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Large genetic study links 72 genes to autism spectrum disorders
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
according to a study published in Nature Genetics. The findings, based on analysis of more than 150,000 people’s genetics, arose from a collaboration of five research groups whose work included comparisons of ASD cohorts with separate cohorts of individuals with developmental delay or schizophrenia.
“We know that many genes, when mutated, contribute to autism,” and this study brought together “multiple types of mutations in a wide array of samples to get a much richer sense of the genes and genetic architecture involved in autism and other neurodevelopmental conditions,” co–senior author Joseph D. Buxbaum, PhD, director of the Seaver Autism Center for Research and Treatment at Mount Sinai and a professor at the Icahn School of Medicine at Mount Sinai, both in New York, said in a prepared statement. “This is significant in that we now have more insights as to the biology of the brain changes that underlie autism and more potential targets for treatment.”
Glen Elliott, PhD, MD, a clinical professor of psychiatry at Stanford (Calif.) University who was not involved in the study, said the paper is important paper for informing clinicians of where the basic research is headed. “We’re still in for a long road” before it bears fruit in terms of therapeutics. The value of studies like these, that investigate which genes are most associated with ASD, is that they may lead toward understanding the pathways in the brain that give rise to certain symptoms of ASD, which can then become therapeutic targets, Dr. Elliott said.
Investigating large cohorts
The researchers analyzed genetic exome sequencing data from 33 ASD cohorts with a total of 63,237 people and then compared these data with another cohort of people with developmental delay and a cohort of people with schizophrenia. The combined ASD cohorts included 15,036 individuals with ASD, 28,522 parents, and 5,492 unaffected siblings. The remaining participants were 5,591 people with ASD and 8,597 matched controls from case control studies.
In the ASD cohorts, the researchers identified 72 genes that were associated with ASD. De novo variants were eight times more likely in cases (4%) than in controls (0.5%). Ten genes occurred at least twice in ASD cases but never occurred in unaffected siblings.
Then the researchers integrated these ASD genetic data with a cohort of 91,605 people that included 31,058 people with developmental delay and their parents. Substantial overlap with gene mutations existed between these two cohorts: 70.1% of the genes related to developmental delay appeared linked to risk for ASD, and 86.6% of genes associated with ASD risk also had associations with developmental delay. Overall, the researchers identified 373 genes strongly associated with ASD and/or developmental delay and 664 genes with a likely association.
“Isolating genes that exert a greater effect on ASD than they do on other developmental delays has remained challenging due to the frequent comorbidity of these phenotypes,” wrote lead author Jack M. Fu, of Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues. “Still, an estimated 13.4% of the transmission and de novo association–ASD genes show little evidence for association in the developmental delay cohort.”
ASD, developmental delay, and schizophrenia
When the researchers compared the cells where the genetic mutations occurred in fetal brains, they found that genes associated with developmental delay more often occurred in less differentiated cell types – less mature cells in the developmental process. Gene mutations associated with ASD, on the other hand, occurred in more mature cell types, particularly in maturing excitatory neurons and related cells.
”Our results are consistent with developmental delay-predominant genes being expressed earlier in development and in less differentiated cells than ASD-predominant genes,” they wrote.
The researchers also compared the specific gene mutations found in these two cohorts with a previously published set of 244 genes associated with schizophrenia. Of these, 234 genes are among those with a transmission and de novo association to ASD and/or developmental delay. Of the 72 genes linked to ASD, eight appear in the set of genes linked to schizophrenia, and 61 were associated with developmental delay, though these two subsets do not overlap each other much.
“The ASD-schizophrenia overlap was significantly enriched, while the developmental delay-schizophrenia overlap was not,” they reported. ”Together, these data suggest that one subset of ASD risk genes may overlap developmental delay while a different subset overlaps schizophrenia.”
Chasing therapy targets by backtracking through genes
The findings are a substantial step forward in understanding the potential genetic contribution to ASD, but they also highlight the challenges of eventually trying to use this information in a clinically meaningful way.
“Given the substantial overlap between the genes implicated in neurodevelopmental disorders writ large and those implicated directly in ASD, disentangling the relative impact of individual genes on neurodevelopment and phenotypic spectra is a daunting yet important challenge,” the researchers wrote. “To identify the key neurobiological features of ASD will likely require convergence of evidence from many ASD genes and studies.”
Dr. Elliott said the biggest takeaway from this study is a better understanding of how the paradigm has shifted away from finding “one gene” for autism or a cure based on genetics and more toward understanding the pathophysiology of symptoms that can point to therapies for better management of the condition.
“Basic researchers have completely changed the strategy for trying to understand the biology of major disorders,” including, in this case, autism, Dr. Elliott said. “The intent is to try to find the underlying systems [in the brain] by backtracking through genes. Meanwhile, given that scientists have made substantial progress in identifying genes that have specific effects on brain development, “the hope is that will mesh with this kind of research, to begin to identify systems that might ultimately be targets for treating.”
The end goal is to be able to offer targeted approaches, based on the pathways causing a symptom, which can be linked backward to a gene.
”So this is not going to offer an immediate cure – it’s probably not going to offer a cure at all – but it may actually lead to much more targeted medications than we currently have for specific types of symptoms within the autism spectrum,” Dr. Elliott said. “What they’re trying to do, ultimately, is to say, when this system is really badly affected because of a genetic abnormality, even though that genetic abnormality is very rare, it leads to these specific kinds of symptoms. If we can find out the neuroregulators underlying that change, then that would be the target, even if that gene were not present.”
The research was funded by the Simons Foundation for Autism Research Initiative, the SPARK project, the National Human Genome Research Institute Home, the National Institute of Mental Health, the National Institute of Child Health and Development, AMED, and the Beatrice and Samuel Seaver Foundation. Five authors reported financial disclosures linked to Desitin, Roche, BioMarin, BrigeBio Pharma, Illumina, Levo Therapeutics, and Microsoft.
FROM NATURE GENETICS
How does not getting enough sleep affect the developing brain?
Children who do not get enough sleep for one night can be cranky, groggy, or meltdown prone the next day.
Over time, though, insufficient sleep may impair neurodevelopment in ways that can be measured on brain scans and tests long term, a new study shows.
Research published in The Lancet Child & Adolescent Health found that 9- and 10-year-olds who do not get at least 9 hours of sleep most nights tend to have less gray matter and smaller areas of the brain responsible for attention, memory, and inhibition control, relative to children who do get enough sleep.
The researchers also found a relationship between insufficient sleep and disrupted connections between the basal ganglia and cortical regions of the brain. These disruptions appeared to be linked to depression, thought problems, and impairments in crystallized intelligence, a type of intelligence that depends on memory.
The overall patterns persisted 2 years later, even as those who got enough sleep at baseline gradually slept less over time, while those who were not getting enough sleep to begin with continued to sleep about the same amount, the researchers reported.
The results bolster the case for delaying school start times, as California recently did, according one researcher who was not involved in the study.
The ABCD Study
To examine how insufficient sleep affects children’s mental health, cognition, brain function, and brain structure over 2 years, Ze Wang, PhD, professor of diagnostic radiology and nuclear medicine at the University of Maryland, Baltimore, and colleagues analyzed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study is tracking the biologic and behavioral development of more than 11,000 children in the United States who were recruited for the study when they were 9 or 10 years old.
For their new analysis, Dr. Wang’s group focused on 6,042 participants: 3,021 children with insufficient sleep who were matched with an equal number of participants who were similar in many respects, including sex, socioeconomic status, and puberty status, except they got at least 9 hours of sleep. They also looked at outcomes 2 years later from 749 of the matched pairs who had results available.
The investigators determined sleep duration based on how parents answered the question: “How many hours of sleep does your child get on most nights in the past 6 months?” Possible answers included at least 9 hours, 8-9 hours, 7-8 hours, 5-7 hours, or less than 5 hours. They also looked at functional and structural MRI scans, test results, and responses to questionnaires.
Negative effects of inadequate sleep were spread over “several different domains including brain structure, function, cognition, behavior, and mental health,” Dr. Wang said.
The strength of the relationship between sleep duration and the various outcomes was “modest” and based on group averages, he said. So, a given child who does not sleep for 9 hours most nights won’t necessarily perform worse than a child who gets enough sleep.
Still, modest effects may accumulate and have lasting consequences, Dr. Wang said.
Crystallized intelligence
The researchers looked at 42 behavioral outcomes, 32 of which were significantly different between the groups. Four outcomes in particular – depression, thought problems, performance on a picture-vocabulary test, and crystallized intelligence – were areas where insufficient sleep seemed to have a larger negative effect.
Sleep duration’s relationship with crystallized intelligence was twice that for fluid intelligence, which does not depend on memory.
“Sleep affects memory,” Dr. Wang said. “Crystallized intelligence depends on learned skills and knowledge, which are memory. In this sense, sleep is related to crystallized intelligence.”
One limitation of the study is that some parents may not accurately report how much sleep their child gets, Dr. Wang acknowledged. Children may be awake when parents think they are asleep, for example.
And although the results show getting 9 hours of sleep may help neurocognitive development, it’s also possible that excessive amounts of sleep could be problematic, the study authors wrote.
Further experiments are needed to prove that insufficient sleep – and not some other, unaccounted for factor – causes the observed impairments in neurodevelopment.
To promote healthy sleep, parents should keep a strict routine for their children, such as a regular bedtime and no electronic devices in the bedroom, Dr. Wang suggested. More physical activity during the day also should help.
If children have high levels of stress and depression, “finding the source is critical,” he said. Likewise, clinicians should consider how mental health can affect their patients’ sleep.
More to healthy sleep than duration
“This study both aligns with and advances existing research on the importance of sufficient sleep for child well-being,” said Ariel A. Williamson, PhD, DBSM, a psychologist and pediatric sleep expert in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia and assistant professor of psychiatry and pediatrics at University of Pennsylvania, also in Philadelphia.
The researchers used rigorous propensity score matching, longitudinal data, and brain imaging, which are “innovative methods that provide more evidence on potential mechanisms linking insufficient sleep and child outcomes,” said Dr. Williamson, who was not involved in the study.
While the investigators focused on sleep duration, child sleep health is multidimensional and includes other elements like timing and perception of sleep quality, Dr. Williamson noted. “For example, some research shows that having a sleep schedule that varies night to night is linked to poor child outcomes.”
Dr. Williamson tells families and clinicians that “sleep is a pillar of health,” equal to diet and exercise. That said, sleep recommendations need to fit within a family’s life – taking into account after school activities and late-night homework sessions. But extending sleep by just “20-30 minutes can make a meaningful difference for daytime functioning,” Dr. Williamson said.
Start school later?
Researchers have only relatively recently begun to understand how insufficient sleep affects adolescent neurocognitive development long term, and this study provides “crucial evidence” about the consequences, Lydia Gabriela Speyer, PhD, said in an editorial published with the study. Dr. Speyer is affiliated with the department of psychology at the University of Cambridge (England).
