Narrowing the diagnostic gap: Autism over 30 years

Paul H. Lipkin

To mark our 30th anniversary, Infectious Diseases in Children will be examining some of the chronic conditions and infectious diseases that have impacted pediatric care over the past 3 decades.

In 1981, English psychiatrist Lorna Wing published an academic paper based on the little-known research of Hans Asperger, an Austrian pediatrician who had described a type of high-functioning autism several years before Leo Kanner’s iconic 1943 article.

Unlike Kanner, Asperger’s research had portrayed autism as an interruption in early brain development rather than a form of cognitive disability. However, as his research was written exclusively in German and seldom translated, Asperger’s contribution to the field remained largely overlooked for nearly 40 years. Discovered anew by Wing, Asperger’s research would later redefine the discussion of developmental disorders and introduce Asperger’s syndrome to the medical lexicon.

Challenging the previously accepted model of autism, Wing used Asperger’s syndrome as supporting evidence for her assertion that autism should be recognized not as a singular disorder but as a spectrum of disorders that shared a common origin. Wing’s influential paper would ignite a heated debate on the appropriate classification of autism disorders, with hundreds of papers published in the ensuing years.

“Over the course of 30 years, we have come to recognize problems that were not focused on previously in terms of children’s development,” Paul H. Lipkin, MD, director of medical informatics and the interactive autism network at Kennedy Krieger Institute and Infectious Diseases in Children editorial board member, said in an interview. “In particular, we have seen improved recognition of autism and related disorders in children, and the important role of social engagement and communication to a child’s development.”

While significant diagnostic progress has been made over the past 30 years, pediatricians still rely heavily on their own examinations in combination with family history and parental perspectives to make an ASD diagnosis. With increasing numbers of children with ASD being seen in the pediatric office, the focus on early diagnosis has never been more pressing.

Addressing an ‘epidemic’

According to 2016 estimates from the CDC’s Autism Developing Disability Monitoring (ADDM) Network, autism spectrum disorders affect one in 68 children – or approximately 1.5% of the U.S. population. Compared with older CDC estimates from the 1980s that cited one in 10,000 children exhibited ASD, this figure represents a staggering rise in the number of children diagnosed with development disabilities.

“More children than ever before are being diagnosed with ASD. [However,] when analyzing changes in ASD prevalence over time, it is important to look at data collection systems using a consistent methodology over time,” Daisy Christensen, PhD, an epidemiologist at the CDC’s National Center on Birth Defects and Developmental Disabilities, told Infectious Diseases in Children. “In 2000, estimated ASD prevalence in the ADDM Network was 6.7 per 1,000 children aged 8 years; by 2012, estimated ASD prevalence more than doubled, to 14.6 per 1,000 children aged 8 years.”

While these baffling increases have led both political officials and lay media outlets to declare an ‘autism epidemic,’ the epidemiology of ASD has never supported this conclusion. There is no argument that the number of ASD diagnoses has increased; however, recent data indicate that, these figures are a result of broadened diagnostic criteria, increased surveillance and improved public awareness.

Susan E. Levy

“The drastic changes in the diagnostic criteria since the 1980s have fueled this reported increase in ASD prevalence,” Susan E. Levy, MD, MPH, a developmental pediatrician at Children’s Hospital of Philadelphia and Chair of the AAP Autism Subcommittee, said in an interview with Infectious Diseases in Children. “The current diagnostic criteria include children with different ranges of ability in categories that would not have been considered in 1980.”

She added, “For instance, the ‘infantile autism’ category that researchers focused on in 1980 was reserved for the profoundly impaired, who probably also exhibited severe intellectual disabilities and behavior problems, and thus included severe autism; diagnostic criteria in the 2000s not only included children with severe autism and intellectual disabilities, but also those with Asperger’s syndrome and the now defunct PDDNOS category.”

Although epidemiological studies over the past decade have not conclusively ruled out a ‘true increase’ in the incidence of ASD, neither do they support one; instead, the rise in ASD numbers appears to be associated more with increased parental awareness and improved early diagnosis by pediatricians.

Pediatricians on the front lines

Early diagnosis of ASD can be exceedingly challenging during primary care visits because, unlike other conditions that may rely on laboratory tests the pediatrician must instead make a diagnosis based on the presence — or lack thereof — of a pattern of symptoms.

“The earlier a child is identified with ASD, the earlier services and treatment can begin,” Christensen said in an interview. “Therefore, to help improve early identification of ASD, in 2007 the AAP recommended that all children should be screened specifically for ASD during regular well-child visits at 18 and 24 months of age.”

Additional screening might be warranted if a child is at high risk for ASD, for example, if they have an older sibling affected by autism or if parents note behaviors that could be associated with ASD. Although parental observations and concerns are often essential to a timely ASD diagnosis, recent research demonstrates that pediatricians occasionally fail to take these concerns seriously, much to the detriment of their patients.

In a study published in The Journal of Pediatrics, among children diagnosed with autism vs. intellectual disabilities and developmental delays, Zuckerman and colleagues found that pediatricians were 14% less likely to take a proactive approach when parents expressed concerns about autism.

