Kaiser Permanente Southern California (KPSC), made what appeared to be an improbable claim: The epidural analgesia given during labor is associated with increased chances of having a child with autism.

Hegvik had never wondered whether epidurals could contribute to autism, and he didn’t think anyone else had seriously considered it either. He assumed the association detailed in the paper was due to confounders — unaccounted-for factors that skew a result. Plus, he had clinical duties to attend to and patients to see. He tried to put it out of his mind.

But the paper continued to plague him. It reminded him of Andrew Wakefield’s infamous fraudulent statement that vaccines cause autism: Though the link was easy to disprove, it was exceedingly difficult to quash in the public consciousness. The epidural paper was not exactly that — Hegvik could see it was honest science — but the potential for harm felt similar. The decision to get an epidural requires clear, straightforward information. The Xiang paper, he worried, would muddy the waters. He couldn’t turn away. So he emailed some of his colleagues and asked: Would anyone be interested in trying to refute this?

Other worried researchers were also talking about the paper, united by the thought that the study’s implied conclusion — that epidurals cause autism — could become a Wakefield-esque fiasco. It is difficult to know exactly what fears will catch fire in the public consciousness, but if it was even a possibility here, they wanted to do something about it.

The first person at JAMA Pediatrics to read the epidural paper was the journal’s chief editor, Dimitri Christakis. Christakis rejects on sight about three-quarters of the papers he receives. The rest go to his team of associate editors, some then go on to peer review, and in the end just 6 percent of submissions are accepted. So it’s safe to say JAMA Pediatrics is a discerning publication. Today, Christakis doesn’t remember anything particularly noteworthy about Xiang’s paper or its peer-review process. (The journal does not make its reviews public.)

What he saw was a study showing that among nearly 148,000 babies born in a KPSC hospital between 2008 and 2015, children whose mothers had an epidural while giving birth were 37 percent more likely to be autistic than those whose mothers did not have one; the longer the epidural exposure, the higher the chance of autism. Christakis felt there were some weaknesses in the data, but the researchers acknowledged them and were cautious in their conclusions. The methodology was not flawed on its face. He felt the question Xiang had introduced deserved an answer.

Christakis’ decision to publish revolved largely around the role of scientific publishing. Part of the job of a journal, he told me, is to present ideas for its community to evaluate. He could find no reason not to present Xiang’s. JAMA Pediatrics accepted the paper on 17 June 2020 and published it on 12 October.

If the Xiang paper presented an intriguing scientific idea, it did not appear to be one the research community had previously cared much about. According to PubMed, before 2020 just one study had ever specifically looked at epidurals and autism together — a 2004 Australian paper that found a small association in about 2,000 people.

“I thought, when it first came out, ‘Oh my goodness, this is just going to permeate every discussion I have for the rest of my career.’” Daniel McIsaac

In their paper, Xiang and her colleagues were careful not to state that epidurals might cause autism. They had simply observed an association and noted that it should be viewed “with caution” and “cannot be interpreted as a demonstration of a causal link.”

But Hegvik thought the cautioning statements did not go far enough.

“When you read the article, they never directly claim that epidurals might cause autism,” Hegvik said. “But it’s like, everywhere you read between the lines, that’s basically what they’re writing.”

Daniel McIsaac, an anesthesiologist at Ottawa Hospital and associate professor of anesthesiology at the University of Ottawa in Canada, felt much the same after reading the Xiang paper. “I thought, when it first came out, ‘Oh my goodness, this is just going to permeate every discussion I have for the rest of my career,’” he said.

McIsaac, like many others, was concerned that the study failed to account for factors that could make a person more likely to both use an epidural and give birth to an autistic child. Xiang and her colleagues, for example, did not control for the mother’s own psychiatric conditions, even though such conditions in parents are widely known to be linked to autism in children. Xiang and her team also excluded women who had received cesarean sections, which often occur because of complications with labor.

What’s more, it’s hard to see how epidurals — which come at the end of a pregnancy and generally last just a few hours — could lead to autism, a condition thought to originate in the earliest stages of fetal development. Because of this, McIsaac couldn’t understand why the research was even done. Typically, to justify doing a major epidemiological study like this one, a researcher needs good reason to think there’s something to find. “Just because you have data,” McIsaac said, “is never the right reason to do a study.”