“Given the novel finding that insufficient sleep is associated with changes in brain structure and connectivity that are long-lasting, early intervention is crucial because such neural changes are probably not reversible and might consequently affect adolescents’ development into adulthood,” Dr. Speyer wrote.
Delaying school start times could be one way to help kids get more sleep. The American Academy of Pediatrics and the American Academy of Sleep Medicine recommend that middle schools and high schools start no earlier than 8:30 a.m. to better align with students’ circadian rhythm, Dr. Speyer noted.
As it is in the United States, most schools start closer to 8 a.m. In California, though, a law that went into effect on July 1 prohibits high schools from starting before 8:30 a.m. Other states are weighing similar legislation.
The research was supported by the National Institutes of Health. Dr. Wang and his coauthors and Dr. Speyer had no conflict of interest disclosures. Dr. Williamson is a sleep expert for the Pediatric Sleep Council (www.babysleep.com), which provides free information about early childhood sleep, but she does not receive compensation for this role.
Children who do not get enough sleep for one night can be cranky, groggy, or meltdown prone the next day.
Over time, though, insufficient sleep may impair neurodevelopment in ways that can be measured on brain scans and tests long term, a new study shows.
Research published in The Lancet Child & Adolescent Health found that 9- and 10-year-olds who do not get at least 9 hours of sleep most nights tend to have less gray matter and smaller areas of the brain responsible for attention, memory, and inhibition control, relative to children who do get enough sleep.
The researchers also found a relationship between insufficient sleep and disrupted connections between the basal ganglia and cortical regions of the brain. These disruptions appeared to be linked to depression, thought problems, and impairments in crystallized intelligence, a type of intelligence that depends on memory.
The overall patterns persisted 2 years later, even as those who got enough sleep at baseline gradually slept less over time, while those who were not getting enough sleep to begin with continued to sleep about the same amount, the researchers reported.
The results bolster the case for delaying school start times, as California recently did, according one researcher who was not involved in the study.
The ABCD Study
To examine how insufficient sleep affects children’s mental health, cognition, brain function, and brain structure over 2 years, Ze Wang, PhD, professor of diagnostic radiology and nuclear medicine at the University of Maryland, Baltimore, and colleagues analyzed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study is tracking the biologic and behavioral development of more than 11,000 children in the United States who were recruited for the study when they were 9 or 10 years old.
For their new analysis, Dr. Wang’s group focused on 6,042 participants: 3,021 children with insufficient sleep who were matched with an equal number of participants who were similar in many respects, including sex, socioeconomic status, and puberty status, except they got at least 9 hours of sleep. They also looked at outcomes 2 years later from 749 of the matched pairs who had results available.
The investigators determined sleep duration based on how parents answered the question: “How many hours of sleep does your child get on most nights in the past 6 months?” Possible answers included at least 9 hours, 8-9 hours, 7-8 hours, 5-7 hours, or less than 5 hours. They also looked at functional and structural MRI scans, test results, and responses to questionnaires.
Negative effects of inadequate sleep were spread over “several different domains including brain structure, function, cognition, behavior, and mental health,” Dr. Wang said.
The strength of the relationship between sleep duration and the various outcomes was “modest” and based on group averages, he said. So, a given child who does not sleep for 9 hours most nights won’t necessarily perform worse than a child who gets enough sleep.
Still, modest effects may accumulate and have lasting consequences, Dr. Wang said.
Crystallized intelligence
The researchers looked at 42 behavioral outcomes, 32 of which were significantly different between the groups. Four outcomes in particular – depression, thought problems, performance on a picture-vocabulary test, and crystallized intelligence – were areas where insufficient sleep seemed to have a larger negative effect.
Sleep duration’s relationship with crystallized intelligence was twice that for fluid intelligence, which does not depend on memory.
“Sleep affects memory,” Dr. Wang said. “Crystallized intelligence depends on learned skills and knowledge, which are memory. In this sense, sleep is related to crystallized intelligence.”
One limitation of the study is that some parents may not accurately report how much sleep their child gets, Dr. Wang acknowledged. Children may be awake when parents think they are asleep, for example.
And although the results show getting 9 hours of sleep may help neurocognitive development, it’s also possible that excessive amounts of sleep could be problematic, the study authors wrote.
Further experiments are needed to prove that insufficient sleep – and not some other, unaccounted for factor – causes the observed impairments in neurodevelopment.
To promote healthy sleep, parents should keep a strict routine for their children, such as a regular bedtime and no electronic devices in the bedroom, Dr. Wang suggested. More physical activity during the day also should help.
If children have high levels of stress and depression, “finding the source is critical,” he said. Likewise, clinicians should consider how mental health can affect their patients’ sleep.
More to healthy sleep than duration
“This study both aligns with and advances existing research on the importance of sufficient sleep for child well-being,” said Ariel A. Williamson, PhD, DBSM, a psychologist and pediatric sleep expert in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia and assistant professor of psychiatry and pediatrics at University of Pennsylvania, also in Philadelphia.
The researchers used rigorous propensity score matching, longitudinal data, and brain imaging, which are “innovative methods that provide more evidence on potential mechanisms linking insufficient sleep and child outcomes,” said Dr. Williamson, who was not involved in the study.
While the investigators focused on sleep duration, child sleep health is multidimensional and includes other elements like timing and perception of sleep quality, Dr. Williamson noted. “For example, some research shows that having a sleep schedule that varies night to night is linked to poor child outcomes.”
Dr. Williamson tells families and clinicians that “sleep is a pillar of health,” equal to diet and exercise. That said, sleep recommendations need to fit within a family’s life – taking into account after school activities and late-night homework sessions. But extending sleep by just “20-30 minutes can make a meaningful difference for daytime functioning,” Dr. Williamson said.
Start school later?
Researchers have only relatively recently begun to understand how insufficient sleep affects adolescent neurocognitive development long term, and this study provides “crucial evidence” about the consequences, Lydia Gabriela Speyer, PhD, said in an editorial published with the study. Dr. Speyer is affiliated with the department of psychology at the University of Cambridge (England).
“Given the novel finding that insufficient sleep is associated with changes in brain structure and connectivity that are long-lasting, early intervention is crucial because such neural changes are probably not reversible and might consequently affect adolescents’ development into adulthood,” Dr. Speyer wrote.
Delaying school start times could be one way to help kids get more sleep. The American Academy of Pediatrics and the American Academy of Sleep Medicine recommend that middle schools and high schools start no earlier than 8:30 a.m. to better align with students’ circadian rhythm, Dr. Speyer noted.
As it is in the United States, most schools start closer to 8 a.m. In California, though, a law that went into effect on July 1 prohibits high schools from starting before 8:30 a.m. Other states are weighing similar legislation.
The research was supported by the National Institutes of Health. Dr. Wang and his coauthors and Dr. Speyer had no conflict of interest disclosures. Dr. Williamson is a sleep expert for the Pediatric Sleep Council (www.babysleep.com), which provides free information about early childhood sleep, but she does not receive compensation for this role.
Children who do not get enough sleep for one night can be cranky, groggy, or meltdown prone the next day.
Over time, though, insufficient sleep may impair neurodevelopment in ways that can be measured on brain scans and tests long term, a new study shows.
Research published in The Lancet Child & Adolescent Health found that 9- and 10-year-olds who do not get at least 9 hours of sleep most nights tend to have less gray matter and smaller areas of the brain responsible for attention, memory, and inhibition control, relative to children who do get enough sleep.
The researchers also found a relationship between insufficient sleep and disrupted connections between the basal ganglia and cortical regions of the brain. These disruptions appeared to be linked to depression, thought problems, and impairments in crystallized intelligence, a type of intelligence that depends on memory.
The overall patterns persisted 2 years later, even as those who got enough sleep at baseline gradually slept less over time, while those who were not getting enough sleep to begin with continued to sleep about the same amount, the researchers reported.
The results bolster the case for delaying school start times, as California recently did, according one researcher who was not involved in the study.
The ABCD Study
To examine how insufficient sleep affects children’s mental health, cognition, brain function, and brain structure over 2 years, Ze Wang, PhD, professor of diagnostic radiology and nuclear medicine at the University of Maryland, Baltimore, and colleagues analyzed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study is tracking the biologic and behavioral development of more than 11,000 children in the United States who were recruited for the study when they were 9 or 10 years old.
For their new analysis, Dr. Wang’s group focused on 6,042 participants: 3,021 children with insufficient sleep who were matched with an equal number of participants who were similar in many respects, including sex, socioeconomic status, and puberty status, except they got at least 9 hours of sleep. They also looked at outcomes 2 years later from 749 of the matched pairs who had results available.
The investigators determined sleep duration based on how parents answered the question: “How many hours of sleep does your child get on most nights in the past 6 months?” Possible answers included at least 9 hours, 8-9 hours, 7-8 hours, 5-7 hours, or less than 5 hours. They also looked at functional and structural MRI scans, test results, and responses to questionnaires.
Negative effects of inadequate sleep were spread over “several different domains including brain structure, function, cognition, behavior, and mental health,” Dr. Wang said.
The strength of the relationship between sleep duration and the various outcomes was “modest” and based on group averages, he said. So, a given child who does not sleep for 9 hours most nights won’t necessarily perform worse than a child who gets enough sleep.
Still, modest effects may accumulate and have lasting consequences, Dr. Wang said.
Crystallized intelligence
The researchers looked at 42 behavioral outcomes, 32 of which were significantly different between the groups. Four outcomes in particular – depression, thought problems, performance on a picture-vocabulary test, and crystallized intelligence – were areas where insufficient sleep seemed to have a larger negative effect.
Sleep duration’s relationship with crystallized intelligence was twice that for fluid intelligence, which does not depend on memory.
“Sleep affects memory,” Dr. Wang said. “Crystallized intelligence depends on learned skills and knowledge, which are memory. In this sense, sleep is related to crystallized intelligence.”
One limitation of the study is that some parents may not accurately report how much sleep their child gets, Dr. Wang acknowledged. Children may be awake when parents think they are asleep, for example.
And although the results show getting 9 hours of sleep may help neurocognitive development, it’s also possible that excessive amounts of sleep could be problematic, the study authors wrote.
Further experiments are needed to prove that insufficient sleep – and not some other, unaccounted for factor – causes the observed impairments in neurodevelopment.
To promote healthy sleep, parents should keep a strict routine for their children, such as a regular bedtime and no electronic devices in the bedroom, Dr. Wang suggested. More physical activity during the day also should help.
If children have high levels of stress and depression, “finding the source is critical,” he said. Likewise, clinicians should consider how mental health can affect their patients’ sleep.
More to healthy sleep than duration
“This study both aligns with and advances existing research on the importance of sufficient sleep for child well-being,” said Ariel A. Williamson, PhD, DBSM, a psychologist and pediatric sleep expert in the department of child and adolescent psychiatry and behavioral sciences at Children’s Hospital of Philadelphia and assistant professor of psychiatry and pediatrics at University of Pennsylvania, also in Philadelphia.
