Why Are Autism Rates Steadily Rising?
Stefania Sterling was just 21 when she had her son, Charlie. She was young and healthy, with no genetic issues apparent in either her or her husband's family, so she expected Charlie to be typical.
"It is surprising that the prevalence of a significant disorder like autism has risen so consistently over a relatively brief period."
It wasn't until she went to a Mommy and Me music class when he was one, and she saw all the other one-year-olds walking, that she realized how different her son was. He could barely crawl, didn't speak, and made no eye contact. By the time he was three, he was diagnosed as being on the lower functioning end of the autism spectrum.
She isn't sure why it happened – and researchers, too, are still trying to understand the basis of the complex condition. Studies suggest that genes can act together with influences from the environment to affect development in ways that lead to Autism Spectrum Disorder (ASD). But rates of ASD are rising dramatically, making the need to figure out why it's happening all the more urgent.
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Indeed, the CDC's latest autism report, released last week, which uses 2016 data, found that the prevalence of ASD in four-year-old children was one in 64 children, or 15.6 affected children per 1,000. That's more than the 14.1 rate they found in 2014, for the 11 states included in the study. New Jersey, as in years past, was the highest, with 25.3 per 1,000, compared to Missouri, which had just 8.8 per 1,000.
The rate for eight-year-olds had risen as well. Researchers found the ASD prevalence nationwide was 18.5 per 1,000, or one in 54, about 10 percent higher than the 16.8 rate found in 2014. New Jersey, again, was the highest, at one in 32 kids, compared to Colorado, which had the lowest rate, at one in 76 kids. For New Jersey, that's a 175 percent rise from the baseline number taken in 2000, when the state had just one in 101 kids.
"It is surprising that the prevalence of a significant disorder like autism has risen so consistently over a relatively brief period," said Walter Zahorodny, an associate professor of pediatrics at Rutgers New Jersey Medical School, who was involved in collecting the data.
The study echoed the findings of a surprising 2011 study in South Korea that found 1 in every 38 students had ASD. That was the the first comprehensive study of autism prevalence using a total population sample: A team of investigators from the U.S., South Korea, and Canada looked at 55,000 children ages 7 to 12 living in a community in South Korea and found that 2.64 percent of them had some level of autism.
Searching for Answers
Scientists can't put their finger on why rates are rising. Some say it's better diagnosis. That is, it's not that more people have autism. It's that we're better at detecting it. Others attribute it to changes in the diagnostic criteria. Specifically, the May 2013 update of the Diagnostic and Statistical Manual of Mental Disorders-5 -- the standard classification of mental disorders -- removed the communication deficit from the autism definition, which made more children fall under that category. Cynical observers believe physicians and therapists are handing out the diagnosis more freely to allow access to services available only to children with autism, but that are also effective for other children.
Alycia Halladay, chief science officer for the Autism Science Foundation in New York, said she wishes there were just one answer, but there's not. While she believes the rising ASD numbers are due in part to factors like better diagnosis and a change in the definition, she does not believe that accounts for the entire rise in prevalence. As for the high numbers in New Jersey, she said the state has always had a higher prevalence of autism compared to other states. It is also one of the few states that does a good job at recording cases of autism in its educational records, meaning that children in New Jersey are more likely to be counted compared to kids in other states.
"Not every state is as good as New Jersey," she said. "That accounts for some of the difference compared to elsewhere, but we don't know if it's all of the difference in prevalence, or most of it, or what."
"What we do know is that vaccinations do not cause autism."
There is simply no defined proven reason for these increases, said Scott Badesch, outgoing president and CEO of the Autism Society of America.
"There are suggestions that it is based on better diagnosis, but there are also suggestions that the incidence of autism is in fact increasing due to reasons that have yet been determined," he said, adding, "What we do know is that vaccinations do not cause autism."
Zahorodny, the pediatrics professor, believes something is going on beyond better detection or evolving definitions.