Beyond citing some preliminary research in people, Xiang and her team also looked at a 1998 study comparing 11 infant rhesus monkeys born to mothers that had received a dose of bupivacaine (one of the drugs in a standard epidural) with eight control rhesus infants. The study showed that “standard clinical doses” of anesthetic drugs can “alter normal behavioral development,” according to Xiang’s paper. But that 1998 study concluded that even though the time course of the exposed rhesus infants’ development was shifted, the drug “does not cause neonatal abnormalities or specific cognitive deficits,” the researchers wrote.

Alexander Butwick, professor of anesthesiology at Stanford University in California, found the rhesus monkey data referenced in Xiang’s paper to be “pretty weak,” he told me. He and a colleague commented on the JAMA Pediatrics website that the dose used in the animal study wasn’t comparable to the one used in the delivery ward and called the researchers’ interpretations of relevant studies in people “at best misleading and at worst erroneous.”

Butwick set out to repeat the Xiang study with fresh data, and to do it quickly. “We really felt like we had a responsibility here to do not just the work but also respond in a timely manner,” Butwick said. “We were worried that the longer this was out there, the more people may feel like there’s a genuine cause-and-effect issue going on.”

He called epidemiologist Elizabeth Wall-Wieler, then assistant professor of community health sciences at the University of Manitoba in Canada (she now works in California), who had access to a dataset that linked clinical data from hospital visits to parent socioeconomic information and long-term outcomes for the child. Butwick and Wall-Wieler pulled numbers on 123,175 babies born in Manitoba from 2005 through 2016, adjusted for more than 30 factors — including maternal anxiety and depression — and found that epidurals were not associated with autism. That finding stood in a secondary analysis of siblings born to the same mother.

The paper was published 19 April 2021, also in JAMA Pediatrics. It was the first time the journal had published conflicting results on the same topic within 12 months — such a rare occurrence that Christakis pointed it out in an editor’s note published the same day.

Still, the papers around epidurals and autism kept coming. JAMA published two on the same day, in late September 2021. One, which looked at nearly 400,000 births in British Columbia, Canada, found a small association, though the authors ascribed it to “residual confounding.” The other, in nearly half a million children from a Danish registry, found no link at all. In a commentary accompanying the two papers, Cynthia Wong, chair of the Department of Anesthesia at the University of Iowa, wrote that “current evidence does not justify” considering the chances of autism when making decisions about epidurals.

In December 2021, the British Journal of Anesthesia published yet another null result, this time in almost 625,000 children born in Denmark. It was closely followed by a commentary from Wong and Butwick in the same journal, asserting “no meaningful association” between epidurals and autism. The case, they argued, was closed.

But four months later, JAMA Network Open published a study involving more than 650,000 mother-child pairs in Ontario, Canada, that found a small link between epidurals and autism — though the research team, which included McIsaac, noted the finding “must be interpreted with caution.” There were two meta-analyses, both of which found little reason to continue investigating the question. In fact, in the two and a half years since Xiang’s paper came out, there have been at least 28 papers addressing the purported connection. If the research community had not been interested in a link between autism and epidurals before Xiang’s study, it certainly was now. (Xiang declined to be interviewed by phone for this story, but in an email sent via a publicist affiliated with Kaiser Permanente, she repeated that her paper had only noted an association and added that she and her team welcomed additional studies. Xiang also stressed the benefits of epidurals for mothers and noted that there is not enough evidence to recommend against them.)

There was one more paper coming. Amir Sariaslan, a psychiatric epidemiologist at the University of Oxford in the U.K., was on the receiving end of Hegvik’s October 2020 email about Xiang’s study. He had never studied epidurals and had limited experience studying autism, but he had worked with Hegvik before and, crucially, could tap national registry data from Finland and Sweden, which contained information on more than 3.5 million births. Hegvik had access to data from another million births in Norway, and together they pulled together a game-changing cohort: 4.5 million people born across 28 years, with more than 1 million of them delivered using an epidural.

It took two years to finish the study; the findings were published online in the American Journal of Obstetrics and Gynecology last August. In a crude analysis, Sariaslan and his team found that children exposed to epidurals were 12 percent more likely to be autistic and 20 percent more likely to have attention-deficit/hyperactivity disorder than their unexposed counterparts.

Other studies had made initial steps beyond these preliminary associations. But because of the size of the cohort, Sariaslan had the power to do a new kind of analysis. He and his team pared their sample down to include only full siblings — other studies had confirmed just a shared mother. They then pulled just those siblings who differed both in their exposure to epidurals and whether or not they had autism or ADHD.

