User login
Prescription video game focuses attention in ADHD
Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.
“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.
“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.
The study was recently published online in PLOS ONE.
Measurable changes
As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.
“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.
In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.
Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.
“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.
There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.
In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
‘Not just another video game’
EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.
The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.
The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.
“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization. 
The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.
“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.
“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.
Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.
“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.
“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.
Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.
A version of this article first appeared on Medscape.com.
Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.
“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.
“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.
The study was recently published online in PLOS ONE.
Measurable changes
As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.
“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.
In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.
Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.
“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.
There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.
In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
‘Not just another video game’
EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.
The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.
The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.
“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.
The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.
“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.
“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.
Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.
“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.
“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.
Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.
A version of this article first appeared on Medscape.com.
Investigators found children who used the video game-based therapy (EndeavorRx) experienced increased brain activity related to attention function, as measured by EEG, which correlated with improvements in objective behavioral measures of attention.
“While the previous multicenter trials show attention improvement for children using EndeavorRx, this is the first study to look at the brain activity in children with a primary concern of ADHD,” principal investigator Elysa Marco, MD, clinical executive for neurodevelopmental medicine at Cortica Healthcare, San Rafael, Calif., said in news release.
“It is exciting to see measurable improvement on the EEGs that correlates with the behavioral benefits,” said Dr. Marco.
The study was recently published online in PLOS ONE.
Measurable changes
As previously reported by this news organization, the Food and Drug Administration approved EndeavorRx in June 2020 as a prescription video game–based therapeutic device for children aged 8-12 years with primarily inattentive or combined-type ADHD, who have a demonstrated attention issue.
“The device is intended for use as part of a therapeutic program that may include clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder,” the FDA said upon approval.
In the current unblinded, single-arm study, the researchers assessed 25 children (aged 8-12 years) with a confirmed diagnosis of ADHD on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention.
Participants were instructed to use EndeavorRx for about 25 minutes a day at least 5 days a week for 4 weeks, as recommended by the FDA.
“EndeavorRx enhanced midline frontal theta (MFT) activity, suggesting that patients who used EndeavorRx for 4 weeks showed changes in measurable brain function,” Anil S. Jina, MD, chief medical officer of Akili Interactive, told this news organization. Dr. Jina was not involved with the study.
There was also a correlation between MFT activity and attention functioning, “suggesting that children who experienced the largest gains in MFT activity as measured by EEG also showed the greatest improvements in computerized performance tests designed to measure attention,” Dr. Jina said.
In addition, parents reported significantly fewer inattention symptoms in children after EndeavorRx treatment, as measured by the Vanderbilt ADHD Diagnostic Rating Scale.
‘Not just another video game’
EndeavorRx has been evaluated in five clinical studies involving more than 600 children with ADHD, including the STARS-ADHD trial, a prospective, randomized, controlled study published in The Lancet Digital Health.
The STARS-ADHD trial randomly allocated 348 children to either EndeavorRx treatment or a controlled intervention, which was a word game.
The researchers reported statistically significant improvements in attentional functioning in the EndeavorRx group as rated by test of variables of attention.
“This is not just another video game,” STARS-ADHD trialist Scott H. Kollins, PhD, MS, a clinical psychologist at Duke Health’s ADHD Clinic in Durham, N.C., who helped developed it, previously told this news organization.
The tool’s adaptive algorithms adjust and monitor task difficulty based on performance, using a video game format and rewards to engage users, he explained. EndeavorRx is a challenge to play by design.
“The treatment was programmed into the gameplay experience and designed to challenge a child’s attentional control during gameplay, requiring focus and flexibility to manage tasks at the same time,” Dr. Jina said in an interview.
“Unlike a video game that is designed only for entertainment purposes, to drive efficacy, EndeavorRx is designed to be challenging and can therefore sometimes feel repetitive, and frustrating to some children,” Dr. Jina said.
Commenting on the study, Stephen Faraone, PhD, distinguished professor of psychiatry and vice chair of research, department of psychiatry, State University of New York, Syracuse, said this study “supports the idea that EndeavorRx improves a neural measure of attention.
“The limitation is that we don’t know if this translates into clinically relevant outcomes,” cautioned Dr. Faraone, who was not associated with the current study.
“The main caveat about EndeavorRx is that it was cleared by the FDA for improving a computer-based measure of inattention, not inattentive symptoms as reported by the parents of children with ADHD,” he noted.
Several authors have disclosed financial relationships with Akili Interactive Labs, which funded the study. Dr. Faraone was an investigator on the STARS-ADHD trial.
A version of this article first appeared on Medscape.com.
Alarming rates of self-harm in adults with autism expose a broken system
When a recent study from Columbia University reported that suicide and self-harm were nearly four times more likely in adults with autism spectrum disorder (ASD) than in the general population, the findings were sobering. But to many in the field, they were not surprising.
Previous analyses showed individuals with ASD were up to six times more likely to attempt suicide and nearly eight times as likely to succeed. However, the recent study published in JAMA Network Open is one of only a few on self-harm and suicide in autism spectrum disorder (ASD) to include a focus on adults.
“Previously there was relatively little information about adults with autism in general and on injury risk among adults with autism specifically,” study investigator Guohua Li, DrPH, MD, professor of epidemiology at Columbia University Mailman School of Public Health, New York, told this news organization.
“How to continue to provide social support and health care services to adults with autism presents a real challenge to society and is a public health issue,” Dr. Li said.
Falling off a ‘services cliff’
The ASD rate among children is at a record-high in the United States, which means the number of adults on the spectrum will also continue to climb. The incidence of adults with newly diagnosed ASD, who are sometimes described as the “lost generation,” is also increasing. Despite these realities, adults with ASD remain largely underserved and understudied.
The data that are available paint a concerning picture. Adolescents with ASD face a “services cliff” as they transition to adulthood and fall into a landscape with a serious lack of services, support, and clinicians trained to treat adults with ASD.
Compared with young adults without ASD, those on the spectrum have significantly lower college graduation rates, have a harder time finding and keeping a job, are more likely to have a co-occurring mental illness, and are far less likely to live independently.
Before 2020, there were no national data on the number of U.S. adults with autism. That year, the Centers for Disease Control and Prevention released its first-ever report on adult autism prevalence, estimated to be 5.4 million.
That figure is almost definitely low, Matthew Maenner, PhD, autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.
Researchers use school and medical records to calculate child ASD rates, but counting adults with the disorder is far more difficult.
The CDC’s estimate was based on modeling reports from 2017 state-based population and mortality records and parent-reported survey data of U.S. children diagnosed with ASD. It was inexact, said Dr. Maenner, but it was a start.
“There are no good data on the prevalence of autism in adults. Anywhere,” he added.
Masking and camouflaging
Only about 3.5% of published studies on autism focus on adults, one review showed. In the recently published “The Lancet Commission on the future of care and clinical research in autism,” the section on research on adolescents and adults was a mere 189 words long.
“The brevity of this paragraph reflects the little data available in this area, not its importance” the authors write.
The recent report of higher self-harm risk in adults on the spectrum offers further evidence that “there just aren’t enough services and research on adults on [the] autism spectrum,” Edward S. Brodkin, MD, associate professor of psychiatry and director of the Adult Autism Spectrum Program at the University of Pennsylvania Perelman School of Medicine in Philadelphia, told this news organization.
Founded by Dr. Brodkin in 2013, the program provides ASD diagnostic and support services for adults with ASD. Like others in the field, Dr. Brodkin has noted a sharp increase in the number of previously undiagnosed adults seeking evaluation for possible ASD.
Many of his patients have recently diagnosed children and realized they share some of the same ASD symptoms. Others have long recognized traits common in autism but have engaged in what clinicians call “masking” or “camouflaging.” This is particularly true in women, who are diagnosed with autism at far lower rates than men.
The “lost generation” of adults who receive an ASD diagnosis later in life have a lower quality of life, studies suggest, and have the highest risk for suicide among all individuals with autism.
The recent study from Dr. Li and colleagues offers new evidence in both children and adults. But although the systematic review and meta-analysis of 31 studies showed high rates of self-injurious behavior and suicidality in both groups, Dr. Li said it’s the data on adults that was most alarming.
The OR of suicidality in children was 2.53, but the risk in adults was significantly higher, with an odds ratio (OR) of 3.84.
Adults were at greater risk for self-harm than children (OR, 1.45; 95% confidence interval, 1.04-2.03), with higher odds of self-injurious behavior (OR, 3.38; 95% CI, 2.54-4.50) and suicidality (OR, 3.84; 95% CI, 2.78-5.30), compared with children (OR, 2.99; 95% CI, 1.93-4.64 for self-injurious behavior, and OR, 2.53; 95% CI, 1.70-3.76 for suicidality).
Lightbulb moment?
Commenting for this news organization, Brenna Maddox, PhD, assistant professor of psychiatry at UNC Chapel Hill and co-chair of the American Association of Suicidology’s Autism and Suicide Committee, said “the sad reality” is that these findings won’t be surprising to many who work in the field.
“But for some clinicians and the public, this will be a lightbulb kind of moment, increasing awareness about a problem many of us have been talking about for a while,” said Dr. Maddox, who was not involved with the current research.
In January, she launched a 5-year, $9 million study to compare the efficacy of two suicide intervention programs in adolescents and young adults with autism.
The interventions use a well-known suicide prevention tool that has been newly modified for use in people with autism. One program would rely on the intervention alone, and the other would add a structured clinical follow-up.
“There has to be much more than awareness. We need more training for clinicians, we need more tools, we need to know which tools are going to work,” Dr. Maddox said.
Her new project could address all of those needs. Funded by the nonprofit Patient-Centered Outcomes Research Institute (PCORI), it will train 150 clinicians at centers in four states to identify suicidal risk among young adults with autism, utilize the prevention tool, and collect data on its efficacy alone or with follow-up.
Clinician training will begin this spring, and researchers hope to have the first patient data in the fall.
Scaling the ‘services cliff’
While Dr. Maddox’s study could yield a potential suicide prevention tool, she is quick to point out that the ultimate goal would be to have fewer people reach the point where such a tool is needed. However, that will take a multidisciplinary approach that begins with access to clinical care, including mental health care, she noted.
“Our mental health care system in general is not great for people on the spectrum, but it’s even worse for adults,” Dr. Maddox said.
Compared with neurotypical adults, adults with autism use more mental health services, have higher hospitalization rates, and are more likely to use primary care services, one recent study showed. The problem, Dr. Maddox notes, is that there are too few clinicians in those areas who are trained in autism care.
One way to address that issue is to mandate autism instruction in the medical curriculum, Catherine Lord, PhD, told this news organization when asked for comment. Dr. Lord is cochair of The Lancet commission on the future of care and clinical research in autism and professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.
“Medical schools offer very little training on ASD, even in standard psychiatry training. For people who don’t specialize in child or adolescence psychiatry, there’s almost none,” Dr. Lord said.
Dr. Maddox agrees. One goal of the PCORI study is to turn their findings into a transportable training program, perhaps available via a webinar for clinicians, crisis center staff, and others who may encounter an adult with autism who is contemplating suicide.
“This is a life and death situation,” Dr. Maddox said. “We have to marshal every resource we have, and we have to do it now. We can’t waste time.”
Dr. Li’s study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Study authors and other sources reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When a recent study from Columbia University reported that suicide and self-harm were nearly four times more likely in adults with autism spectrum disorder (ASD) than in the general population, the findings were sobering. But to many in the field, they were not surprising.
Previous analyses showed individuals with ASD were up to six times more likely to attempt suicide and nearly eight times as likely to succeed. However, the recent study published in JAMA Network Open is one of only a few on self-harm and suicide in autism spectrum disorder (ASD) to include a focus on adults.
“Previously there was relatively little information about adults with autism in general and on injury risk among adults with autism specifically,” study investigator Guohua Li, DrPH, MD, professor of epidemiology at Columbia University Mailman School of Public Health, New York, told this news organization.
“How to continue to provide social support and health care services to adults with autism presents a real challenge to society and is a public health issue,” Dr. Li said.
Falling off a ‘services cliff’
The ASD rate among children is at a record-high in the United States, which means the number of adults on the spectrum will also continue to climb. The incidence of adults with newly diagnosed ASD, who are sometimes described as the “lost generation,” is also increasing. Despite these realities, adults with ASD remain largely underserved and understudied.
The data that are available paint a concerning picture. Adolescents with ASD face a “services cliff” as they transition to adulthood and fall into a landscape with a serious lack of services, support, and clinicians trained to treat adults with ASD.
Compared with young adults without ASD, those on the spectrum have significantly lower college graduation rates, have a harder time finding and keeping a job, are more likely to have a co-occurring mental illness, and are far less likely to live independently.
Before 2020, there were no national data on the number of U.S. adults with autism. That year, the Centers for Disease Control and Prevention released its first-ever report on adult autism prevalence, estimated to be 5.4 million.
That figure is almost definitely low, Matthew Maenner, PhD, autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.
Researchers use school and medical records to calculate child ASD rates, but counting adults with the disorder is far more difficult.
The CDC’s estimate was based on modeling reports from 2017 state-based population and mortality records and parent-reported survey data of U.S. children diagnosed with ASD. It was inexact, said Dr. Maenner, but it was a start.
“There are no good data on the prevalence of autism in adults. Anywhere,” he added.
Masking and camouflaging
Only about 3.5% of published studies on autism focus on adults, one review showed. In the recently published “The Lancet Commission on the future of care and clinical research in autism,” the section on research on adolescents and adults was a mere 189 words long.
“The brevity of this paragraph reflects the little data available in this area, not its importance” the authors write.
The recent report of higher self-harm risk in adults on the spectrum offers further evidence that “there just aren’t enough services and research on adults on [the] autism spectrum,” Edward S. Brodkin, MD, associate professor of psychiatry and director of the Adult Autism Spectrum Program at the University of Pennsylvania Perelman School of Medicine in Philadelphia, told this news organization.
Founded by Dr. Brodkin in 2013, the program provides ASD diagnostic and support services for adults with ASD. Like others in the field, Dr. Brodkin has noted a sharp increase in the number of previously undiagnosed adults seeking evaluation for possible ASD.
Many of his patients have recently diagnosed children and realized they share some of the same ASD symptoms. Others have long recognized traits common in autism but have engaged in what clinicians call “masking” or “camouflaging.” This is particularly true in women, who are diagnosed with autism at far lower rates than men.
The “lost generation” of adults who receive an ASD diagnosis later in life have a lower quality of life, studies suggest, and have the highest risk for suicide among all individuals with autism.
The recent study from Dr. Li and colleagues offers new evidence in both children and adults. But although the systematic review and meta-analysis of 31 studies showed high rates of self-injurious behavior and suicidality in both groups, Dr. Li said it’s the data on adults that was most alarming.
The OR of suicidality in children was 2.53, but the risk in adults was significantly higher, with an odds ratio (OR) of 3.84.
Adults were at greater risk for self-harm than children (OR, 1.45; 95% confidence interval, 1.04-2.03), with higher odds of self-injurious behavior (OR, 3.38; 95% CI, 2.54-4.50) and suicidality (OR, 3.84; 95% CI, 2.78-5.30), compared with children (OR, 2.99; 95% CI, 1.93-4.64 for self-injurious behavior, and OR, 2.53; 95% CI, 1.70-3.76 for suicidality).
Lightbulb moment?
Commenting for this news organization, Brenna Maddox, PhD, assistant professor of psychiatry at UNC Chapel Hill and co-chair of the American Association of Suicidology’s Autism and Suicide Committee, said “the sad reality” is that these findings won’t be surprising to many who work in the field.
“But for some clinicians and the public, this will be a lightbulb kind of moment, increasing awareness about a problem many of us have been talking about for a while,” said Dr. Maddox, who was not involved with the current research.
In January, she launched a 5-year, $9 million study to compare the efficacy of two suicide intervention programs in adolescents and young adults with autism.
The interventions use a well-known suicide prevention tool that has been newly modified for use in people with autism. One program would rely on the intervention alone, and the other would add a structured clinical follow-up.
“There has to be much more than awareness. We need more training for clinicians, we need more tools, we need to know which tools are going to work,” Dr. Maddox said.
Her new project could address all of those needs. Funded by the nonprofit Patient-Centered Outcomes Research Institute (PCORI), it will train 150 clinicians at centers in four states to identify suicidal risk among young adults with autism, utilize the prevention tool, and collect data on its efficacy alone or with follow-up.
Clinician training will begin this spring, and researchers hope to have the first patient data in the fall.
Scaling the ‘services cliff’
While Dr. Maddox’s study could yield a potential suicide prevention tool, she is quick to point out that the ultimate goal would be to have fewer people reach the point where such a tool is needed. However, that will take a multidisciplinary approach that begins with access to clinical care, including mental health care, she noted.
“Our mental health care system in general is not great for people on the spectrum, but it’s even worse for adults,” Dr. Maddox said.
Compared with neurotypical adults, adults with autism use more mental health services, have higher hospitalization rates, and are more likely to use primary care services, one recent study showed. The problem, Dr. Maddox notes, is that there are too few clinicians in those areas who are trained in autism care.
One way to address that issue is to mandate autism instruction in the medical curriculum, Catherine Lord, PhD, told this news organization when asked for comment. Dr. Lord is cochair of The Lancet commission on the future of care and clinical research in autism and professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.
“Medical schools offer very little training on ASD, even in standard psychiatry training. For people who don’t specialize in child or adolescence psychiatry, there’s almost none,” Dr. Lord said.
Dr. Maddox agrees. One goal of the PCORI study is to turn their findings into a transportable training program, perhaps available via a webinar for clinicians, crisis center staff, and others who may encounter an adult with autism who is contemplating suicide.
“This is a life and death situation,” Dr. Maddox said. “We have to marshal every resource we have, and we have to do it now. We can’t waste time.”
Dr. Li’s study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Study authors and other sources reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
When a recent study from Columbia University reported that suicide and self-harm were nearly four times more likely in adults with autism spectrum disorder (ASD) than in the general population, the findings were sobering. But to many in the field, they were not surprising.
Previous analyses showed individuals with ASD were up to six times more likely to attempt suicide and nearly eight times as likely to succeed. However, the recent study published in JAMA Network Open is one of only a few on self-harm and suicide in autism spectrum disorder (ASD) to include a focus on adults.
“Previously there was relatively little information about adults with autism in general and on injury risk among adults with autism specifically,” study investigator Guohua Li, DrPH, MD, professor of epidemiology at Columbia University Mailman School of Public Health, New York, told this news organization.
“How to continue to provide social support and health care services to adults with autism presents a real challenge to society and is a public health issue,” Dr. Li said.
Falling off a ‘services cliff’
The ASD rate among children is at a record-high in the United States, which means the number of adults on the spectrum will also continue to climb. The incidence of adults with newly diagnosed ASD, who are sometimes described as the “lost generation,” is also increasing. Despite these realities, adults with ASD remain largely underserved and understudied.
The data that are available paint a concerning picture. Adolescents with ASD face a “services cliff” as they transition to adulthood and fall into a landscape with a serious lack of services, support, and clinicians trained to treat adults with ASD.