"Changes in awareness and shifts in how children are identified or diagnosed are relevant, but they only take you so far in accounting for an increase of this magnitude," he said. "We don't know what is driving the surge in autism recorded by the ADDM Network and others."
He suggested that the increase in prevalence could be due to non-genetic environmental triggers or risk factors we do not yet know about, citing possibilities including parental age, prematurity, low birth rate, multiplicity, breech presentation, or C-section delivery. It may not be one, but rather several factors combined, he said.
"Increases in ASD prevalence have affected the whole population, so the triggers or risks must be very widely dispersed across all strata," he added.
There are studies that find new risk factors for ASD almost on a daily basis, said Idan Menashe, assistant professor in the Department of Health at Ben-Gurion University of the Negev, the fastest growing research university in Israel.
"There are plenty of studies that find new genetic variants (and new genes)," he said. In addition, various prenatal and perinatal risk factors are associated with a risk of ASD. He cited a study his university conducted last year on the relationship between C-section births and ASD, which found that exposure to general anesthesia may explain the association.
Whatever the cause, health practitioners are seeing the consequences in real time.
"People say rates are higher because of the changes in the diagnostic criteria," said Dr. Roseann Capanna-Hodge, a psychologist in Ridgefield, CT. "And they say it's easier for children to get identified. I say that's not the truth and that I've been doing this for 30 years, and that even 10 years ago, I did not see the level of autism that I do see today."
Sure, we're better at detecting autism, she added, but the detection improvements have largely occurred at the low- to mid- level part of the spectrum. The higher rates of autism are occurring at the more severe end, in her experience.
A Polarizing Theory
Among the more controversial risk factors scientists are exploring is the role environmental toxins may play in the development of autism. Some scientists, doctors and mental health experts suspect that toxins like heavy metals, pesticides, chemicals, or pollution may interrupt the way genes are expressed or the way endocrine systems function, manifesting in symptoms of autism. But others firmly resist such claims, at least until more evidence comes forth. To date, studies have been mixed and many have been more associative than causative.
"Today, scientists are still trying to figure out whether there are other environmental changes that can explain this rise, but studies of this question didn't provide any conclusive answer," said Menashe, who also serves as the scientific director of the National Autism Research Center at BGU.
"It's not everything that makes Charlie. He's just like any other kid."
That inconclusiveness has not dissuaded some doctors from taking the perspective that toxins do play a role. "Autism rates are rising because there is a mismatch between our genes and our environment," said Julia Getzelman, a pediatrician in San Francisco. "The majority of our evolution didn't include the kinds of toxic hits we are experiencing. The planet has changed drastically in just the last 75 years –- it has become more and more polluted with tens of thousands of unregulated chemicals being used by industry that are having effects on our most vulnerable."
She cites BPA, an industrial chemical that has been used since the 1960s to make certain plastics and resins. A large body of research, she says, has shown its impact on human health and the endocrine system. BPA binds to our own hormone receptors, so it may negatively impact the thyroid and brain. A study in 2015 was the first to identify a link between BPA and some children with autism, but the relationship was associative, not causative. Meanwhile, the Food and Drug Administration maintains that BPA is safe at the current levels occurring in food, based on its ongoing review of the available scientific evidence.
Michael Mooney, President of St. Louis-based Delta Genesis, a non-profit organization that treats children struggling with neurodevelopmental delays like autism, suspects a strong role for epigenetics, which refers to changes in how genes are expressed as a result of environmental influences, lifestyle behaviors, age, or disease states.
He believes some children are genetically predisposed to the disorder, and some unknown influence or combination of influences pushes them over the edge, triggering epigenetic changes that result in symptoms of autism.
For Stefania Sterling, it doesn't really matter how or why she had an autistic child. That's only one part of Charlie.
"It's not everything that makes Charlie," she said. "He's just like any other kid. He comes with happy moments. He comes with sad moments. Just like my other three kids."
A Rare Disease Just "Messed with the Wrong Mother." Now She's Fighting to Beat It Once and For All.