The researchers used rigorous propensity score matching, longitudinal data, and brain imaging, which are “innovative methods that provide more evidence on potential mechanisms linking insufficient sleep and child outcomes,” said Dr. Williamson, who was not involved in the study.
While the investigators focused on sleep duration, child sleep health is multidimensional and includes other elements like timing and perception of sleep quality, Dr. Williamson noted. “For example, some research shows that having a sleep schedule that varies night to night is linked to poor child outcomes.”
Dr. Williamson tells families and clinicians that “sleep is a pillar of health,” equal to diet and exercise. That said, sleep recommendations need to fit within a family’s life – taking into account after school activities and late-night homework sessions. But extending sleep by just “20-30 minutes can make a meaningful difference for daytime functioning,” Dr. Williamson said.
Start school later?
Researchers have only relatively recently begun to understand how insufficient sleep affects adolescent neurocognitive development long term, and this study provides “crucial evidence” about the consequences, Lydia Gabriela Speyer, PhD, said in an editorial published with the study. Dr. Speyer is affiliated with the department of psychology at the University of Cambridge (England).
“Given the novel finding that insufficient sleep is associated with changes in brain structure and connectivity that are long-lasting, early intervention is crucial because such neural changes are probably not reversible and might consequently affect adolescents’ development into adulthood,” Dr. Speyer wrote.
Delaying school start times could be one way to help kids get more sleep. The American Academy of Pediatrics and the American Academy of Sleep Medicine recommend that middle schools and high schools start no earlier than 8:30 a.m. to better align with students’ circadian rhythm, Dr. Speyer noted.
As it is in the United States, most schools start closer to 8 a.m. In California, though, a law that went into effect on July 1 prohibits high schools from starting before 8:30 a.m. Other states are weighing similar legislation.
The research was supported by the National Institutes of Health. Dr. Wang and his coauthors and Dr. Speyer had no conflict of interest disclosures. Dr. Williamson is a sleep expert for the Pediatric Sleep Council (www.babysleep.com), which provides free information about early childhood sleep, but she does not receive compensation for this role.
FROM THE LANCET CHILD & ADOLESCENT HEALTH
FDA unveils 5-year plan for ALS and other neurodegenerative diseases
The agency’s Action Plan for Rare Neurodegenerative Diseases including Amyotrophic Lateral Sclerosis (ALS) aims to advance the development of safe and effective medical products and facilitate patient access to novel treatments.
“The effects of rare neurodegenerative diseases are devastating, with very few effective therapeutic options available to patients. We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” FDA Commissioner Robert M. Califf, MD, said in a news release.
“To face that challenge and to accelerate drug development, we need innovative approaches to better understand these diseases while also building on current scientific and research capabilities,” Dr. Califf acknowledged.
“This action plan, especially including the use of public-private partnerships and direct involvement of patients, will ensure the FDA is working toward meeting the task set forth by Congress to enhance the quality of life for those suffering by facilitating access to new therapies,” Dr. Califf added.
Blueprint to ‘aggressively’ move forward
The action plan represents a “blueprint” for how the agency will “aggressively” move forward to address challenges in drug development for rare neurodegenerative diseases to improve patient health, the FDA said.
The plan was created in accordance with provisions in the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) that President Biden signed into law in late 2021.
Targeted activities include establishing the FDA Rare Neurodegenerative Diseases Task Force and the public-private partnership for rare neurodegenerative diseases, developing disease-specific science strategies over the next 5 years, and leveraging ongoing FDA regulatory science efforts.
The ALS Science Strategy is part of the plan focused specifically on ALS. It provides a “forward-leaning” framework for FDA activities, which include efforts to improve characterization of disease pathogenesis and natural history, boost clinical trial infrastructure and agility to enable early selection of promising therapeutic candidates for further development, optimize clinical trial design, improve access to the trials, streamline clinical trial operations, and reduce the time and cost of drug development.
The FDA says patient engagement, public workshops, research projects, coordination across FDA centers and offices, and collaboration with the National Institutes of Health will be key to the success of implementation of the ALS Science Strategy.
A version of this article first appeared on Medscape.com.
The agency’s Action Plan for Rare Neurodegenerative Diseases including Amyotrophic Lateral Sclerosis (ALS) aims to advance the development of safe and effective medical products and facilitate patient access to novel treatments.
“The effects of rare neurodegenerative diseases are devastating, with very few effective therapeutic options available to patients. We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” FDA Commissioner Robert M. Califf, MD, said in a news release.
“To face that challenge and to accelerate drug development, we need innovative approaches to better understand these diseases while also building on current scientific and research capabilities,” Dr. Califf acknowledged.
“This action plan, especially including the use of public-private partnerships and direct involvement of patients, will ensure the FDA is working toward meeting the task set forth by Congress to enhance the quality of life for those suffering by facilitating access to new therapies,” Dr. Califf added.
Blueprint to ‘aggressively’ move forward
The action plan represents a “blueprint” for how the agency will “aggressively” move forward to address challenges in drug development for rare neurodegenerative diseases to improve patient health, the FDA said.
The plan was created in accordance with provisions in the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) that President Biden signed into law in late 2021.
Targeted activities include establishing the FDA Rare Neurodegenerative Diseases Task Force and the public-private partnership for rare neurodegenerative diseases, developing disease-specific science strategies over the next 5 years, and leveraging ongoing FDA regulatory science efforts.
The ALS Science Strategy is part of the plan focused specifically on ALS. It provides a “forward-leaning” framework for FDA activities, which include efforts to improve characterization of disease pathogenesis and natural history, boost clinical trial infrastructure and agility to enable early selection of promising therapeutic candidates for further development, optimize clinical trial design, improve access to the trials, streamline clinical trial operations, and reduce the time and cost of drug development.
The FDA says patient engagement, public workshops, research projects, coordination across FDA centers and offices, and collaboration with the National Institutes of Health will be key to the success of implementation of the ALS Science Strategy.
A version of this article first appeared on Medscape.com.
The agency’s Action Plan for Rare Neurodegenerative Diseases including Amyotrophic Lateral Sclerosis (ALS) aims to advance the development of safe and effective medical products and facilitate patient access to novel treatments.
“The effects of rare neurodegenerative diseases are devastating, with very few effective therapeutic options available to patients. We recognize the urgent need for new treatments that can both improve and extend the lives of people diagnosed with these diseases,” FDA Commissioner Robert M. Califf, MD, said in a news release.
“To face that challenge and to accelerate drug development, we need innovative approaches to better understand these diseases while also building on current scientific and research capabilities,” Dr. Califf acknowledged.
“This action plan, especially including the use of public-private partnerships and direct involvement of patients, will ensure the FDA is working toward meeting the task set forth by Congress to enhance the quality of life for those suffering by facilitating access to new therapies,” Dr. Califf added.
Blueprint to ‘aggressively’ move forward
The action plan represents a “blueprint” for how the agency will “aggressively” move forward to address challenges in drug development for rare neurodegenerative diseases to improve patient health, the FDA said.
The plan was created in accordance with provisions in the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS) that President Biden signed into law in late 2021.
Targeted activities include establishing the FDA Rare Neurodegenerative Diseases Task Force and the public-private partnership for rare neurodegenerative diseases, developing disease-specific science strategies over the next 5 years, and leveraging ongoing FDA regulatory science efforts.
The ALS Science Strategy is part of the plan focused specifically on ALS. It provides a “forward-leaning” framework for FDA activities, which include efforts to improve characterization of disease pathogenesis and natural history, boost clinical trial infrastructure and agility to enable early selection of promising therapeutic candidates for further development, optimize clinical trial design, improve access to the trials, streamline clinical trial operations, and reduce the time and cost of drug development.
The FDA says patient engagement, public workshops, research projects, coordination across FDA centers and offices, and collaboration with the National Institutes of Health will be key to the success of implementation of the ALS Science Strategy.
A version of this article first appeared on Medscape.com.
Cochlear implants benefit deaf children with developmental delays
Deaf babies and toddlers with developmental delays may benefit significantly from receiving cochlear implants over hearing aids.
A new study, published in the journal Pediatrics, pushes against the notion that children with low nonverbal cognition and adaptive functioning skills won’t improve if given cochlear implants. Some insurers cover hearing aids for children with developmental disorders but not the implants, which can cost between $60,000 and $100,000 per ear.
“We were surprised [by] the large magnitude of the improvements, not only in quality of life, but also in cognition, ability to function in daily living situations, and speech and language,” lead author John S. Oghalai, MD, of the University of Southern California, Los Angeles, told this news organization. “Remember, these are children with substantial developmental delays. Any improvements are incredibly important and meaningful.”
All children with severe hearing loss should be referred for cochlear implant evaluation, “regardless of the presence of other disabilities,” Dr. Oghalai said. “The younger this referral happens, the better the outcomes will be.”
Dr. Oghalai and his colleagues reviewed data from 204 children approximately 1-3 years old with hearing aids receiving treatment in Texas and California. Of these, 138 received a cochlear implant and had normal cognitive skills and social competence (referred to as adaptive behavior). Another 37 received a cochlear implant and also met criteria for early developmental impairment (EDI), defined by measures of nonverbal cognitive scores and adaptive functioning.
A third group of 29 children with EDI continued with hearing aids without a cochlear implant.
The children were evaluated annually for 1-5 years, with the average follow-up of 2 years. At baseline, no significant differences were noted between the children with EDI who received implants and those who did not on cognition, language, auditory skills, or measures of parental or child stress.
Overall, children who received implants scored higher on cognitive and social measures than those who continued using hearing aids.
Compared with children with EDI who received implants, children without EDI who received implants had significantly higher developmental scores by the study’s end (P ≤ .001), whereas children with EDI who did not receive implants had significantly lower scores (P ≤ .04).
Children who received implants, and their parents, also experienced less stress than those who did not receive the devices, according to the researchers.
Dr. Oghalai and colleagues also measured developmental trajectories for each cohort. Children without delays who received implants had the best outcomes, but those with EDI who received implants had better outcomes than those with EDI and hearing aids.
Findings ‘overdue’
“This study is overdue,” Howard Francis, MD, chair of the department of head and neck surgery & communication sciences at Duke University, Durham, N.C., told this news organization.
Dr. Francis called the new research “reasonably powered and designed,” and said it “documents benefits in the cognitive, language, and patient-child relationship domains” in children who received cochlear implants “compared to children with similar levels of developmental delay whose hearing loss was treated using hearing aids.”
However, “larger studies will be needed to account for potential effects of older age at intervention in the hearing aid group,” he said. Socioeconomic effects are a topic for future research as well, Dr. Francis added.