Compared with young adults without ASD, those on the spectrum have significantly lower college graduation rates, have a harder time finding and keeping a job, are more likely to have a co-occurring mental illness, and are far less likely to live independently.
Before 2020, there were no national data on the number of U.S. adults with autism. That year, the Centers for Disease Control and Prevention released its first-ever report on adult autism prevalence, estimated to be 5.4 million.
That figure is almost definitely low, Matthew Maenner, PhD, autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.
Researchers use school and medical records to calculate child ASD rates, but counting adults with the disorder is far more difficult.
The CDC’s estimate was based on modeling reports from 2017 state-based population and mortality records and parent-reported survey data of U.S. children diagnosed with ASD. It was inexact, said Dr. Maenner, but it was a start.
“There are no good data on the prevalence of autism in adults. Anywhere,” he added.
Masking and camouflaging
Only about 3.5% of published studies on autism focus on adults, one review showed. In the recently published “The Lancet Commission on the future of care and clinical research in autism,” the section on research on adolescents and adults was a mere 189 words long.
“The brevity of this paragraph reflects the little data available in this area, not its importance” the authors write.
The recent report of higher self-harm risk in adults on the spectrum offers further evidence that “there just aren’t enough services and research on adults on [the] autism spectrum,” Edward S. Brodkin, MD, associate professor of psychiatry and director of the Adult Autism Spectrum Program at the University of Pennsylvania Perelman School of Medicine in Philadelphia, told this news organization.
Founded by Dr. Brodkin in 2013, the program provides ASD diagnostic and support services for adults with ASD. Like others in the field, Dr. Brodkin has noted a sharp increase in the number of previously undiagnosed adults seeking evaluation for possible ASD.
Many of his patients have recently diagnosed children and realized they share some of the same ASD symptoms. Others have long recognized traits common in autism but have engaged in what clinicians call “masking” or “camouflaging.” This is particularly true in women, who are diagnosed with autism at far lower rates than men.
The “lost generation” of adults who receive an ASD diagnosis later in life have a lower quality of life, studies suggest, and have the highest risk for suicide among all individuals with autism.
The recent study from Dr. Li and colleagues offers new evidence in both children and adults. But although the systematic review and meta-analysis of 31 studies showed high rates of self-injurious behavior and suicidality in both groups, Dr. Li said it’s the data on adults that was most alarming.
The OR of suicidality in children was 2.53, but the risk in adults was significantly higher, with an odds ratio (OR) of 3.84.
Adults were at greater risk for self-harm than children (OR, 1.45; 95% confidence interval, 1.04-2.03), with higher odds of self-injurious behavior (OR, 3.38; 95% CI, 2.54-4.50) and suicidality (OR, 3.84; 95% CI, 2.78-5.30), compared with children (OR, 2.99; 95% CI, 1.93-4.64 for self-injurious behavior, and OR, 2.53; 95% CI, 1.70-3.76 for suicidality).
Lightbulb moment?
Commenting for this news organization, Brenna Maddox, PhD, assistant professor of psychiatry at UNC Chapel Hill and co-chair of the American Association of Suicidology’s Autism and Suicide Committee, said “the sad reality” is that these findings won’t be surprising to many who work in the field.
“But for some clinicians and the public, this will be a lightbulb kind of moment, increasing awareness about a problem many of us have been talking about for a while,” said Dr. Maddox, who was not involved with the current research.
In January, she launched a 5-year, $9 million study to compare the efficacy of two suicide intervention programs in adolescents and young adults with autism.
The interventions use a well-known suicide prevention tool that has been newly modified for use in people with autism. One program would rely on the intervention alone, and the other would add a structured clinical follow-up.
“There has to be much more than awareness. We need more training for clinicians, we need more tools, we need to know which tools are going to work,” Dr. Maddox said.
Her new project could address all of those needs. Funded by the nonprofit Patient-Centered Outcomes Research Institute (PCORI), it will train 150 clinicians at centers in four states to identify suicidal risk among young adults with autism, utilize the prevention tool, and collect data on its efficacy alone or with follow-up.
Clinician training will begin this spring, and researchers hope to have the first patient data in the fall.
Scaling the ‘services cliff’
While Dr. Maddox’s study could yield a potential suicide prevention tool, she is quick to point out that the ultimate goal would be to have fewer people reach the point where such a tool is needed. However, that will take a multidisciplinary approach that begins with access to clinical care, including mental health care, she noted.
“Our mental health care system in general is not great for people on the spectrum, but it’s even worse for adults,” Dr. Maddox said.
Compared with neurotypical adults, adults with autism use more mental health services, have higher hospitalization rates, and are more likely to use primary care services, one recent study showed. The problem, Dr. Maddox notes, is that there are too few clinicians in those areas who are trained in autism care.
One way to address that issue is to mandate autism instruction in the medical curriculum, Catherine Lord, PhD, told this news organization when asked for comment. Dr. Lord is cochair of The Lancet commission on the future of care and clinical research in autism and professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.
“Medical schools offer very little training on ASD, even in standard psychiatry training. For people who don’t specialize in child or adolescence psychiatry, there’s almost none,” Dr. Lord said.
Dr. Maddox agrees. One goal of the PCORI study is to turn their findings into a transportable training program, perhaps available via a webinar for clinicians, crisis center staff, and others who may encounter an adult with autism who is contemplating suicide.
“This is a life and death situation,” Dr. Maddox said. “We have to marshal every resource we have, and we have to do it now. We can’t waste time.”
Dr. Li’s study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Study authors and other sources reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Autism, ADHD linked to increased mortality risk
All-cause mortality is significantly higher for individuals with autism spectrum disorder or attention-deficit/hyperactivity disorder than for the general population, based on data from more than 600,000 individuals.
Studies of individuals with mental disorders have suggested an increased mortality risk, compared with the general population, but similar studies of individuals with autism spectrum disorder (ASD) or ADHD have yielded inconsistent results, Ferrán Catalá-López, PhD, of the Institute of Health Carlos III, Madrid, and colleagues wrote.
In a systematic review and meta-analysis published in JAMA Pediatrics, the researchers examined 27 studies including 642,260 individuals; 154,238 with ASD and 396,488 with ADHD. The studies were published up to April 1, 2021, and included deaths from natural causes (such as respiratory illness or cancer) and unnatural (external) causes, such as accident, injury, or poisoning. The proportion of females in the studies ranged from 14% to 100%; the follow-up ranged from 3 to 33 years; and three studies included first-degree relatives.
Overall, all-cause mortality was significantly higher among individuals with ASD (rate ratio, 2.37) and ADHD (RR, 2.13), compared with the general population. Among individuals with ASD, deaths from natural causes and unnatural causes were significantly increased, compared with the general population (RR, 3.80 and RR, 2.50, respectively). Among individuals with ADHD, deaths from natural causes were not significantly increased (RR, 1.62), but deaths from unnatural causes were significantly increased, compared with the general population (RR, 2.81).
Potential mechanisms to explain the excess mortality among individuals with ASD and ADHD include health determinants and biological pathways, but the complex nature of the associations make the establishment of causality a challenge, the researchers wrote in their discussion of the findings. In general, “severe mental and behavioral disorders appear to be associated with reduced life expectancy, both in terms of mortality from external causes and mortality from other medical conditions or diseases.” With regard to ASD/ADHD in particular, these individuals often experience emotional and social problems as they enter adulthood. “Behaviors such as impulsivity and/or inattention can be contributing factors for injuries and unintentional incidents in children with ASD/ADHD,” they added.
The study findings were limited by several factors including the possible omission of studies and the use of study-level data rather than individual participant data, as well as the limitation of electronic health records, the researchers noted. Also, the studies were mostly conducted in Western countries and the results may not be generalizable to other countries.
Although ASD and ADHD were associated with a significant increased risk of all-cause mortality, “the results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks,” the researchers said. However, the results were strengthened by the large study sample, and offer a comprehensive look at the evidence supporting increased mortality risk among individuals with ASD or ADHD, and highlight the need to identify modifiable risk factors.
“Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health,” they said.
Recent research support associations
The study was important because ASD and ADHD may persist into adulthood, but data from previous epidemiological studies on the impact of these disorders on mortality are inconsistent, lead author Dr. Catalá-López said in an interview.
“We conducted a systematic review and meta-analysis to evaluate all available studies of mortality associations in people with these disorders, which provide the most updated and evidence-based approach,” he explained. “Our study has only become possible in the past few years because several large population-based epidemiological studies have been available reporting similar mortality-related outcomes.”
Dr. Catalá-López said that the study findings have value in clinical practice. “We found that people with autism or attention-deficit/hyperactivity disorders would have an increased risk of mortality when compared to the general population. In our opinion, understanding the causes and mechanisms of these associations can lead to specific strategies to prevent avoidable deaths.
“Autism and attention-hyperactivity/deficit disorder are problems that can be managed with adequate and concrete programs at an early age, and most premature deaths, at least deaths from unnatural causes, can be prevented,” Dr. Catalá-López said.
“Furthermore, we believe that these results may shed some light for future research. For example, more prospective studies would be needed, particularly to examine cause-specific mortality, in larger populations of children and youth with autism/attention-deficit/hyperactivity disorder, including some of the more common comorbidities,” Dr. Catalá-López added.
Findings support need for screening and prevention strategies
The clear message that individuals with ASD or ADHD often die of preventable or unnatural causes demands attention and “demands widespread recognition and the implementation of systematic screening and preventive approaches,” Russell A. Barkley, PhD, of Virginia Commonwealth University, Richmond, and Geraldine Dawson, PhD, of Duke University, Durham, N.C., wrote in an accompanying editorial.
The studies included in the review also demonstrate that ADHD is associated with more than a twofold risk of early mortality in children and a more than a fourfold risk in mortality by age 45 years, they said.
The editorialists noted that the increased mortality risk may explain the ongoing conundrum among clinicians as to why the prevalence of ADHD seems to decline with age, “such that 5%-8% of children may meet diagnostic criteria for ADHD while that figure falls to 4%-5% of adults and 2%-3% of older adults,” despite evidence that a majority of childhood cases will be rediagnosed in adulthood. However, the current study offers an alternative. “This systematic review and meta-analysis and the studies included within it make plain that another explanation is the greater loss of individuals with these conditions from the population over time owing to heightened mortality, compared with typical peers,” they said.
“In addition to ADHD diagnosis, ASD diagnosis is also associated with other psychiatric comorbidities that are correlated with increased risk for mortality, including anxiety and affective disorders,” the editorialists noted. Other considerations for increased mortality among individuals with ASD include different protective and risk factors associated with suicide risk, compared with the general population, as well as poorer social and daily living skills compared to the general population.
The study findings “argue for individuals with ADHD and individuals with ASD being viewed through a public health lens with screening and prevention strategies offered beginning in early childhood. These findings should also give impetus to efforts to try to reduce the first order risk factors that are predisposing to reduced life expectancy, such as obesity, substance use, poor diet, poor sleep, and limited exercise among children and adults with ASD and ADHD,” they said.
“A preventive strategy would necessitate primary care physicians becoming more aware of the linkage between both ASD diagnosis and ADHD diagnosis and early mortality as well as their link to reduced [estimated life expectancy],” and such an approach could potentially reduce the higher mortality risk identified in the current review, they concluded.
Dr. Barkley reported speaking and other fees from Takeda, Medice Pharmaceutical, and AstraZeneca; book royalties from Guilford Publications and the American Psychological Association; and course royalties from ContiningEdCourses.net and Premier Educational Seminars. Dr. Dawson reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health during the submitted work and personal fees from Apple. Dr. Dawson also disclosed a patent for license to Apple, and Dr. Dawson and Duke University have benefited financially from technology and data that have been licensed to Apple. The study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Researchers including lead author Dr. Catalá-López received funding from sources including the Centro de Investigación Biomédica en Red de Salud Mental; one coauthor received support from an Australian Research Council Discovery Early Career Researcher Award, a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network, the Spanish Health Services Research on Chronic Patients Network, and Institute of Health Carlos III. The researchers had no financial conflicts to disclose.
All-cause mortality is significantly higher for individuals with autism spectrum disorder or attention-deficit/hyperactivity disorder than for the general population, based on data from more than 600,000 individuals.
Studies of individuals with mental disorders have suggested an increased mortality risk, compared with the general population, but similar studies of individuals with autism spectrum disorder (ASD) or ADHD have yielded inconsistent results, Ferrán Catalá-López, PhD, of the Institute of Health Carlos III, Madrid, and colleagues wrote.
In a systematic review and meta-analysis published in JAMA Pediatrics, the researchers examined 27 studies including 642,260 individuals; 154,238 with ASD and 396,488 with ADHD. The studies were published up to April 1, 2021, and included deaths from natural causes (such as respiratory illness or cancer) and unnatural (external) causes, such as accident, injury, or poisoning. The proportion of females in the studies ranged from 14% to 100%; the follow-up ranged from 3 to 33 years; and three studies included first-degree relatives.
Overall, all-cause mortality was significantly higher among individuals with ASD (rate ratio, 2.37) and ADHD (RR, 2.13), compared with the general population. Among individuals with ASD, deaths from natural causes and unnatural causes were significantly increased, compared with the general population (RR, 3.80 and RR, 2.50, respectively). Among individuals with ADHD, deaths from natural causes were not significantly increased (RR, 1.62), but deaths from unnatural causes were significantly increased, compared with the general population (RR, 2.81).
Potential mechanisms to explain the excess mortality among individuals with ASD and ADHD include health determinants and biological pathways, but the complex nature of the associations make the establishment of causality a challenge, the researchers wrote in their discussion of the findings. In general, “severe mental and behavioral disorders appear to be associated with reduced life expectancy, both in terms of mortality from external causes and mortality from other medical conditions or diseases.” With regard to ASD/ADHD in particular, these individuals often experience emotional and social problems as they enter adulthood. “Behaviors such as impulsivity and/or inattention can be contributing factors for injuries and unintentional incidents in children with ASD/ADHD,” they added.
The study findings were limited by several factors including the possible omission of studies and the use of study-level data rather than individual participant data, as well as the limitation of electronic health records, the researchers noted. Also, the studies were mostly conducted in Western countries and the results may not be generalizable to other countries.
Although ASD and ADHD were associated with a significant increased risk of all-cause mortality, “the results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks,” the researchers said. However, the results were strengthened by the large study sample, and offer a comprehensive look at the evidence supporting increased mortality risk among individuals with ASD or ADHD, and highlight the need to identify modifiable risk factors.
“Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health,” they said.
Recent research support associations
The study was important because ASD and ADHD may persist into adulthood, but data from previous epidemiological studies on the impact of these disorders on mortality are inconsistent, lead author Dr. Catalá-López said in an interview.
“We conducted a systematic review and meta-analysis to evaluate all available studies of mortality associations in people with these disorders, which provide the most updated and evidence-based approach,” he explained. “Our study has only become possible in the past few years because several large population-based epidemiological studies have been available reporting similar mortality-related outcomes.”
Dr. Catalá-López said that the study findings have value in clinical practice. “We found that people with autism or attention-deficit/hyperactivity disorders would have an increased risk of mortality when compared to the general population. In our opinion, understanding the causes and mechanisms of these associations can lead to specific strategies to prevent avoidable deaths.
“Autism and attention-hyperactivity/deficit disorder are problems that can be managed with adequate and concrete programs at an early age, and most premature deaths, at least deaths from unnatural causes, can be prevented,” Dr. Catalá-López said.
“Furthermore, we believe that these results may shed some light for future research. For example, more prospective studies would be needed, particularly to examine cause-specific mortality, in larger populations of children and youth with autism/attention-deficit/hyperactivity disorder, including some of the more common comorbidities,” Dr. Catalá-López added.
Findings support need for screening and prevention strategies
The clear message that individuals with ASD or ADHD often die of preventable or unnatural causes demands attention and “demands widespread recognition and the implementation of systematic screening and preventive approaches,” Russell A. Barkley, PhD, of Virginia Commonwealth University, Richmond, and Geraldine Dawson, PhD, of Duke University, Durham, N.C., wrote in an accompanying editorial.
The studies included in the review also demonstrate that ADHD is associated with more than a twofold risk of early mortality in children and a more than a fourfold risk in mortality by age 45 years, they said.
The editorialists noted that the increased mortality risk may explain the ongoing conundrum among clinicians as to why the prevalence of ADHD seems to decline with age, “such that 5%-8% of children may meet diagnostic criteria for ADHD while that figure falls to 4%-5% of adults and 2%-3% of older adults,” despite evidence that a majority of childhood cases will be rediagnosed in adulthood. However, the current study offers an alternative. “This systematic review and meta-analysis and the studies included within it make plain that another explanation is the greater loss of individuals with these conditions from the population over time owing to heightened mortality, compared with typical peers,” they said.
“In addition to ADHD diagnosis, ASD diagnosis is also associated with other psychiatric comorbidities that are correlated with increased risk for mortality, including anxiety and affective disorders,” the editorialists noted. Other considerations for increased mortality among individuals with ASD include different protective and risk factors associated with suicide risk, compared with the general population, as well as poorer social and daily living skills compared to the general population.
The study findings “argue for individuals with ADHD and individuals with ASD being viewed through a public health lens with screening and prevention strategies offered beginning in early childhood. These findings should also give impetus to efforts to try to reduce the first order risk factors that are predisposing to reduced life expectancy, such as obesity, substance use, poor diet, poor sleep, and limited exercise among children and adults with ASD and ADHD,” they said.
“A preventive strategy would necessitate primary care physicians becoming more aware of the linkage between both ASD diagnosis and ADHD diagnosis and early mortality as well as their link to reduced [estimated life expectancy],” and such an approach could potentially reduce the higher mortality risk identified in the current review, they concluded.
Dr. Barkley reported speaking and other fees from Takeda, Medice Pharmaceutical, and AstraZeneca; book royalties from Guilford Publications and the American Psychological Association; and course royalties from ContiningEdCourses.net and Premier Educational Seminars. Dr. Dawson reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health during the submitted work and personal fees from Apple. Dr. Dawson also disclosed a patent for license to Apple, and Dr. Dawson and Duke University have benefited financially from technology and data that have been licensed to Apple. The study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Researchers including lead author Dr. Catalá-López received funding from sources including the Centro de Investigación Biomédica en Red de Salud Mental; one coauthor received support from an Australian Research Council Discovery Early Career Researcher Award, a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network, the Spanish Health Services Research on Chronic Patients Network, and Institute of Health Carlos III. The researchers had no financial conflicts to disclose.
All-cause mortality is significantly higher for individuals with autism spectrum disorder or attention-deficit/hyperactivity disorder than for the general population, based on data from more than 600,000 individuals.
Studies of individuals with mental disorders have suggested an increased mortality risk, compared with the general population, but similar studies of individuals with autism spectrum disorder (ASD) or ADHD have yielded inconsistent results, Ferrán Catalá-López, PhD, of the Institute of Health Carlos III, Madrid, and colleagues wrote.