That specific group was about 2 percent of the original 4.5 million. But it was still 94,000 people. That was sufficient to find that people with either condition were no more likely than their siblings without a neurodevelopmental condition to have been exposed to an epidural.

In other words, the association between autism and epidurals completely disappeared.

“I personally think we’re done with this,” Wong said after Sariaslan’s study came out. There would be nothing to gain from mining more databases or a larger dataset. “There’s no place to go.”

The point of scientific publishing is to go “wherever science leads,” Christakis told me. Much of the pushback after the Xiang paper was published, he said, was by people worried that “this is going to panic women” about epidurals. “But that’s not a reason to not publish science. It’s just not.”

Science works only when researchers are free to publish their findings, regardless of what societal structures they may upend or whom they might upset. That march toward truth relies on the free flow of information. But the human brain is not always so rational. When encountering a new concept, people tend to focus on and remember the parts that cause negative emotions, like fear and anger. When that happens, collective efforts to debunk new ideas can sometimes just reinforce them.

“We were worried that the longer this was out there, the more people may feel like there’s a genuine cause and effect issue going on.” Alexander Butwick

That could have happened with Xiang’s work. The paper alarmed not only scientists but also doctors, and on the initial day of publication, five U.S. medical societies representing more than 100,000 physicians posted a response saying the study “does not provide credible scientific evidence” for the association and urging women not to be fearful of epidurals. By the end of that month, the Royal College of Anaesthetists, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists and the Canadian Anesthesiologists’ Society had also all pushed back against the paper’s findings.

Their intention was much the same as Hegvik’s: to quickly refute what they saw as a potentially harmful conclusion in a paper based on science that could be challenged. But Dominique Brossard, an expert in the communication of science and risk at the University of Wisconsin-Madison, told me that rushing out a press release was, in her mind, exactly what not to do. The collective statement from physicians on the day of the publication, and those in the days that followed, could have stirred up a long-lasting media buzz — the kind that leaves the public recalling a shadowy link between epidurals and autism, and not much else.

Yet it did not. As far as anyone could tell me, the sweeping fear over epidurals hasn’t materialized in the general population. No one could cite more than a handful of instances from the past three years of a pregnant person asking about the link between autism and epidurals; most said they had never been asked about it. Searches for the topic turned up little on social media. It’s possible this is because the press was otherwise occupied in October 2020: It was furiously covering the global pandemic, and the United States was a month away from a contentious presidential election. Major national outlets such as The New York Times, The Washington Post and The Los Angeles Times, as well as popular science news sites such as Scientific American and New Scientist, did not cover Xiang’s study. (Spectrum ran a story the day after the study came out.)

That’s one theory. But Brossard has another. And that is that there was no organized movement eagerly waiting to pounce on new data about epidurals, no group that could use it to further a specific viewpoint. There is no anti-epidural lobbying group, for instance, and there is no epidural-alternative product to sell. If there had been people seeking to amplify Xiang’s study for personal gain, maybe it would have caught fire in the public consciousness.

Instead, though, the issue fizzled. That just left the scientists, gathering their evidence, publishing the story it told.

Cite this article: https://doi.org/10.53053/KXEV1638

José Ramón Alonso, doctor en Biología de la Universidad de Salamanca explica los avances en investigación, las nuevas estrategias de diagnóstico y tratamiento sobre autismo, que según descubrimientos recientes está afectando a una gran cantidad de población que hasta hoy se desconocía.

Explica José Ramón que son muchos los esfuerzos que se están realizando para descubrir sus posibles causas pero que también se le está dando importancia al aspecto social, en apoyo a quienes la padecen y familias afectadas.

“Autismo es un trastorno del desarrollo y por lo que sabemos se inicia antes del nacimiento”. También, menciona múltiples equivocaciones relacionadas con teorías que han tratado de explicar sus orígenes, así como el uso de instrumentos que se están utilizando para su detección

Northwestern Investigators Develop New Therapy for Autism Subtype

A team of Northwestern investigators led by Peter Penzes, PhD, the Ruth and Evelyn Dunbar Professor of Psychiatry and Behavioral Sciences and director of the Center for Autism and Neurodevelopment, has developed a new therapy that could treat Phelan-McDermid syndrome, a subtype of autism spectrum disorder (ASD), according to findings published in Molecular Psychiatry.  