The researchers initially wanted to perform a controlled clinical trial. However, by the time they secured funding, health insurance policy had changed to cover cochlear implants for children without EDI because of demonstrated benefits shown in studies.
They also were unable to determine the reasons for families’ decisions to choose implants or hearing aids and were unable to assess the impact of insurance on the choice of implantation. But they did find that families with insurers who would cover implants often did choose the devices. Children were also followed for an average of 2 years, so long-term outcomes are unknown.
Despite these limitations, the results support the value of cochlear implantation in children with disabilities and developmental delays, and it should be discussed with parents, the researchers concluded.
“Cochlear implants are just a tool; they do not provide speech and language,” Dr. Oghalai said. “Any child with severe hearing loss requires significant therapy and education via sign language, auditory-verbal therapy, or both. Making the decision about what type of therapy to do is personal, and it depends upon the family and the options that are available to them in their community.”
The study was funded by the National Institutes of Health. The researchers and Dr. Francis have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Deaf babies and toddlers with developmental delays may benefit significantly from receiving cochlear implants over hearing aids.
A new study, published in the journal Pediatrics, pushes against the notion that children with low nonverbal cognition and adaptive functioning skills won’t improve if given cochlear implants. Some insurers cover hearing aids for children with developmental disorders but not the implants, which can cost between $60,000 and $100,000 per ear.
“We were surprised [by] the large magnitude of the improvements, not only in quality of life, but also in cognition, ability to function in daily living situations, and speech and language,” lead author John S. Oghalai, MD, of the University of Southern California, Los Angeles, told this news organization. “Remember, these are children with substantial developmental delays. Any improvements are incredibly important and meaningful.”
All children with severe hearing loss should be referred for cochlear implant evaluation, “regardless of the presence of other disabilities,” Dr. Oghalai said. “The younger this referral happens, the better the outcomes will be.”
Dr. Oghalai and his colleagues reviewed data from 204 children approximately 1-3 years old with hearing aids receiving treatment in Texas and California. Of these, 138 received a cochlear implant and had normal cognitive skills and social competence (referred to as adaptive behavior). Another 37 received a cochlear implant and also met criteria for early developmental impairment (EDI), defined by measures of nonverbal cognitive scores and adaptive functioning.
A third group of 29 children with EDI continued with hearing aids without a cochlear implant.
The children were evaluated annually for 1-5 years, with the average follow-up of 2 years. At baseline, no significant differences were noted between the children with EDI who received implants and those who did not on cognition, language, auditory skills, or measures of parental or child stress.
Overall, children who received implants scored higher on cognitive and social measures than those who continued using hearing aids.
Compared with children with EDI who received implants, children without EDI who received implants had significantly higher developmental scores by the study’s end (P ≤ .001), whereas children with EDI who did not receive implants had significantly lower scores (P ≤ .04).
Children who received implants, and their parents, also experienced less stress than those who did not receive the devices, according to the researchers.
Dr. Oghalai and colleagues also measured developmental trajectories for each cohort. Children without delays who received implants had the best outcomes, but those with EDI who received implants had better outcomes than those with EDI and hearing aids.
Findings ‘overdue’
“This study is overdue,” Howard Francis, MD, chair of the department of head and neck surgery & communication sciences at Duke University, Durham, N.C., told this news organization.
Dr. Francis called the new research “reasonably powered and designed,” and said it “documents benefits in the cognitive, language, and patient-child relationship domains” in children who received cochlear implants “compared to children with similar levels of developmental delay whose hearing loss was treated using hearing aids.”
However, “larger studies will be needed to account for potential effects of older age at intervention in the hearing aid group,” he said. Socioeconomic effects are a topic for future research as well, Dr. Francis added.
The researchers initially wanted to perform a controlled clinical trial. However, by the time they secured funding, health insurance policy had changed to cover cochlear implants for children without EDI because of demonstrated benefits shown in studies.
They also were unable to determine the reasons for families’ decisions to choose implants or hearing aids and were unable to assess the impact of insurance on the choice of implantation. But they did find that families with insurers who would cover implants often did choose the devices. Children were also followed for an average of 2 years, so long-term outcomes are unknown.
Despite these limitations, the results support the value of cochlear implantation in children with disabilities and developmental delays, and it should be discussed with parents, the researchers concluded.
“Cochlear implants are just a tool; they do not provide speech and language,” Dr. Oghalai said. “Any child with severe hearing loss requires significant therapy and education via sign language, auditory-verbal therapy, or both. Making the decision about what type of therapy to do is personal, and it depends upon the family and the options that are available to them in their community.”
The study was funded by the National Institutes of Health. The researchers and Dr. Francis have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Deaf babies and toddlers with developmental delays may benefit significantly from receiving cochlear implants over hearing aids.
A new study, published in the journal Pediatrics, pushes against the notion that children with low nonverbal cognition and adaptive functioning skills won’t improve if given cochlear implants. Some insurers cover hearing aids for children with developmental disorders but not the implants, which can cost between $60,000 and $100,000 per ear.
“We were surprised [by] the large magnitude of the improvements, not only in quality of life, but also in cognition, ability to function in daily living situations, and speech and language,” lead author John S. Oghalai, MD, of the University of Southern California, Los Angeles, told this news organization. “Remember, these are children with substantial developmental delays. Any improvements are incredibly important and meaningful.”
All children with severe hearing loss should be referred for cochlear implant evaluation, “regardless of the presence of other disabilities,” Dr. Oghalai said. “The younger this referral happens, the better the outcomes will be.”
Dr. Oghalai and his colleagues reviewed data from 204 children approximately 1-3 years old with hearing aids receiving treatment in Texas and California. Of these, 138 received a cochlear implant and had normal cognitive skills and social competence (referred to as adaptive behavior). Another 37 received a cochlear implant and also met criteria for early developmental impairment (EDI), defined by measures of nonverbal cognitive scores and adaptive functioning.
A third group of 29 children with EDI continued with hearing aids without a cochlear implant.
The children were evaluated annually for 1-5 years, with the average follow-up of 2 years. At baseline, no significant differences were noted between the children with EDI who received implants and those who did not on cognition, language, auditory skills, or measures of parental or child stress.
Overall, children who received implants scored higher on cognitive and social measures than those who continued using hearing aids.
Compared with children with EDI who received implants, children without EDI who received implants had significantly higher developmental scores by the study’s end (P ≤ .001), whereas children with EDI who did not receive implants had significantly lower scores (P ≤ .04).
Children who received implants, and their parents, also experienced less stress than those who did not receive the devices, according to the researchers.
Dr. Oghalai and colleagues also measured developmental trajectories for each cohort. Children without delays who received implants had the best outcomes, but those with EDI who received implants had better outcomes than those with EDI and hearing aids.
Findings ‘overdue’
“This study is overdue,” Howard Francis, MD, chair of the department of head and neck surgery & communication sciences at Duke University, Durham, N.C., told this news organization.
Dr. Francis called the new research “reasonably powered and designed,” and said it “documents benefits in the cognitive, language, and patient-child relationship domains” in children who received cochlear implants “compared to children with similar levels of developmental delay whose hearing loss was treated using hearing aids.”
However, “larger studies will be needed to account for potential effects of older age at intervention in the hearing aid group,” he said. Socioeconomic effects are a topic for future research as well, Dr. Francis added.
The researchers initially wanted to perform a controlled clinical trial. However, by the time they secured funding, health insurance policy had changed to cover cochlear implants for children without EDI because of demonstrated benefits shown in studies.
They also were unable to determine the reasons for families’ decisions to choose implants or hearing aids and were unable to assess the impact of insurance on the choice of implantation. But they did find that families with insurers who would cover implants often did choose the devices. Children were also followed for an average of 2 years, so long-term outcomes are unknown.
Despite these limitations, the results support the value of cochlear implantation in children with disabilities and developmental delays, and it should be discussed with parents, the researchers concluded.
“Cochlear implants are just a tool; they do not provide speech and language,” Dr. Oghalai said. “Any child with severe hearing loss requires significant therapy and education via sign language, auditory-verbal therapy, or both. Making the decision about what type of therapy to do is personal, and it depends upon the family and the options that are available to them in their community.”
The study was funded by the National Institutes of Health. The researchers and Dr. Francis have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM PEDIATRICS
Abnormal growth of the amygdala in infants tied to autism
A new study suggests that overgrowth of the amygdala in infants during the first 6-12 months of life is tied to a later diagnosis of autism spectrum disorder (ASD).
“The faster the amygdala grew in infancy, the more social difficulties the child showed when diagnosed with autism a year later,” first author Mark Shen, PhD, assistant professor of psychiatry and neuroscience, University of North Carolina, Chapel Hill, told this news organization.
The study was published online in the American Journal of Psychiatry.
Unique to autism
The amygdala plays a key role in processing memory, emotional responses, and decisionmaking.
It’s long been known that the amygdala is abnormally large in school-aged children with ASD, but until now, it was not known precisely when aberrant amygdala growth happens, what the clinical consequences may be, and whether amygdala overgrowth is unique to autism.
To investigate, Dr. Shen and colleagues evaluated 1,099 longitudinal MRI scans obtained during natural sleep at 6, 12, and 24 months of age in 408 infants in the Infant Brain Imaging Study (IBIS) Network.
The cohort included 58 infants at high likelihood of developing ASD who were later diagnosed with the disorder, 212 infants at high likelihood of ASD who did not develop ASD, 109 typically-developing control infants, and 29 infants with fragile X syndrome.
At 6 months, infants who developed ASD had typically sized amygdala volumes but showed significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had significantly larger amygdala volume (Cohen’s d = 0.56), compared with all other groups.
Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the children were diagnosed with ASD.
“We found that the amygdala grows too rapidly between 6 and 12 months of age, during a presymptomatic period in autism, prior to when the diagnostic symptoms of autism (social difficulties and repetitive behaviors) are evident and lead to the later diagnosis of autism,” Dr. Shen said in an interview.
This brain growth pattern appears to be unique to autism, as babies with the genetic disorder fragile X syndrome – another neurodevelopmental condition – showed a markedly different brain growth pattern: no differences in amygdala growth but enlargement of a different brain structure, the caudate, which was linked to increased repetitive behaviors, the investigators found.
Earlier intervention
Prior research has shown that children who are later diagnosed with ASD often display problems in infancy with how they attend to visual stimuli in their surroundings.
These early problems with processing visual and sensory information may put increased stress on the amygdala, potentially leading to amygdala hyperactivity, deficits in pruning dendritic connections, and overgrowth, Dr. Shen and colleagues hypothesize.
Amygdala overgrowth has also been linked to chronic stress in studies of other psychiatric conditions, such as depression and anxiety, and may provide a clue to understanding this observation in infants who later develop autism.
“This research suggests that an optimal time to begin supports for children who are at the highest likelihood of developing autism may be during the first year of life: to improve early precursors to social development, such as sensory processing, in babies even before social difficulties arise,” Dr. Shen said.
Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said, “What makes this study important is the finding of abnormally increased amygdala growth rate in autism using a longitudinal design that focuses on earlier development.”
“While we are typically used to understanding brain structure as abnormally decreasing over time in certain disorders like Alzheimer’s disease, this study challenges us to understand that too much brain volume growth can also be abnormal in specific conditions,” Dr. Raji added.
This research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, and National Institute of Mental Health, along with Autism Speaks and the Simons Foundation. Dr. Shen and Dr. Raji have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study suggests that overgrowth of the amygdala in infants during the first 6-12 months of life is tied to a later diagnosis of autism spectrum disorder (ASD).
“The faster the amygdala grew in infancy, the more social difficulties the child showed when diagnosed with autism a year later,” first author Mark Shen, PhD, assistant professor of psychiatry and neuroscience, University of North Carolina, Chapel Hill, told this news organization.
The study was published online in the American Journal of Psychiatry.
Unique to autism
The amygdala plays a key role in processing memory, emotional responses, and decisionmaking.
It’s long been known that the amygdala is abnormally large in school-aged children with ASD, but until now, it was not known precisely when aberrant amygdala growth happens, what the clinical consequences may be, and whether amygdala overgrowth is unique to autism.
To investigate, Dr. Shen and colleagues evaluated 1,099 longitudinal MRI scans obtained during natural sleep at 6, 12, and 24 months of age in 408 infants in the Infant Brain Imaging Study (IBIS) Network.
The cohort included 58 infants at high likelihood of developing ASD who were later diagnosed with the disorder, 212 infants at high likelihood of ASD who did not develop ASD, 109 typically-developing control infants, and 29 infants with fragile X syndrome.
At 6 months, infants who developed ASD had typically sized amygdala volumes but showed significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had significantly larger amygdala volume (Cohen’s d = 0.56), compared with all other groups.
Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the children were diagnosed with ASD.
“We found that the amygdala grows too rapidly between 6 and 12 months of age, during a presymptomatic period in autism, prior to when the diagnostic symptoms of autism (social difficulties and repetitive behaviors) are evident and lead to the later diagnosis of autism,” Dr. Shen said in an interview.
This brain growth pattern appears to be unique to autism, as babies with the genetic disorder fragile X syndrome – another neurodevelopmental condition – showed a markedly different brain growth pattern: no differences in amygdala growth but enlargement of a different brain structure, the caudate, which was linked to increased repetitive behaviors, the investigators found.
Earlier intervention
Prior research has shown that children who are later diagnosed with ASD often display problems in infancy with how they attend to visual stimuli in their surroundings.
These early problems with processing visual and sensory information may put increased stress on the amygdala, potentially leading to amygdala hyperactivity, deficits in pruning dendritic connections, and overgrowth, Dr. Shen and colleagues hypothesize.
Amygdala overgrowth has also been linked to chronic stress in studies of other psychiatric conditions, such as depression and anxiety, and may provide a clue to understanding this observation in infants who later develop autism.
“This research suggests that an optimal time to begin supports for children who are at the highest likelihood of developing autism may be during the first year of life: to improve early precursors to social development, such as sensory processing, in babies even before social difficulties arise,” Dr. Shen said.
Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said, “What makes this study important is the finding of abnormally increased amygdala growth rate in autism using a longitudinal design that focuses on earlier development.”
“While we are typically used to understanding brain structure as abnormally decreasing over time in certain disorders like Alzheimer’s disease, this study challenges us to understand that too much brain volume growth can also be abnormal in specific conditions,” Dr. Raji added.
This research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, and National Institute of Mental Health, along with Autism Speaks and the Simons Foundation. Dr. Shen and Dr. Raji have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study suggests that overgrowth of the amygdala in infants during the first 6-12 months of life is tied to a later diagnosis of autism spectrum disorder (ASD).
“The faster the amygdala grew in infancy, the more social difficulties the child showed when diagnosed with autism a year later,” first author Mark Shen, PhD, assistant professor of psychiatry and neuroscience, University of North Carolina, Chapel Hill, told this news organization.
The study was published online in the American Journal of Psychiatry.
Unique to autism
The amygdala plays a key role in processing memory, emotional responses, and decisionmaking.
It’s long been known that the amygdala is abnormally large in school-aged children with ASD, but until now, it was not known precisely when aberrant amygdala growth happens, what the clinical consequences may be, and whether amygdala overgrowth is unique to autism.
To investigate, Dr. Shen and colleagues evaluated 1,099 longitudinal MRI scans obtained during natural sleep at 6, 12, and 24 months of age in 408 infants in the Infant Brain Imaging Study (IBIS) Network.
The cohort included 58 infants at high likelihood of developing ASD who were later diagnosed with the disorder, 212 infants at high likelihood of ASD who did not develop ASD, 109 typically-developing control infants, and 29 infants with fragile X syndrome.
At 6 months, infants who developed ASD had typically sized amygdala volumes but showed significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had significantly larger amygdala volume (Cohen’s d = 0.56), compared with all other groups.
Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the children were diagnosed with ASD.
“We found that the amygdala grows too rapidly between 6 and 12 months of age, during a presymptomatic period in autism, prior to when the diagnostic symptoms of autism (social difficulties and repetitive behaviors) are evident and lead to the later diagnosis of autism,” Dr. Shen said in an interview.
This brain growth pattern appears to be unique to autism, as babies with the genetic disorder fragile X syndrome – another neurodevelopmental condition – showed a markedly different brain growth pattern: no differences in amygdala growth but enlargement of a different brain structure, the caudate, which was linked to increased repetitive behaviors, the investigators found.
Earlier intervention
Prior research has shown that children who are later diagnosed with ASD often display problems in infancy with how they attend to visual stimuli in their surroundings.
These early problems with processing visual and sensory information may put increased stress on the amygdala, potentially leading to amygdala hyperactivity, deficits in pruning dendritic connections, and overgrowth, Dr. Shen and colleagues hypothesize.
Amygdala overgrowth has also been linked to chronic stress in studies of other psychiatric conditions, such as depression and anxiety, and may provide a clue to understanding this observation in infants who later develop autism.
“This research suggests that an optimal time to begin supports for children who are at the highest likelihood of developing autism may be during the first year of life: to improve early precursors to social development, such as sensory processing, in babies even before social difficulties arise,” Dr. Shen said.
Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University, St. Louis, said, “What makes this study important is the finding of abnormally increased amygdala growth rate in autism using a longitudinal design that focuses on earlier development.”
“While we are typically used to understanding brain structure as abnormally decreasing over time in certain disorders like Alzheimer’s disease, this study challenges us to understand that too much brain volume growth can also be abnormal in specific conditions,” Dr. Raji added.
This research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, and National Institute of Mental Health, along with Autism Speaks and the Simons Foundation. Dr. Shen and Dr. Raji have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Neonatal hypoglycemia doesn’t affect childhood academics
Children at risk of neonatal hypoglycemia who were screened and treated if needed showed no difference in educational achievement from controls at age 9-10 years, based on data from 480 children.
Previous studies have shown an increased risk of poor executive and visual-motor function in children with neonatal hypoglycemia, but the effect on later childhood academic performance remains unclear, wrote Rajesh Shah, PhD, of the University of Auckland, New Zealand, and colleagues.
In a prospective cohort study published in JAMA, the researchers enrolled moderate to late preterm and term infants born at increased risk for hypoglycemia; those with episodes of hypoglycemia were treated to maintain a blood glucose concentration of at least 47 mg/dL.
The study population was enrolled between 2006 and 2010 at a regional perinatal center in New Zealand, and their educational achievement was assessed 9-10 years later. The primary outcome of low educational achievement was defined as performing below the normal curriculum level in standardized tests of reading comprehension or math. The researchers also identified 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.
Rates of low educational achievement were not significantly different for children with and without neonatal hypoglycemia (47% vs. 48%, adjusted risk ratio 0.95).
No significant differences appeared between the two groups for any secondary outcomes, including reading comprehension, math, behavior manifestations of executive function, fine motor function, autism traits, and overall well-being, the researchers noted.
However, children with neonatal hypoglycemia were significantly less likely to be rated as below or well below reading curriculum level by teachers compared to those without neonatal hypoglycemia (24% vs. 31%).
The researchers cited a previous study of the same patient cohort at age 4.5 years, which suggested an association between adverse neurodevelopmental outcomes and infant hypoglycemia. However, the reason this association did not persist at age 9-10 years remains unclear, the researchers wrote in their discussion. “Early disturbances in brain development may have diminishing effects over time due to neuroplasticity, that is, reorganization of neural networks, or delayed maturation with mid-childhood catch-up in neurocognitive function,” they said.
The study findings were limited by several factors including the lack of data on several measures of cognition, notably processing speed, and a lack of adjustment for intelligence quotient at age 4.5 years, the lack of data on any treatment for developmental impairment, and the inclusion of a population with well-managed hypoglycemia, the researchers said.
However, the results were strengthened by having a sample size large enough to detect associations, the prospective design, and the accurate measure of neonatal glycemic exposure, they said. Although the results suggest that at-risk children reach similar endpoints by the end of primary school, “efforts to prevent and optimize adverse pregnancy conditions remain important, and developmental surveillance after birth should be considered for at-risk infants,” they concluded.
In a related study published in JAMA, Taygen Edwards and colleagues found that prophylactic oral dextrose gel had no significant effect on neurosensory function.
The study, a prospective follow-up of a multicenter randomized trial, included 1,197 later preterm or term infants deemed at risk for neonatal hypoglycemia. The infants (49% of whom were female) were randomized to prophylactic 40% dextrose gel or a placebo, massaged into the buccal mucosa at 1 hour after birth.
The primary outcome was neurosensory impairment at 2 years of age, which was assessed by neurologic examination, parent-reported medical questionnaires, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), performance-based executive function, Behavior Rating Inventory of Executive Function–Preschool Version, motion coherence thresholds, growth, and body composition.
At 2 years of age, the prevalence of neurosensory impairment was 21% and 19%, respectively, in infants randomized to prophylactic oral dextrose gel and placebo, a nonsignificant difference. No differences between the two groups were noted for cognitive and language delays, or low performance-based overall executive function. However, infants randomized to dextrose gel had significantly higher risk of motor delay compared to placebo (2.5% vs. 0.7%) and significantly lower Bayley-III composite scores for cognitive, language, and motor performance.
No significant differences were noted between the groups in the areas of moderate or severe neurosensory impairment, hearing impairment, cerebral palsy, developmental delay, above-average development, socioemotional and adaptive behavior, questionnaire-based executive function, low visual processing, history of seizures, allergic and infectious diseases, growth, and body composition.
The results are consistent with previous studies on the safety of dextrose gel, the researchers wrote in their discussion. However, the absolute difference of 7% in the primary outcome may be clinically important, they noted. “Caution is warranted before using prophylactic dextrose gel,” they said.