In a systematic review and meta-analysis published in JAMA Pediatrics, the researchers examined 27 studies including 642,260 individuals; 154,238 with ASD and 396,488 with ADHD. The studies were published up to April 1, 2021, and included deaths from natural causes (such as respiratory illness or cancer) and unnatural (external) causes, such as accident, injury, or poisoning. The proportion of females in the studies ranged from 14% to 100%; the follow-up ranged from 3 to 33 years; and three studies included first-degree relatives.
Overall, all-cause mortality was significantly higher among individuals with ASD (rate ratio, 2.37) and ADHD (RR, 2.13), compared with the general population. Among individuals with ASD, deaths from natural causes and unnatural causes were significantly increased, compared with the general population (RR, 3.80 and RR, 2.50, respectively). Among individuals with ADHD, deaths from natural causes were not significantly increased (RR, 1.62), but deaths from unnatural causes were significantly increased, compared with the general population (RR, 2.81).
Potential mechanisms to explain the excess mortality among individuals with ASD and ADHD include health determinants and biological pathways, but the complex nature of the associations make the establishment of causality a challenge, the researchers wrote in their discussion of the findings. In general, “severe mental and behavioral disorders appear to be associated with reduced life expectancy, both in terms of mortality from external causes and mortality from other medical conditions or diseases.” With regard to ASD/ADHD in particular, these individuals often experience emotional and social problems as they enter adulthood. “Behaviors such as impulsivity and/or inattention can be contributing factors for injuries and unintentional incidents in children with ASD/ADHD,” they added.
The study findings were limited by several factors including the possible omission of studies and the use of study-level data rather than individual participant data, as well as the limitation of electronic health records, the researchers noted. Also, the studies were mostly conducted in Western countries and the results may not be generalizable to other countries.
Although ASD and ADHD were associated with a significant increased risk of all-cause mortality, “the results should be interpreted with caution because there was evidence of heterogeneity between study estimates of the mortality risks,” the researchers said. However, the results were strengthened by the large study sample, and offer a comprehensive look at the evidence supporting increased mortality risk among individuals with ASD or ADHD, and highlight the need to identify modifiable risk factors.
“Understanding the mechanisms of these associations may lead to targeted strategies to prevent avoidable deaths in high-risk groups of children and young people as an approach to improve public health,” they said.
Recent research support associations
The study was important because ASD and ADHD may persist into adulthood, but data from previous epidemiological studies on the impact of these disorders on mortality are inconsistent, lead author Dr. Catalá-López said in an interview.
“We conducted a systematic review and meta-analysis to evaluate all available studies of mortality associations in people with these disorders, which provide the most updated and evidence-based approach,” he explained. “Our study has only become possible in the past few years because several large population-based epidemiological studies have been available reporting similar mortality-related outcomes.”
Dr. Catalá-López said that the study findings have value in clinical practice. “We found that people with autism or attention-deficit/hyperactivity disorders would have an increased risk of mortality when compared to the general population. In our opinion, understanding the causes and mechanisms of these associations can lead to specific strategies to prevent avoidable deaths.
“Autism and attention-hyperactivity/deficit disorder are problems that can be managed with adequate and concrete programs at an early age, and most premature deaths, at least deaths from unnatural causes, can be prevented,” Dr. Catalá-López said.
“Furthermore, we believe that these results may shed some light for future research. For example, more prospective studies would be needed, particularly to examine cause-specific mortality, in larger populations of children and youth with autism/attention-deficit/hyperactivity disorder, including some of the more common comorbidities,” Dr. Catalá-López added.
Findings support need for screening and prevention strategies
The clear message that individuals with ASD or ADHD often die of preventable or unnatural causes demands attention and “demands widespread recognition and the implementation of systematic screening and preventive approaches,” Russell A. Barkley, PhD, of Virginia Commonwealth University, Richmond, and Geraldine Dawson, PhD, of Duke University, Durham, N.C., wrote in an accompanying editorial.
The studies included in the review also demonstrate that ADHD is associated with more than a twofold risk of early mortality in children and a more than a fourfold risk in mortality by age 45 years, they said.
The editorialists noted that the increased mortality risk may explain the ongoing conundrum among clinicians as to why the prevalence of ADHD seems to decline with age, “such that 5%-8% of children may meet diagnostic criteria for ADHD while that figure falls to 4%-5% of adults and 2%-3% of older adults,” despite evidence that a majority of childhood cases will be rediagnosed in adulthood. However, the current study offers an alternative. “This systematic review and meta-analysis and the studies included within it make plain that another explanation is the greater loss of individuals with these conditions from the population over time owing to heightened mortality, compared with typical peers,” they said.
“In addition to ADHD diagnosis, ASD diagnosis is also associated with other psychiatric comorbidities that are correlated with increased risk for mortality, including anxiety and affective disorders,” the editorialists noted. Other considerations for increased mortality among individuals with ASD include different protective and risk factors associated with suicide risk, compared with the general population, as well as poorer social and daily living skills compared to the general population.
The study findings “argue for individuals with ADHD and individuals with ASD being viewed through a public health lens with screening and prevention strategies offered beginning in early childhood. These findings should also give impetus to efforts to try to reduce the first order risk factors that are predisposing to reduced life expectancy, such as obesity, substance use, poor diet, poor sleep, and limited exercise among children and adults with ASD and ADHD,” they said.
“A preventive strategy would necessitate primary care physicians becoming more aware of the linkage between both ASD diagnosis and ADHD diagnosis and early mortality as well as their link to reduced [estimated life expectancy],” and such an approach could potentially reduce the higher mortality risk identified in the current review, they concluded.
Dr. Barkley reported speaking and other fees from Takeda, Medice Pharmaceutical, and AstraZeneca; book royalties from Guilford Publications and the American Psychological Association; and course royalties from ContiningEdCourses.net and Premier Educational Seminars. Dr. Dawson reported grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health during the submitted work and personal fees from Apple. Dr. Dawson also disclosed a patent for license to Apple, and Dr. Dawson and Duke University have benefited financially from technology and data that have been licensed to Apple. The study was supported by the Institute of Health Carlos III and Generalitat Valenciana. Researchers including lead author Dr. Catalá-López received funding from sources including the Centro de Investigación Biomédica en Red de Salud Mental; one coauthor received support from an Australian Research Council Discovery Early Career Researcher Award, a new investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network, the Spanish Health Services Research on Chronic Patients Network, and Institute of Health Carlos III. The researchers had no financial conflicts to disclose.
FROM JAMA PEDIATRICS
Screen time in first year may raise autism risk at age 3
Boys exposed to at least 2 hours a day of screen time by 1 year of age were significantly more likely to have an autism spectrum disorder (ASD) diagnosis at 3 years, based on data from more than 80,000 children.
The World Health Organization and the American Academy of Pediatrics recommend against any screen time for infants up to 1 year of age and 18 months of age, respectively, wrote Megumi Kushima, MA, of the University of Yamanashi (Japan), and colleagues on behalf of the Japan Environment and Children’s Study Group.
The extent to which screen time duration in infancy is associated with subsequent ASD diagnosis remains unclear, the researchers said. The ongoing COVID-19 pandemic has increased screen time among children worldwide, which makes an examination of the impact of screen time on children’s health an important public health issue.
In a study published in JAMA Pediatrics, the researchers recruited pregnant women between 2011 and 2014; data were analyzed in December 2020. The final study population included 84,030 mother-child pairs. The primary exposure of screen time at 1 year of age was assessed by questionnaire, in which mothers were asked to report their number of hours they let their child watch TV or DVDs daily. Responses were none (no screen time), less than 1 hour, 1 hour or more but less than 2 hours, 2 hours or more but less than 4 hours, and 4 hours or more.
The primary outcome was ASD diagnosis at 3 years of age, and mothers were asked via questionnaire whether their 3-year-old had been diagnosed with ASD from age 2.
The study was conducted by the Japan Environment and Children’s Study Group at 15 regional centers across Japan.
Overall, 330 children had received an ASD diagnosis at age 3 years, a prevalence of 0.4%. Of these, 251 (76%) were boys, and 79 (24%) were girls. Independent of ASD, the most common response for screen time was less than 1 hour, which was reported by 27,707 mothers. The proportion of children with ASD at age 3 increased as screen time at age 1 increased, the percentages were 5.8%, 22.3%, 30.2%, and 31.7% for children with no screen time, less than 1 hour, 1 to less than 2 hours, and 2 to less than 4 hours, respectively. The percentage of children with ASD diagnoses who had 4 hours or more of daily screen time was 10%.
Logistic regression analysis showed that longer screen time at age 1 year was significantly associated with higher odds of ASD at 3 years in boys, but not in girls. The researchers controlled for variables including maternal maltreatment and children’s predisposition to ASD. Among boys, the adjusted odds ratios for screen times of less than 1 hour, 1 hour to less than 2 hours, 2 hours to less than 4 hours, and more than 4 hours were 1.38, 2.16, 3.48, and 3.02, respectively.
Screen time at age 3 years was not associated with ASD diagnosis at age 3 years, potentially “because the association with environmental factors on brain development varies with age,” the researchers noted.
The study findings were limited by several factors including the reliance on parental reports of screen time and potential for reporting bias, the researchers noted. Other limitations included the possible missed diagnoses of mild ASD cases at 3 years, and the inability to consider variables such as childcare environment, living conditions, diseases, genetics, and disabilities.
However, the results were strengthened by the large study population and examination of screen time in early childhood, they said. More research is needed to examine other factors that contribute to the association between ASD and screen time, but given the rapid increase in device use in children, “it is necessary to review its health effects on infants and control excessive screen time.”
Strong study, but some gaps appear
The study is strong in many respects, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.
However, “what I am not sure they addressed is that children on the spectrum are often not entertained by basic toys and may be hard to manage behaviorally,” Dr. Kinsella said. Consequently, parents may be more inclined to offer screen time as a way to pacify children with behavioral difficulties. “Parents also may see that their children are happier interacting with devices, so they may be more apt to let them continue with screen time.We know screen time is not good for the developing brain, however; I worry that the message from this study is that screen time causes autism in boys.
“What I would have liked to know from the parents who allowed more screen time was why they were offering it,” Dr. Kinsella said. “Was it because their child was difficult behaviorally or because that is the one place that they seemed to have satisfaction? To me, that would indicate the reverse hypothesis.” That said, the study findings “remind us to counsel families about screen time, especially in the age of COVID-19. Kids are home much longer than usual, which ultimately leads to more screen time.”
The study was funded by the Japanese Ministry of Environment. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.
Boys exposed to at least 2 hours a day of screen time by 1 year of age were significantly more likely to have an autism spectrum disorder (ASD) diagnosis at 3 years, based on data from more than 80,000 children.
The World Health Organization and the American Academy of Pediatrics recommend against any screen time for infants up to 1 year of age and 18 months of age, respectively, wrote Megumi Kushima, MA, of the University of Yamanashi (Japan), and colleagues on behalf of the Japan Environment and Children’s Study Group.
The extent to which screen time duration in infancy is associated with subsequent ASD diagnosis remains unclear, the researchers said. The ongoing COVID-19 pandemic has increased screen time among children worldwide, which makes an examination of the impact of screen time on children’s health an important public health issue.
In a study published in JAMA Pediatrics, the researchers recruited pregnant women between 2011 and 2014; data were analyzed in December 2020. The final study population included 84,030 mother-child pairs. The primary exposure of screen time at 1 year of age was assessed by questionnaire, in which mothers were asked to report their number of hours they let their child watch TV or DVDs daily. Responses were none (no screen time), less than 1 hour, 1 hour or more but less than 2 hours, 2 hours or more but less than 4 hours, and 4 hours or more.
The primary outcome was ASD diagnosis at 3 years of age, and mothers were asked via questionnaire whether their 3-year-old had been diagnosed with ASD from age 2.
The study was conducted by the Japan Environment and Children’s Study Group at 15 regional centers across Japan.
Overall, 330 children had received an ASD diagnosis at age 3 years, a prevalence of 0.4%. Of these, 251 (76%) were boys, and 79 (24%) were girls. Independent of ASD, the most common response for screen time was less than 1 hour, which was reported by 27,707 mothers. The proportion of children with ASD at age 3 increased as screen time at age 1 increased, the percentages were 5.8%, 22.3%, 30.2%, and 31.7% for children with no screen time, less than 1 hour, 1 to less than 2 hours, and 2 to less than 4 hours, respectively. The percentage of children with ASD diagnoses who had 4 hours or more of daily screen time was 10%.
Logistic regression analysis showed that longer screen time at age 1 year was significantly associated with higher odds of ASD at 3 years in boys, but not in girls. The researchers controlled for variables including maternal maltreatment and children’s predisposition to ASD. Among boys, the adjusted odds ratios for screen times of less than 1 hour, 1 hour to less than 2 hours, 2 hours to less than 4 hours, and more than 4 hours were 1.38, 2.16, 3.48, and 3.02, respectively.
Screen time at age 3 years was not associated with ASD diagnosis at age 3 years, potentially “because the association with environmental factors on brain development varies with age,” the researchers noted.
The study findings were limited by several factors including the reliance on parental reports of screen time and potential for reporting bias, the researchers noted. Other limitations included the possible missed diagnoses of mild ASD cases at 3 years, and the inability to consider variables such as childcare environment, living conditions, diseases, genetics, and disabilities.
However, the results were strengthened by the large study population and examination of screen time in early childhood, they said. More research is needed to examine other factors that contribute to the association between ASD and screen time, but given the rapid increase in device use in children, “it is necessary to review its health effects on infants and control excessive screen time.”
Strong study, but some gaps appear
The study is strong in many respects, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.
However, “what I am not sure they addressed is that children on the spectrum are often not entertained by basic toys and may be hard to manage behaviorally,” Dr. Kinsella said. Consequently, parents may be more inclined to offer screen time as a way to pacify children with behavioral difficulties. “Parents also may see that their children are happier interacting with devices, so they may be more apt to let them continue with screen time.We know screen time is not good for the developing brain, however; I worry that the message from this study is that screen time causes autism in boys.
“What I would have liked to know from the parents who allowed more screen time was why they were offering it,” Dr. Kinsella said. “Was it because their child was difficult behaviorally or because that is the one place that they seemed to have satisfaction? To me, that would indicate the reverse hypothesis.” That said, the study findings “remind us to counsel families about screen time, especially in the age of COVID-19. Kids are home much longer than usual, which ultimately leads to more screen time.”
The study was funded by the Japanese Ministry of Environment. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.
Boys exposed to at least 2 hours a day of screen time by 1 year of age were significantly more likely to have an autism spectrum disorder (ASD) diagnosis at 3 years, based on data from more than 80,000 children.
The World Health Organization and the American Academy of Pediatrics recommend against any screen time for infants up to 1 year of age and 18 months of age, respectively, wrote Megumi Kushima, MA, of the University of Yamanashi (Japan), and colleagues on behalf of the Japan Environment and Children’s Study Group.
The extent to which screen time duration in infancy is associated with subsequent ASD diagnosis remains unclear, the researchers said. The ongoing COVID-19 pandemic has increased screen time among children worldwide, which makes an examination of the impact of screen time on children’s health an important public health issue.
In a study published in JAMA Pediatrics, the researchers recruited pregnant women between 2011 and 2014; data were analyzed in December 2020. The final study population included 84,030 mother-child pairs. The primary exposure of screen time at 1 year of age was assessed by questionnaire, in which mothers were asked to report their number of hours they let their child watch TV or DVDs daily. Responses were none (no screen time), less than 1 hour, 1 hour or more but less than 2 hours, 2 hours or more but less than 4 hours, and 4 hours or more.
The primary outcome was ASD diagnosis at 3 years of age, and mothers were asked via questionnaire whether their 3-year-old had been diagnosed with ASD from age 2.
The study was conducted by the Japan Environment and Children’s Study Group at 15 regional centers across Japan.
Overall, 330 children had received an ASD diagnosis at age 3 years, a prevalence of 0.4%. Of these, 251 (76%) were boys, and 79 (24%) were girls. Independent of ASD, the most common response for screen time was less than 1 hour, which was reported by 27,707 mothers. The proportion of children with ASD at age 3 increased as screen time at age 1 increased, the percentages were 5.8%, 22.3%, 30.2%, and 31.7% for children with no screen time, less than 1 hour, 1 to less than 2 hours, and 2 to less than 4 hours, respectively. The percentage of children with ASD diagnoses who had 4 hours or more of daily screen time was 10%.
Logistic regression analysis showed that longer screen time at age 1 year was significantly associated with higher odds of ASD at 3 years in boys, but not in girls. The researchers controlled for variables including maternal maltreatment and children’s predisposition to ASD. Among boys, the adjusted odds ratios for screen times of less than 1 hour, 1 hour to less than 2 hours, 2 hours to less than 4 hours, and more than 4 hours were 1.38, 2.16, 3.48, and 3.02, respectively.
Screen time at age 3 years was not associated with ASD diagnosis at age 3 years, potentially “because the association with environmental factors on brain development varies with age,” the researchers noted.
The study findings were limited by several factors including the reliance on parental reports of screen time and potential for reporting bias, the researchers noted. Other limitations included the possible missed diagnoses of mild ASD cases at 3 years, and the inability to consider variables such as childcare environment, living conditions, diseases, genetics, and disabilities.
However, the results were strengthened by the large study population and examination of screen time in early childhood, they said. More research is needed to examine other factors that contribute to the association between ASD and screen time, but given the rapid increase in device use in children, “it is necessary to review its health effects on infants and control excessive screen time.”
Strong study, but some gaps appear
The study is strong in many respects, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.
However, “what I am not sure they addressed is that children on the spectrum are often not entertained by basic toys and may be hard to manage behaviorally,” Dr. Kinsella said. Consequently, parents may be more inclined to offer screen time as a way to pacify children with behavioral difficulties. “Parents also may see that their children are happier interacting with devices, so they may be more apt to let them continue with screen time.We know screen time is not good for the developing brain, however; I worry that the message from this study is that screen time causes autism in boys.
“What I would have liked to know from the parents who allowed more screen time was why they were offering it,” Dr. Kinsella said. “Was it because their child was difficult behaviorally or because that is the one place that they seemed to have satisfaction? To me, that would indicate the reverse hypothesis.” That said, the study findings “remind us to counsel families about screen time, especially in the age of COVID-19. Kids are home much longer than usual, which ultimately leads to more screen time.”
The study was funded by the Japanese Ministry of Environment. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.
FROM JAMA PEDIATRICS
Augmented autism screening pays big dividends
A new, augmented autism-screening strategy boosted the number of boys diagnosed with the condition, especially Spanish speakers, a new study finds. The research was published in JAMA Pediatrics
The number of diagnoses in girls didn’t budge significantly, however, surprising researchers. Still, the findings suggest that “multistage screening and appropriate access to diagnostic services can really move the needle on the early detection of autism and reducing disparities in autism diagnosis and detection,” said lead author R. Christopher Sheldrick, PhD, a Boston University research associate professor of health law, policy, and management, in an interview.