“Children who are diagnosed earlier and receive early intervention quickly perform better in all developmental areas,” Levy said. “Pediatricians should be routinely asking parents if they have any questions regarding their child’s development or behavior. It is essential that pediatricians and families work together with other providers to screen for autism, act on concerns expressed by parents and obtain referrals for further evaluations.”

Striking the root

More so than other childhood conditions, the search for potential causes of ASD has been plagued by red herrings as parent groups attempt to link ASD to specific ‘controllable’ environmental factors; pediatricians are still living in the shadow of the famously debunked 1998 research of Andrew Wakefield linking autism to measles-mumps-rubella vaccines. Although researchers continue to investigate a variety of environmental factors, in recent years, research has shown genetic predisposition to be the leading risk factor for ASD.

“Children who have a sibling with ASD are at a higher risk of also having ASD, and ASD tends to occur more often in people who have certain genetic or chromosomal conditions, such as fragile X syndrome or tuberous sclerosis,” Christensen said.

Additionally, in a recent study published in JAMA Psychiatry, Colvert and colleagues determined that genetic heritability of ASD was high compared with other risk factors; in their analysis of 258 twins, researchers estimated that 56-95% of the autism effect had a genetic origin.

“What has become clear is that there are a wide range of gene abnormalities that we now know are causing problems in the autism spectrum,” Lipkin said. “Our hope is that by better understanding these gene abnormalities, clinicians will be able to make improvements in the health and well-being of children with ASD through medical interventions.”

Researchers have not yet identified a single gene that can be held responsible for ASD development; however, investigations into its root cause continue with research investigating the possibility of a multiple gene involvement, a latent susceptibility to ASD, problems during pregnancy, as well as environmental factors including metabolic imbalance and chemical exposure.

“Children born to older parents, born at low birth weight or premature are at greater risk for ASD,” Christensen said. “In addition, maternal use of certain prescription drugs during pregnancy, such as valproic acid and thalidomide, has been linked with a higher risk of ASD.”

Considering the dramatic shifts in the diagnosis of ASD in children over the past 3 decades, ongoing surveillance and feedback from experienced pediatricians is essential for the future of autism analysis and treatment. As the first contact for children with ASD, pediatricians will be vital in identifying the possible risk factors and causes of ASD, as well as developing the resources needed to address developmental issues early on. – by Kate Sherrer and Bob Stott

Disclosures: Lipkin receives support from the Simon Foundation and Patients and Outcomes Researchers (PECOR). Christensen and Levy report no relevant financial disclosures.

Paul H. Lipkin

To mark our 30th anniversary, Infectious Diseases in Children will be examining some of the chronic conditions and infectious diseases that have impacted pediatric care over the past 3 decades.

In 1981, English psychiatrist Lorna Wing published an academic paper based on the little-known research of Hans Asperger, an Austrian pediatrician who had described a type of high-functioning autism several years before Leo Kanner’s iconic 1943 article.

Unlike Kanner, Asperger’s research had portrayed autism as an interruption in early brain development rather than a form of cognitive disability. However, as his research was written exclusively in German and seldom translated, Asperger’s contribution to the field remained largely overlooked for nearly 40 years. Discovered anew by Wing, Asperger’s research would later redefine the discussion of developmental disorders and introduce Asperger’s syndrome to the medical lexicon.

Challenging the previously accepted model of autism, Wing used Asperger’s syndrome as supporting evidence for her assertion that autism should be recognized not as a singular disorder but as a spectrum of disorders that shared a common origin. Wing’s influential paper would ignite a heated debate on the appropriate classification of autism disorders, with hundreds of papers published in the ensuing years.

“Over the course of 30 years, we have come to recognize problems that were not focused on previously in terms of children’s development,” Paul H. Lipkin, MD, director of medical informatics and the interactive autism network at Kennedy Krieger Institute and Infectious Diseases in Children editorial board member, said in an interview. “In particular, we have seen improved recognition of autism and related disorders in children, and the important role of social engagement and communication to a child’s development.”

While significant diagnostic progress has been made over the past 30 years, pediatricians still rely heavily on their own examinations in combination with family history and parental perspectives to make an ASD diagnosis. With increasing numbers of children with ASD being seen in the pediatric office, the focus on early diagnosis has never been more pressing.

Addressing an ‘epidemic’

According to 2016 estimates from the CDC’s Autism Developing Disability Monitoring (ADDM) Network, autism spectrum disorders affect one in 68 children – or approximately 1.5% of the U.S. population. Compared with older CDC estimates from the 1980s that cited one in 10,000 children exhibited ASD, this figure represents a staggering rise in the number of children diagnosed with development disabilities.

“More children than ever before are being diagnosed with ASD. [However,] when analyzing changes in ASD prevalence over time, it is important to look at data collection systems using a consistent methodology over time,” Daisy Christensen, PhD, an epidemiologist at the CDC’s National Center on Birth Defects and Developmental Disabilities, told Infectious Diseases in Children. “In 2000, estimated ASD prevalence in the ADDM Network was 6.7 per 1,000 children aged 8 years; by 2012, estimated ASD prevalence more than doubled, to 14.6 per 1,000 children aged 8 years.”