Amber Freed felt she was the happiest mother on earth when she gave birth to twins in March 2017. But that euphoric feeling began to fade over the next few months, as she realized her son wasn't making the same developmental milestones as his sister. "I had a perfect benchmark because they were twins, and I saw that Maxwell was floppy—he didn't have muscle tone and couldn't hold his neck up," she recalls. At first doctors placated her with statements that boys sometimes develop slower than girls, but the difference was just too drastic. At 10 month old, Maxwell had never reached to grab a toy. In fact, he had never even used his hands.
Thinking that perhaps Maxwell couldn't see well, Freed took him to an ophthalmologist who was the first to confirm her worst fears. He didn't find Maxwell to have vision problems, but he thought there was something wrong with the boy's brain. He had seen similar cases before and they always turned out to be rare disorders, and always fatal. "Start preparing yourself for your child not to live," he had said.
Getting the diagnosis took months of painful, invasive procedures, as well as fighting with the health insurance to get the genetic testing approved. Finally, in June 2018, doctors at the Children's Hospital Colorado gave the Freeds their son's diagnosis—a genetic mutation so rare it didn't even have a name, just a bunch of letters jammed together into a word SLC6A1—same as the name of the mutated gene. The mutation, with only 40 cases known worldwide at the time, caused developmental disabilities, movement and speech disorders, and a debilitating form of epilepsy.
The doctors didn't know much about the disorder, but they said that Maxwell would also regress in his development when he turned three or four. They couldn't tell how long he would live. "Hopefully you would become an expert and educate us about it," they said, as they gave Freed a five-page paper on the SLC6A1 and told her to start calling scientists if she wanted to help her son in any way. When she Googled the name, nothing came up. She felt horrified. "Our disease was too rare to care."
Freed's husband, a 6'2'' college football player broke down in sobs and she realized that if anything could be done to help Maxwell, she'd have be the one to do it. "I understood that I had to fight like a mother," she says. "And a determined mother can do a lot of things."
The Freed family.
Courtesy Amber Freed
She quit her job as an equity analyst the day of the diagnosis and became a full-time SLC6A1 citizen scientist looking for researchers studying mutations of this gene. In the wee hours of the morning, she called scientists in Europe. As the day progressed, she called researchers on the East Coast, followed by the West in the afternoon. In the evening, she switched to Asia and Australia. She asked them the same question. "Can you help explain my gene and how do we fix it?"
Scientists need money to do research, so Freed launched Milestones for Maxwell fundraising campaign, and a SLC6A1 Connect patient advocacy nonprofit, dedicated to improving the lives of children and families battling this rare condition. And then it became clear that the mutation wasn't as rare as it seemed. As other parents began to discover her nonprofit, the number of known cases rose from 40 to 100, and later to 400, Freed says. "The disease is only rare until it messes with the wrong mother."
It took one mother to find another to start looking into what's happening inside Maxwell's brain. Freed came across Jeanne Paz, a Gladstone Institutes researcher who studies epilepsy with particular interest in absence or silent seizures—those that don't manifest by convulsions, but rather make patients absently stare into space—and that's one type of seizures Maxwell has. "It's like a brief period of silence in the brain during which the person doesn't pay attention to what's happening, and as soon as they come out of the seizure they are back to life," Paz explains. "It's like a pause button on consciousness." She was working to understand the underlying biology.
To understand how seizures begin, spread and stop, Paz uses optogenetics in mice. From words "genetic" and "optikós," which means visible in Greek, the optogenetics technique involves two steps. First, scientists introduce a light-sensitive gene into a specific brain cell type—for example into excitatory neurons that release glutamate, a neurotransmitter, which activates other cells in the brain. Then they implant a very thin optical fiber into the brain area where they forged these light-sensitive neurons. As they shine the light through the optical fiber, researchers can make excitatory neurons to release glutamate—or instead tell them to stop being active and "shut up". The ability to control what these neurons of interest do, quite literally sheds light onto where seizures start, how they propagate and what cells are involved in stopping them.