While early intervention is considered crucial, U.S. research suggests that several groups of children – the poor, racial and ethnic minorities, and non-English speakers – are more likely to be diagnosed with autism spectrum disorder (ASD) later in life. “They have much lower access to appropriate services, both to get kids diagnosed and to get the kinds of interventions that can be helpful for families,” Dr. Sheldrick said. “Our study is about trying to close the gap around diagnosis, the first step.”
For the new study, the researchers implemented an intervention strategy in Massachusetts at three Early Intervention (EI) programs, which provide autism screening to children who are referred by pediatricians or parents. The researchers then tracked the programs, all in Boston, and nine comparison programs from the greater Boston area from 2012 to 2018.
Overall, 33,326 children were assessed, all aged 14-36 months. Those at the intervention programs were chosen because they had high levels of poverty. Children at those programs were more likely to be Black than those at the comparison programs (30.7% vs. 12.2%), to be Spanish speakers (28.9% vs. 12.5%), and to be in the lowest household income bracket (66.9% vs. 54.2%). In both groups, about 64% of the children were male.
The intervention strategy aimed to reduce the reliance on screening tests. Instead, the study authors write, “our protocol emphasizes ASD screening as a process that includes clinician and parent decision-making.”
As Dr. Sheldrick explained, parents and specialists observe children together “and then decide whether it’s worth taking the next step, which is a full diagnostic assessment with a licensed professional.” According to the study, either the parent(s) or the specialists could make the referral for a full, university-based assessment.
The goal was to help specialists use their professional judgment more, he said, and refer children who don’t show signs of ASD via a screening instrument but still spark concern, he said. “We’re really trying to create a system in which the screening tools support professional judgment, but don’t really replace it.”
After weighting, the researchers found that diagnoses of ASD were more common in the intervention sites vs. comparison sites (incidence rate ratio, 1.6; 95% confidence interval, 1.3-2.1, P < .001), accounting for an extra 8.1 diagnoses per 1,000 per quarter. Among Spanish-speaking families only, diagnoses grew even more in the intervention sites vs. comparison sites (IRR, 2.6; 95% CI, 1.6-4.3; P < .001), representing 15.4 additional diagnoses per 1,000 children per quarter.
There was also an increase in diagnoses among boys in the intervention sites vs. comparison sites (IRR, 1.8; 95% CI, 1.4-2.3; P < .001), accounting for 14.8 additional diagnoses per 1,000 children per quarter. However, there was no statistically significant increase in diagnosis among girls (IRR, 1.1; 95% CI, 0.6-1.7; P = .84).
The finding about girls surprised the researchers. “The program was highly effective for boys, but really didn’t have any effect for girls,” Dr. Sheldrick said. “Even though autism is considered to be more common in boys, there are questions about whether it’s underidentified in girls. These data would be consistent with that view. So there’s work to do to be able to recognize how a young girl with autism might present and how you might note that in a sensitive way and then respond appropriately.”
The overall message of the study is “that screening with appropriate supports can make a difference,” he said. However, he acknowledged that the extra cost of the program is unclear. “We did not systematically collect data on cost,” he said, noting that the funding for the study paid for both the intervention and the analysis.
For now, he said, researchers are following the children in the study to see if they were able to access treatment services. Some of the investigators are also taking part in a randomized study to evaluate an intervention in children with social communication disorders, he said.
In an accompanying commentary, three pediatric specialists noted that the study is the first to analyze ASD screening in EI. “This study supports the notion of ASD screening as an iterative, multistep process that optimally involves multiple community stakeholders with varying levels of developmental expertise who have done the work to build trust with families,” write pediatrician Kate E. Wallis, MD, MPH, of Children’s Hospital of Philadelphia, graduate student Monica M. Abdul-Chani, MA, of the University of Alabama at Birmingham, and pediatrician Katharine E. Zuckerman, MD, MPH, of Oregon Health & Science University, Portland.
In regard to disparities in diagnosis in Spanish-speaking families, the commentary authors write that “locating a greater proportion of the ASD identification process in EI, which families are already familiar with, has no to low cost for families, and is likely geographically closer for families, can reduce structural barriers to identification.”
They add that the emphasis within Latino families on the “building of warm and caring relationships with others based on mutual trust and respect” can allow EI specialists to “develop relationships with families who may be afraid or skeptical of sharing what could be considered personal details of their family life.”
The commentary authors also note that “it remains all too common for language delays to be attributed to child exposure to two languages, even though data do not support this attribution. Bilingual EI staff can help to demystify this perpetual myth and better estimate a child’s communication and social skills in both languages as they communicate and play.”
The study was funded by grants from the Health Resources Services Administration and the National Institute of Mental Health. Dr. Sheldrick is cocreator of the Parent’s Observations of Social Interaction (POSI), which is one of the two first-stage screeners used in this study. He conducts research related to this instrument but receives no royalties. He reports grants from the National Institutes of Health. Coauthor Alice S. Carter, PhD, is cocreator of the POSI but receives no royalties. She is also cocreator of the Brief Infant Toddler Social Emotional Assessment, which is one of the two first-stage screeners used in this study, and receives royalties on the sale of the instrument. She reports grants from the National Institutes of Health and the Health Resources and Services Administration. Study coauthor Thomas I. Mackie, PhD, MPH, reports grants from the National Institute of Mental Health. Study coauthor Noah Hoch reports grants from the Health Resources Services Administration and the National Institute of Mental Health. No other disclosures from study authors are reported. Dr. Zuckerman reported grants from the National Institutes of Health and National Institute of Mental Health and consulting fees from H2N related to autism. The other commentary authors report no disclosures.
A new, augmented autism-screening strategy boosted the number of boys diagnosed with the condition, especially Spanish speakers, a new study finds. The research was published in JAMA Pediatrics
The number of diagnoses in girls didn’t budge significantly, however, surprising researchers. Still, the findings suggest that “multistage screening and appropriate access to diagnostic services can really move the needle on the early detection of autism and reducing disparities in autism diagnosis and detection,” said lead author R. Christopher Sheldrick, PhD, a Boston University research associate professor of health law, policy, and management, in an interview.
While early intervention is considered crucial, U.S. research suggests that several groups of children – the poor, racial and ethnic minorities, and non-English speakers – are more likely to be diagnosed with autism spectrum disorder (ASD) later in life. “They have much lower access to appropriate services, both to get kids diagnosed and to get the kinds of interventions that can be helpful for families,” Dr. Sheldrick said. “Our study is about trying to close the gap around diagnosis, the first step.”
For the new study, the researchers implemented an intervention strategy in Massachusetts at three Early Intervention (EI) programs, which provide autism screening to children who are referred by pediatricians or parents. The researchers then tracked the programs, all in Boston, and nine comparison programs from the greater Boston area from 2012 to 2018.
Overall, 33,326 children were assessed, all aged 14-36 months. Those at the intervention programs were chosen because they had high levels of poverty. Children at those programs were more likely to be Black than those at the comparison programs (30.7% vs. 12.2%), to be Spanish speakers (28.9% vs. 12.5%), and to be in the lowest household income bracket (66.9% vs. 54.2%). In both groups, about 64% of the children were male.
The intervention strategy aimed to reduce the reliance on screening tests. Instead, the study authors write, “our protocol emphasizes ASD screening as a process that includes clinician and parent decision-making.”
As Dr. Sheldrick explained, parents and specialists observe children together “and then decide whether it’s worth taking the next step, which is a full diagnostic assessment with a licensed professional.” According to the study, either the parent(s) or the specialists could make the referral for a full, university-based assessment.
The goal was to help specialists use their professional judgment more, he said, and refer children who don’t show signs of ASD via a screening instrument but still spark concern, he said. “We’re really trying to create a system in which the screening tools support professional judgment, but don’t really replace it.”
After weighting, the researchers found that diagnoses of ASD were more common in the intervention sites vs. comparison sites (incidence rate ratio, 1.6; 95% confidence interval, 1.3-2.1, P < .001), accounting for an extra 8.1 diagnoses per 1,000 per quarter. Among Spanish-speaking families only, diagnoses grew even more in the intervention sites vs. comparison sites (IRR, 2.6; 95% CI, 1.6-4.3; P < .001), representing 15.4 additional diagnoses per 1,000 children per quarter.
There was also an increase in diagnoses among boys in the intervention sites vs. comparison sites (IRR, 1.8; 95% CI, 1.4-2.3; P < .001), accounting for 14.8 additional diagnoses per 1,000 children per quarter. However, there was no statistically significant increase in diagnosis among girls (IRR, 1.1; 95% CI, 0.6-1.7; P = .84).
The finding about girls surprised the researchers. “The program was highly effective for boys, but really didn’t have any effect for girls,” Dr. Sheldrick said. “Even though autism is considered to be more common in boys, there are questions about whether it’s underidentified in girls. These data would be consistent with that view. So there’s work to do to be able to recognize how a young girl with autism might present and how you might note that in a sensitive way and then respond appropriately.”
The overall message of the study is “that screening with appropriate supports can make a difference,” he said. However, he acknowledged that the extra cost of the program is unclear. “We did not systematically collect data on cost,” he said, noting that the funding for the study paid for both the intervention and the analysis.
For now, he said, researchers are following the children in the study to see if they were able to access treatment services. Some of the investigators are also taking part in a randomized study to evaluate an intervention in children with social communication disorders, he said.
In an accompanying commentary, three pediatric specialists noted that the study is the first to analyze ASD screening in EI. “This study supports the notion of ASD screening as an iterative, multistep process that optimally involves multiple community stakeholders with varying levels of developmental expertise who have done the work to build trust with families,” write pediatrician Kate E. Wallis, MD, MPH, of Children’s Hospital of Philadelphia, graduate student Monica M. Abdul-Chani, MA, of the University of Alabama at Birmingham, and pediatrician Katharine E. Zuckerman, MD, MPH, of Oregon Health & Science University, Portland.
In regard to disparities in diagnosis in Spanish-speaking families, the commentary authors write that “locating a greater proportion of the ASD identification process in EI, which families are already familiar with, has no to low cost for families, and is likely geographically closer for families, can reduce structural barriers to identification.”
They add that the emphasis within Latino families on the “building of warm and caring relationships with others based on mutual trust and respect” can allow EI specialists to “develop relationships with families who may be afraid or skeptical of sharing what could be considered personal details of their family life.”
The commentary authors also note that “it remains all too common for language delays to be attributed to child exposure to two languages, even though data do not support this attribution. Bilingual EI staff can help to demystify this perpetual myth and better estimate a child’s communication and social skills in both languages as they communicate and play.”
The study was funded by grants from the Health Resources Services Administration and the National Institute of Mental Health. Dr. Sheldrick is cocreator of the Parent’s Observations of Social Interaction (POSI), which is one of the two first-stage screeners used in this study. He conducts research related to this instrument but receives no royalties. He reports grants from the National Institutes of Health. Coauthor Alice S. Carter, PhD, is cocreator of the POSI but receives no royalties. She is also cocreator of the Brief Infant Toddler Social Emotional Assessment, which is one of the two first-stage screeners used in this study, and receives royalties on the sale of the instrument. She reports grants from the National Institutes of Health and the Health Resources and Services Administration. Study coauthor Thomas I. Mackie, PhD, MPH, reports grants from the National Institute of Mental Health. Study coauthor Noah Hoch reports grants from the Health Resources Services Administration and the National Institute of Mental Health. No other disclosures from study authors are reported. Dr. Zuckerman reported grants from the National Institutes of Health and National Institute of Mental Health and consulting fees from H2N related to autism. The other commentary authors report no disclosures.
A new, augmented autism-screening strategy boosted the number of boys diagnosed with the condition, especially Spanish speakers, a new study finds. The research was published in JAMA Pediatrics
The number of diagnoses in girls didn’t budge significantly, however, surprising researchers. Still, the findings suggest that “multistage screening and appropriate access to diagnostic services can really move the needle on the early detection of autism and reducing disparities in autism diagnosis and detection,” said lead author R. Christopher Sheldrick, PhD, a Boston University research associate professor of health law, policy, and management, in an interview.
While early intervention is considered crucial, U.S. research suggests that several groups of children – the poor, racial and ethnic minorities, and non-English speakers – are more likely to be diagnosed with autism spectrum disorder (ASD) later in life. “They have much lower access to appropriate services, both to get kids diagnosed and to get the kinds of interventions that can be helpful for families,” Dr. Sheldrick said. “Our study is about trying to close the gap around diagnosis, the first step.”
For the new study, the researchers implemented an intervention strategy in Massachusetts at three Early Intervention (EI) programs, which provide autism screening to children who are referred by pediatricians or parents. The researchers then tracked the programs, all in Boston, and nine comparison programs from the greater Boston area from 2012 to 2018.
Overall, 33,326 children were assessed, all aged 14-36 months. Those at the intervention programs were chosen because they had high levels of poverty. Children at those programs were more likely to be Black than those at the comparison programs (30.7% vs. 12.2%), to be Spanish speakers (28.9% vs. 12.5%), and to be in the lowest household income bracket (66.9% vs. 54.2%). In both groups, about 64% of the children were male.
The intervention strategy aimed to reduce the reliance on screening tests. Instead, the study authors write, “our protocol emphasizes ASD screening as a process that includes clinician and parent decision-making.”
As Dr. Sheldrick explained, parents and specialists observe children together “and then decide whether it’s worth taking the next step, which is a full diagnostic assessment with a licensed professional.” According to the study, either the parent(s) or the specialists could make the referral for a full, university-based assessment.
The goal was to help specialists use their professional judgment more, he said, and refer children who don’t show signs of ASD via a screening instrument but still spark concern, he said. “We’re really trying to create a system in which the screening tools support professional judgment, but don’t really replace it.”
After weighting, the researchers found that diagnoses of ASD were more common in the intervention sites vs. comparison sites (incidence rate ratio, 1.6; 95% confidence interval, 1.3-2.1, P < .001), accounting for an extra 8.1 diagnoses per 1,000 per quarter. Among Spanish-speaking families only, diagnoses grew even more in the intervention sites vs. comparison sites (IRR, 2.6; 95% CI, 1.6-4.3; P < .001), representing 15.4 additional diagnoses per 1,000 children per quarter.
There was also an increase in diagnoses among boys in the intervention sites vs. comparison sites (IRR, 1.8; 95% CI, 1.4-2.3; P < .001), accounting for 14.8 additional diagnoses per 1,000 children per quarter. However, there was no statistically significant increase in diagnosis among girls (IRR, 1.1; 95% CI, 0.6-1.7; P = .84).
The finding about girls surprised the researchers. “The program was highly effective for boys, but really didn’t have any effect for girls,” Dr. Sheldrick said. “Even though autism is considered to be more common in boys, there are questions about whether it’s underidentified in girls. These data would be consistent with that view. So there’s work to do to be able to recognize how a young girl with autism might present and how you might note that in a sensitive way and then respond appropriately.”
The overall message of the study is “that screening with appropriate supports can make a difference,” he said. However, he acknowledged that the extra cost of the program is unclear. “We did not systematically collect data on cost,” he said, noting that the funding for the study paid for both the intervention and the analysis.
For now, he said, researchers are following the children in the study to see if they were able to access treatment services. Some of the investigators are also taking part in a randomized study to evaluate an intervention in children with social communication disorders, he said.
In an accompanying commentary, three pediatric specialists noted that the study is the first to analyze ASD screening in EI. “This study supports the notion of ASD screening as an iterative, multistep process that optimally involves multiple community stakeholders with varying levels of developmental expertise who have done the work to build trust with families,” write pediatrician Kate E. Wallis, MD, MPH, of Children’s Hospital of Philadelphia, graduate student Monica M. Abdul-Chani, MA, of the University of Alabama at Birmingham, and pediatrician Katharine E. Zuckerman, MD, MPH, of Oregon Health & Science University, Portland.
In regard to disparities in diagnosis in Spanish-speaking families, the commentary authors write that “locating a greater proportion of the ASD identification process in EI, which families are already familiar with, has no to low cost for families, and is likely geographically closer for families, can reduce structural barriers to identification.”
They add that the emphasis within Latino families on the “building of warm and caring relationships with others based on mutual trust and respect” can allow EI specialists to “develop relationships with families who may be afraid or skeptical of sharing what could be considered personal details of their family life.”
The commentary authors also note that “it remains all too common for language delays to be attributed to child exposure to two languages, even though data do not support this attribution. Bilingual EI staff can help to demystify this perpetual myth and better estimate a child’s communication and social skills in both languages as they communicate and play.”
The study was funded by grants from the Health Resources Services Administration and the National Institute of Mental Health. Dr. Sheldrick is cocreator of the Parent’s Observations of Social Interaction (POSI), which is one of the two first-stage screeners used in this study. He conducts research related to this instrument but receives no royalties. He reports grants from the National Institutes of Health. Coauthor Alice S. Carter, PhD, is cocreator of the POSI but receives no royalties. She is also cocreator of the Brief Infant Toddler Social Emotional Assessment, which is one of the two first-stage screeners used in this study, and receives royalties on the sale of the instrument. She reports grants from the National Institutes of Health and the Health Resources and Services Administration. Study coauthor Thomas I. Mackie, PhD, MPH, reports grants from the National Institute of Mental Health. Study coauthor Noah Hoch reports grants from the Health Resources Services Administration and the National Institute of Mental Health. No other disclosures from study authors are reported. Dr. Zuckerman reported grants from the National Institutes of Health and National Institute of Mental Health and consulting fees from H2N related to autism. The other commentary authors report no disclosures.
FROM JAMA PEDIATRICS
Record-breaking autism rates reported with new CDC criteria
Childhood autism rates are at the highest level since the Centers for Disease Control and Prevention began tracking the disorder in 2000, new data released Dec. 2 show.
The increase likely reflects improvements in diagnosis and identification of autism spectrum disorder (ASD), not an increase in incidence, study authors with the CDC’s Autism and Developmental Disabilities Monitoring (ADDM) Network told this news organization.
Using a new surveillance methodology, researchers found that 2.3% of 8-year-olds in communities in 11 states across the United States had an autism diagnosis in 2018, up from 1.9% in 2016.
A separate report on early identification in 4-year-olds shows that children born in 2014 were 50% more likely to receive an autism diagnosis or ASD special education classification by 48 months of age than those born in 2010, signaling improved early diagnosis.
Taken together, the data suggest efforts to raise awareness about autism are working, though researchers were quick to say much work remains.
“It was not surprising to me and in fact it was reassuring that the number of children diagnosed with autism is higher and is actually approaching prevalence of autism that has been noted in some national surveys of parents,” Stuart Shapira, MD, PhD, associate director for science in CDC’s National Center on Birth Defects and Developmental Disability, told this news organization.
“It means we’re doing a better job of identifying children, which helps to get them into services earlier so they can achieve their best developmental outcome.”
The studies, published online in Morbidity and Mortality Weekly Report, are the first to use a new ASD surveillance protocol that relies on ASD diagnosis or special education classification and billing codes and eliminates comprehensive records analysis by trained clinician reviewers.