The researchers noted the results of a dose-finding trial that suggested improved scores on language, executive function, and motor skills in unadjusted analysis with higher doses of dextrose gel, but the reason for these findings remains unknown, they said.
The study findings were limited by the potential underpowering to detect small, but significant differences, and possible lack of generalizability because the majority of the participants were children of mothers with diabetes.
The results were strengthened by the high follow-up rate and comprehensive assessments, and highlight the need for additional research with longer follow-up, the researchers said.
Findings fuel further exploration
Although hypoglycemia is common in newborns, its management and potential outcomes remain subjects for debate, Paul J. Rozance, MD, of the University of Colorado, Aurora, wrote in an editorial accompanying both studies.
“Often, the same features that increase the risk of hypoglycemia in newborns also increase the risk for poor outcomes independent of hypoglycemia,” he said.
The study by Shah and colleagues was not a randomized trial of a specific management strategy, Dr. Rozance noted. However, the high rate of low educational attainment in children not exposed to dextrose gel emphasizes the need for more effective management of infant hypoglycemia, he said. “The findings also suggest that antenatal conditions that are associated with increased risk of hypoglycemia among newborns are associated with increased risk for impaired neurodevelopment and educational achievement, independent of neonatal hypoglycemia,” he said. The study findings contrast with those of an earlier study showing low academic achievement association with early transient hypoglycemia, which could argue for earlier intervention, he noted.
The study by Edwards and colleagues addressed the potential value of dextrose gel as an early intervention to prevent neonatal hypoglycemia, said Dr. Rozance.
“The 95% CI for the primary outcome of neurosensory impairment included up to a 7% increased risk for neurosensory impairment in the prophylactic dextrose gel group. The 7% increased risk was defined by the investigators as potentially clinically important, and the study may have been underpowered to detect small differences in the primary outcome,” he wrote.
Although the reasons for adverse outcomes in children given prophylactic dextrose gel remain unclear, “incorporation of prophylactic dextrose gel into clinical practice should await further research,” he said.
Regarding such research, Dr. Rozance proposed an “ideal study,” that would “randomize newborns with hypoglycemia to treatment or no treatment, although equipoise and ethical support for such a study are lacking. Another strategy would be to randomize newborns with hypoglycemia to receive low- or high-treatment glucose concentration goals,” he noted.
The relationship between hypoglycemia and impaired neurodevelopment is yet to be determined, but the two studies provide new evidence for the clinical importance and need for management of neonatal hypoglycemia and subsequent neurodevelopmental outcomes, he concluded.
The study by Shah and colleagues was supported by the Health Research Council of New Zealand and the Maurice and Phyllis Paykel Trust. Dr. Shah disclosed a doctoral fellowship from the University of Auckland. The study by Edwards and colleagues was supported by the Health Research Council of New Zealand and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Ms. Edwards had no financial conflicts to disclose. Dr. Rozance disclosed receiving a StatStrip from Nova Biomedical for use in his laboratory.
Children at risk of neonatal hypoglycemia who were screened and treated if needed showed no difference in educational achievement from controls at age 9-10 years, based on data from 480 children.
Previous studies have shown an increased risk of poor executive and visual-motor function in children with neonatal hypoglycemia, but the effect on later childhood academic performance remains unclear, wrote Rajesh Shah, PhD, of the University of Auckland, New Zealand, and colleagues.
In a prospective cohort study published in JAMA, the researchers enrolled moderate to late preterm and term infants born at increased risk for hypoglycemia; those with episodes of hypoglycemia were treated to maintain a blood glucose concentration of at least 47 mg/dL.
The study population was enrolled between 2006 and 2010 at a regional perinatal center in New Zealand, and their educational achievement was assessed 9-10 years later. The primary outcome of low educational achievement was defined as performing below the normal curriculum level in standardized tests of reading comprehension or math. The researchers also identified 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.
Rates of low educational achievement were not significantly different for children with and without neonatal hypoglycemia (47% vs. 48%, adjusted risk ratio 0.95).
No significant differences appeared between the two groups for any secondary outcomes, including reading comprehension, math, behavior manifestations of executive function, fine motor function, autism traits, and overall well-being, the researchers noted.
However, children with neonatal hypoglycemia were significantly less likely to be rated as below or well below reading curriculum level by teachers compared to those without neonatal hypoglycemia (24% vs. 31%).
The researchers cited a previous study of the same patient cohort at age 4.5 years, which suggested an association between adverse neurodevelopmental outcomes and infant hypoglycemia. However, the reason this association did not persist at age 9-10 years remains unclear, the researchers wrote in their discussion. “Early disturbances in brain development may have diminishing effects over time due to neuroplasticity, that is, reorganization of neural networks, or delayed maturation with mid-childhood catch-up in neurocognitive function,” they said.
The study findings were limited by several factors including the lack of data on several measures of cognition, notably processing speed, and a lack of adjustment for intelligence quotient at age 4.5 years, the lack of data on any treatment for developmental impairment, and the inclusion of a population with well-managed hypoglycemia, the researchers said.
However, the results were strengthened by having a sample size large enough to detect associations, the prospective design, and the accurate measure of neonatal glycemic exposure, they said. Although the results suggest that at-risk children reach similar endpoints by the end of primary school, “efforts to prevent and optimize adverse pregnancy conditions remain important, and developmental surveillance after birth should be considered for at-risk infants,” they concluded.
In a related study published in JAMA, Taygen Edwards and colleagues found that prophylactic oral dextrose gel had no significant effect on neurosensory function.
The study, a prospective follow-up of a multicenter randomized trial, included 1,197 later preterm or term infants deemed at risk for neonatal hypoglycemia. The infants (49% of whom were female) were randomized to prophylactic 40% dextrose gel or a placebo, massaged into the buccal mucosa at 1 hour after birth.
The primary outcome was neurosensory impairment at 2 years of age, which was assessed by neurologic examination, parent-reported medical questionnaires, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), performance-based executive function, Behavior Rating Inventory of Executive Function–Preschool Version, motion coherence thresholds, growth, and body composition.
At 2 years of age, the prevalence of neurosensory impairment was 21% and 19%, respectively, in infants randomized to prophylactic oral dextrose gel and placebo, a nonsignificant difference. No differences between the two groups were noted for cognitive and language delays, or low performance-based overall executive function. However, infants randomized to dextrose gel had significantly higher risk of motor delay compared to placebo (2.5% vs. 0.7%) and significantly lower Bayley-III composite scores for cognitive, language, and motor performance.
No significant differences were noted between the groups in the areas of moderate or severe neurosensory impairment, hearing impairment, cerebral palsy, developmental delay, above-average development, socioemotional and adaptive behavior, questionnaire-based executive function, low visual processing, history of seizures, allergic and infectious diseases, growth, and body composition.
The results are consistent with previous studies on the safety of dextrose gel, the researchers wrote in their discussion. However, the absolute difference of 7% in the primary outcome may be clinically important, they noted. “Caution is warranted before using prophylactic dextrose gel,” they said.
The researchers noted the results of a dose-finding trial that suggested improved scores on language, executive function, and motor skills in unadjusted analysis with higher doses of dextrose gel, but the reason for these findings remains unknown, they said.
The study findings were limited by the potential underpowering to detect small, but significant differences, and possible lack of generalizability because the majority of the participants were children of mothers with diabetes.
The results were strengthened by the high follow-up rate and comprehensive assessments, and highlight the need for additional research with longer follow-up, the researchers said.
Findings fuel further exploration
Although hypoglycemia is common in newborns, its management and potential outcomes remain subjects for debate, Paul J. Rozance, MD, of the University of Colorado, Aurora, wrote in an editorial accompanying both studies.
“Often, the same features that increase the risk of hypoglycemia in newborns also increase the risk for poor outcomes independent of hypoglycemia,” he said.
The study by Shah and colleagues was not a randomized trial of a specific management strategy, Dr. Rozance noted. However, the high rate of low educational attainment in children not exposed to dextrose gel emphasizes the need for more effective management of infant hypoglycemia, he said. “The findings also suggest that antenatal conditions that are associated with increased risk of hypoglycemia among newborns are associated with increased risk for impaired neurodevelopment and educational achievement, independent of neonatal hypoglycemia,” he said. The study findings contrast with those of an earlier study showing low academic achievement association with early transient hypoglycemia, which could argue for earlier intervention, he noted.
The study by Edwards and colleagues addressed the potential value of dextrose gel as an early intervention to prevent neonatal hypoglycemia, said Dr. Rozance.
“The 95% CI for the primary outcome of neurosensory impairment included up to a 7% increased risk for neurosensory impairment in the prophylactic dextrose gel group. The 7% increased risk was defined by the investigators as potentially clinically important, and the study may have been underpowered to detect small differences in the primary outcome,” he wrote.
Although the reasons for adverse outcomes in children given prophylactic dextrose gel remain unclear, “incorporation of prophylactic dextrose gel into clinical practice should await further research,” he said.
Regarding such research, Dr. Rozance proposed an “ideal study,” that would “randomize newborns with hypoglycemia to treatment or no treatment, although equipoise and ethical support for such a study are lacking. Another strategy would be to randomize newborns with hypoglycemia to receive low- or high-treatment glucose concentration goals,” he noted.
The relationship between hypoglycemia and impaired neurodevelopment is yet to be determined, but the two studies provide new evidence for the clinical importance and need for management of neonatal hypoglycemia and subsequent neurodevelopmental outcomes, he concluded.
The study by Shah and colleagues was supported by the Health Research Council of New Zealand and the Maurice and Phyllis Paykel Trust. Dr. Shah disclosed a doctoral fellowship from the University of Auckland. The study by Edwards and colleagues was supported by the Health Research Council of New Zealand and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Ms. Edwards had no financial conflicts to disclose. Dr. Rozance disclosed receiving a StatStrip from Nova Biomedical for use in his laboratory.
Children at risk of neonatal hypoglycemia who were screened and treated if needed showed no difference in educational achievement from controls at age 9-10 years, based on data from 480 children.
Previous studies have shown an increased risk of poor executive and visual-motor function in children with neonatal hypoglycemia, but the effect on later childhood academic performance remains unclear, wrote Rajesh Shah, PhD, of the University of Auckland, New Zealand, and colleagues.
In a prospective cohort study published in JAMA, the researchers enrolled moderate to late preterm and term infants born at increased risk for hypoglycemia; those with episodes of hypoglycemia were treated to maintain a blood glucose concentration of at least 47 mg/dL.
The study population was enrolled between 2006 and 2010 at a regional perinatal center in New Zealand, and their educational achievement was assessed 9-10 years later. The primary outcome of low educational achievement was defined as performing below the normal curriculum level in standardized tests of reading comprehension or math. The researchers also identified 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.
Rates of low educational achievement were not significantly different for children with and without neonatal hypoglycemia (47% vs. 48%, adjusted risk ratio 0.95).