According to the Centers for Disease Control and Prevention, one in 44 children in the U.S. have been diagnosed with ASD and each patient presents diverse clinical and developmental symptoms, which may include delayed speech, motor skills and learning skills, epilepsy, poor eating and sleeping habits, and gastrointestinal issues.  

Phelan-McDermid syndrome is known to be caused by a specific genetic mutation in SHANK3, a well-known ASD candidate gene. Due to the heterogeneity of ASD, the development of effective targeted therapies has been extremely challenging, leaving patients with treatment options that improve disease management. 

Based on the urgent need for new therapies, Penzes’ team developed a derivative of an insulin-like growth factor-binding protein, IGFBP2, which is found in structures of the brain affected in ASD and has been shown to improve neuroplasticity and cognitive functions.  

In the current study, the investigators administered the IGFBP2-derived peptide, called JB2, to mice with SHANK3 mutations. Through advanced brain imaging, they found that the drug improved neuroplasticity, behavior impairments and cellular processes in the mices’ brains.  

These changes were directly correlated with improvements in the mices’ learning and memory skills, motor function and communication through ultrasonic vocalizations, findings that could be translated to social behaviors in humans, according to Penzes. 

“In patients with autism, speech doesn’t develop at all, or it develops very late, or it’s very simplified, so these ultrasonic vocalizations in mice are thought to somehow model that in mice,” said Penzes, who is also professor of Neuroscience and of Pharmacology. 

Using electroencephalography to measure the mice’s brain activity, the team also discovered that JB2 normalized neuronal excitability, or how neurons respond to stimuli with an electric charge, and seizure susceptibility.  

While the drug is still in early stages, Penzes said, theoretically, routinely administering the drug into patients’ bloodstreams while they are young either through regular injections or in pill form would be ideal.   

“Because this is a neurodevelopmental condition, the brain still changes after birth, even into adulthood. The earlier one could intervene, the better. So, it would be preferable to start it as a pediatric medication, but those are more difficult to get approval for,” Penzes said.   

Penzes noted that initial clinical trials would involve participants with Phelan-McDermid syndrome and if successful, could eventually expand to include patients with other types of ASD.  

“The assumption is that similar changes are happening in the brains of patients with other types of autism and in Phelan-McDermid syndrome, but these patients would have a better response,” Penzes said.  

Co-authors of the study include Sehyoun Yoon, PhD, research assistant professor of Neuroscience, Jeffrey Burgdorf, PhD, adjunct professor of Biomedical Engineering at the McCormick School of Engineering, Marc Dos Santos, PhD, a postdoctoral fellow in the Penzes laboratory, and Joseph Moskal, PhD, professor of Biomedical Engineering at the McCormick School of Engineering.  

This work, part of ongoing efforts by the Center for Autism and Neurodevelopment to develop new therapies, was supported by National Institute of Mental Health grant R41MH121140. 

FUENTE:Northwestern Investigators Develop New Therapy for Autism Subtype – News Center

Dr. Temple Grandin comes to Google to talk about her book: The Autistic Brain: Thinking Across the Spectrum.

When Temple Grandin was born in 1947, autism had only just been named.

Today it is more prevalent than ever, with one in 88 children diagnosed on the spectrum.

And our thinking about it has undergone a transformation in her lifetime: Autism studies have moved from the realm of psychology to neurology and genetics, and there is far more hope today than ever before thanks to groundbreaking new research into causes and treatments.

Now Temple Grandin reports from the forefront of autism science, bringing her singular perspective to a thrilling journey into the heart of the autism revolution.

Weaving her own experience with remarkable new discoveries, Grandin introduces the neuroimaging advances and genetic research that link brain science to behavior, even sharing her own brain scan to show us which anomalies might explain common symptoms.

We meet the scientists and self-advocates who are exploring innovative theories of what causes autism and how we can diagnose and best treat it. Grandin also highlights long-ignored sensory problems and the transformative effects we can have by treating autism symptom by symptom, rather than with an umbrella diagnosis.

Most exciting, she argues that raising and educating kids on the spectrum isn’t just a matter of focusing on their weaknesses; in the science that reveals their long-overlooked strengths she shows us new ways to foster their unique contributions.

From the “aspies” in Silicon Valley to the five-year-old without language, Grandin understands the true meaning of the word spectrum.

The Autistic Brain is essential reading from the most respected and beloved voices in the field.