Racial disparities
The updated methodology was less labor intensive and reduced the time it took to produce the report, but it is not without its critics, who claim the new protocol will undercount the number of children with ASD.
Created in 2000 and funded by the CDC, the ADDM Network is the only surveillance program in the United States that tracks the number and characteristics of children with ASD in multiple communities in the U.S.
When ADDM released its first report in 2007 from six states and based on data from the year 2000, ASD prevalence was 6.7 per 1,000 children, or 1 in 150 children.
In the latest report, which includes data from 2018, the autism prevalence rate across 11 states was 23.0 per 1,000 children, or 1 in 44 children.
That rate is closer to reported autism prevalence from the National Survey of Children’s Health and the National Health Interview Survey, both of which rely on parent-reported ASD diagnoses.
in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin.
Children were counted as having autism if their records included an ASD diagnosis, a special education classification of ASD, or an ASD International Classification of Diseases (ICD) code. A total of 5,058 children met those criteria.
Rates of ASD ranged from a low of 1.7% in Missouri to 3.9% in California and were 4.2 times higher in boys than in girls. Just under half of the children with ASD were evaluated by age 36 months.
Although the overall ASD prevalence was similar among White, Black, Hispanic, and Asian/Pacific Islander children, the report highlighted a number of other racial disparities overall and in individual states.
For example, among those with ASD and data on cognitive ability, 35.2% had an intelligence quotient score of 70 or lower. Black children with ASD were far more likely to have an IQ of 70 or less (49.8%) than Hispanic (33.1%) or White (29.7%) children.
“The persistent disparities in co-occurring intellectual disabilities in children with autism is something that we continue to see and suggests that we need to better understand exactly what’s happening,” Matthew Maenner, PhD, an epidemiologist and autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.
Another long-standing trend observed again in the new report on prevalence among 8-year-olds is low ASD prevalence among Hispanic children. While the overall estimate showed similar autism rates, a closer review of state-level data reveals a different picture.
“In almost half of the sites, Hispanic children were less likely to be identified as having ASD,” he said. “This gets lost if you look only at the overall estimate.”
New methodology
When ADDM released its first report in 2007, autism diagnosis was widely inadequate in the United States. Relying on only confirmed ASD diagnoses would significantly underestimate the number of children with the disorder, so the CDC added “active case finding” to the protocol.
Trained clinician reviewers analyzed individual notes from medical and educational records for every 8-year-old in ADDM Network sites, looking for evidence of characteristics and behaviors associated with autism. The process was labor- and time-intensive and took up to 4 years to complete.
In 2018, the CDC began investigating ways to speed the process and came up with the strategy used in the latest report. The new protocol was faster, easier, and less expensive. Although he says cost was never the deciding factor, Dr. Maenner acknowledges that had they stuck with the original protocol, they would have been forced to reduce the number of ADDM Network sites.
Dr. Maenner argues that a comparison of the two protocols shows the new method doesn’t compromise accuracy and may actually capture children who lacked the medical or educational records the previous protocol required for a count. But not everyone agrees.
“I thought the point was to be as accurate and complete as possible in doing the surveillance,” Walter Zahorodny, PhD, associate professor of pediatrics at Rutgers University, New Brunswick, N.J., and principal investigator of the New Jersey ADDM Network site, told this news organization. “In states where there’s a high detail of information in records, like New Jersey, it’s going to underestimate the count.”
Dr. Zahorodny says the latest data prove his point. In 2016, under the old methodology, ASD prevalence was 3.1% in the state. In 2018, under the new protocol, prevalence was 2.84%, a decrease of about 20% that Dr. Zahorodny pins squarely on the elimination of ADDM clinical reviewers.
But New Jersey is the only state that participated in both the 2016 and 2018 surveillance periods to report a decrease in ASD prevalence. The other eight states all found autism rates in their states went up.
Sydney Pettygrove, PhD, associate professor of public health and pediatrics at the University of Arizona, Tucson, and a principal investigator for the ADDM site in Arizona, told this news organization that when she first learned the CDC was rolling out a new methodology, she and other investigators were concerned.
“People were really upset. I was really upset,” she said. “I had formed an opinion based on the earlier data that this would not be a good idea.”
In 2000, when ASD surveillance began in Arizona, nearly 30% of children identified by ADDM clinical reviewers as having autism had no mention of the disorder in their records. Today, that percentage is closer to 5%.
“In 2000 it would have been catastrophic to try to estimate the prevalence of autism with the new protocol,” said Dr. Pettygrove. As it turns out, under the new protocol, prevalence rates in Arizona increased from 16.0 per 1,000 children in 2016 to 24.9 in 2018.
Built-in bias eliminated?
In addition to speeding up the process, the new methodology might have other benefits as well. Under the old ADDM surveillance protocol, children who lacked certain medical or educational records did not meet the ASD case definition and weren’t counted.
A 2019 study showed that this disproportionately affected Black and Hispanic children, who had significantly less access to health care professionals than White children.
As a result, “the old methodology had a bias built into it,” Maureen Durkin, PhD, DrPH, coauthor of that study and chair of population health sciences at the University of Wisconsin–Madison and principal investigator for the ADDM site in Wisconsin, told this news organization.
“Clinician reviewers ended up putting these children in the ‘suspected ASD’ category because they couldn’t call it a case under the case definition,” Dr. Durkin said. “There was a fairly large percentage of suspected cases and a disproportionate number of those kids were children of color.”
Although she can’t say for sure, Dr. Durkin said it’s possible the new protocol could eliminate some of that bias.
CDC researchers also attribute the new method to an expanded study of early diagnosis among 4-year-olds. In previous years, only a handful of the ADDM Network sites participating in the 8-year-old surveillance project also studied early diagnosis in 4-year-olds.
This year, all 11 sites took part in the early diagnosis analysis, tripling the number of children included in the analysis. That made it possible to include, for the first time, Asian/Pacific Islander children in this analysis.
In the past, ASD prevalence has trended higher in White children, compared with other racial groups. The new data found that ASD prevalence among 4-year-olds was significantly lower in White children (12.9 per 1,000 children) than in Black, Hispanic, or Asian/Pacific Islander children (16.6, 21.1, and 22.7 per 1,000, respectively). Prevalence in American Indian/Alaska Native children was the lowest among all racial groups (11.5 per 1,000).
It’s the first time researchers have seen this pattern in any ADDM report, Kelly Shaw, PhD, lead author of that study and an epidemiologist with the National Center on Birth Defects and Developmental Disability at the CDC, told this news organization.
These data don’t provide clues about the potential cause of that disparity, Dr. Shaw said. It’s likely an indication of better identification of ASD in those communities, she said, and not a sign of increased incidence of autism among Black, Hispanic, or Asian/Pacific Islander children.
“We don’t have any evidence to suggest or expect that autism would be increasing differentially among groups,” Dr. Shaw said.
The data suggest “we are making some progress but there certainly is still room for improvement,” Dr. Shaw said.
Study authors report no conflicts of interest.
A version of this article first appeared on Medscape.com.
Childhood autism rates are at the highest level since the Centers for Disease Control and Prevention began tracking the disorder in 2000, new data released Dec. 2 show.
The increase likely reflects improvements in diagnosis and identification of autism spectrum disorder (ASD), not an increase in incidence, study authors with the CDC’s Autism and Developmental Disabilities Monitoring (ADDM) Network told this news organization.
Using a new surveillance methodology, researchers found that 2.3% of 8-year-olds in communities in 11 states across the United States had an autism diagnosis in 2018, up from 1.9% in 2016.
A separate report on early identification in 4-year-olds shows that children born in 2014 were 50% more likely to receive an autism diagnosis or ASD special education classification by 48 months of age than those born in 2010, signaling improved early diagnosis.
Taken together, the data suggest efforts to raise awareness about autism are working, though researchers were quick to say much work remains.
“It was not surprising to me and in fact it was reassuring that the number of children diagnosed with autism is higher and is actually approaching prevalence of autism that has been noted in some national surveys of parents,” Stuart Shapira, MD, PhD, associate director for science in CDC’s National Center on Birth Defects and Developmental Disability, told this news organization.
“It means we’re doing a better job of identifying children, which helps to get them into services earlier so they can achieve their best developmental outcome.”
The studies, published online in Morbidity and Mortality Weekly Report, are the first to use a new ASD surveillance protocol that relies on ASD diagnosis or special education classification and billing codes and eliminates comprehensive records analysis by trained clinician reviewers.
Racial disparities
The updated methodology was less labor intensive and reduced the time it took to produce the report, but it is not without its critics, who claim the new protocol will undercount the number of children with ASD.
Created in 2000 and funded by the CDC, the ADDM Network is the only surveillance program in the United States that tracks the number and characteristics of children with ASD in multiple communities in the U.S.
When ADDM released its first report in 2007 from six states and based on data from the year 2000, ASD prevalence was 6.7 per 1,000 children, or 1 in 150 children.
In the latest report, which includes data from 2018, the autism prevalence rate across 11 states was 23.0 per 1,000 children, or 1 in 44 children.
That rate is closer to reported autism prevalence from the National Survey of Children’s Health and the National Health Interview Survey, both of which rely on parent-reported ASD diagnoses.
in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin.
Children were counted as having autism if their records included an ASD diagnosis, a special education classification of ASD, or an ASD International Classification of Diseases (ICD) code. A total of 5,058 children met those criteria.
Rates of ASD ranged from a low of 1.7% in Missouri to 3.9% in California and were 4.2 times higher in boys than in girls. Just under half of the children with ASD were evaluated by age 36 months.
Although the overall ASD prevalence was similar among White, Black, Hispanic, and Asian/Pacific Islander children, the report highlighted a number of other racial disparities overall and in individual states.
For example, among those with ASD and data on cognitive ability, 35.2% had an intelligence quotient score of 70 or lower. Black children with ASD were far more likely to have an IQ of 70 or less (49.8%) than Hispanic (33.1%) or White (29.7%) children.
“The persistent disparities in co-occurring intellectual disabilities in children with autism is something that we continue to see and suggests that we need to better understand exactly what’s happening,” Matthew Maenner, PhD, an epidemiologist and autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.
Another long-standing trend observed again in the new report on prevalence among 8-year-olds is low ASD prevalence among Hispanic children. While the overall estimate showed similar autism rates, a closer review of state-level data reveals a different picture.
“In almost half of the sites, Hispanic children were less likely to be identified as having ASD,” he said. “This gets lost if you look only at the overall estimate.”
New methodology
When ADDM released its first report in 2007, autism diagnosis was widely inadequate in the United States. Relying on only confirmed ASD diagnoses would significantly underestimate the number of children with the disorder, so the CDC added “active case finding” to the protocol.
Trained clinician reviewers analyzed individual notes from medical and educational records for every 8-year-old in ADDM Network sites, looking for evidence of characteristics and behaviors associated with autism. The process was labor- and time-intensive and took up to 4 years to complete.
In 2018, the CDC began investigating ways to speed the process and came up with the strategy used in the latest report. The new protocol was faster, easier, and less expensive. Although he says cost was never the deciding factor, Dr. Maenner acknowledges that had they stuck with the original protocol, they would have been forced to reduce the number of ADDM Network sites.
Dr. Maenner argues that a comparison of the two protocols shows the new method doesn’t compromise accuracy and may actually capture children who lacked the medical or educational records the previous protocol required for a count. But not everyone agrees.
“I thought the point was to be as accurate and complete as possible in doing the surveillance,” Walter Zahorodny, PhD, associate professor of pediatrics at Rutgers University, New Brunswick, N.J., and principal investigator of the New Jersey ADDM Network site, told this news organization. “In states where there’s a high detail of information in records, like New Jersey, it’s going to underestimate the count.”
Dr. Zahorodny says the latest data prove his point. In 2016, under the old methodology, ASD prevalence was 3.1% in the state. In 2018, under the new protocol, prevalence was 2.84%, a decrease of about 20% that Dr. Zahorodny pins squarely on the elimination of ADDM clinical reviewers.
But New Jersey is the only state that participated in both the 2016 and 2018 surveillance periods to report a decrease in ASD prevalence. The other eight states all found autism rates in their states went up.
Sydney Pettygrove, PhD, associate professor of public health and pediatrics at the University of Arizona, Tucson, and a principal investigator for the ADDM site in Arizona, told this news organization that when she first learned the CDC was rolling out a new methodology, she and other investigators were concerned.
“People were really upset. I was really upset,” she said. “I had formed an opinion based on the earlier data that this would not be a good idea.”
In 2000, when ASD surveillance began in Arizona, nearly 30% of children identified by ADDM clinical reviewers as having autism had no mention of the disorder in their records. Today, that percentage is closer to 5%.
“In 2000 it would have been catastrophic to try to estimate the prevalence of autism with the new protocol,” said Dr. Pettygrove. As it turns out, under the new protocol, prevalence rates in Arizona increased from 16.0 per 1,000 children in 2016 to 24.9 in 2018.
Built-in bias eliminated?
In addition to speeding up the process, the new methodology might have other benefits as well. Under the old ADDM surveillance protocol, children who lacked certain medical or educational records did not meet the ASD case definition and weren’t counted.
A 2019 study showed that this disproportionately affected Black and Hispanic children, who had significantly less access to health care professionals than White children.
As a result, “the old methodology had a bias built into it,” Maureen Durkin, PhD, DrPH, coauthor of that study and chair of population health sciences at the University of Wisconsin–Madison and principal investigator for the ADDM site in Wisconsin, told this news organization.
“Clinician reviewers ended up putting these children in the ‘suspected ASD’ category because they couldn’t call it a case under the case definition,” Dr. Durkin said. “There was a fairly large percentage of suspected cases and a disproportionate number of those kids were children of color.”
Although she can’t say for sure, Dr. Durkin said it’s possible the new protocol could eliminate some of that bias.
CDC researchers also attribute the new method to an expanded study of early diagnosis among 4-year-olds. In previous years, only a handful of the ADDM Network sites participating in the 8-year-old surveillance project also studied early diagnosis in 4-year-olds.
This year, all 11 sites took part in the early diagnosis analysis, tripling the number of children included in the analysis. That made it possible to include, for the first time, Asian/Pacific Islander children in this analysis.
In the past, ASD prevalence has trended higher in White children, compared with other racial groups. The new data found that ASD prevalence among 4-year-olds was significantly lower in White children (12.9 per 1,000 children) than in Black, Hispanic, or Asian/Pacific Islander children (16.6, 21.1, and 22.7 per 1,000, respectively). Prevalence in American Indian/Alaska Native children was the lowest among all racial groups (11.5 per 1,000).
It’s the first time researchers have seen this pattern in any ADDM report, Kelly Shaw, PhD, lead author of that study and an epidemiologist with the National Center on Birth Defects and Developmental Disability at the CDC, told this news organization.
These data don’t provide clues about the potential cause of that disparity, Dr. Shaw said. It’s likely an indication of better identification of ASD in those communities, she said, and not a sign of increased incidence of autism among Black, Hispanic, or Asian/Pacific Islander children.
“We don’t have any evidence to suggest or expect that autism would be increasing differentially among groups,” Dr. Shaw said.
The data suggest “we are making some progress but there certainly is still room for improvement,” Dr. Shaw said.
Study authors report no conflicts of interest.
A version of this article first appeared on Medscape.com.
Childhood autism rates are at the highest level since the Centers for Disease Control and Prevention began tracking the disorder in 2000, new data released Dec. 2 show.
The increase likely reflects improvements in diagnosis and identification of autism spectrum disorder (ASD), not an increase in incidence, study authors with the CDC’s Autism and Developmental Disabilities Monitoring (ADDM) Network told this news organization.
Using a new surveillance methodology, researchers found that 2.3% of 8-year-olds in communities in 11 states across the United States had an autism diagnosis in 2018, up from 1.9% in 2016.
A separate report on early identification in 4-year-olds shows that children born in 2014 were 50% more likely to receive an autism diagnosis or ASD special education classification by 48 months of age than those born in 2010, signaling improved early diagnosis.
Taken together, the data suggest efforts to raise awareness about autism are working, though researchers were quick to say much work remains.
“It was not surprising to me and in fact it was reassuring that the number of children diagnosed with autism is higher and is actually approaching prevalence of autism that has been noted in some national surveys of parents,” Stuart Shapira, MD, PhD, associate director for science in CDC’s National Center on Birth Defects and Developmental Disability, told this news organization.
“It means we’re doing a better job of identifying children, which helps to get them into services earlier so they can achieve their best developmental outcome.”
The studies, published online in Morbidity and Mortality Weekly Report, are the first to use a new ASD surveillance protocol that relies on ASD diagnosis or special education classification and billing codes and eliminates comprehensive records analysis by trained clinician reviewers.
Racial disparities
The updated methodology was less labor intensive and reduced the time it took to produce the report, but it is not without its critics, who claim the new protocol will undercount the number of children with ASD.
Created in 2000 and funded by the CDC, the ADDM Network is the only surveillance program in the United States that tracks the number and characteristics of children with ASD in multiple communities in the U.S.
When ADDM released its first report in 2007 from six states and based on data from the year 2000, ASD prevalence was 6.7 per 1,000 children, or 1 in 150 children.
In the latest report, which includes data from 2018, the autism prevalence rate across 11 states was 23.0 per 1,000 children, or 1 in 44 children.
That rate is closer to reported autism prevalence from the National Survey of Children’s Health and the National Health Interview Survey, both of which rely on parent-reported ASD diagnoses.
in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin.
Children were counted as having autism if their records included an ASD diagnosis, a special education classification of ASD, or an ASD International Classification of Diseases (ICD) code. A total of 5,058 children met those criteria.
Rates of ASD ranged from a low of 1.7% in Missouri to 3.9% in California and were 4.2 times higher in boys than in girls. Just under half of the children with ASD were evaluated by age 36 months.
Although the overall ASD prevalence was similar among White, Black, Hispanic, and Asian/Pacific Islander children, the report highlighted a number of other racial disparities overall and in individual states.
For example, among those with ASD and data on cognitive ability, 35.2% had an intelligence quotient score of 70 or lower. Black children with ASD were far more likely to have an IQ of 70 or less (49.8%) than Hispanic (33.1%) or White (29.7%) children.
“The persistent disparities in co-occurring intellectual disabilities in children with autism is something that we continue to see and suggests that we need to better understand exactly what’s happening,” Matthew Maenner, PhD, an epidemiologist and autism surveillance team lead with the CDC’s National Center on Birth Defects and Developmental Disabilities, told this news organization.
Another long-standing trend observed again in the new report on prevalence among 8-year-olds is low ASD prevalence among Hispanic children. While the overall estimate showed similar autism rates, a closer review of state-level data reveals a different picture.
“In almost half of the sites, Hispanic children were less likely to be identified as having ASD,” he said. “This gets lost if you look only at the overall estimate.”
New methodology
When ADDM released its first report in 2007, autism diagnosis was widely inadequate in the United States. Relying on only confirmed ASD diagnoses would significantly underestimate the number of children with the disorder, so the CDC added “active case finding” to the protocol.