No significant differences appeared between the two groups for any secondary outcomes, including reading comprehension, math, behavior manifestations of executive function, fine motor function, autism traits, and overall well-being, the researchers noted.
However, children with neonatal hypoglycemia were significantly less likely to be rated as below or well below reading curriculum level by teachers compared to those without neonatal hypoglycemia (24% vs. 31%).
The researchers cited a previous study of the same patient cohort at age 4.5 years, which suggested an association between adverse neurodevelopmental outcomes and infant hypoglycemia. However, the reason this association did not persist at age 9-10 years remains unclear, the researchers wrote in their discussion. “Early disturbances in brain development may have diminishing effects over time due to neuroplasticity, that is, reorganization of neural networks, or delayed maturation with mid-childhood catch-up in neurocognitive function,” they said.
The study findings were limited by several factors including the lack of data on several measures of cognition, notably processing speed, and a lack of adjustment for intelligence quotient at age 4.5 years, the lack of data on any treatment for developmental impairment, and the inclusion of a population with well-managed hypoglycemia, the researchers said.
However, the results were strengthened by having a sample size large enough to detect associations, the prospective design, and the accurate measure of neonatal glycemic exposure, they said. Although the results suggest that at-risk children reach similar endpoints by the end of primary school, “efforts to prevent and optimize adverse pregnancy conditions remain important, and developmental surveillance after birth should be considered for at-risk infants,” they concluded.
In a related study published in JAMA, Taygen Edwards and colleagues found that prophylactic oral dextrose gel had no significant effect on neurosensory function.
The study, a prospective follow-up of a multicenter randomized trial, included 1,197 later preterm or term infants deemed at risk for neonatal hypoglycemia. The infants (49% of whom were female) were randomized to prophylactic 40% dextrose gel or a placebo, massaged into the buccal mucosa at 1 hour after birth.
The primary outcome was neurosensory impairment at 2 years of age, which was assessed by neurologic examination, parent-reported medical questionnaires, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), performance-based executive function, Behavior Rating Inventory of Executive Function–Preschool Version, motion coherence thresholds, growth, and body composition.
At 2 years of age, the prevalence of neurosensory impairment was 21% and 19%, respectively, in infants randomized to prophylactic oral dextrose gel and placebo, a nonsignificant difference. No differences between the two groups were noted for cognitive and language delays, or low performance-based overall executive function. However, infants randomized to dextrose gel had significantly higher risk of motor delay compared to placebo (2.5% vs. 0.7%) and significantly lower Bayley-III composite scores for cognitive, language, and motor performance.
No significant differences were noted between the groups in the areas of moderate or severe neurosensory impairment, hearing impairment, cerebral palsy, developmental delay, above-average development, socioemotional and adaptive behavior, questionnaire-based executive function, low visual processing, history of seizures, allergic and infectious diseases, growth, and body composition.
The results are consistent with previous studies on the safety of dextrose gel, the researchers wrote in their discussion. However, the absolute difference of 7% in the primary outcome may be clinically important, they noted. “Caution is warranted before using prophylactic dextrose gel,” they said.
The researchers noted the results of a dose-finding trial that suggested improved scores on language, executive function, and motor skills in unadjusted analysis with higher doses of dextrose gel, but the reason for these findings remains unknown, they said.
The study findings were limited by the potential underpowering to detect small, but significant differences, and possible lack of generalizability because the majority of the participants were children of mothers with diabetes.
The results were strengthened by the high follow-up rate and comprehensive assessments, and highlight the need for additional research with longer follow-up, the researchers said.
Findings fuel further exploration
Although hypoglycemia is common in newborns, its management and potential outcomes remain subjects for debate, Paul J. Rozance, MD, of the University of Colorado, Aurora, wrote in an editorial accompanying both studies.
“Often, the same features that increase the risk of hypoglycemia in newborns also increase the risk for poor outcomes independent of hypoglycemia,” he said.
The study by Shah and colleagues was not a randomized trial of a specific management strategy, Dr. Rozance noted. However, the high rate of low educational attainment in children not exposed to dextrose gel emphasizes the need for more effective management of infant hypoglycemia, he said. “The findings also suggest that antenatal conditions that are associated with increased risk of hypoglycemia among newborns are associated with increased risk for impaired neurodevelopment and educational achievement, independent of neonatal hypoglycemia,” he said. The study findings contrast with those of an earlier study showing low academic achievement association with early transient hypoglycemia, which could argue for earlier intervention, he noted.
The study by Edwards and colleagues addressed the potential value of dextrose gel as an early intervention to prevent neonatal hypoglycemia, said Dr. Rozance.
“The 95% CI for the primary outcome of neurosensory impairment included up to a 7% increased risk for neurosensory impairment in the prophylactic dextrose gel group. The 7% increased risk was defined by the investigators as potentially clinically important, and the study may have been underpowered to detect small differences in the primary outcome,” he wrote.
Although the reasons for adverse outcomes in children given prophylactic dextrose gel remain unclear, “incorporation of prophylactic dextrose gel into clinical practice should await further research,” he said.
Regarding such research, Dr. Rozance proposed an “ideal study,” that would “randomize newborns with hypoglycemia to treatment or no treatment, although equipoise and ethical support for such a study are lacking. Another strategy would be to randomize newborns with hypoglycemia to receive low- or high-treatment glucose concentration goals,” he noted.
The relationship between hypoglycemia and impaired neurodevelopment is yet to be determined, but the two studies provide new evidence for the clinical importance and need for management of neonatal hypoglycemia and subsequent neurodevelopmental outcomes, he concluded.
The study by Shah and colleagues was supported by the Health Research Council of New Zealand and the Maurice and Phyllis Paykel Trust. Dr. Shah disclosed a doctoral fellowship from the University of Auckland. The study by Edwards and colleagues was supported by the Health Research Council of New Zealand and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Ms. Edwards had no financial conflicts to disclose. Dr. Rozance disclosed receiving a StatStrip from Nova Biomedical for use in his laboratory.
FROM JAMA
Neurodevelopmental disorders prevalent with extremely preterm birth
A large registry-based cohort study in Sweden has revealed that 75% of children born before 24 weeks of gestation had neurodevelopmental disorders, including intellectual disabilities and autism, and required habilitative services.
In addition, somatic disorders such as asthma and failure to thrive/short stature were diagnosed in 88% of the cohort. The findings, published in Acta Paediatrica, emphasize the need for further study of this population, especially as survival rates continue to increase.
“The primary aim of this large, retrospective, national study was to report clinical diagnoses registered after children born before 24 weeks were discharged from neonatal care,” explained lead author Eva Morsing, MD, PhD, of Lund (Sweden) University, and colleagues.
Data on diagnoses of neurodevelopmental disorders and selected somatic diagnoses were obtained from national Swedish registries. Study participants’ individual medical files were also examined by the researchers.
Results
The study cohort comprised 383 infants born at a median of 23.3 weeks of gestation (range, 21.9-23.9 weeks). The median birthweight of participants was 565 grams (range, 340-874 grams), with a median birthweight standard deviation (SD) of −0.40 (range, −3.63–3.17).
The majority (75%) of infants had a neurodevelopmental disorder, including speech disorders (52%), intellectual disabilities (40%), attention-deficit/hyperactivity disorder (30%), autism spectrum disorder (24%), visual impairment (22%), cerebral palsy (17%), epilepsy (10%), and hearing impairment (5%).
With respect to gender, a greater number of boys than girls born at 23 weeks had intellectual disabilities (45% vs. 27%; P < .01) and visual impairment (25% vs. 14%; P < .01). Moreover, 55% of the participants were referred for habilitative services.
With respect to somatic diagnoses, failure to thrive/short stature was diagnosed in 39% of the cohort, and it occurred more often in those born at 21 and 22 weeks than in those born at 23 weeks (49% vs. 36%; P < .05).
In addition, asthma and childhood bronchopulmonary dysplasia, pulmonary hypertension, and vocal cord paresis were diagnosed in 63%, 12%, and 13% of participants, respectively.
“Several studies have reported higher rates of preterm morbidities, and poor neurodevelopmental outcomes after extremely preterm birth in boys rather than girls,” study author Ann Hellström, MD, PhD, of the University of Gothenburg, Sweden, said in an interview.
“While the reasons for this were not studied in the present paper, reports in the literature suggest that boys have a higher average growth rate than girls and appear to be more sensitive to suboptimal neonatal nutrition than girls,” Dr. Hellström explained.
“We also know that sex steroids differ in relation to intrauterine life depending on the sex after preterm birth,” Dr. Hellström added.
In an accompanying editorial, Neil Marlow, MD, of University College London, wrote, “One headline from this study [that is interesting] is the high prevalence of autistic spectrum disorders recorded.
“This is a particular finding in extremely preterm cohorts from Sweden, who record more diagnoses than in other longitudinal studies,” Dr. Marlow added. “It certainly warrants further investigation and understanding.”
The researchers acknowledged that a key limitation of the study was the broad age range at the most recent follow-up visit, which ranged from 2 to 13 years, explaining that some diagnoses may occur later in childhood.
“Neonatal clinical practice needs to adopt a long-term perspective and clinicians treating children and adults should be aware of the complicated health problems of children born before 24 weeks,” they concluded.
This study was supported by the Swedish Medical Research Council, the Gothenburg Medical Society, and by grant funding from the Swedish government. The authors reported no relevant disclosures.
A large registry-based cohort study in Sweden has revealed that 75% of children born before 24 weeks of gestation had neurodevelopmental disorders, including intellectual disabilities and autism, and required habilitative services.
In addition, somatic disorders such as asthma and failure to thrive/short stature were diagnosed in 88% of the cohort. The findings, published in Acta Paediatrica, emphasize the need for further study of this population, especially as survival rates continue to increase.
“The primary aim of this large, retrospective, national study was to report clinical diagnoses registered after children born before 24 weeks were discharged from neonatal care,” explained lead author Eva Morsing, MD, PhD, of Lund (Sweden) University, and colleagues.
Data on diagnoses of neurodevelopmental disorders and selected somatic diagnoses were obtained from national Swedish registries. Study participants’ individual medical files were also examined by the researchers.
Results
The study cohort comprised 383 infants born at a median of 23.3 weeks of gestation (range, 21.9-23.9 weeks). The median birthweight of participants was 565 grams (range, 340-874 grams), with a median birthweight standard deviation (SD) of −0.40 (range, −3.63–3.17).
The majority (75%) of infants had a neurodevelopmental disorder, including speech disorders (52%), intellectual disabilities (40%), attention-deficit/hyperactivity disorder (30%), autism spectrum disorder (24%), visual impairment (22%), cerebral palsy (17%), epilepsy (10%), and hearing impairment (5%).
With respect to gender, a greater number of boys than girls born at 23 weeks had intellectual disabilities (45% vs. 27%; P < .01) and visual impairment (25% vs. 14%; P < .01). Moreover, 55% of the participants were referred for habilitative services.