While these baffling increases have led both political officials and lay media outlets to declare an ‘autism epidemic,’ the epidemiology of ASD has never supported this conclusion. There is no argument that the number of ASD diagnoses has increased; however, recent data indicate that, these figures are a result of broadened diagnostic criteria, increased surveillance and improved public awareness.

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Susan E. Levy

“The drastic changes in the diagnostic criteria since the 1980s have fueled this reported increase in ASD prevalence,” Susan E. Levy, MD, MPH, a developmental pediatrician at Children’s Hospital of Philadelphia and Chair of the AAP Autism Subcommittee, said in an interview with Infectious Diseases in Children. “The current diagnostic criteria include children with different ranges of ability in categories that would not have been considered in 1980.”

She added, “For instance, the ‘infantile autism’ category that researchers focused on in 1980 was reserved for the profoundly impaired, who probably also exhibited severe intellectual disabilities and behavior problems, and thus included severe autism; diagnostic criteria in the 2000s not only included children with severe autism and intellectual disabilities, but also those with Asperger’s syndrome and the now defunct PDDNOS category.”

Although epidemiological studies over the past decade have not conclusively ruled out a ‘true increase’ in the incidence of ASD, neither do they support one; instead, the rise in ASD numbers appears to be associated more with increased parental awareness and improved early diagnosis by pediatricians.

Pediatricians on the front lines

Early diagnosis of ASD can be exceedingly challenging during primary care visits because, unlike other conditions that may rely on laboratory tests the pediatrician must instead make a diagnosis based on the presence — or lack thereof — of a pattern of symptoms.

“The earlier a child is identified with ASD, the earlier services and treatment can begin,” Christensen said in an interview. “Therefore, to help improve early identification of ASD, in 2007 the AAP recommended that all children should be screened specifically for ASD during regular well-child visits at 18 and 24 months of age.”

Additional screening might be warranted if a child is at high risk for ASD, for example, if they have an older sibling affected by autism or if parents note behaviors that could be associated with ASD. Although parental observations and concerns are often essential to a timely ASD diagnosis, recent research demonstrates that pediatricians occasionally fail to take these concerns seriously, much to the detriment of their patients.

In a study published in The Journal of Pediatrics, among children diagnosed with autism vs. intellectual disabilities and developmental delays, Zuckerman and colleagues found that pediatricians were 14% less likely to take a proactive approach when parents expressed concerns about autism.

“Children who are diagnosed earlier and receive early intervention quickly perform better in all developmental areas,” Levy said. “Pediatricians should be routinely asking parents if they have any questions regarding their child’s development or behavior. It is essential that pediatricians and families work together with other providers to screen for autism, act on concerns expressed by parents and obtain referrals for further evaluations.”

Striking the root

More so than other childhood conditions, the search for potential causes of ASD has been plagued by red herrings as parent groups attempt to link ASD to specific ‘controllable’ environmental factors; pediatricians are still living in the shadow of the famously debunked 1998 research of Andrew Wakefield linking autism to measles-mumps-rubella vaccines. Although researchers continue to investigate a variety of environmental factors, in recent years, research has shown genetic predisposition to be the leading risk factor for ASD.

“Children who have a sibling with ASD are at a higher risk of also having ASD, and ASD tends to occur more often in people who have certain genetic or chromosomal conditions, such as fragile X syndrome or tuberous sclerosis,” Christensen said.

Additionally, in a recent study published in JAMA Psychiatry, Colvert and colleagues determined that genetic heritability of ASD was high compared with other risk factors; in their analysis of 258 twins, researchers estimated that 56-95% of the autism effect had a genetic origin.

“What has become clear is that there are a wide range of gene abnormalities that we now know are causing problems in the autism spectrum,” Lipkin said. “Our hope is that by better understanding these gene abnormalities, clinicians will be able to make improvements in the health and well-being of children with ASD through medical interventions.”

Researchers have not yet identified a single gene that can be held responsible for ASD development; however, investigations into its root cause continue with research investigating the possibility of a multiple gene involvement, a latent susceptibility to ASD, problems during pregnancy, as well as environmental factors including metabolic imbalance and chemical exposure.

PAGE BREAK

“Children born to older parents, born at low birth weight or premature are at greater risk for ASD,” Christensen said. “In addition, maternal use of certain prescription drugs during pregnancy, such as valproic acid and thalidomide, has been linked with a higher risk of ASD.”

Considering the dramatic shifts in the diagnosis of ASD in children over the past 3 decades, ongoing surveillance and feedback from experienced pediatricians is essential for the future of autism analysis and treatment. As the first contact for children with ASD, pediatricians will be vital in identifying the possible risk factors and causes of ASD, as well as developing the resources needed to address developmental issues early on. – by Kate Sherrer and Bob Stott

Disclosures: Lipkin receives support from the Simon Foundation and Patients and Outcomes Researchers (PECOR). Christensen and Levy report no relevant financial disclosures.