Trained clinician reviewers analyzed individual notes from medical and educational records for every 8-year-old in ADDM Network sites, looking for evidence of characteristics and behaviors associated with autism. The process was labor- and time-intensive and took up to 4 years to complete.
In 2018, the CDC began investigating ways to speed the process and came up with the strategy used in the latest report. The new protocol was faster, easier, and less expensive. Although he says cost was never the deciding factor, Dr. Maenner acknowledges that had they stuck with the original protocol, they would have been forced to reduce the number of ADDM Network sites.
Dr. Maenner argues that a comparison of the two protocols shows the new method doesn’t compromise accuracy and may actually capture children who lacked the medical or educational records the previous protocol required for a count. But not everyone agrees.
“I thought the point was to be as accurate and complete as possible in doing the surveillance,” Walter Zahorodny, PhD, associate professor of pediatrics at Rutgers University, New Brunswick, N.J., and principal investigator of the New Jersey ADDM Network site, told this news organization. “In states where there’s a high detail of information in records, like New Jersey, it’s going to underestimate the count.”
Dr. Zahorodny says the latest data prove his point. In 2016, under the old methodology, ASD prevalence was 3.1% in the state. In 2018, under the new protocol, prevalence was 2.84%, a decrease of about 20% that Dr. Zahorodny pins squarely on the elimination of ADDM clinical reviewers.
But New Jersey is the only state that participated in both the 2016 and 2018 surveillance periods to report a decrease in ASD prevalence. The other eight states all found autism rates in their states went up.
Sydney Pettygrove, PhD, associate professor of public health and pediatrics at the University of Arizona, Tucson, and a principal investigator for the ADDM site in Arizona, told this news organization that when she first learned the CDC was rolling out a new methodology, she and other investigators were concerned.
“People were really upset. I was really upset,” she said. “I had formed an opinion based on the earlier data that this would not be a good idea.”
In 2000, when ASD surveillance began in Arizona, nearly 30% of children identified by ADDM clinical reviewers as having autism had no mention of the disorder in their records. Today, that percentage is closer to 5%.
“In 2000 it would have been catastrophic to try to estimate the prevalence of autism with the new protocol,” said Dr. Pettygrove. As it turns out, under the new protocol, prevalence rates in Arizona increased from 16.0 per 1,000 children in 2016 to 24.9 in 2018.
Built-in bias eliminated?
In addition to speeding up the process, the new methodology might have other benefits as well. Under the old ADDM surveillance protocol, children who lacked certain medical or educational records did not meet the ASD case definition and weren’t counted.
A 2019 study showed that this disproportionately affected Black and Hispanic children, who had significantly less access to health care professionals than White children.
As a result, “the old methodology had a bias built into it,” Maureen Durkin, PhD, DrPH, coauthor of that study and chair of population health sciences at the University of Wisconsin–Madison and principal investigator for the ADDM site in Wisconsin, told this news organization.
“Clinician reviewers ended up putting these children in the ‘suspected ASD’ category because they couldn’t call it a case under the case definition,” Dr. Durkin said. “There was a fairly large percentage of suspected cases and a disproportionate number of those kids were children of color.”
Although she can’t say for sure, Dr. Durkin said it’s possible the new protocol could eliminate some of that bias.
CDC researchers also attribute the new method to an expanded study of early diagnosis among 4-year-olds. In previous years, only a handful of the ADDM Network sites participating in the 8-year-old surveillance project also studied early diagnosis in 4-year-olds.
This year, all 11 sites took part in the early diagnosis analysis, tripling the number of children included in the analysis. That made it possible to include, for the first time, Asian/Pacific Islander children in this analysis.
In the past, ASD prevalence has trended higher in White children, compared with other racial groups. The new data found that ASD prevalence among 4-year-olds was significantly lower in White children (12.9 per 1,000 children) than in Black, Hispanic, or Asian/Pacific Islander children (16.6, 21.1, and 22.7 per 1,000, respectively). Prevalence in American Indian/Alaska Native children was the lowest among all racial groups (11.5 per 1,000).
It’s the first time researchers have seen this pattern in any ADDM report, Kelly Shaw, PhD, lead author of that study and an epidemiologist with the National Center on Birth Defects and Developmental Disability at the CDC, told this news organization.
These data don’t provide clues about the potential cause of that disparity, Dr. Shaw said. It’s likely an indication of better identification of ASD in those communities, she said, and not a sign of increased incidence of autism among Black, Hispanic, or Asian/Pacific Islander children.
“We don’t have any evidence to suggest or expect that autism would be increasing differentially among groups,” Dr. Shaw said.
The data suggest “we are making some progress but there certainly is still room for improvement,” Dr. Shaw said.
Study authors report no conflicts of interest.
A version of this article first appeared on Medscape.com.
Intranasal oxytocin for autism promising – then came the data
When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.
Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.
“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”
Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.
The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
Increase in off-label use
Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.
On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.
However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?
Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.
Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.
These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.
Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
High hopes
With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.
The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.
A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.
The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.
The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.
“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.
In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.
Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
‘It just didn’t work’
Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.
Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.
But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.
“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”
From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.
A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.
Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.
“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”
The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
Too soon to walk away?
Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.
“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.
The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.
Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.
“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”
Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.
The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.
It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.
A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.
“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.
A version of this article first appeared on Medscape.com.
When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.
Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.
“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”
Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.
The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
Increase in off-label use
Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.
On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.
However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?
Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.
Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.
These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.
Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
High hopes
With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.
The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.
A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.
The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.
The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.
“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.
In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.
Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
‘It just didn’t work’
Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.
Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.
But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.
“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”
From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.
A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.
Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.
“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”
The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
Too soon to walk away?
Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.
“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.
The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.
Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.
“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”
Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.
The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.
It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.
A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.
“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.
A version of this article first appeared on Medscape.com.
When parents of children with autism spectrum disorder (ASD) participating in the largest clinical trial of intranasal oxytocin to date came in for follow-up visits with investigators, they reported marked improvement in the children’s social functioning.
Kids who rarely communicated with their families began to interact more. Those who usually preferred to isolate themselves started joining their parents for meals. It all seemed so promising – until the data came in.
“Those sounded like real improvements to me, and it seemed like they increased over the period of the study,” lead investigator Linmarie Sikich, MD, an associate clinical professor of psychiatry with Duke University School of Medicine and the Duke Center for Autism and Brain Development, Durham, N.C., told this news organization. “Turns out it wasn’t oxytocin that was making that difference.”
Researchers found that after 24 weeks of daily treatment with intranasal oxytocin, there were no significant differences in social functioning between children who received active treatment and those in the placebo group.
The much-anticipated results were published online in The New England Journal of Medicine. To say that they are disappointing, Dr. Sikich said, is an understatement.
Increase in off-label use
Most studies in mouse models of ASD and small trials in children produced conflicting results, although there were modest improvements in social functioning associated with the use of intranasal oxytocin. Some clinicians were already prescribing it off label.
On the basis of this research and early feedback from parents of children, Dr. Sikich and colleagues were hopeful.
However, results from a rigorous, 5-year, $11.4 million randomized trial were negative. Yet, parents were convinced their child improved during the study, and there was a significant increase in off-label prescribing of a treatment her research says doesn’t work. What’s next for oxytocin?
Known as the “love hormone,” oxytocin is a neurotransmitter that is primarily synthesized in the hypothalamus. It plays a role in childbirth and lactation and is also involved in the regulation of social functioning and emotions. Research suggests low oxytocin levels are associated with diminished social functioning, regardless of ASD status.
Its potential as an autism therapy for children has been under study for a decade. Some findings link its use to improvements in core deficits associated with ASD, including repetitive behaviors, fixated or restricted interest, and social communication. A study published in 2020 showed that the treatment improved symptoms in high-functioning adults with ASD.
These were mostly small studies and were underpowered to reliably detect an effect of the therapy on social functioning. They often involved only a single dose of oxytocin. Some studies showed improvements, but others did not.
Still, interest in the treatment grew. Physicians began prescribing it for children with ASD, and parents began buying products containing oxytocin on the internet. Researchers feared this off-label use was becoming widespread, despite inconclusive evidence of efficacy.
High hopes
With support from a National Institutes of Health grant, Dr. Sikich and her team designed a phase 2, multicenter, randomized, double-blind, placebo-controlled study to determine whether the use of oxytocin in children with ASD works and is safe.
The challenges began before they even enrolled a single child. A number of behavioral assessment tools are used to measure social function in ASD, but there is no consensus on which one is best.
A simple blood test could determine how much oxytocin from the nasal spray was absorbed in the blood, but identifying how much made it to the brain would require fMRI, which is expensive and is challenging to use in this study population. Then there was the acquisition of the drug itself.
The Food and Drug Administration has approved intravenous oxytocin for inducing labor. Intranasal oxytocin is not approved for any indication and isn’t available commercially in the United States. Patients or researchers must secure the drug from a manufacturer in a country where it is approved or order it from a U.S. pharmacy that is capable of compounding IV oxytocin into an intranasal formulation.
The pharmacy in Switzerland Dr. Sikich planned to use couldn’t make enough for the study. Contracting with a compounding pharmacy in the United States was significantly more expensive and time consuming, but it was the researchers’ only option.
“If it hadn’t been something we expected to have a major benefit, I think we would have given up the project at multiple points along the line due to all of these challenges,” said Dr. Sikich.
In August 2014, with all the pieces finally in place, researchers began enrolling children aged 3-17 years. The final cohort included 290 participants with ASD, 146 in the oxytocin group and 144 in the placebo group. Of these, 48% had minimal verbal fluency, and 52% had fluent verbal speech.
Participants received daily synthetic oxytocin or placebo via a nasal spray for 24 weeks. The daily oxytocin dose was 48 IU for the first 7 weeks. After that, the dosage could be titrated to a maximum of 80 IU/d. The mean maximal total daily dose of oxytocin throughout the study was 67.6 ± 16.9 IU.
‘It just didn’t work’
Both study groups showed improvement in social withdrawal beginning at 4 weeks and continuing throughout the trial, as determined on the basis of caretakers’ responses on the Aberrant Behavior Checklist Modified Social Withdrawal Subscale, the study’s primary outcome measure.
Sociability and social motivation also improved in both groups, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale.
But by the end of the trial, the difference between the groups in improvement of social function wasn’t significant (difference, -0.2 points; P = .61) after adjusting for age, verbal fluency, and baseline oxytocin level.
“We were so convinced that it would work,” Dr. Sikich said, “but it just didn’t.”
From observation, parents were also convinced the therapy was working. At the trial’s conclusion, fewer than half of caregivers correctly guessed whether their child was in the treatment group or the placebo group.
A lot of development changes can happen in a child over 6 months. It’s possible the improvements would have occurred regardless of the trial, Dr. Sikich said. Parents’ perceptions could also be a placebo effect. Their child was in a clinical trial of a drug they believed could improve social functioning, so in their mind, it did.
Caregivers received training in how to identify certain behavioral changes, which may have helped them spot an existing positive change they had previously overlooked. Or they may have worked with their child more intently as a result of their participation in the trial.
“People may start doing more things or doing them more intensively or purposefully, consciously or subconsciously, to try to help their child improve the skills or behaviors targeted by the active therapy in the study,” Dr. Sikich said. “These are things that might really help the child move forward which are completely separate from the medication being studied.”
The safety analysis offered more hopeful results. Only one serious adverse event from the treatment was reported: A 17-year-old participant taking a daily dose of 48 IU experienced a sedating effect while driving and had an accident.
Too soon to walk away?
Perhaps the most important take-away from the study is that even if it’s safe, intranasal oxytocin as it is currently used doesn’t work and clinicians shouldn’t prescribe it, said Daniel Geschwind, MD, PhD, director of the University of California, Los Angeles (UCLA) Center for Autism Research, who penned a commentary on the study and discussed the findings with this news organization.
“This study shows that using oxytocin the way it’s used in the community right now is not helping anybody, so why put a child through that?” added Dr. Geschwind, who also is a professor of genetics, neurology, and psychiatry at UCLA.
The trial highlights areas that need to be addressed in order to improve research in the field, he said. Establishing a consensus process to measure social functioning and figuring out a better way to access intranasal oxytocin would lead to studies that are more conclusive, comparable, and less expensive. Dr. Sikich agrees.
Despite the findings, Dr. Geschwind and other autism researchers say it’s too soon to walk away from oxytocin altogether, although it may be time to change the approach to autism research.
“We have to take a page from the playbook of modern medicine in other areas and begin to recognize that these syndromes are incredibly heterogeneous,” Dr. Geschwind says. “We can surmise, although we don’t know, that there might be different biological forms of autism that have different pathways involved that are going to respond differently to different medications.”
Calling the researchers’ efforts “heroic,” Karen Parker, PhD, an associate professor and associate chair of psychiatry and behavioral sciences at Stanford (Calif.) University, says efficacy trials such as this one are critical. However, Dr. Parker said in an interview, there are a number of questions that the study didn’t address.
The majority of medication dispensed in a standard intranasal device is sprayed into the back of the throat. Regular blood tests confirmed that oxytocin was getting into participants’ system, but, given how quickly oxytocin degrades in the blood, Dr. Parker said it’s hard to know just how much reached the brain.
It’s also unclear whether the results would have been different had the treatment been paired with behavioral therapy, an approach Dr. Parker suggests might benefit a subset of children with ASD.
A 2017 study from Dr. Parker’s lab found that children with ASD whose use of oxytocin at baseline was low derived greater benefit from synthetic oxytocin, something the new study failed to find. Still, Dr. Parker said, it’s possible oxytocin might increase social motivation and increase a child’s receptiveness to behavioral therapy.
“When you see a negative trial like this, it decreases enthusiasm for the therapy for autism in this context,” Dr. Parker said. “I hope people who are studying these syndromes will continue to explore oxytocin as a therapy.”
The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Autism Centers of Excellence Program and the Department of Psychiatry and Behavioral Sciences at Duke University. Full disclosures of the authors’ possible conflicts of interest are available online.
A version of this article first appeared on Medscape.com.
Moms’ cannabis use in pregnancy tied to anxiety and hyperactivity in offspring
Mothers who use cannabis during pregnancy risk disrupting immune gene networks in the placenta and potentially increasing the risk of anxiety and hyperactivity in their children.
These findings emerged from a study led by Yasmin Hurd, PhD, a professor of psychiatry and director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, New York, and Yoko Nomura, PhD, a professor of behavioral neuroscience at Queen’s College, City University of New York, that was published online in Proceedings of the National Academy of Sciences.
The analysis assessed the effects of gestational maternal cannabis use on psychosocial and physiological measures in young children as well as its potentially immunomodulatory effect on the in utero environment as reflected in the placental transcriptome.
Participants were drawn from a larger cohort in a study launched in 2012; the investigators evaluated offspring aged 3-6 years for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children survey, and heart rate variability (HRV) at rest and during auditory startle.
The cohort consisted of 322 mother-child dyads and children with prenatal exposure to cannabis were compared with those having no exposure. The cohort consisted of 251 non–cannabis-using mothers and 71 cannabis-using mothers, with mean maternal ages in the two groups of 28.46 years and 25.91 years, respectively, The mothers gave birth at Mount Sinai and they and their children were assessed annually at affiliated medical centers in Mount Sinai’s catchment area.
For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing.
Among the findings:
- Maternal cannabis use was associated with reduced maternal and paternal age, more single-mother pregnancies, state anxiety, trait anxiety, depression, cigarette smoking, and African American race.
- Hair hormone analysis revealed increased cortisol levels in the children of cannabis-using mothers, and was associated with greater anxiety, aggression, and hyperactivity.
- Affected children showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone.
- In the placenta, there was reduced expression of many genes involved in immune system function. These included genes for type I interferon, neutrophil, and cytokine-signaling pathways.
Several of these genes organized into coexpression networks that correlated with child anxiety and hyperactivity.
The principal active component of cannabis, tetrahydrocannabinol (THC), targets the endocannabinoid system in placental tissue and the developing brain, the authors noted. Exposure during pregnancy is associated with a range of adverse outcomes from fetal growth restriction to low birth weight and preterm birth.
“There are cannabinoid receptors on immune cells, and it is known that cannabinoids can alter immune function, which is important for maintaining maternal tolerance and protecting the fetus,” Dr. Hurd said. “It’s not surprising that something that affects the immune cells can have an impact on the developing fetus.”
“Overall, our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood,” Dr. Hurd and colleagues wrote, adding that the results have significant implications for defining mental health issues in the children gestated by cannabis-smoking mothers.
Their results align with previous research indicating a greater risk for psychiatric illness in children with prenatal cannabis exposure from maternal use.
“While data are pretty limited in this realm, there are other studies that demonstrate a relationship between early child developmental and behavioral measures and cannabis use during pregnancy,” Camille Hoffman, MD, MSc, a high-risk obstetrics specialist and an associate professor at the University of Colorado at Denver, Aurora, said in an interview. “Our research group found children exposed to cannabis in utero at 10 weeks’ gestation and beyond were less interactive and more withdrawn than children who were not exposed.”
And THC remains in maternal breast milk even 6 weeks after usage stops.
The long-term effects of prenatal cannabis exposure remain to be determined and it is unknown whether the effects of gestational THC might attenuate as a child grows older. “We use early childhood measures in research as a proxy for the later development of diagnosed mental health conditions or behavioral problems,” Dr. Hoffman explained. “We know when we do this that not every child with an abnormal score early will go on to develop an actual condition. Fortunately, or unfortunately, other factors and exposures during childhood can change the trajectory for the better or worse.”
According to Dr. Hurd, child development is a dynamic process and epigenetic events in utero need not be deterministic. “The important thing is to identify children at risk early and to be able to go in and try to improve the environment they’re being raised in – not in terms of impoverishment but in terms of positive nurturing and giving the mother and family support.”
At the prenatal level, what’s the best advice for cannabis-using mothers-to-be? “If a woman doesn’t know she’s pregnant and has been using cannabis, taking extra choline for the remainder of the pregnancy can help buffer the potential negative impact of the cannabis exposure,” Dr. Hoffman said. The Food and Drug Administration and the American Medical Association recommend a dose of 550 mg daily. “The same is true for alcohol, which we know is also very bad for fetal brain development. This is not to say go ahead and use these substances and just take choline. The choline is more to try and salvage damage to the fetal brain that may have already occurred.”
This study was supported by the National Institute of Mental Health and the National Institute on Drug Abuse. The authors declared no competing interests. Dr. Hoffman disclosed no conflicts of interest with respect to her comments.
Mothers who use cannabis during pregnancy risk disrupting immune gene networks in the placenta and potentially increasing the risk of anxiety and hyperactivity in their children.
These findings emerged from a study led by Yasmin Hurd, PhD, a professor of psychiatry and director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, New York, and Yoko Nomura, PhD, a professor of behavioral neuroscience at Queen’s College, City University of New York, that was published online in Proceedings of the National Academy of Sciences.
The analysis assessed the effects of gestational maternal cannabis use on psychosocial and physiological measures in young children as well as its potentially immunomodulatory effect on the in utero environment as reflected in the placental transcriptome.