With respect to somatic diagnoses, failure to thrive/short stature was diagnosed in 39% of the cohort, and it occurred more often in those born at 21 and 22 weeks than in those born at 23 weeks (49% vs. 36%; P < .05).
In addition, asthma and childhood bronchopulmonary dysplasia, pulmonary hypertension, and vocal cord paresis were diagnosed in 63%, 12%, and 13% of participants, respectively.
“Several studies have reported higher rates of preterm morbidities, and poor neurodevelopmental outcomes after extremely preterm birth in boys rather than girls,” study author Ann Hellström, MD, PhD, of the University of Gothenburg, Sweden, said in an interview.
“While the reasons for this were not studied in the present paper, reports in the literature suggest that boys have a higher average growth rate than girls and appear to be more sensitive to suboptimal neonatal nutrition than girls,” Dr. Hellström explained.
“We also know that sex steroids differ in relation to intrauterine life depending on the sex after preterm birth,” Dr. Hellström added.
In an accompanying editorial, Neil Marlow, MD, of University College London, wrote, “One headline from this study [that is interesting] is the high prevalence of autistic spectrum disorders recorded.
“This is a particular finding in extremely preterm cohorts from Sweden, who record more diagnoses than in other longitudinal studies,” Dr. Marlow added. “It certainly warrants further investigation and understanding.”
The researchers acknowledged that a key limitation of the study was the broad age range at the most recent follow-up visit, which ranged from 2 to 13 years, explaining that some diagnoses may occur later in childhood.
“Neonatal clinical practice needs to adopt a long-term perspective and clinicians treating children and adults should be aware of the complicated health problems of children born before 24 weeks,” they concluded.
This study was supported by the Swedish Medical Research Council, the Gothenburg Medical Society, and by grant funding from the Swedish government. The authors reported no relevant disclosures.
A large registry-based cohort study in Sweden has revealed that 75% of children born before 24 weeks of gestation had neurodevelopmental disorders, including intellectual disabilities and autism, and required habilitative services.
In addition, somatic disorders such as asthma and failure to thrive/short stature were diagnosed in 88% of the cohort. The findings, published in Acta Paediatrica, emphasize the need for further study of this population, especially as survival rates continue to increase.
“The primary aim of this large, retrospective, national study was to report clinical diagnoses registered after children born before 24 weeks were discharged from neonatal care,” explained lead author Eva Morsing, MD, PhD, of Lund (Sweden) University, and colleagues.
Data on diagnoses of neurodevelopmental disorders and selected somatic diagnoses were obtained from national Swedish registries. Study participants’ individual medical files were also examined by the researchers.
Results
The study cohort comprised 383 infants born at a median of 23.3 weeks of gestation (range, 21.9-23.9 weeks). The median birthweight of participants was 565 grams (range, 340-874 grams), with a median birthweight standard deviation (SD) of −0.40 (range, −3.63–3.17).
The majority (75%) of infants had a neurodevelopmental disorder, including speech disorders (52%), intellectual disabilities (40%), attention-deficit/hyperactivity disorder (30%), autism spectrum disorder (24%), visual impairment (22%), cerebral palsy (17%), epilepsy (10%), and hearing impairment (5%).
With respect to gender, a greater number of boys than girls born at 23 weeks had intellectual disabilities (45% vs. 27%; P < .01) and visual impairment (25% vs. 14%; P < .01). Moreover, 55% of the participants were referred for habilitative services.
With respect to somatic diagnoses, failure to thrive/short stature was diagnosed in 39% of the cohort, and it occurred more often in those born at 21 and 22 weeks than in those born at 23 weeks (49% vs. 36%; P < .05).
In addition, asthma and childhood bronchopulmonary dysplasia, pulmonary hypertension, and vocal cord paresis were diagnosed in 63%, 12%, and 13% of participants, respectively.
“Several studies have reported higher rates of preterm morbidities, and poor neurodevelopmental outcomes after extremely preterm birth in boys rather than girls,” study author Ann Hellström, MD, PhD, of the University of Gothenburg, Sweden, said in an interview.
“While the reasons for this were not studied in the present paper, reports in the literature suggest that boys have a higher average growth rate than girls and appear to be more sensitive to suboptimal neonatal nutrition than girls,” Dr. Hellström explained.
“We also know that sex steroids differ in relation to intrauterine life depending on the sex after preterm birth,” Dr. Hellström added.
In an accompanying editorial, Neil Marlow, MD, of University College London, wrote, “One headline from this study [that is interesting] is the high prevalence of autistic spectrum disorders recorded.
“This is a particular finding in extremely preterm cohorts from Sweden, who record more diagnoses than in other longitudinal studies,” Dr. Marlow added. “It certainly warrants further investigation and understanding.”
The researchers acknowledged that a key limitation of the study was the broad age range at the most recent follow-up visit, which ranged from 2 to 13 years, explaining that some diagnoses may occur later in childhood.
“Neonatal clinical practice needs to adopt a long-term perspective and clinicians treating children and adults should be aware of the complicated health problems of children born before 24 weeks,” they concluded.
This study was supported by the Swedish Medical Research Council, the Gothenburg Medical Society, and by grant funding from the Swedish government. The authors reported no relevant disclosures.
FROM ACTA PAEDIATRICA
Markers in saliva tied to gut disorders in children with autism
Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.
These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.
“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.
The study was published online Jan. 20 in Frontiers in Psychiatry.
Anxiety a key driver?
GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.
Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.
“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.
The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).
The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).
ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.
Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.
TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
Links to GI disturbance, behavior
Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.
As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).
However, rates of GI disturbances in children with ASD were similar to those with DD.
Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.
Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.
Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.
They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.
The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.
The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
First exploration
However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”
The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.
The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.
Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.
The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”
The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.
A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.
The study received funding from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.
These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.
“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.
The study was published online Jan. 20 in Frontiers in Psychiatry.
Anxiety a key driver?
GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.
Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.
“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.
The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).
The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).
ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.
Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.
TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
Links to GI disturbance, behavior
Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.
As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).
However, rates of GI disturbances in children with ASD were similar to those with DD.
Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.
Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.
Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.
They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.
The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.
The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
First exploration
However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”
The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.
The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.
Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.
The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”
The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.
A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.
The study received funding from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
Researchers have identified markers in saliva that are differentially expressed in children with autism spectrum disorder (ASD) who have gastrointestinal (GI) disturbances.
These findings mark the beginning of an understanding of the biological differences separating kids with ASD with and without GI disturbances, study investigator David Q. Beversdorf, MD, professor of radiology, neurology and psychology, department of psychological sciences, University of Missouri, Columbia, told this news organization.
“The hope is this will lead us in future to markers that help guide targeted precision treatments of gastrointestinal disorders” in children with autism, with the ultimate goal of improving their quality of life, said Dr. Beversdorf.
The study was published online Jan. 20 in Frontiers in Psychiatry.
Anxiety a key driver?
GI disorders, particularly constipation, are common in children with ASD. Previous research by Dr. Beversdorf and colleagues suggests that anxiety may be driving the relationship between gut disturbances and autism.
Research shows some children with ASD respond well to traditional treatments such as laxatives, while others do not. However, the reasons for this are unclear.
“It would be great to know who those great responders are,” said Dr. Beversdorf. “Subtyping and using biomarkers might be biologically meaningful” because this could identify distinct groups.
The case-control study included 898 children aged 18-73 months recruited from outpatient pediatric clinics affiliated with seven academic medical centers across the United States. The average age of the sample was 44 months and participants were mainly White (76%), non-Hispanic (89%), and male (73%).
The children fell into three neurodevelopmental categories: ASD (n = 503), non-ASD developmental delay (DD, n = 205), and typical development (TD, n = 190).
ASD was diagnosed using standardized assessment tools including the Autism Diagnostic Observation Scale, second edition (ADOS-2). DD participants had delays in gross motor skills, fine motor skills, language, or cognitive development but did not meet criteria for ASD.
Including children with DD could address whether biological markers are specific to autism or to developmental disorders in general, noted Dr. Beversdorf.
TD participants, recruited at the time of their annual well-child visit, did not exhibit developmental delays.
Links to GI disturbance, behavior
Researchers subdivided participants into those with GI disturbances (n = 184) and those without these disturbances (n = 714). This was based on medical record review and parental report of disorders such as constipation, reflux, chronic diarrhea or abdominal pain, and food intolerance.
As expected, investigators found more children with ASD reported GI disturbance (22%) than with TD (10%). In children with ASD, rates of constipation (11%) and reflux (6%) were higher than rates among those with TD (3% and 0.5%, respectively).
However, rates of GI disturbances in children with ASD were similar to those with DD.
Investigators used a swab to obtain a saliva sample from participants in a nonfasting state. Saliva is a feasible and often favored source for sampling GI-related biology. Unlike stool microbiome, the saliva microbiome can be repeatedly sampled on demand and has shown resilience to antibiotics.
Researchers examined numerous RNAs, which are “incredibly biologically relevant,” said Dr. Beversdorf.
Investigators compared levels of 1,821 micro-transcriptome features across neurodevelopmental status and the presence or absence of GI disorders.
They also examined micro-transcriptome levels among GI subgroups (constipation, reflux, food intolerance, other GI condition, no GI condition). In addition, they identified RNAs that differed among children taking three common GI medications. These included probiotics, reflux medication, or laxatives.
The investigators found five piwi-interacting RNAs, which are small noncoding RNA molecules and three microbial RNAs in saliva that displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI subgroups, with microRNA differences found between food intolerance and reflux groups being the most common.
The analysis identified 12 microRNAs that displayed relationships with GI disturbance, behavior, and GI medication use.
First exploration
However, Dr. Beversdorf cautioned about the medication finding. “I can’t speak confidently about what we see there because with each group you get much, much smaller sample sizes with each individual treatment approach.”
The researchers looked at downstream targets of the 12 microRNAs and found involvement with 13 physiologic pathways. These included long-term depression, metabolism, and digestion pathways.
The metabolism and digestion pathways make sense, but it’s unclear why an addiction-related pathway would be involved, said Dr. Beversdorf. However, he noted children with autism do display obsessive features.
Experts don’t know if RNA changes are a cause of, or a response to, GI problems. “It could be the pain of constipation is triggering, say, these addiction pathway changes,” said Dr. Beversdorf.
The study is the “first exploration” into possible specific targets for treating GI disturbances in autism, said Dr. Beversdorf. “We hope these biomarkers will eventually give us an indication of which patients are going to respond to the individual approach to treating their constipation, their diarrhea, or whatever it is.”
The investigators plan to study whether RNA biomarkers determine which patients respond to different treatments targeting constipation, said Dr. Beversdorf.
A study limitation was that GI disturbances were not assessed by physicians. In addition, the term “GI disturbance” groups together loosely related pathology occurring in the GI tract, although there are important physiologic differences between conditions such as constipation and reflux.
The study received funding from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
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.