"Let's say a seizure started and we shine the light that reduces the activity of specific neurons," Paz explains. "If that stops the seizure, we know that activating those cells was necessary to maintain the seizure." Likewise, shutting down their activity will make the seizure stop.
Freed reached out to Paz in 2019 and the two women had an instant connection. They were both passionate about brain and seizures research, even if for different reasons. Freed asked Paz if she would study her son's seizures and Paz agreed.
To do that, Paz needed mice that carried the SLC6A1 mutation, so Freed found a company in China that created them to specs. The company replaced a mouse SLC6A1 gene with a human mutated one and shipped them over to Paz's lab. "We call them Maxwell mice," Paz says, "and we are now implanting electrodes into them to see which brain regions generate seizures." That would help them understand what goes wrong and what brain cells are malfunctioning in the SLC6A1 mice—and help scientists better understand what might cause seizures in children.
Bred to carry SLC6A1 mutation, these "Maxwell mice" will help better understand this debilitating genetic disease. (These mice are from Vanderbilt University, where researchers are also studying SLC6A1.)
Courtesy Amber Freed
This information—along with other research Amber is funding in other institutions—will inform the development of a novel genetic treatment, in which scientists would deploy a harmless virus to deliver a healthy, working copy of the SLC6A1 gene into the mice brains. They would likely deliver the therapeutic via a spinal tap infusion, and if it works and doesn't produce side effects in mice, the human trials will follow.
In the meantime, Freed is raising money to fund other research of various stop-gap measures. On April 22, 2021, she updated her Milestone for Maxwell page with a post that her nonprofit is funding yet another effort. It is a trial at Weill Cornell Medicine in New York City, in which doctors will use an already FDA-approved drug, which was recently repurposed for the SLC6A1 condition to treat epilepsy in these children. "It will buy us time," Freed says—while the gene therapy effort progresses.
Freed is determined to beat SLC6A1 before it beats down her family. She hopes to put an end to this disease—and similar genetic diseases—once and for all. Her goal is not only to have scientists create a remedy, but also to add the mutation to a newborn screening panel. That way, children born with this condition in the future would receive gene therapy before they even leave the hospital.
"I don't want there to be another Maxwell Freed," she says, "and that's why I am fighting like a mother." The gene therapy trial still might be a few years away, but the Weill Cornell one aims to launch very soon—possibly around Mother's Day. This is yet another milestone for Maxwell, another baby step forward—and the best gift a mother can get.
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
This virtual event convened leading scientific and medical experts to address the public's questions and concerns about Covid-19 vaccines in kids and teens. Highlight video below.
DATE:
Thursday, May 13th, 2021
12:30 p.m. - 1:45 p.m. EDT
Dr. H. Dele Davies, M.D., MHCM
Senior Vice Chancellor for Academic Affairs and Dean for Graduate Studies at the University of Nebraska Medical (UNMC). He is an internationally recognized expert in pediatric infectious diseases and a leader in community health.
Dr. Emily Oster, Ph.D.
Professor of Economics at Brown University. She is a best-selling author and parenting guru who has pioneered a method of assessing school safety.
Dr. Tina Q. Tan, M.D.
Professor of Pediatrics at the Feinberg School of Medicine, Northwestern University. She has been involved in several vaccine survey studies that examine the awareness, acceptance, barriers and utilization of recommended preventative vaccines.
Dr. Inci Yildirim, M.D., Ph.D., M.Sc.
Associate Professor of Pediatrics (Infectious Disease); Medical Director, Transplant Infectious Diseases at Yale School of Medicine; Associate Professor of Global Health, Yale Institute for Global Health. She is an investigator for the multi-institutional COVID-19 Prevention Network's (CoVPN) Moderna mRNA-1273 clinical trial for children 6 months to 12 years of age.
About the Event Series
This event is the second of a four-part series co-hosted by Leaps.org, the Aspen Institute Science & Society Program, and the Sabin–Aspen Vaccine Science & Policy Group, with generous support from the Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute.
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Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.