Participants were drawn from a larger cohort in a study launched in 2012; the investigators evaluated offspring aged 3-6 years for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children survey, and heart rate variability (HRV) at rest and during auditory startle.
The cohort consisted of 322 mother-child dyads and children with prenatal exposure to cannabis were compared with those having no exposure. The cohort consisted of 251 non–cannabis-using mothers and 71 cannabis-using mothers, with mean maternal ages in the two groups of 28.46 years and 25.91 years, respectively, The mothers gave birth at Mount Sinai and they and their children were assessed annually at affiliated medical centers in Mount Sinai’s catchment area.
For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing.
Among the findings:
- Maternal cannabis use was associated with reduced maternal and paternal age, more single-mother pregnancies, state anxiety, trait anxiety, depression, cigarette smoking, and African American race.
- Hair hormone analysis revealed increased cortisol levels in the children of cannabis-using mothers, and was associated with greater anxiety, aggression, and hyperactivity.
- Affected children showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone.
- In the placenta, there was reduced expression of many genes involved in immune system function. These included genes for type I interferon, neutrophil, and cytokine-signaling pathways.
Several of these genes organized into coexpression networks that correlated with child anxiety and hyperactivity.
The principal active component of cannabis, tetrahydrocannabinol (THC), targets the endocannabinoid system in placental tissue and the developing brain, the authors noted. Exposure during pregnancy is associated with a range of adverse outcomes from fetal growth restriction to low birth weight and preterm birth.
“There are cannabinoid receptors on immune cells, and it is known that cannabinoids can alter immune function, which is important for maintaining maternal tolerance and protecting the fetus,” Dr. Hurd said. “It’s not surprising that something that affects the immune cells can have an impact on the developing fetus.”
“Overall, our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood,” Dr. Hurd and colleagues wrote, adding that the results have significant implications for defining mental health issues in the children gestated by cannabis-smoking mothers.
Their results align with previous research indicating a greater risk for psychiatric illness in children with prenatal cannabis exposure from maternal use.
“While data are pretty limited in this realm, there are other studies that demonstrate a relationship between early child developmental and behavioral measures and cannabis use during pregnancy,” Camille Hoffman, MD, MSc, a high-risk obstetrics specialist and an associate professor at the University of Colorado at Denver, Aurora, said in an interview. “Our research group found children exposed to cannabis in utero at 10 weeks’ gestation and beyond were less interactive and more withdrawn than children who were not exposed.”
And THC remains in maternal breast milk even 6 weeks after usage stops.
The long-term effects of prenatal cannabis exposure remain to be determined and it is unknown whether the effects of gestational THC might attenuate as a child grows older. “We use early childhood measures in research as a proxy for the later development of diagnosed mental health conditions or behavioral problems,” Dr. Hoffman explained. “We know when we do this that not every child with an abnormal score early will go on to develop an actual condition. Fortunately, or unfortunately, other factors and exposures during childhood can change the trajectory for the better or worse.”
According to Dr. Hurd, child development is a dynamic process and epigenetic events in utero need not be deterministic. “The important thing is to identify children at risk early and to be able to go in and try to improve the environment they’re being raised in – not in terms of impoverishment but in terms of positive nurturing and giving the mother and family support.”
At the prenatal level, what’s the best advice for cannabis-using mothers-to-be? “If a woman doesn’t know she’s pregnant and has been using cannabis, taking extra choline for the remainder of the pregnancy can help buffer the potential negative impact of the cannabis exposure,” Dr. Hoffman said. The Food and Drug Administration and the American Medical Association recommend a dose of 550 mg daily. “The same is true for alcohol, which we know is also very bad for fetal brain development. This is not to say go ahead and use these substances and just take choline. The choline is more to try and salvage damage to the fetal brain that may have already occurred.”
This study was supported by the National Institute of Mental Health and the National Institute on Drug Abuse. The authors declared no competing interests. Dr. Hoffman disclosed no conflicts of interest with respect to her comments.
Mothers who use cannabis during pregnancy risk disrupting immune gene networks in the placenta and potentially increasing the risk of anxiety and hyperactivity in their children.
These findings emerged from a study led by Yasmin Hurd, PhD, a professor of psychiatry and director of the Addiction Institute at the Icahn School of Medicine at Mount Sinai, New York, and Yoko Nomura, PhD, a professor of behavioral neuroscience at Queen’s College, City University of New York, that was published online in Proceedings of the National Academy of Sciences.
The analysis assessed the effects of gestational maternal cannabis use on psychosocial and physiological measures in young children as well as its potentially immunomodulatory effect on the in utero environment as reflected in the placental transcriptome.
Participants were drawn from a larger cohort in a study launched in 2012; the investigators evaluated offspring aged 3-6 years for hair hormone levels, neurobehavioral traits on the Behavioral Assessment System for Children survey, and heart rate variability (HRV) at rest and during auditory startle.
The cohort consisted of 322 mother-child dyads and children with prenatal exposure to cannabis were compared with those having no exposure. The cohort consisted of 251 non–cannabis-using mothers and 71 cannabis-using mothers, with mean maternal ages in the two groups of 28.46 years and 25.91 years, respectively, The mothers gave birth at Mount Sinai and they and their children were assessed annually at affiliated medical centers in Mount Sinai’s catchment area.
For a subset of children with behavioral assessments, placental specimens collected at birth were processed for RNA sequencing.
Among the findings:
- Maternal cannabis use was associated with reduced maternal and paternal age, more single-mother pregnancies, state anxiety, trait anxiety, depression, cigarette smoking, and African American race.
- Hair hormone analysis revealed increased cortisol levels in the children of cannabis-using mothers, and was associated with greater anxiety, aggression, and hyperactivity.
- Affected children showed a reduction in the high-frequency component of HRV at baseline, reflecting reduced vagal tone.
- In the placenta, there was reduced expression of many genes involved in immune system function. These included genes for type I interferon, neutrophil, and cytokine-signaling pathways.
Several of these genes organized into coexpression networks that correlated with child anxiety and hyperactivity.
The principal active component of cannabis, tetrahydrocannabinol (THC), targets the endocannabinoid system in placental tissue and the developing brain, the authors noted. Exposure during pregnancy is associated with a range of adverse outcomes from fetal growth restriction to low birth weight and preterm birth.
“There are cannabinoid receptors on immune cells, and it is known that cannabinoids can alter immune function, which is important for maintaining maternal tolerance and protecting the fetus,” Dr. Hurd said. “It’s not surprising that something that affects the immune cells can have an impact on the developing fetus.”
“Overall, our findings reveal a relationship between [maternal cannabis use] and immune response gene networks in the placenta as a potential mediator of risk for anxiety-related problems in early childhood,” Dr. Hurd and colleagues wrote, adding that the results have significant implications for defining mental health issues in the children gestated by cannabis-smoking mothers.
Their results align with previous research indicating a greater risk for psychiatric illness in children with prenatal cannabis exposure from maternal use.
“While data are pretty limited in this realm, there are other studies that demonstrate a relationship between early child developmental and behavioral measures and cannabis use during pregnancy,” Camille Hoffman, MD, MSc, a high-risk obstetrics specialist and an associate professor at the University of Colorado at Denver, Aurora, said in an interview. “Our research group found children exposed to cannabis in utero at 10 weeks’ gestation and beyond were less interactive and more withdrawn than children who were not exposed.”
And THC remains in maternal breast milk even 6 weeks after usage stops.
The long-term effects of prenatal cannabis exposure remain to be determined and it is unknown whether the effects of gestational THC might attenuate as a child grows older. “We use early childhood measures in research as a proxy for the later development of diagnosed mental health conditions or behavioral problems,” Dr. Hoffman explained. “We know when we do this that not every child with an abnormal score early will go on to develop an actual condition. Fortunately, or unfortunately, other factors and exposures during childhood can change the trajectory for the better or worse.”
According to Dr. Hurd, child development is a dynamic process and epigenetic events in utero need not be deterministic. “The important thing is to identify children at risk early and to be able to go in and try to improve the environment they’re being raised in – not in terms of impoverishment but in terms of positive nurturing and giving the mother and family support.”
At the prenatal level, what’s the best advice for cannabis-using mothers-to-be? “If a woman doesn’t know she’s pregnant and has been using cannabis, taking extra choline for the remainder of the pregnancy can help buffer the potential negative impact of the cannabis exposure,” Dr. Hoffman said. The Food and Drug Administration and the American Medical Association recommend a dose of 550 mg daily. “The same is true for alcohol, which we know is also very bad for fetal brain development. This is not to say go ahead and use these substances and just take choline. The choline is more to try and salvage damage to the fetal brain that may have already occurred.”
This study was supported by the National Institute of Mental Health and the National Institute on Drug Abuse. The authors declared no competing interests. Dr. Hoffman disclosed no conflicts of interest with respect to her comments.
FROM PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES
More than half of U.S. children under 6 years show detectable blood lead levels
Lead poisoning remains a significant threat to the health of young children in the United States, based on data from blood tests of more than 1 million children.
Any level of lead is potentially harmful, although blood lead levels have decreased over the past several decades in part because of the elimination of lead from many consumer products, as well as from gas, paint, and plumbing fixtures, wrote Marissa Hauptman, MD, of Boston Children’s Hospital and colleagues.
However, “numerous environmental sources of legacy lead still exist,” and children living in poverty and in older housing in particular remain at increased risk for lead exposure, they noted.
In a study published in JAMA Pediatrics, the researchers analyzed deidentified results from blood lead tests performed at a single clinical laboratory for 1,141,441 children younger than 6 years between Oct. 1, 2018, and Feb. 29, 2020. The mean age of the children was 2.3 years; approximately half were boys.
Overall, 50.5% of the children tested (576,092 children) had detectable blood lead levels (BLLs), defined as 1.0 mcg/dL or higher, and 1.9% (21,172 children) had elevated BLLs, defined as 5.0 mcg/dL or higher.
In multivariate analysis, both detectable BLLs and elevated BLLs were significantly more common among children with public insurance (adjusted odds ratios, 2.01 and 1.08, respectively).
Children in the highest vs. lowest quintile of pre-1950s housing had significantly greater odds of both detectable and elevated BLLs (aOR, 1.65 and aOR, 3.06); those in the highest vs. lowest quintiles of poverty showed similarly increased risk of detectable and elevated BLLs (aOR, 1.89 and aOR, 1.99, respectively; P < .001 for all).
When the data were broken out by ZIP code, children in predominantly Black non-Hispanic and non-Latino neighborhoods were more likely than those living in other ZIP codes to have detectable BLLs (aOR, 1.13), but less likely to have elevated BLLs (aOR, 0.83). States with the highest overall proportions of children with detectable BLLs were Nebraska (83%), Missouri (82%), and Michigan (78%).
The study findings were limited by several factors, especially the potential for selection bias because of the use of a single reference laboratory (Quest Diagnostics), that does not perform all lead testing in the United States, the researchers noted. Other limitations included variability in testing at the state level, and the use of ZIP code–level data to estimate race, ethnicity, housing, and poverty, they said.
However, the results suggest that lead exposure remains a problem in young children, with significant disparities at the individual and community level, and national efforts must focus on further reductions of lead exposure in areas of highest risk, they concluded.
Step up lead elimination efforts
“The removal of lead from gasoline and new paint produced a precipitous decrease in blood lead levels from a population mean of 17 mcg/dL (all ages) in 1976 to 4 mcg/dL in the early 1990s to less than 2 mcg/dL today,” wrote Philip J. Landrigan, MD, of Boston College and David Bellinger, PhD, of Harvard University, Boston, in an accompanying editorial. However, “The findings from this study underscore the urgent need to eliminate all sources of lead exposure from U.S. children’s environments,” and highlight the persistent disparities in children’s lead exposure, they said.
The authors emphasized the need to remove existing lead paint from U.S. homes, as not only the paint itself, but the dust that enters the environment as the pain wears over time, continue to account for most detectable and elevated BLLs in children. A comprehensive lead paint removal effort would be an investment that would protect children now and would protect future generations, they emphasized. They proposed “creating a lead paint removal workforce through federally supported partnerships between city governments and major unions,” that would not only protect children from disease and disability, but could potentially provide jobs and vocational programs that would have a significant impact on communities.
Elevated lead levels may be underreported
In fact, the situation of children’s lead exposure in the United States may be more severe than indicated by the study findings, given the variation in testing at the state and local levels, said Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.
“There are no available lead test kits in our offices, so I do worry that many elevated lead levels will be missed,” she said.
“The recent case of elevated lead levels in drinking water in Flint, Michigan, was largely detected through pediatric clinic screening and showed that elevated lead levels may remain a major issue in some communities,” said Tim Joos, MD, a clinician in combined internal medicine/pediatrics in Seattle, Wash., in an interview.
“It is important to highlight to what extent baseline and point-source lead contamination still exists, monitor progress towards lowering levels, and identify communities at high risk,” Dr. Joos emphasized. “The exact prevalence of elevated lead levels among the general pediatric populations is hard to estimate from this study because of the methodology, which looked at demographic characteristics of the subset of the pediatric population that had venous samples sent to Quest Lab,” he noted.
“As the authors pointed out, it is hard to know what biases went into deciding whether to screen or not, and whether these were confirmatory tests for elevated point of care testing done earlier in the clinic,” said Dr. Joos. “Nonetheless, it does point to the role of poverty and pre-1950s housing in elevated blood lead levels,” he added. “The study also highlights that, as the CDC considers lowering the level for what is considered an ‘elevated blood lead level’ from 5.0 to perhaps 3.5 mcg/dL, we still have a lot more work to do,” he said.
The study was funded by Quest Diagnostics and the company provided salaries to several coauthors during the study. Dr. Hauptmann disclosed support from the National Institutes of Health/National Institute of Environmental Health Sciences during the current study and support from the Agency for Toxic Substances and Disease Registry and the U.S. Environmental Protection Agency unrelated to the current study. Dr. Landrigan had no financial conflicts to disclose. Dr. Bellinger disclosed fees from attorneys for testimony in cases unrelated to the editorial. Dr. Kinsella had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News. Dr. Joos had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.
Lead poisoning remains a significant threat to the health of young children in the United States, based on data from blood tests of more than 1 million children.
Any level of lead is potentially harmful, although blood lead levels have decreased over the past several decades in part because of the elimination of lead from many consumer products, as well as from gas, paint, and plumbing fixtures, wrote Marissa Hauptman, MD, of Boston Children’s Hospital and colleagues.
However, “numerous environmental sources of legacy lead still exist,” and children living in poverty and in older housing in particular remain at increased risk for lead exposure, they noted.
In a study published in JAMA Pediatrics, the researchers analyzed deidentified results from blood lead tests performed at a single clinical laboratory for 1,141,441 children younger than 6 years between Oct. 1, 2018, and Feb. 29, 2020. The mean age of the children was 2.3 years; approximately half were boys.
Overall, 50.5% of the children tested (576,092 children) had detectable blood lead levels (BLLs), defined as 1.0 mcg/dL or higher, and 1.9% (21,172 children) had elevated BLLs, defined as 5.0 mcg/dL or higher.
In multivariate analysis, both detectable BLLs and elevated BLLs were significantly more common among children with public insurance (adjusted odds ratios, 2.01 and 1.08, respectively).
Children in the highest vs. lowest quintile of pre-1950s housing had significantly greater odds of both detectable and elevated BLLs (aOR, 1.65 and aOR, 3.06); those in the highest vs. lowest quintiles of poverty showed similarly increased risk of detectable and elevated BLLs (aOR, 1.89 and aOR, 1.99, respectively; P < .001 for all).
When the data were broken out by ZIP code, children in predominantly Black non-Hispanic and non-Latino neighborhoods were more likely than those living in other ZIP codes to have detectable BLLs (aOR, 1.13), but less likely to have elevated BLLs (aOR, 0.83). States with the highest overall proportions of children with detectable BLLs were Nebraska (83%), Missouri (82%), and Michigan (78%).
The study findings were limited by several factors, especially the potential for selection bias because of the use of a single reference laboratory (Quest Diagnostics), that does not perform all lead testing in the United States, the researchers noted. Other limitations included variability in testing at the state level, and the use of ZIP code–level data to estimate race, ethnicity, housing, and poverty, they said.
However, the results suggest that lead exposure remains a problem in young children, with significant disparities at the individual and community level, and national efforts must focus on further reductions of lead exposure in areas of highest risk, they concluded.
Step up lead elimination efforts
“The removal of lead from gasoline and new paint produced a precipitous decrease in blood lead levels from a population mean of 17 mcg/dL (all ages) in 1976 to 4 mcg/dL in the early 1990s to less than 2 mcg/dL today,” wrote Philip J. Landrigan, MD, of Boston College and David Bellinger, PhD, of Harvard University, Boston, in an accompanying editorial. However, “The findings from this study underscore the urgent need to eliminate all sources of lead exposure from U.S. children’s environments,” and highlight the persistent disparities in children’s lead exposure, they said.
The authors emphasized the need to remove existing lead paint from U.S. homes, as not only the paint itself, but the dust that enters the environment as the pain wears over time, continue to account for most detectable and elevated BLLs in children. A comprehensive lead paint removal effort would be an investment that would protect children now and would protect future generations, they emphasized. They proposed “creating a lead paint removal workforce through federally supported partnerships between city governments and major unions,” that would not only protect children from disease and disability, but could potentially provide jobs and vocational programs that would have a significant impact on communities.
Elevated lead levels may be underreported
In fact, the situation of children’s lead exposure in the United States may be more severe than indicated by the study findings, given the variation in testing at the state and local levels, said Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.
“There are no available lead test kits in our offices, so I do worry that many elevated lead levels will be missed,” she said.
“The recent case of elevated lead levels in drinking water in Flint, Michigan, was largely detected through pediatric clinic screening and showed that elevated lead levels may remain a major issue in some communities,” said Tim Joos, MD, a clinician in combined internal medicine/pediatrics in Seattle, Wash., in an interview.
“It is important to highlight to what extent baseline and point-source lead contamination still exists, monitor progress towards lowering levels, and identify communities at high risk,” Dr. Joos emphasized. “The exact prevalence of elevated lead levels among the general pediatric populations is hard to estimate from this study because of the methodology, which looked at demographic characteristics of the subset of the pediatric population that had venous samples sent to Quest Lab,” he noted.
“As the authors pointed out, it is hard to know what biases went into deciding whether to screen or not, and whether these were confirmatory tests for elevated point of care testing done earlier in the clinic,” said Dr. Joos. “Nonetheless, it does point to the role of poverty and pre-1950s housing in elevated blood lead levels,” he added. “The study also highlights that, as the CDC considers lowering the level for what is considered an ‘elevated blood lead level’ from 5.0 to perhaps 3.5 mcg/dL, we still have a lot more work to do,” he said.
The study was funded by Quest Diagnostics and the company provided salaries to several coauthors during the study. Dr. Hauptmann disclosed support from the National Institutes of Health/National Institute of Environmental Health Sciences during the current study and support from the Agency for Toxic Substances and Disease Registry and the U.S. Environmental Protection Agency unrelated to the current study. Dr. Landrigan had no financial conflicts to disclose. Dr. Bellinger disclosed fees from attorneys for testimony in cases unrelated to the editorial. Dr. Kinsella had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News. Dr. Joos had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.
Lead poisoning remains a significant threat to the health of young children in the United States, based on data from blood tests of more than 1 million children.
Any level of lead is potentially harmful, although blood lead levels have decreased over the past several decades in part because of the elimination of lead from many consumer products, as well as from gas, paint, and plumbing fixtures, wrote Marissa Hauptman, MD, of Boston Children’s Hospital and colleagues.
However, “numerous environmental sources of legacy lead still exist,” and children living in poverty and in older housing in particular remain at increased risk for lead exposure, they noted.
In a study published in JAMA Pediatrics, the researchers analyzed deidentified results from blood lead tests performed at a single clinical laboratory for 1,141,441 children younger than 6 years between Oct. 1, 2018, and Feb. 29, 2020. The mean age of the children was 2.3 years; approximately half were boys.
Overall, 50.5% of the children tested (576,092 children) had detectable blood lead levels (BLLs), defined as 1.0 mcg/dL or higher, and 1.9% (21,172 children) had elevated BLLs, defined as 5.0 mcg/dL or higher.
In multivariate analysis, both detectable BLLs and elevated BLLs were significantly more common among children with public insurance (adjusted odds ratios, 2.01 and 1.08, respectively).
Children in the highest vs. lowest quintile of pre-1950s housing had significantly greater odds of both detectable and elevated BLLs (aOR, 1.65 and aOR, 3.06); those in the highest vs. lowest quintiles of poverty showed similarly increased risk of detectable and elevated BLLs (aOR, 1.89 and aOR, 1.99, respectively; P < .001 for all).
When the data were broken out by ZIP code, children in predominantly Black non-Hispanic and non-Latino neighborhoods were more likely than those living in other ZIP codes to have detectable BLLs (aOR, 1.13), but less likely to have elevated BLLs (aOR, 0.83). States with the highest overall proportions of children with detectable BLLs were Nebraska (83%), Missouri (82%), and Michigan (78%).
The study findings were limited by several factors, especially the potential for selection bias because of the use of a single reference laboratory (Quest Diagnostics), that does not perform all lead testing in the United States, the researchers noted. Other limitations included variability in testing at the state level, and the use of ZIP code–level data to estimate race, ethnicity, housing, and poverty, they said.
However, the results suggest that lead exposure remains a problem in young children, with significant disparities at the individual and community level, and national efforts must focus on further reductions of lead exposure in areas of highest risk, they concluded.
Step up lead elimination efforts
“The removal of lead from gasoline and new paint produced a precipitous decrease in blood lead levels from a population mean of 17 mcg/dL (all ages) in 1976 to 4 mcg/dL in the early 1990s to less than 2 mcg/dL today,” wrote Philip J. Landrigan, MD, of Boston College and David Bellinger, PhD, of Harvard University, Boston, in an accompanying editorial. However, “The findings from this study underscore the urgent need to eliminate all sources of lead exposure from U.S. children’s environments,” and highlight the persistent disparities in children’s lead exposure, they said.
The authors emphasized the need to remove existing lead paint from U.S. homes, as not only the paint itself, but the dust that enters the environment as the pain wears over time, continue to account for most detectable and elevated BLLs in children. A comprehensive lead paint removal effort would be an investment that would protect children now and would protect future generations, they emphasized. They proposed “creating a lead paint removal workforce through federally supported partnerships between city governments and major unions,” that would not only protect children from disease and disability, but could potentially provide jobs and vocational programs that would have a significant impact on communities.
Elevated lead levels may be underreported
In fact, the situation of children’s lead exposure in the United States may be more severe than indicated by the study findings, given the variation in testing at the state and local levels, said Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.
“There are no available lead test kits in our offices, so I do worry that many elevated lead levels will be missed,” she said.
“The recent case of elevated lead levels in drinking water in Flint, Michigan, was largely detected through pediatric clinic screening and showed that elevated lead levels may remain a major issue in some communities,” said Tim Joos, MD, a clinician in combined internal medicine/pediatrics in Seattle, Wash., in an interview.
“It is important to highlight to what extent baseline and point-source lead contamination still exists, monitor progress towards lowering levels, and identify communities at high risk,” Dr. Joos emphasized. “The exact prevalence of elevated lead levels among the general pediatric populations is hard to estimate from this study because of the methodology, which looked at demographic characteristics of the subset of the pediatric population that had venous samples sent to Quest Lab,” he noted.
“As the authors pointed out, it is hard to know what biases went into deciding whether to screen or not, and whether these were confirmatory tests for elevated point of care testing done earlier in the clinic,” said Dr. Joos. “Nonetheless, it does point to the role of poverty and pre-1950s housing in elevated blood lead levels,” he added. “The study also highlights that, as the CDC considers lowering the level for what is considered an ‘elevated blood lead level’ from 5.0 to perhaps 3.5 mcg/dL, we still have a lot more work to do,” he said.
The study was funded by Quest Diagnostics and the company provided salaries to several coauthors during the study. Dr. Hauptmann disclosed support from the National Institutes of Health/National Institute of Environmental Health Sciences during the current study and support from the Agency for Toxic Substances and Disease Registry and the U.S. Environmental Protection Agency unrelated to the current study. Dr. Landrigan had no financial conflicts to disclose. Dr. Bellinger disclosed fees from attorneys for testimony in cases unrelated to the editorial. Dr. Kinsella had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News. Dr. Joos had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.
FROM JAMA PEDIATRICS
Parent-led intervention linked with decreased autism symptoms in at-risk infants
These findings, which were published in JAMA Pediatrics, were the first evidence worldwide that a preemptive intervention during infancy could lead to such a significant improvement in children’s social development, resulting in “three times fewer diagnoses of autism at age 3,” said lead author Andrew Whitehouse, PhD, in a statement.
“No trial of a preemptive infant intervention, applied prior to diagnosis, has to date shown such an effect to impact diagnostic outcomes – until now,” he said.
Study intervention is a nontraditonal approach
Dr. Whitehouse, who is professor of Autism Research at Telethon Kids and University of Western Australia, and Director of CliniKids in Perth, said the intervention is a departure from traditional approaches. “Traditionally, therapy seeks to train children to learn ‘typical’ behaviors,” he said in an email. “The difference of this therapy is that we help parents understand the unique abilities of their baby, and to use these strengths as a foundation for future development.”
Dr. Whitehouse’s study included 103 children (aged approximately 12 months), who displayed at least three of five behaviors indicating a high likelihood of ASD as defined by the Social Attention and Communication Surveillance–Revised (SACS-R) 12-month checklist. The infants were randomized to receive either usual care or the intervention, which is called the iBASIS–Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care was delivered by community physicians, whereas the intervention involved 10 sessions delivered at home by a trained therapist.
“The iBASIS-VIPP uses video-feedback as a means of helping parents recognize their baby’s communication cues so they can respond in a way that builds their social communication development,” Dr. Whitehouse explained in an interview. “The therapist then provides guidance to the parent as to how their baby is communicating with them, and they can communicate back to have back-and-forth conversations.”
“We know these back-and-forth conversations are crucial to support early social communication development, and are a precursor to more complex skills, such as verbal language,” he added.
Reassessment of the children at age 3 years showed a “small but enduring” benefit of the intervention, noted the authors. Children in the intervention group had a reduction in ASD symptom severity (P = .04), and reduced odds of ASD classification, compared with children receiving usual care (6.7% vs. 20.5%; odds ratio, 0.18; P = .02).
The findings provide “initial evidence of efficacy for a new clinical model that uses a specific developmentally focused intervention,” noted the authors. “The children falling below the diagnostic threshold still had developmental difficulties, but by working with each child’s unique differences, rather than trying to counter them, the therapy has effectively supported their development through the early childhood years,” noted Dr. Whitehouse in a statement.
Other research has shown benefits of new study approach
This is a “solid” study, “but, as acknowledged by the authors, the main effects are small in magnitude, and longer-term outcomes will be important to capture,” said Jessica Brian, PhD, C Psych, associate professor in the department of pediatrics at the University of Toronto, colead at the Autism Research Centre, and psychologist and clinician-investigator at Holland Bloorview Kids Rehab Hospital in Toronto.
Dr. Brian said she and her coauthors of a paper published in Autism Research and others have shown that the kind of approach used in the new study can be helpful for enhancing different areas of toddler development, but “the specific finding of reduced likelihood of a clinical ASD diagnosis is a bit different.”
The goal of reducing the likelihood of an ASD diagnosis “needs to be considered carefully, from the perspective of autism acceptance,” she added. “From an acceptance lens, the primary objective of early intervention in ASD might be better positioned as aiming to enhance or support a young child’s development, help them make developmental progress, build on their strengths, optimize outcomes, or reduce impairment. … I think the authors do a good job of balancing this perspective.”
New study shows value of parent-mediated interventions
Overall, Dr. Brian, who coauthored the Canadian Paediatric Society’s position statement on ASD diagnosis, lauded the findings as good news.
“It shows the value of using parent-mediated interventions, which are far less costly and are more resource-efficient than most therapist-delivered models.”
“In cases where parent-mediated approaches are made available to families prior to diagnosis, there is potential for strong effects, when the brain is most amenable to learning. Such models may also be an ideal fit before diagnosis, since they are less resource-intensive than therapist-delivered models, which may only be funded by governments once a diagnosis is confirmed,” she said.
“Finally, parent-mediated programs have the potential to support parents during what, for many families, is a particularly challenging time as they identify their child’s developmental differences or receive a diagnosis. Such programs have potential to increase parents’ confidence in parenting a young child with unique learning needs.”
What Dr. Brian thought was missing from the paper was acknowledgment that, “despite early developmental gains from parent-mediated interventions, it is likely that most children with ASD will need additional supports throughout development.”
This study was sponsored by the Telethon Kids Institute. Dr. Whitehouse reported no conflicts of interest. Dr. Brian codeveloped a parent-mediated intervention for toddlers with probable or confirmed ASD (the Social ABCs), for which she does not receive any royalties.
These findings, which were published in JAMA Pediatrics, were the first evidence worldwide that a preemptive intervention during infancy could lead to such a significant improvement in children’s social development, resulting in “three times fewer diagnoses of autism at age 3,” said lead author Andrew Whitehouse, PhD, in a statement.
“No trial of a preemptive infant intervention, applied prior to diagnosis, has to date shown such an effect to impact diagnostic outcomes – until now,” he said.
Study intervention is a nontraditonal approach
Dr. Whitehouse, who is professor of Autism Research at Telethon Kids and University of Western Australia, and Director of CliniKids in Perth, said the intervention is a departure from traditional approaches. “Traditionally, therapy seeks to train children to learn ‘typical’ behaviors,” he said in an email. “The difference of this therapy is that we help parents understand the unique abilities of their baby, and to use these strengths as a foundation for future development.”
Dr. Whitehouse’s study included 103 children (aged approximately 12 months), who displayed at least three of five behaviors indicating a high likelihood of ASD as defined by the Social Attention and Communication Surveillance–Revised (SACS-R) 12-month checklist. The infants were randomized to receive either usual care or the intervention, which is called the iBASIS–Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care was delivered by community physicians, whereas the intervention involved 10 sessions delivered at home by a trained therapist.
“The iBASIS-VIPP uses video-feedback as a means of helping parents recognize their baby’s communication cues so they can respond in a way that builds their social communication development,” Dr. Whitehouse explained in an interview. “The therapist then provides guidance to the parent as to how their baby is communicating with them, and they can communicate back to have back-and-forth conversations.”
“We know these back-and-forth conversations are crucial to support early social communication development, and are a precursor to more complex skills, such as verbal language,” he added.
Reassessment of the children at age 3 years showed a “small but enduring” benefit of the intervention, noted the authors. Children in the intervention group had a reduction in ASD symptom severity (P = .04), and reduced odds of ASD classification, compared with children receiving usual care (6.7% vs. 20.5%; odds ratio, 0.18; P = .02).
The findings provide “initial evidence of efficacy for a new clinical model that uses a specific developmentally focused intervention,” noted the authors. “The children falling below the diagnostic threshold still had developmental difficulties, but by working with each child’s unique differences, rather than trying to counter them, the therapy has effectively supported their development through the early childhood years,” noted Dr. Whitehouse in a statement.
Other research has shown benefits of new study approach
This is a “solid” study, “but, as acknowledged by the authors, the main effects are small in magnitude, and longer-term outcomes will be important to capture,” said Jessica Brian, PhD, C Psych, associate professor in the department of pediatrics at the University of Toronto, colead at the Autism Research Centre, and psychologist and clinician-investigator at Holland Bloorview Kids Rehab Hospital in Toronto.
Dr. Brian said she and her coauthors of a paper published in Autism Research and others have shown that the kind of approach used in the new study can be helpful for enhancing different areas of toddler development, but “the specific finding of reduced likelihood of a clinical ASD diagnosis is a bit different.”
The goal of reducing the likelihood of an ASD diagnosis “needs to be considered carefully, from the perspective of autism acceptance,” she added. “From an acceptance lens, the primary objective of early intervention in ASD might be better positioned as aiming to enhance or support a young child’s development, help them make developmental progress, build on their strengths, optimize outcomes, or reduce impairment. … I think the authors do a good job of balancing this perspective.”
New study shows value of parent-mediated interventions
Overall, Dr. Brian, who coauthored the Canadian Paediatric Society’s position statement on ASD diagnosis, lauded the findings as good news.
“It shows the value of using parent-mediated interventions, which are far less costly and are more resource-efficient than most therapist-delivered models.”
“In cases where parent-mediated approaches are made available to families prior to diagnosis, there is potential for strong effects, when the brain is most amenable to learning. Such models may also be an ideal fit before diagnosis, since they are less resource-intensive than therapist-delivered models, which may only be funded by governments once a diagnosis is confirmed,” she said.
“Finally, parent-mediated programs have the potential to support parents during what, for many families, is a particularly challenging time as they identify their child’s developmental differences or receive a diagnosis. Such programs have potential to increase parents’ confidence in parenting a young child with unique learning needs.”
What Dr. Brian thought was missing from the paper was acknowledgment that, “despite early developmental gains from parent-mediated interventions, it is likely that most children with ASD will need additional supports throughout development.”
This study was sponsored by the Telethon Kids Institute. Dr. Whitehouse reported no conflicts of interest. Dr. Brian codeveloped a parent-mediated intervention for toddlers with probable or confirmed ASD (the Social ABCs), for which she does not receive any royalties.
These findings, which were published in JAMA Pediatrics, were the first evidence worldwide that a preemptive intervention during infancy could lead to such a significant improvement in children’s social development, resulting in “three times fewer diagnoses of autism at age 3,” said lead author Andrew Whitehouse, PhD, in a statement.
“No trial of a preemptive infant intervention, applied prior to diagnosis, has to date shown such an effect to impact diagnostic outcomes – until now,” he said.
Study intervention is a nontraditonal approach
Dr. Whitehouse, who is professor of Autism Research at Telethon Kids and University of Western Australia, and Director of CliniKids in Perth, said the intervention is a departure from traditional approaches. “Traditionally, therapy seeks to train children to learn ‘typical’ behaviors,” he said in an email. “The difference of this therapy is that we help parents understand the unique abilities of their baby, and to use these strengths as a foundation for future development.”
Dr. Whitehouse’s study included 103 children (aged approximately 12 months), who displayed at least three of five behaviors indicating a high likelihood of ASD as defined by the Social Attention and Communication Surveillance–Revised (SACS-R) 12-month checklist. The infants were randomized to receive either usual care or the intervention, which is called the iBASIS–Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care was delivered by community physicians, whereas the intervention involved 10 sessions delivered at home by a trained therapist.
“The iBASIS-VIPP uses video-feedback as a means of helping parents recognize their baby’s communication cues so they can respond in a way that builds their social communication development,” Dr. Whitehouse explained in an interview. “The therapist then provides guidance to the parent as to how their baby is communicating with them, and they can communicate back to have back-and-forth conversations.”
“We know these back-and-forth conversations are crucial to support early social communication development, and are a precursor to more complex skills, such as verbal language,” he added.
Reassessment of the children at age 3 years showed a “small but enduring” benefit of the intervention, noted the authors. Children in the intervention group had a reduction in ASD symptom severity (P = .04), and reduced odds of ASD classification, compared with children receiving usual care (6.7% vs. 20.5%; odds ratio, 0.18; P = .02).
The findings provide “initial evidence of efficacy for a new clinical model that uses a specific developmentally focused intervention,” noted the authors. “The children falling below the diagnostic threshold still had developmental difficulties, but by working with each child’s unique differences, rather than trying to counter them, the therapy has effectively supported their development through the early childhood years,” noted Dr. Whitehouse in a statement.
Other research has shown benefits of new study approach
This is a “solid” study, “but, as acknowledged by the authors, the main effects are small in magnitude, and longer-term outcomes will be important to capture,” said Jessica Brian, PhD, C Psych, associate professor in the department of pediatrics at the University of Toronto, colead at the Autism Research Centre, and psychologist and clinician-investigator at Holland Bloorview Kids Rehab Hospital in Toronto.
Dr. Brian said she and her coauthors of a paper published in Autism Research and others have shown that the kind of approach used in the new study can be helpful for enhancing different areas of toddler development, but “the specific finding of reduced likelihood of a clinical ASD diagnosis is a bit different.”
The goal of reducing the likelihood of an ASD diagnosis “needs to be considered carefully, from the perspective of autism acceptance,” she added. “From an acceptance lens, the primary objective of early intervention in ASD might be better positioned as aiming to enhance or support a young child’s development, help them make developmental progress, build on their strengths, optimize outcomes, or reduce impairment. … I think the authors do a good job of balancing this perspective.”
New study shows value of parent-mediated interventions
Overall, Dr. Brian, who coauthored the Canadian Paediatric Society’s position statement on ASD diagnosis, lauded the findings as good news.
“It shows the value of using parent-mediated interventions, which are far less costly and are more resource-efficient than most therapist-delivered models.”
“In cases where parent-mediated approaches are made available to families prior to diagnosis, there is potential for strong effects, when the brain is most amenable to learning. Such models may also be an ideal fit before diagnosis, since they are less resource-intensive than therapist-delivered models, which may only be funded by governments once a diagnosis is confirmed,” she said.
“Finally, parent-mediated programs have the potential to support parents during what, for many families, is a particularly challenging time as they identify their child’s developmental differences or receive a diagnosis. Such programs have potential to increase parents’ confidence in parenting a young child with unique learning needs.”
What Dr. Brian thought was missing from the paper was acknowledgment that, “despite early developmental gains from parent-mediated interventions, it is likely that most children with ASD will need additional supports throughout development.”
This study was sponsored by the Telethon Kids Institute. Dr. Whitehouse reported no conflicts of interest. Dr. Brian codeveloped a parent-mediated intervention for toddlers with probable or confirmed ASD (the Social ABCs), for which she does not receive any royalties.
FROM JAMA PEDIATRICS